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Printed in the USA
Libr ar y of Congress Cataloging-in-Publication Data
9-780-7817-7823-7
0-7817-7823-9
Marino, Paul L.
The little ICU book of facts and formulas / Paul L. Marino ; with contributions from
Kenneth M. Sutin.
p. ; cm.
Based on: The ICU book / Paul L. Marino. 2007.
Includes bibliographical references and index.
ISBN-13: 978-0-7817-7823-7
ISBN-10: 0-7817-7823-9
1. Critical care medicine--Handbooks, manuals, etc. 2. Intensive care units--Handbooks,
manuals, etc. I. Sutin, Kenneth M. II. Marino, Paul L. ICU book. III. Title.
[DNLM: 1. Critical Care--Handbooks. 2. Intensive Care Units--Handbooks.
WX 39 M339L 2008]
RC86.8.M3864 2008
616.02'8--dc22
2008018875
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pleteness, or accuracy of the contents of the publication. Application of the information in
a particular situation remains the professional responsibility of the practitioner.
The authors, editors, and publisher have exerted every effort to ensure that drug selection
and dosage set forth in this text are in accordance with current recommendations and prac-
tice at the time of publication. However, in view of ongoing research, changes in govern-
ment regulations, and the constant flow of information relating to drug therapy and drug
reactions, the reader is urged to check the package insert for each drug for any change in
indications and dosage and for added warnings and precautions. This is particularly impor-
tant when the recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in the publication have Food and Drug Admin-
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bility of the health care provider to ascertain the FDA status of each drug or device planned
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10 9 8 7 6 5 4 3 2 1
To Daniel Joseph Marino,
my 20-year-old son,
who is raising his sails,
and waiting for that breeze.
A wise man recognizes the convenience of a general statement,
but he bows to the authority of a particular fact.
OLIVER WENDELL HOLMES
(1872)
Preface

As the title im p lies, The Little ICU Book is a sm aller, m ore con-
d ensed version of its old er sibling, The ICU Book, and is in-
tend ed as com pact reference for the bed sid e. A m ajority of
the chap ter titles in The ICU Book have been retained in the
little book, but each chap ter has been com p letely rew ritten
to inclu d e only the m ost essential inform ation, and the con-
tent is presented in ou tline form for easy access. Althou gh
sm all in stature, The Little ICU Book is d ensely packed w ith
facts and form u las that represent the essentials of patient
care in the (ad u lt) ICU.

ix
Acknowledgments

This w ork ow es its existence to the consid erable efforts and


expertise of Patricia Gast, w ho is resp onsible for all the illu s-
trations, tables, and p age layou ts in this book. H er p atience
and cap acity for exhau stive w ork are exceed ed only by her
talent.
Also to Brian Brow n and N icole Dernoski at Lippincott Wil-
liam s & Wilkins, for their tru st and end u ring su pp ort.
And finally to Vivienne DeStefano, w ho has becom e so im -
p ortant to this au thor and his w ork in so m any w ays.
PLM

xi
Contents

I. PREVENTIVE PRACTICES IN THE CRITICALLY ILL


1 Infection Control in the ICU 1
2 Stress-Related Mu cosal Inju ry 19
3 Venous Throm boem bolism 31

II.VASCULAR ACCESS
4 Vascu lar Catheters 53
5 Establishing Venou s Access 61
6 The Ind w elling Vascu lar Catheter 77

III. HEMODYNAMIC MONITORING


7 The Pu lm onary Artery Catheter 97
8 Card iac Filling Pressu res 113
9 System ic Oxygenation 125

IV. DISORDERS OF CIRCULATORY FLOW


10 H em orrhage and H ypovolem ia 139
11 Colloid and Crystalloid Resu scitation 157
12 Acu te H eart Failu re(s) 173
13 Card iac Arrest 189

xiii
xiv Contents

V. CRITICAL CARE CARDIOLOGY


14 Acu te Coronary Synd rom es 209
15 Tachycard ias 233

VI. COMMON PULMONARY DISORDERS


16 Acu te Respiratory Distress Synd rom e 255
17 Asthm a and COPD in the ICU 269

VII. MECHANICALVENTILATION
18 Basics of Mechanical Ventilation 283
19 Mod es of Positive-Pressu re Breathing 299
20 The Ventilator-Dep end ent Patient 315
21 Discontinu ing Mechanical Ventilation 333

VIII. ACID-BASE DISORDERS


22 Acid -Base Interp retations 349
23 Organic Acid oses 363
24 Metabolic Alkalosis 379

IX. RENAL AND ELECTROLYTE DISORDERS


25 Oligu ria and Acu te Renal Failu re 391
26 H yp ertonic and H yp otonic Cond itions 409
27 Potassiu m 427
28 Magnesiu m 443
29 Calciu m and Phosphoru s 457

X.TRANSFUSION PRACTICES IN CRITICAL CARE


30 Anem ia and Erythrocyte Transfu sions 477
31 Throm bocytopenia and Platelet Transfu sions 493
Contents xv

XI. INFLAMMATION AND INFECTION IN THE ICU


32 Fever in the ICU 505
33 Infection, Inflam m ation, and Mu ltiorgan Inju ry 521
34 Pneu m onia in the ICU 535
35 Sep sis from the Abd om en and Pelvis 549

XII. NUTRITION AND METABOLISM


36 N u tritional Requ irem ents 563
37 Enteral Tube Feed ing 577
38 Total Parenteral N u trition 591
39 Ad renal and Thyroid Dysfu nction 603

XIII. CRITICAL CARE NEUROLOGY


40 Disord ers of Mentation 613
41 Disord ers of Movem ent 627
42 Acu te Stroke 641

XIV. PARENTERAL DRUGTHERAPIES IN THE ICU


43 Analgesia and Sed ation 653
44 Antim icrobial Therap y 671
45 H em od ynam ic Dru gs 689

XV.TOXICOLOGY
46 Pharm aceutical Toxins & Antid otes 705

XVI. APPENDICES
1 Units and Conversions 719
2 Selected Reference Ranges 725
3 Ad d itional Form u las 731
Ind ex 735
Chapter 1
INFECTION CONTROL
INTHE ICU
This chap ter d escribes the p atient care p ractices that are
d esigned to prevent the grow th and spread of pathogenic
organism s in the hosp ital setting.

I. SKIN HYGIENE
Com m on organism s isolated from the skin of ICU p ersonnel
are (in ord er of d ecreasing p revalence): Staphylococcus epider-
midis (over 90% of peop le cu ltu red ), gram -negative aerobic
bacilli (20%), Cand id a sp ecies (15%) and Staphylococcus au-
reus (5 10%). Erad icating these organism s from the skin is
a m ajor concern of infection control.

A. Soap and Water


Soap s are d etergents that can d isp erse p articu late and organ-
ic m atter, bu t they lack antim icrobial activity. Cleaning the
skin w ith p lain soap and w ater w ill rem ove d irt and grease
bu t w ill not erad icate the m icrobial flora on the skin. The
erad ication of m icrobes (called decontamination) requ ires the
ap p lication of agents that have antim icrobial activity.

B. Antiseptic Agents
Antim icrobial agents used to d econtam inate the skin are
called antiseptics, and those u sed to d econtam inate inanim ate
objects are called disinfectants. The antiseptic agents used
most com m only are d escribed below (see Table 1.1) (1-3).

1
2 Preventive Practices in the Critically Ill

TABLE 1.1 Common Antiseptic Agents


Agent Major Advantage Major Disadvantage
Alcohol Broad coverage Little residual activity
Iodophors Broad coverage Inconsistent residual
activity
Chlorhexidine Good residual activity Limited coverage
( 6 hrs)
From References 13.

1. Alcohols
The alcohols (ethanol, p rop anol, isop rop yl alcohol) are
germ icid al against m ost bacteria, fungi, and viru ses
(includ ing H IV).
a. Alcohols have a rapid onset of action, bu t have little
p ersistent (resid u al) activity.
b. Repeated use of aqu eou s alcohol solu tions can cause
d rying and irritation of the skin. This effect is m in-
im ized w hen a w aterless alcohol gel is u sed .
c. The alcohols are less effective in the p resence of d irt
and organic m atter, so skin that is d irty or soiled w ith
bod y fluid s shou ld be cleaned before applying alcohol.

2. Iodophors
Iod ine has broad -sp ectru m germ icid al activity (like the
alcohols), but it is irritating to the skin and soft tissues.
Skin irritation is red u ced by em p loying a carrier m ole-
cu le to release iod ine slow ly. Iod ine p reparations that use
a carrier m olecule are called iod op hors. The m ost p opu -
lar iod op hor in the United States is p ovid one-iod ine.
a. Since the active ingred ient in iod op hors (iod ine) is re-
leased slow ly, iod op hors m u st be left in contact w ith
the skin for a few minutes to achieve maxim um anti-
Infection Control in the ICU 3

sep sis. Prolonged contact w ith iod ine can be irritating,


so iod ophors shou ld be w iped from the skin after d ry-
ing. This rem oval lim its the persistent (resid u al) anti-
sep tic activity.
b. Iod ophors are neu tralized by organic m atter, so skin
that is soiled w ith blood and bod y flu id s shou ld be
cleaned before applying an iod ophor.

3. Chlorhexidine
Chlorhexid ine gluconate is a germ icid al agent that is
effective against gram -p ositive bacteria, bu t has less ac-
tivity than alcohol and iod op hors against gram -negative
bacilli and fu ngi.
a. The m ajor ad vantage of chlorhexid ine is its prolonged
activity, w hich can last for 6 hou rs or longer (2). This
activity is red uced by soaps and hand creams.
b. Chlorhexid ine is available in 0.5% to 4% aqu eou s solu -
tions. The 4% solu tion is m ost effective, bu t rep eated
u se can cau se skin irritation. Chlorhexid ine is also an
ocu lar irritant, and care should be taken to avoid con-
tact w ith the eyes.

4. Spore-Forming Organisms
Antiseptic agents are not effective against spore-form ing
organism s like Clostridium difficile and Bacillus anthracis
(1). Prop er u se of gloves is requ ired to p revent the sp read
of these organism s.

C. Handwashing
Appropriate hand w ashing is the cornerstone of infection
control, and Table 1.2 p resents the gu id elines for hand w ash-
ing issu ed by the Centers for Disease Control.

1. General Recommendations
a. Antisep tic soap s and gels are p referred to p lain soap
and w ater for hand w ashing.
4 Preventive Practices in the Critically Ill

TABLE 1.2 Recommendations for Handwashing


I. Handwashing with soap (plain or antiseptic) and water is
recommended:
1. When hands are dirty or soiled with blood or body fluids.
2. Before eating.
3. After leaving a restroom.
II. Handwashing with an antiseptic preparation* is recommended:
1. Before direct contact with a patient.
2. After contact with a patients skin (intact or non-intact).
3. After contact with body fluids, secretions, excretions, mucous
membranes, wound dressings, and contaminated items.
4. Before donning sterile gloves to insert central intravascular
catheters or other invasive devices that do not require a
surgical procedure.
5. Before inserting urinary catheters, peripheral venous
catheters, or other invasive devices that do not require a
surgical procedure.
6. After removing gloves.
7. When moving from a contaminated to a clean body site.
8. After contact with inanimate objects in the immediate vicinity
of the patient.
*A waterless alcohol gel is preferred to antiseptic soaps, but the
hands must be clean prior to application.
From References 2 and 3.

b. If the hand s are not visibly soiled , a w aterless alcohol


gel is recom m end ed for hand w ashing (alcohol has
proven m ore effective than iod op hors or chlorhexid ine
for red u cing bacterial cou nts on the hand s) (3). The gel
shou ld be ru bbed into the hand s u ntil the hand s feel
d ry.
c. Antiseptic soap s are recom m end ed w hen the hand s
are d irty or soiled w ith bod y flu id s. The soap shou ld
Infection Control in the ICU 5

be ru bbed over the entire su rface of the hand s for at


least 30 second s (2,3). The soap is then rem oved w ith a
tap w ater rinse, and the hand s shou ld be d ried com -
p letely (resid u al m oistu re on the skin w ill prom ote
microbial grow th).
d . H ot w ater is not recom m end ed for hand w ashing (3)
becau se it is not m ore effective than w arm or cold
w ater for rem oving skin m icrobes (4), and it can be ir-
ritating to the skin.
e. Du ring hand w ashing, sp ecial attention shou ld be gi-
ven to the su bu ngu al areas u nd er the fingernails,
w here m icrobes tend to congregate.
Despite the im p ortance of hand w ashing, surveys reveal
that only a sm all p ercentage of ICU p ersonnel ad here to
the hand w ashing gu id elines, and p hysicians are consis-
tently the w orst offend ers (1-3).

II. PROTECTIVE BARRIERS


Protective barriers like gloves, gow ns, m asks, and eye
shield s p rovid e a p hysical im p ed im ent to the transm ission
of infectiou s agents in blood and bod y flu id s.

A. Gloves
1. Indications
The tasks that requ ire gloves (sterile and nonsterile) are
listed in Table 1.3.
a. Sterile gloves are requ ired w hen catheters are p laced
in arteries, large central veins, and closed sp aces
(inclu d ing the ep id u ral and su barachnoid sp aces).
b. N onsterile gloves are used for contact w ith blood ,
bod y flu id s, secretions, excretions, nonintact skin, and
m u cou s m em branes.
6 Preventive Practices in the Critically Ill

c. N onsterile gloves can be used for insertion of periph-


eral vein catheters as long as a no tou ch techniqu e is
used (i.e., the gloved hand s d o not tou ch the shaft of
the catheter).

2. Gloves and Handwashing


a. The u se of gloves d oes not elim inate the need for
hand w ashing.
b. H and w ashing is recom m end ed both before d onning
gloves, and again after the gloves are rem oved .

3. Latex Allergy
Latex is a natu ral rubber prod uct that is u sed in the m an-
ufactu re of several m ed ical p rod u cts, inclu d ing gloves,
face m asks, blood pressure cu ffs, and catheters. Rep eated
exposu re to latex can p rom ote hyp ersensitivity reactions.
a. Latex hyp ersensitivity is rep orted in 10% to 20% of
hospital w orkers, com p ared to 1% of the general p op-
ulation (8). It is particu larly p revalent in p atients w ith
spina bifid a (u p to 40% of patients), for u nclear rea-
sons.
b. The clinical m anifestations of latex allergy can inclu d e
atop ic d erm atitis (u rticaria or eczem a), anap hylaxis,
rhinoconju nctivitis, or asthm a (8,9).
c. The d iagnosis of latex allergy can be elu sive because
the clinical p resentation is nonspecific, and some of the
manifestations (rhinoconjunctivitis and asthm a) d o
ap pear w ithout d irect contact w ith latex. Allergic reac-
tions that are w ork-related (i.e., ap p ear w hen at w ork
and d isap p ear w hen aw ay from w ork) shou ld raise
su sp icion of latex allergy.
d . There are tw o tests for latex hypersensitivity: a skin
test, and an assay for latex-sp ecific IgE levels in the
blood stream . Both have shortcom ings. The latex-spe-
cific IgE assay is cu rrently the favored test, bu t the sen-
sitivity can be low (10).
Infection Control in the ICU 7

TABLE 1.3 Recommendations for Glove Use in the ICU


I. Sterile gloves must be worn for the following procedures:
1. Central venous catheterization.
2. Peripherally-inserted central catheters.
3. Arterial catheterization.
4. Placement of drainage catheters in a closed space (pleural,
pericardial. or peritoneal cavities).
5. Insertion of epidural or intraventricular catheters.
II. Nonsterile gloves are recommended for the following situations:
1. When there is contact with blood, body fluids, secretions,
excretions, nonintact skin, and mucous membranes.
2. Insertion of peripheral venous catheters (the gloved hands
must not touch the catheter).
III. General recommendations:
1. Handwashing is recommended before glove use, and again
after gloves are removed.
2. Gloves should be changed between tasks involving the same
patient if there has been contact with potentially infectious
material.
3. Gloves should be removed immediately after use. before con-
tact with noncontaminated objects in the environment, and
before going to another patient.
From References 57.

e. The treatm ent of latex allergy includ es sym ptom relief


and rem oval of latex from the su bjects environm ent.
Latex-free (vinyl) gloves are available in m ost hosp i-
tals, bu t com p lete rem oval of latex from the hospital
environm ent is often not possible becau se of the large
nu m ber of med ical prod u cts that contain latex (it is
even found on tongue d epressors).
8 Preventive Practices in the Critically Ill

B. Masks & Other Barriers


Face m asks, eye shield s, and gow ns are also u sed as p hysical
barriers to infectious agents. These barriers are recom m end -
ed for any proced ure or patient care activity that cou ld gen-
erate a sp lash of blood , bod y flu id s, secretions, or excretions.

1. Face Masks
There are tw o general typ es of face m asks: su rgical m asks
and resp irators.
a. Surgical m asks d o not p rovid e an effective barrier for
airborne p athogens, and they shou ld not be u sed as a
p reventive m easu re for airborne illnesses. The p op u-
larity of these m asks in the ICU is u nfou nd ed .
b. Respirators are d evices that protect the w earer from
inhaling a d angerou s su bstance. Particu late resp ira-
tors block particu late m atter, and can block the inhala-
tion of airborne p athogens, especially the tu bercle
bacillu s. The m ost effective of these d evices is the
N 95 respirator (11): the N ind icates that the m ask
w ill block non-oil based or aqu eou s aerosols (the type
that transm its the tu bercle bacillu s), and the 95 ind i-
cates the m ask w ill block 95% of the intend ed p articles.

2. Airborne Illness
Infectiou s p articles that are cap able of airborne trans-
mission are d ivid ed into tw o categories: those greater
than 5 m icrons (> 5) in d iam eter, and those that are
5 m icrons or less ( 5) in d iam eter. The organism s and
airborne illnesses in each category are show n in Figu re
1.1.
a. The larger airborne particles (> 5 in d iam eter) u su al-
ly travel no farther than 3 feet throu gh the air, and
to prevent transm ission of these particles, a su rgical
m ask is recom m end ed (d esp ite lack of p roven effica-
cy!) w hen hosp ital staff or visitors are w ithin 3 feet of
the patient (5).
Infection Control in the ICU 9

b. The sm aller ( 5 in d iam eter) infectiou s p articles can


travel long d istances in the air. To p revent transm is-
sion of these p articles, p atients shou ld be isolated in
p rivate room s that are m aintained at a negative pres-
su re relative to the su rrou nd ing areas.
c. For patients w ith infectious tuberculosis (pulm onary
or laryngeal), all hosp ital staff and visitors shou ld
w ear an N 95 resp irator m ask w hile in the room (5,12).

RES PIRATORY PRECAUTIONS FOR AIRBORNE INFECTIONS

PATHOGENS & INFECTIONS

Larg e Dro ple ts (> 5 in diame te r)


RES P IRATORY P RECAUTIONS
He mophilus influe nza (type b),
e piglottitis, pne umonia , a nd me ningitis
Ne is s e ria me ningitidis pne umonia , 1. P la ce pa tie nt in priva te room.
a nd me ningitis If unava ila ble , pa tie nt s hould
not be within 3 fe e t of othe r
Ba cte ria l re s pira tory infe ctions : noninfe ctious pa tie nts.
A. Diphthe ria (pha rynge a l)
B. Mycopla s ma pne umonia 2. Hos pita l s ta ff a nd vis itors
C. Group A s tre p pha ryngitis s hould we a r a s urgica l ma s k
a nd pne umonia whe n within 3 fe e t of the pa tie nt.
Vira l re s pira tory infe ctions :
A. Influe nza
B. Ade novirus
C. Mumps
D. Rube lla

S mall Dro ple ts ( 5 in diame te r)


1. P la ce pa tie nt in ne ga tive
Mycoba cte rium tube rculos is pre s s ure is ola tion room.
(pulmona ry a nd la rynge a l TB)
2. For infe ctious pulmona ry TB,
Me a s le s hos pita l s ta ff a nd vis itors
Va rice lla s hould we a r N95 re s pira tor
(including dis s e mina te d zos te r) ma s ks while in the room.
3. For infe ctious me a s le s or
va rice lla , thos e without a prove n
his tory of infe ction s hould not
e nte r the room, or s hould we a r
a n N95 re s pira tor ma s k while in
the room.

FIGURE 1.1. Recommendations for preventing the spread of airborne


pathogens. (From Reference 5).
10 Preventive Practices in the Critically Ill

d . For p atients in the infectiou s stages of ru beola


(m easles) and varicella (chickenpox or herpes zoster),
ind ivid uals w ith no prior history of these infections
w ho are also p regnant, im m u nocom p rom ised , or
d ebilitated by d isease shou ld not be allow ed in the
patients room . Other su scep tible ind ivid u als can en-
ter the room , bu t they m u st w ear an N 95 resp irator
mask.

III. BLOOD-BORNE INFECTIONS


The greatest infectiou s risk for ICU p ersonnel is exp osu re to
blood -borne p athogens like H IV, hep atitis B viru s (H BV),
and hepatitis C viru s (H CV). This section w ill d escribe the
occu p ational risks and p reventive m easu res for blood -borne
illnesses.

A. Needlestick Injuries
Transm ission of blood -borne infections to hosp ital w orkers
occurs p rim arily via need lestick inju ries. Each year, about
10% of hosp ital w orkers su stain a need lestick inju ry (13),
and over 50% of hou sestaff and m ed ical stu d ents rep ort a
need lestick inju ry at som e time d u ring their training (14).

1. Safety-Engineered Needles
Outsid e the op erating room , m ost need lestick injuries
occu r d u ring recap p ing and d isp osal of u sed need les
(13). To p revent need lestick inju ries d u ring recap p ing,
hollow need les are now equ ip p ed w ith a p rotective plas-
tic hou sing that snap s in p lace over the need le after it is
used . Su ch safety-engineered need les are now m and at-
ed by law in all health care facilities in the United States.
Infection Control in the ICU 11

B. Human Immunodeficiency Virus (HIV)


The sp read of H IV to hosp ital w orkers is u niversally feared ,
bu t is rare. In fact, there are only 56 cases of H IV seroconver-
sion in healthcare w orkers that can be d efinitely linked to
H IV transm ission in the w orkp lace (13).

1. Percutaneous Exposures
Transm ission of H IV via need lestick inju ries is u ncom -
mon.
a. A single need lestick inju ry w ith blood from an H IV-
infected p atient carries an average 0.3% risk of H IV
seroconversion (13,15). Factors that increase the risk of
transm ission inclu d e a d eep skin p u nctu re, visible
blood on the need le, and inju ry from a need le that w as
p laced in an artery or vein of the sou rce p atient.

2. Mucous Membrane Exposures


The risk of H IV transm ission throu gh m u cou s m em -
branes or nonintact skin is even less than the risk from
need lestick injuries.
a. A single exp osu re of broken skin or m u cou s m em -
branes to blood from an H IV-infected p atient carries
an average 0.09% risk of H IV seroconversion (13,15).

3. Postexposure Management
When a hospital w orker su stains a need lestick inju ry, the
H IV statu s of the source patient is used to d eterm ine the
need for H IV p rop hylaxis w ith antiretroviral d ru gs. This
is ou tlined in Table 1.4.
a. If H IV infection is p roven or su sp ected in the sou rce
p atient, p rop hylaxis w ith 2 antiretroviral agents is
started im m ed iately. A third d ru g is ad d ed if the
sou rce p atient has sym p tom atic H IV infection.
12 Preventive Practices in the Critically Ill

TABLE 1.4 Indications for Antiretroviral Drugs Following


Possible HIV Exposure
No Drugs Two Drugs 1 Three Drugs 2
1. When source is 1.When source is 1.When source is
HIV-negative HIV-positive but HIV-positive and
asymptomatic symptomatic
2. When HIVstatus 2.When HIVstatus 2.When source is
of source is not of source is not HIV-positive and
known but HIV known but HIV asymptomatic
is unlikely3 is likely3 but exposure is
severe5
3. When source is 3.When source is
not known but not known but
HIVis unlikely4 HIVis likely4
From Reference 15.
1 The recommended two-drug regimen is zidovudine (200 mg TID)

plus lamivudine (150 mg BID) for 4 weeks . The two agents are
available together as COMBIVIR.
2 Add one of the following drugs to the two-drug regimen: efavirenz

(600 mg at bedtime), indinavir (800 mg every 8 hrs , between


meals ), or nelfinavir (2.5 g daily in 2 or 3 divided dos es , with
meals ).
3 When the HIV s tatus of the s ource is unknown, the likelihood of

HIV is bas ed on the pres ence or abs ence of ris k factors .


4 When the s ource is unknown, the likelihood of HIV is bas ed on the

prevalence of HIV in the population s erved.


5 Severe expos ure is defined as : deep injury, needle s oiled with

blood from s ource patient, and expos ure from needle ins erted into
artery or vein of s ource patient.

b. If the H IV statu s of the sou rce p atient is u nknow n and


the patient is available, a rap id H IV-antibod y test can
be p erform ed on the source p atient. The resu lts of this
bed sid e test, w hich are available in m inutes, can be
used to d eterm ine the need for antiretroviral d ru gs. A
negative test not only eliminates the fear of acquiring
Infection Control in the ICU 13

the illness, it also avoid s the u se of d rugs that tend to


be p oorly tolerated . A p ositive test resu lt m u st be con-
firm ed by stand ard laboratory tests (e.g., a Western
Blot or im m u noflu orescent antibod y assay).
c. The antibod y responses to H IV infection can take 4 to
6 w eeks to becom e evid ent. Therefore, anyone w ith
d ocum ented exposure to H IV infection shou ld have
serial tests for H IV antibod ies at 6 w eeks, 3 m onths,
and 6 m onths p ost-exp osu re (5).

C. Hepatitis B Virus (HBV)


H ep atitis B is the m ost read ily transm itted blood -borne ill-
ness, bu t there is a vaccine available that can prod uce life-
long im m u nity to H BV.

1. Hepatitis BVaccine
The hep atitis B vaccine confers im m u nity by stim u lating
prod u ction of an antibod y to the hepatitis B su rface anti-
gen (anti-H Bs). This vaccine is recom m end ed for anyone
w ho has contact w ith blood , bod y flu id s, and sharp
instru m ents. The only contraind ication to the vaccine is a
history of anap hylaxis from baker s yeast (15).
a. The vaccine is ad m inistered in 3 d oses: the first tw o
d oses are given 4 w eeks ap art, and the 3rd d ose is ad -
ministered 5 m onths later.
b. If the vaccination series is interru pted , it is not neces-
sary to repeat the fu ll sequ ence. If the second d ose is
missed , that d ose is given as soon as p ossible, and the
3rd d ose is given 2 m onths later. If the 3rd d ose is
missed , that d ose is given to com p lete the vaccination
series.
Because the initial vaccination sequ ence d oes not alw ays
confer im m u nity, the final d ose of H BV vaccine shou ld
be follow ed (in 1 to 2 m onths) by an assay for the anti-
bod y to the hepatitis B surface antigen (anti-H Bs).
14 Preventive Practices in the Critically Ill

c. Im m u nity is ind icated by an anti-H Bs level that is


10 m IU/ m L. If this level is not achieved , the 3-d ose
vaccination series shou ld be rep eated .
N onresp ond ers have a 30% to 50% chance of resp ond ing
to the second vaccination series (15). Failu re to achieve
im m u nity after the second vaccination series is consid -
ered a vaccination failu re, and nothing fu rther is d one.
Resp ond ers d o not requ ire a booster d ose of the vaccine,
even thou gh antibod y levels w ane w ith tim e (15).

2. Risk of HBVTransmission
The risk of acqu iring H BV follow ing an exp osu re is d e-
term ined by the im mu nity of the exp osed ind ivid u al.
a. For ind ivid u als w ho lack H BV im m u nity (u nvaccinat-
ed or unresponsive), exp osu re to H BV-infected blood
carries a 60% risk of acqu iring H BV, and a 30% risk of
d evelop ing sym ptom atic hep atitis (15).
b. For those w ho are vaccinated and resp ond ap p ropri-
ately, there is virtu ally no risk of acqu iring H BV infec-
tion.

3. Management Following Possible HBV Exposure


The m anagem ent of a su bject w ith p ossible exp osu re to
H BV is ou tlined in Table 1.5. The choices are gu id ed by
the vaccination status of the exp osed ind ivid u al, and the
presence or absence of the hep atitis B su rface antigen
(H BsAg) in the blood of the sou rce patient.
a. For ind ivid u als w ith vaccine-ind u ced im m u nity, no
treatm ent is necessary follow ing H BV exp osu re.
b. For p ossible exp osu re in non-im m u ne ind ivid u als,
proof or su spicion of H BV infection in the sou rce
patient shou ld p rom p t treatm ent w ith hep atitis B
im m u ne globu lin (0.06 m L/ kg by intram u scu lar injec-
tion), follow ed by H BV vaccination.
Infection Control in the ICU 15

TABLE 1.5 Management of Possible Exposure to


Hepatitis B Virus (HBV)
HBsAg in Source Patient
Immunity
of Exposed HBsAg (+) HBsAg () HBsAg (?)
Person
Not HBIGa and Start HBV Start HBV
vaccinated start HBV vaccination vaccination
vaccination
Vaccinated &
immunec Do nothing Do nothing Do nothing
Vaccinated &
not immuned HBIGa and Do nothing If source is high
start HBV risk for HBV,
revaccination treat as if source
or HBIG x 2b is HBsAg (+)
Immunity
unknown Check anti-HBs Do nothing Check anti-HBs
in exposed in exposed
person: person:
1.If immune,c 1.If immune,c
no treatment no treatment
2.If not immune,d 2.If not immune,
HBIGa and vaccine booster
vaccine booster & recheck titer
in 12 months
From Reference 15. HBs Ag = hepatitis B s urface antigen.
Anti-HBs = antibody to hepatitis B s urface antigen.
aHBIG = hepatitis B immune globulin, 0.06 mL/kg by intramuscular injec-

tion immediately after expos ure.


b HBIG x 2 = s ame as (a) above plus s econd dose one month later.
c Immunity defined as pos tvaccination anti-HBs 10 mIU/mL.
d Nonimmunity defined as pos tvaccination anti-HBs <10 mIU/mL.

D. Hepatitis CVirus (HCV)


H CV is a blood -borne pathogen of som e concern because
infection often lead s to chronic hep atitis.
16 Preventive Practices in the Critically Ill

1. Risk of HCVTransmission
a. The p revalence of anti-H CV antibod ies in hosp ital p er-
sonnel is only 1% to 2% (16), w hich m eans that the risk
of H CV transm ission in the hosp ital setting is low.
b. Follow ing a need lestick inju ry w ith H CV-infected
blood , the average risk of H CV transm ission is only
1.8% (15). Tran sm ission from m u cou s m em bran e
exposu re is rare, and there are no d ocu m ented cases of
H CV transm ission throu gh breaks in the skin.

2. Postexposure Management
a. There is no effective p rop hylaxis for H CV follow ing
exposu re to infected blood .
b. Follow ing a d ocu m ented exp osure to H CV-infected
blood , serial m easu rem ents of anti-H CV antibod ies is
recom m end ed for 6 m onths (16).

REFERENCES
1. Larson EL, Rackoff WR, Weim an M, et al. APIC guid eline for
hand antisepsis in health-care settings. Am J Infect Control 1995;
23:251-269.
2. Centers for Disease Control and Prevention. Guid elines for H and
H ygiene in H ealth-Care Settings: Recom m end ations of the
H ealthcare Infection Control Practices Ad visory Com m ittee and
the H ICPAC/ SH EA/ APIC/ IDSA H and H ygiene Task Force.
MMWR 2002; 51 (N o.RR-16):1-45.
3. Katz JD. H and w ashing and hand d isinfection: m ore than you r
m other tau ght you . Anesthesiol Clin N orth Am 2004; 22:457-471.
4. Laestad ius JG, Dim berg L. H ot w ater for hand w ashing w here is
the proof? J Occup Environ Med 2005; 47:434-435.
5. Garner JS, H ospital Infection Control Practices Ad visory Com -
m itee. Guid eline for isolation p recau tions in hosp itals. Am J
Infect Control 1996; 24:24-52.
6. Centers for Disease Control and Prevention. Gu id elines for the
prevention of intravascu lar catheter-related infections. MMWR
2002; 51(N o. RR-10): 1-29.
Infection Control in the ICU 17

7. Division of H ealthcare Qu ality Prom otion, N ational Center for


Infectiou s Diseases, Centers for Disease Control and Prevention.
Stand ard p recau tions: excerpted from Gu id eline for Isolation
Precau tions in H osp itals. Accessed at w w w.cd c.gov/ ncid od
/ hip/ ISOLAT/ std _p rec_excerpt.htm
8. Charous L, Charou s MA. Is occu pational latex allergy cau sing
you r p atients asthm a? J Resp ir Dis 2002; 23:250-256.
9. Guin JD. Clinical presentation of patients sensitive to natu ral
ru bber latex. Derm atitis 2004; 4:192-196.
10. H am ilton RG, Peterson EL, Ow nby DR. Clinical and laboratory-
based m ethod s in the d iagnosis of natural ru bber latex allergy.
J Allergy Clin Im m u nol 2002; 110 (su pp l 2): S47-S56.
11. Fennelly KP. Personal resp iratory p rotection against M ycobac-
terium tuberculosis. Clin Chest Med 1997; 18:1-17.
12. Division of H ealthcare Qu ality Prom otion, N ational Center for
Infectiou s Diseases, Centers for Disease Control and Prevention.
Airborne precautions: excerp ted from Guid eline for Isolation
Precau tions in H osp itals. Accessed at w w w.cd c.gov/ ncid od
/ hip/ ISOLAT/ airborne_prec_excerp t.htm
13. N ational Institu te for Occu pational Safety and H ealth. Prevent-
ing N eed lestick Inju ries in H ealth Care Settings. DH H S (N IOSH )
Pu blication N o. 2000-108, 1999.
14. Rad echi S, Abbott A, Eloi L. Occu pational hum an im m u nod efi-
ciency viru s exposure am ong resid ents and m ed ical stu d ents.
Arch Intern Med 2000; 160:3107-3100.
15. Centers for Disease Control and Prevention. Upd ated U.S. Pu blic
H ealth Service Gu id elines for the m anagem ent of occu p ational
exposu res to H BV, H CV, and H IV and recom m end ations for
postexposu re prop hylaxis. MMWR 2001; 50 (N o. RR-11):1-52.
16. Centers for Disease Control and Prevention. Im m u nization of
H ealth-care w orkers: Recom m end ations of the Ad visory Com -
m ittee on Im m u nization Practices (ACIP) and the H osp ital
Infection Control Practices Ad visory Com m ittee (H ICPAC).
MMWR 1997, 46(RR-18): 1-42.
Chapter 2
STRESS-RELATED
MUCOSAL INJURY
Stress-related m u cosal inju ry (SRMI) is a term u sed to d e-
scribe erosions in the gastric m u cosa that occu r in p atients
w ith acu te, life-threatening illness (1,2). This chapter w ill
d escribe the m ethod s used to prevent troublesom e bleed ing
from these lesions.

I. GENERAL FEATURES

A. Pathogenesis
1. The gastric erosions that ap p ear in acu te, life-threatening
illness are likely caused by inad equ ate nutrient blood
flow in the gastric m u cosa. The erosions are u su ally su -
p erficial and confined to the su rface m u cosa, bu t d eep er
craters that extend into the su bm u cosa can d evelop . The
d eep er erosions resemble ulcer craters, and are called
stress ulcers. (The term stress u lcer is often u sed to rep-
resent all types of stress-related gastric erosions. This
chapter u ses the term in a similar m anner.)

2. Stress-related gastric erosions have no p rotective cover-


ing, and the acid ity of gastric secretions can aggravate
these lesions and p rom ote further mu cosal inju ry. The
acid ic environm ent in the stom ach can also p rom ote
bleed ing from the erosions by exerting a throm bolytic
effect. The d eleteriou s actions of gastric acid ity is the
basis for the p op u larity of gastric acid su p ression as a
p rophylactic strategy in this cond ition (see later).
19
20 Preventive Practices in the Critically Ill

B. Clinical Manifestations
1. Erosions in the gastric m u cosa can be d em onstrated in
75% to 100% of p atients w ithin 24 hou rs of ad m ission to
the ICU (3). These lesions are often clinically silent, bu t
they can p rom ote m u cosal bleed ing.

2. Withou t ap p rop riate p reventive measu res (see later),


gastric erosions can cau se clinically apparent bleed ing in
as m any as 25% of ICU p atients (3). H ow ever, significant
bleed ing (i.e., cau sing hyp otension or requ iring transfu -
sion) occurs in less than 5% of ICU patients (3,4).

TABLE 2.1 Indications for Stress Ulcer Prophylaxis


Any of the Conditions Two or More of the
OR
Listed Below Conditions Listed Below
1. Mechanical ventilation > 48 hrs. 1. Hypotension
2. Coagulopathy: 2. Severe sepsis
a. Platelets <50,000/mL or 3. Severe head injury
b. INR > 1.5 or 4. Multisystem trauma
c. PTT > 2x control 5. Renal failure
3. History of gastritis or peptic ulcer 6. Hepatic failure
disease, or prior episode of upper
GI bleeding. 7. Burns involving
>30% of the body
surface area
From References 1,4.

C. Predisposing Conditions
The cond itions listed in Table 2.1 are associated w ith an in-
creased risk of troublesom e bleed ing from gastric erosions.

1. The 3 cond itions in the left colu m n (p rolonged m echani-


cal ventilation, coagu lop athy, and a history of gastritis,
Stress-Related Mucosal Injury 21

p ep tic ulcer d isease, or u p per GI hem orrhage) are ind e-


p end ent risk factors, so the presence of any of these con-
d itions represents a risk for significant bleed ing.

2. The cond itions listed in the right colu m n are not ind e-
p end ent risk factors, and at least 2 of these cond itions
mu st be present to create a risk for significant bleed ing.

3. The p red isp osing cond itions in Table 2.1 shou ld also
be u sed as ind ications for the p reventive m easures d e-
scribed next.

II. PREVENTIVE MEASURES


The goal of the p reventive m easu res d escribed here is not to
p revent the ap p earance of gastric erosions (since this m ay
be imp ossible), bu t rather to p revent trou blesom e bleed ing
from these lesions.

A. Enteral Tube Feedings


1. Enteral tu be feed ings exert a trop hic effect on the bow el
mu cosa that help s to maintain the stru ctu ral and func-
tional integrity of the m ucosa (see Chapter 37).

2. Clinical stu d ies have show n that enteral tube feed ings
are effective in p reventing overt bleed ing from gastric
erosions (5,6).

3. Enteral tu be feed ings shou ld be consid ered ad equate


p rophylaxis for SRMI-ind u ced bleed ing in m ost p atients.
Possible excep tions are p atients w ith a coagu lop athy,
a p rior history of bleed ing from gastritis or p ep tic u lcer
d isease, or active p ep tic u lcer d isease.
22 Preventive Practices in the Critically Ill

B. Reduced Gastric Acidity


The m ost p op u lar p reventive m easu re for bleed ing related to
stress ulcers is the u se of d ru gs that can red u ce the acid ity of
gastric secretions (7). The goal of acid su p p ression therap y is
to m aintain a p H > 4.0 in gastric secretions.

1. Histamine Type-2 Receptor Antagonists


a. The stand ard acid -su p p ressing d ru gs for stress u lcer
p rophylaxis are the histam ine typ e-2 recep tor antago-
nists (H 2-blockers). N u m erou s clinical trials have
show n that these d rugs red u ce the incid ence of stress
u lcer bleed ing to 3% in high-risk p atients (8,9).
b. The H 2-blockers m ost often u sed for stress u lcer
prop hylaxis are fam otid ine (Pep cid ) and ranitid ine
(Zantac). Both are given intravenou sly in the d osing
regim ens show n in Table 2.2 (10,11). Fam otid ine is
longer-lasting than ranitid ine (1012 hrs. vs. 68 hrs.),
and is given less frequ ently. Both d ru gs are equ ivalent
in their ability to red uce the risk of bleed ing from
stress u lcers.
c. Famotid ine and ranitid ine are excreted u nchanged in
the u rine, and these d ru gs can accum u late in renal
insufficiency and prod u ce a neurotoxic cond ition char-
acterized by confu sion, agitation and seizures (10,11).
The d osage of these d ru gs shou ld be red u ced in renal
insufficiency (see Table 2.3).

2. Proton Pump Inhibitors


a. Proton p u m p inhibitors (PPIs) block gastric acid secre-
tion by irreversibly bind ing to the hyd rogen ion p u m p
in gastric parietal cells. These agents have 2 p otential
ad vantages over H 2-blockers: they are m ore effective
in red u cing gastric acid ity (and m aintaining gastric
pH above 4.0), and their effect is not d iminished w ith
rep eated u se (12).
Stress-Related Mucosal Injury 23

b. In the ICU setting, PPIs have been used p rim arily to


p revent rebleed ing follow ing an ep isod e of acu te (non-
variceal) u pp er GI bleed ing. There is lim ited exp eri-
ence w ith these agents for stress u lcer prophylaxis.
c. There are 2 PPIs available for intravenou s u se: om e-
p razole (Prilosec) and p antop razole (Protonix). The
d osage recomm end ations for each d rug are show n in
Table 2.2. N ote that a continu ous infu sion is used
w hen the d ru gs are given to p revent rebleed ing.
d . Despite the potential ad vantage of PPIs over H 2-block-
ers for gastric acid su p p ression, there is no evid ence

TABLE 2.2 Drugs Used to Prevent Bleeding from


Stress Ulcers
Agent Route Dose Recommendations
1. Histamine H2-Receptor
Antagonists
Famotidine IV a. 20 mg every 12 hrs.
b. Reduce dose in renal
insufficiency (see Table 2.3).
Ranitidine IV a. 50 mg every 8 hrs.
b. Reduce dose in renal
insufficiency (see Table 2.3).
2. Proton Pump Inhibitors
Omeprazole IV a. 80 mg daily as a single dose
b. To prevent rebleeding after
GI bleed, follow initial dose
with a continuous infusion
at 8 mg/hr for 13 days.
Pantoprazol IV a. 40 mg daily as a single dose
b. Same as above for
omeprazole.
3. Cytoprotective Agent
Sucralfate NG Tube a. 1 g (as a slurry) every 6 hrs.
b. Avoid drug interactions.
24 Preventive Practices in the Critically Ill

that PPIs p rovid e m ore p rotection against stress u lcer


bleed ing than H 2-blockers. At the p resent tim e, there is
no reason to favor PPIs over H 2-blockers for stress
ulcer p rophylaxis.

TABLE 2.3 Dosage Adjustment of H2-Blockers


in Renal Insufficiency
Percent of Usual Dose
Creatinine Clearance
(mL/min) Ranitidine Famotidine

51 75 75% 50%
10 50 50% 25%
< 10 25% 10%
From Self TH. Mental confus ion induced by H2 -receptor anatgonis ts :
How to avoid. J Crit Illnes s 2000;15:47.

3. The Hazards of Gastric Acid Suppression


Most m icroorganism s d o not su rvive in an acid envir-
onment, as d em onstrated in Figu re 2.1. In this case,
Escherichia coli is comp letely erad icated in one hour w hen
the pH of the grow th m ed iu m is red u ced from 5 to 3 pH
u nits. The antim icrobial effects of an acid environm ent
w ere ap p reciated by Sir Joseph Lister, the father of anti-
septic practices in m ed icine, w ho u sed carbolic acid as the
first antiseptic agent for the skin.
a. In light of the germ icid al actions of acid ity, it is likely
that gastric acid serves as a bu ilt-in antiseptic agent
that erad icates m icroorganism s sw allow ed in saliva
and food .
b. Loss of the norm al antiseptic actions of gastric acid
w ill resu lt in bacterial overgrow th in the stom ach, and
this can p red isp ose to certain infections, inclu d ing in-
fectiou s gastroenteritis and asp iration p neu m onia (13).
Stress-Related Mucosal Injury 25

c. Several clinical stud ies have revealed that stress u lcer


p rop hylaxis w ith H 2-blockers is associated w ith an
increased incid ence of p neu m onia (9). This is d em on-
strated in Figu re 2.2 (this figu re is exp lained later in
the chapter).
d . The loss of antim icrobial d efenses w ith gastric acid
sup p ression is reason to consid er preventive m easu res
for stress u lcer bleed ing that d o not involve gastric
acid su p pression. One su ch m easu re is d escribed next.

FIGURE 2.1. The influence of pH on the growth of Escherichia coli. (From


Gianella J et al. Gut 1972;13:251.).

C. Gastric Cytoprotection
1. Sucralfate
a. Su cralfate is an alu m inu m salt of su crose su lfate that
acts as a cytoprotective agent by form ing a p rotective
26 Preventive Practices in the Critically Ill

covering on the gastric m u cosa (10). The p H of gastric


secretions is not altered .
b. The recom m end ed d ose of su cralfate to p revent stress
u lcer bleed ing is show n in Table 2.2. The d ru g is u su -
ally given as a liqu id slu rry that is instilled through a
nasogastric tu be.
c. Su cralfate can bind to a num ber of d rugs in the bow el
lu m en to red u ce d ru g absorp tion (14). The d ru g inter-
actions m ost likely in ICU p atients includ e cou m ad in,
d igoxin, flu oroqu inolones, p hen ytoin, qu in id in e,
ranitid ine, tetracycline, thyroxine, theop hylline. These
d ru gs shou ld be given at least 2 hou rs before su cral-
fate to avoid d ru g interactions.
d . The alu minum in su cralfate can also bind phosphate
in the bow el, bu t hyp op hosphatem ia is u ncom m on
(15). Sucralfate should not be u sed in p atients w ith
p ersistent or severe hypop hosp hatemia. Prolonged
u se of su cralfate d oes not elevate p lasm a alu m inu m
levels.

D. Cytoprotection vs. Reduced Gastric Acidity


Several clinical trials have evalu ated the relative effects of
gastric cytoprotection w ith su cralfate and gastric acid su p-
pression w ith ranitid ine in patients at risk for stress u lcer
bleed ing. The resu lts of one of these trials are show n in
Figu re 2.2 (8). This stu d y involved 1,200 ventilator-d ep end -
ent p atients in 16 ICUs w ho w ere rand om ized to receive
su cralfate or ranitid ine in the u su al d oses. The results show
the follow ing:

1. Significant bleed ing occu rs infrequ ently (< 5%), regard -


less of the p rop hylactic d ru g regim en. This ind icates that
ranitid ine and su cralfate are both effective agents for
stress u lcer p rop hylaxis.

2. Prophylaxis w ith ranitid ine is associated w ith few er


episod es of bleed ing (absolu te d ifference = 2.1%), w hile
Stress-Related Mucosal Injury 27

Incide nce of Incide nce of


5 Ble e ding P ne umonia 20

(19%)
4 19
(3.8%)

3 18
% %
2 17
(1.7%)

(16%)
1 16

0 0
S ucra lfa te Ra nitidine S ucra lfa te Ra nitidine

FIGURE 2.2. A comparison of the effects of stress ulcer prophylaxis with


sucralfate and ranitidine on the incidence of clinically significant bleed-
ing and hospital-acquired pneumonia in ventilator-dependent patients.
(From Reference 8).

p rophylaxis w ith su cralfate is associated w ith few er


episod es of p neu m onia (absolu te d ifference = 2.9%).

3. The increased incid ence of p neu m onia associated w ith


ranitid ine is consistent w ith the com bined resu lts of 8
other clinical trials (9). This association is p red icted by
the loss of the antibacterial d efenses in the u p per GI tract
as a consequence of red u ced gastric acid ity, as d escribed
earlier.

4. Reasons to Avoid Gastric Acid Suppression with Ranitidine


a. The benefit d erived from gastric acid su p p ression w ith
ranitid ine (i.e., few er ep isod es of bleed ing from stress
u lcers) m ust be w eighed against the associated risk
(i.e., more frequ ent ep isod es of p neu m onia). Since
nosocom ial pneu m onia has a higher m ortality rate
than stress u lcer bleed ing (50% vs. 10%), gastric acid
28 Preventive Practices in the Critically Ill

su p p ression w ith ranitid ine can resu lt in m ore lives


lost from p neu m onia than lives saved from few er
bleed ing episod es. This is one reason to avoid the use
of gastric acid su p p ression w ith ranitid ine (or any
other d ru g) as a p reventive strategy for stress-related
gastric erosions.
b. Severe sep sis and septic shock are am ong the lead ing
cau ses of d eath in ICU patients, and the gastrointesti-
nal tract is an im portant reservoir for pathogens in
these cond itions (16). The su p p ression of gastric acid -
ity (by any m eans) w ill ad d to this p roblem by prom ot-
ing m icrobial p roliferation in the u p p er GI tract. For
this reason, gastric acid ity should be p reserved w hen-
ever p ossible to preserve the antimicrobial d efense
system in the bow el and red u ce the risk of sep sis from
bow el p athogens.

REFERENCES
1. Steinberg KP. Stress-related m u cosal d isease in the critically ill
p atient: Risk factors and strategies to prevent stress-related
bleed ing in the intensive care u nit. Crit Care Med 2002; 30
(Sup pl):S362-S364.
2. Fennerty MB. Pathophysiology of the u p per gastrointestinal
tract in the critically ill p atient: rationale for the therap eutic ben-
efits of acid su ppression. Crit Care Med 2002; 30(Sup p l):S351-
S355.
3. Mu thu GM, Mu tlu EA, Factor P. GI com p lications in patients
receiving m echanical ventilation. Chest 2001; 119:1222-1241.
4. Cook DJ, Fuller MB, Gu yatt GH . Risk factors for gastrointestinal
bleed ing in critically ill p atients. N Engl J Med 1994; 330:377381.
5. Raff T, Germ ann G, H artm ann B. The valu e of early enteral nu tri-
tion in the prophylaxis of stress u lceration in the severely bu rned
p atient. Bu rns 1997; 23:313-318.
6. Pingleton SK, H ad zim a SK. Enteral alim entation and gastroin-
testinal bleed ing in m echanically ventilated patients. Crit Care
Med 1983; 11:13-16.
Stress-Related Mucosal Injury 29

7. Daley RJ, Rebu ck JA, Welage LS, Rogers FB. Prevention of stress
u lceration: cu rrent trend s in critical care. Crit Care Med 2004; 32:
2008-2013.
8. Cook D, Gu yatt G, Marshall J, et al. A com p arison of su cralfate
and ranitid ine for the prevention of u pper gastrointestinal bleed -
ing in patients requ iring m echanical ventilation. N ew Engl J Med
1998; 338:791-797.
9. Messori A, Trip poli S, Vaiani M, et al. Bleed ing and p neu m onia
in intensive care p atients given ranitid ine and su cralfate for p re-
vention of stress u lcer: m eta-analysis of rand om ized controlled
trials. Br Med J 2000; 321:1-7.
10. Fam otid ine. Mosbys Dru g Consult. Mosby, Inc., 2006. Accessed
at w w w.m d consu lt.com in March, 2007.
11. Ranitid ine. Mosbys Drug Consu lt. Mosby, Inc., 2006. Accessed at
w w w.m d consu lt.com . in March, 2007.
12. Morgan D. Intravenou s p roton p u m p inhibitors in the critical
care setting. Crit Care Med 2002; 30(Su pp l): S369-S372.
13. Laheij R, Sturkenboom M, H assing R-J, et al. Risk of com m u nity-
acqu ired pneum onia and use of gastric acid -supp ressive d rugs.
JAMA 2004; 292:1955-1960.
14. McEvoy GK, ed . AH FS Dru g Inform ation, 1995. Bethesd a, MD:
Am erican Society of H ealth System Pharm acists, 1995:20212065.
15. Miller SJ, Sim p son J. Med icationnu trient interactions: hyp o-
p hosphatem ia associated w ith su cralfate in the intensive care
u nit. N utr Clin Pract 1991; 6:199201.
16. Marshall JC, Christou N V, Meakins JL, et al. The gastrointestinal
tract: the und rained abscess of m u ltiple organ failure. Ann
Surg 1993; 218:111119.
Chapter 3
VENOUS
THROMBOEMBOLISM
Venous throm boem bolism (venous throm bosis and pu lm o-
nary em bolism ) is resp onsible for an estim ated 10% of all
hospital d eaths (1). This is an alarm ing estim ate consid ering
that venou s throm boem bolism (VTE) is consid ered p revent-
able in m ost cases. This chap ter d escribes the p revention,
d iagnosis, and treatm ent of VTE in hosp italized p atients,
w ith em p hasis on p revention.

I. THE PATIENT AT RISK


The clinical cond itions that are m ost often accom p anied by
VTE are listed in Table 3.1 (1-3). A p atient w ho has any of
these cond itions shou ld receive p rop hylaxis for VTE.

A. Major Surgery
Major su rgery (p erform ed u nd er general anesthesia and last-
ing longer than 30 m inu tes) is the m ost com m on high-risk
cond ition for VTE in hosp italized patients. The m ajor factors
p rom oting VTE after m ajor su rgery are vascu lar inju ry and
throm bop lastin release from inju red tissu es (w hich p rod u ces
a hyp ercoagu lable state).

1. General Surgery
The risk of VTE after general su rgery is d eterm ined by 3
factors: the age of the p atient, the typ e of proced u re, and
the presence or absence of other risk factors for VTE.

31
32 Preventive Practices in the Critically Ill

Table 3.2 show s how these factors are u sed in the risk
assessm ent for VTE follow ing general su rgery.
a. The low est risk of VTE occu rs after m inor p roced ures
p erform ed on you ng p atients (age < 40) w ho have no
other risk factors for VTE .

TABLE 3.1 Risk Assessment for Venous Thromboembolism


If the patient has any of the conditions listed below, place a check-
mark in the corresponding box. Check only conditions that are cur-
rently present or have occurred within the past week.
Patient Profile
Prior history of thromboembolism
Malignancy
Hypercoagulable state (e.g., estrogen Rx)
Surgery
Major surgery (e.g., abdominal, intracranial)
Orthopedic surgery involving the hip or knee
Trauma
Spinal cord injury or spinal fracture
Fractures involving the pelvis, hip, or leg
Multisystem trauma
Acute Medical Illness
Stroke or acute myocardial infarction
Neuromuscular weakness (e.g., Guillain-Barr)
ICU-Related Conditions
Mechanical ventilation > 48 hrs.
Drug-induced neuromuscular paralysis
Central venous or femoral vein catheter
If any of the above boxes is checked, the patient should receive
prophylaxis for venous thromboembolism.

From References 13
Venous Thromboembolism 33

b. The highest risk of VTE occu rs after major su rgery in


old er p atients (age > 40) w ho have at least one ad d i-
tional risk factor for VTE.
The incid ence of VTE in high-risk general su rgery pa-
tients is 20% to 40% (1).

2. Orthopedic Surgery
The highest incid ence of p ostoperative VTE (40 to 60%)
occu rs after m ajor su rgery involving the hip or knee (1).

3. Other Surgeries
a. VTE is a risk after intracranial su rgery, op en u rologic
p roced u res, and gynecologic su rgery. The incid ence of
VTE follow ing these p roced ures is 20% to 40% (1).
b. Lap aroscop y, arterial recon stru ction su rgery, an d
closed u rologic p roced u res (e.g., transurethral prosta-
tectom y) have a low risk of VTE, and d o not requ ire
throm bop rop hylaxis u nless the p atient has an inherent
risk of VTE (1).

B. Major Trauma
1. Victim s of m ajor trau m a have a greater than 50% chance
of d eveloping VTE w hile hosp italized , and p ulm onary
em bolism is the lead ing cau se of d eath in those w ho su r-
vive the first w eek (1).

2. The trau m a cond itions w ith the highest risk of VTE are
sp inal cord inju ries and fractu res of the sp ine and p elvis
(1,3).

C. Medical Conditions
1. The acu te m ed ical illnesses w ith a high risk of VTE are
stroke, acute m yocard ial infarction, and neu rom u scular
34 Preventive Practices in the Critically Ill

w eakness synd rom es (e.g., Gu illain-Barr). Of these,


stroke has the highest incid ence of VTE (20% to 50%) (1).

2. ICU patients can have ad d itional risk factors for VTE


su ch as p rolonged m echanical ventilation, d ru g-ind u ced
neu rom u scular p aralysis, and central venou s catheteriza-
tion (4).

TABLE 3.2 Thromboprophylaxis for General Surgery


Risk Categories Prophylaxis Regimens
I. Low Risk I. Early mobilization
Minor surgery, age <40 yrs.
and no other risk factorsa
II. Moderate Risk II. LDUH1 or LMWH1, start
Major surgery, age <40 yrs. 2 hr before surgery.
and no other risk factors
III. High Risk III. LDUH2 or LMWH2, start
Major surgery, age >40 yrs. 2 hr before surgery.
or other risk factors
IV. Highest Risk IV. LDUH2 or LMWH2, (start
Major surgery, age >40 yrs. 2 hr before surgery) plus
and other risk factors mechanical compression.
Prophylaxis Regimens
Low-Dose Unfractionated Heparin (LDUH):
LDUH1: 5000 units subcutaneous every 12 hrs.
LDUH2: 5000 units subcutaneous every 8 hrs.
Low-Molecular-Weight Heparin (LMWH):
LMWH1: Enoxaparin, 40 mg subcutaneous once daily or
Dalteparin, 2500 units subcutaneous once daily.
LMWH2: Enoxaparin, 30 mg subcutaneous every 12 hrs. or
Dalteparin, 5000 units subcutaneous once daily.
Mechanical Compression:
Compression stockings or intermittent pneumatic compression.
aO ther
ris k factors : cancer, obes ity, prior his tory of thromboembolis m,
hypercoagulable s tate (e.g., es trogen Rx).
Adapted from Reference 1.
Venous Thromboembolism 35

II.THROMBOPROPHYLAXIS

A. Mechanical Compression Devices


The follow ing m echanical com p ression d evices are u sed as
an ad ju nct to anticoagu lant p rop hylaxis, or as an alternative
to anticoagu lant p rop hylaxis in p atients w ho are bleed ing or
have a high risk of bleed ing.

1. Graded Compression Stockings


a. Grad ed com p ression stockings are d esigned to create
18 m m H g external p ressu re at the ankles and 8 m m
H g external p ressu re in the thigh (5). The resulting
10 m m H g p ressure grad ient p rom otes venou s ou tflow
from the legs.
b. Althou gh effective w hen used alone after abd om inal
su rgery and neurosu rgery (6), these stockings are the
least effective method of throm bop rophylaxis, and are
never u sed alone in patients w ith a m od erate or high
risk of VTE.

2. Pneumatic Compression Devices


a. Interm ittent pneu m atic comp ression (IPC) d evices u se
an air p u m p to p eriod ically inflate and d eflate d isten-
sible blad d ers that are w rap p ed arou nd the low er legs.
When inflated , the blad d ers create 35 mm H g external
p ressu re at the ankle and 20 m m H g external pressu re
at the thigh (5).
b. IPC d evices are m ore effective than grad ed com pres-
sion stockings for p rop hylaxis of VTE (1), and they
can be u sed alone for patients w ho are not suitable for
anticoagu lant p rop hylaxis. These d evices are favored
after intracranial su rgery, sp inal cord inju ry, and
mu ltisystem trau m a (see Table 3.3).
36 Preventive Practices in the Critically Ill

B. Low-Dose Heparin
H ep arin is an ind irect-acting anticoagu lant that bind s to a
cofactor (antithrom bin III or AT) to p rod u ce its effect. The
hep arin-AT com plex is cap able of inactivating several coag-
ulation factors, inclu d ing Factors IIa (throm bin), IXa, Xa, XIa,
and XIIa. The inactivation of Factor IIa (antithrom bin effect)
is a sensitive reaction that occu rs at heparin d oses far below
those need ed to inactivate the other coagu lation factors (7).
This m eans that sm all d oses of hep arin can inhibit throm bu s
form ation w ithou t p rod u cing fu ll anticoagu lation.

1. Dosing Regimen
a. The stand ard heparin p rep aration is called u nfraction-
ated hep arin to d istingu ish it from low -molecu lar-
w eight hep arin (see later).
b. The regim en for low -d ose u nfractionated hep arin
(LDUH ) is 5,000 units given by su bcu taneou s injection
tw o or three tim es d aily. The m ore frequ ent d osing
regim en (three tim es d aily) is recom m end ed for high-
er risk cond itions (see the LDUH 2 regim en in Tables
3.2 and 3.3).
c. When LDUH is u sed for su rgical p rop hylaxis, the first
d ose shou ld be given 2 hou rs before the p roced u re
(becau se throm bosis can begin d uring the proced u re).
Postop erative p rop hylaxis is continu ed for 7 to 10
d ays, or u ntil the p atient is fully ambulatory.
d . Monitoring laboratory tests of coagulation is not nec-
essary w ith low -d ose heparin.

2. Indications
a. LDUH p rovid es effective throm bop rop hylaxis for
high-risk m ed ical cond itions and m ost non-orthoped ic
su rgical p roced u res (see Tables 3.2 and 3.3).
b. LDUH is not recom m end ed for throm boprophylaxis in
m ajor trau ma (inclu d ing spinal cord inju ry), and for
orthoped ic surgery involving the hip and knee.
Venous Thromboembolism 37

3. Complications
a. Bleed ing is not consid ered a com p lication of low -d ose
hep arin.
b. The heparin-antithrom bin III com plex bind s to p latelet
Factor 4, and som e p atients d evelop a hep arin-in-
d u ced antibod y that cross-reacts w ith this platelet
bind ing site to p rod u ce p latelet clu m p ing and su bse-
qu ent throm bocytop enia. This is called heparin-induced
thrombocytopenia, and it prom otes throm bosis rather
than bleed ing (see Chap ter 31).

TABLE 3.3 Thromboprophylaxis for Selected Conditions


Clinical Conditions Prophylaxis Regimens
1. Major trauma 1. LMWH2 or IPC
2. Spinal cord injury 2. LMWH2 plus IPC
3. Intracranial surgery 3. IPC
4. Gynecologic surgery
a. Benign disease 4a. LDUH1
b. Malignancy 4b. LDUH2 or LMWH2
5. Urologic surgery
a. Closed procedures 5a. Early mobilization
b. Open procedures 5b. LDUH1 or IPC
6. High-risk medical condition 6. LDUH2 or LMWH1
Prophylaxis Regimens
Low-Dose Unfractionated Heparin (LDUH):
LDUH1: 5000 units subcutaneous every 12 hrs.
LDUH2: 5000 units subcutaneous every 8 hrs.
Low-Molecular-Weight Heparin (LMWH):
LMWH1: Enoxaparin, 40 mg subcutaneous once daily or
Dalteparin, 2500 units subcutaneous once daily.
LMWH2: Enoxaparin, 30 mg subcutaneous every 12 hrs. or
Dalteparin, 5000 units subcutaneous once daily.
Intermittent Pneumatic Compression (IPC)
Adapted from Reference 1.
38 Preventive Practices in the Critically Ill

C. Low-Molecular-Weight Heparin
1. Comparison of Heparin Preparations
a. Stand ard (u nfractionated ) hep arin contains m olecu les
that vary w id ely in size. The anticoagu lant activity of
hep arin is d epend ent on the size of the m olecules
(sm aller molecu les have m ore activity), so the variable
size of the m olecu les in u nfractionated hep arin gives it
variable anticoagu lant activity.
b. H ep arin m olecu les of variable size can be cleaved
enzym atically to prod u ce sm aller m olecules of m ore
u niform size. Becau se sm aller m olecu les have m ore
anticoagu lant activity, the resu ltan t low-molecular-
weight heparin (LMWH ) is m ore p otent and has m ore
u niform anticoagu lant activity than u nfractionated
hep arin.
c. The ad vantages of LMWH over u nfractionated hep-
arin includ e less frequ ent d osing, a low er risk of bleed -
ing and hep arin-ind u ced throm bocytop enia, and no
need to m onitor anticoagu lant activity (7,8).

2. Indications for LMWH


LMWH is preferred to u nfractionated heparin for throm -
bop rop hylaxis in:
a. Major trauma, including spinal cord injury (see Table 3.3).
b. Orthoped ic proced u res involving the hip and knee
(see Table 3.4).
For other cond itions w here anticoagulant p rophylaxis is
recom m end ed , LMWH can be u sed as an alternative to
low -d ose u nfractionated heparin.

3. Drugs and Dosing Regimens


Tw o LMWH p rep arations have been stu d ied for throm -
bop rop h ylaxis: enoxaparin (Loven ox) an d dalteparin
(Fragm in). Both d ru gs are given by su bcu taneou s injec-
tion in the d oses show n in Tables 3.23.4 (see LMWH 1
and LMWH 2).
Venous Thromboembolism 39

a. Enoxap arin: 40 mg once d aily for mod erate-risk cond i-


tions, and 30 m g tw ice d aily for high-risk cond itions.
b. Daltep arin: 2500 u nits once d aily for m od erate-risk
cond itions, and 5000 units once d aily for high-risk con-
d itions.
c. For hip and knee su rgery, the first d ose of LMWH
shou ld be given 6 hou rs after su rgery (9). For other
su rgical p roced u res, the first d ose of LMWH can be
given 2 hou rs before the p roced u re (1).
d . For p atients w ith renal failu re, the prop hylactic d ose of
enoxap arin shou ld be d ecreased from 30 m g tw ice
d aily to 40 m g once d aily for high-risk p atients (1). N o
d ose ad justm ent is need ed for d alteparin.

TABLE 3.4 Thromboprophylaxis for Hip and Knee Surgery


Drug Regimens
1. Low-molecular-weight heparin (LMWH)
a. Enoxaparin, 30 mg subcutaneous every 12 hrs. or
b. Dalteparin, 2500 units subcutaneous initially, then 5000 units
subcutaneous once daily.
c. Give first dose 6 hrs. after surgery.
2. Fondaparinux
a. 2.5 mg by subcutaneous injection once daily.
b. Give first dose 6 hrs. after surgery.
c. Contraindicated when creatinine clearance < 30 mL/min.
3. Adjusted-dose warfarin
a. 10 mg initially, then 2.5 mg daily. Adjust dose to achieve
INR = 2 3.
b. Give first dose the evening before surgery.
Duration of Prophylaxis
1. For elective hip and knee surgery, continue for 10 days after
surgery.
2. For hip fracture surgery, continue for 28 to 35 days after
surgery.
Adapted from Reference 1.
40 Preventive Practices in the Critically Ill

e. The use of LMWH w ith spinal anesthesia for hip and


knee su rgery can resu lt in spinal hematom a and p aral-
ysis. When spinal anesthesia is u sed , the first d ose of
LMWH shou ld be d elayed u ntil 12 to 24 hou rs after
su rgery (9), or ad ju sted -d ose w arfarin shou ld be u sed
for throm boprophylaxis.

D. Adjusted-Dose Warfarin
Ad justed -d ose w arfarin is one of three effective regim ens for
hip and knee su rgery (see Table 3.4) It is the m ost p op u lar
prophylactic regim en for hip rep lacem ent su rgery in N orth
America, d esp ite evid ence that LMWH is m ore effective (1).
Warfarin m ay be preferred in patients w ho requ ire pro-
longed p rop hylaxis after hosp ital d ischarge (see later), be-
cau se of the convenience of oral d osing. For the d osing reg-
im en, see Table 3.4. The target IN R of 2 to 3 is not reached
for at least 3 d ays.

E. Fondaparinux
Fond aparinux (Arixtra, GlaxoSm ithKline) is a synthetic anti-
coagulant that selectively inhibits coagu lation Factor Xa. The
benefits of fond ap arinu x over hep arin inclu d e a p red ictable
anticoagu lant effect (obviating the need for laboratory m on-
itoring), and lack of an im m u ne-m ed iated throm bocytop enia
(8,10).

1. Dosing Regimen
a. The p rop hylactic d ose of fond ap arinu x is 2.5 m g given
once d aily as a su bcu taneou s injection. When u sed for
su rgical p rop hylaxis, the first d ose shou ld be given
6 hou rs after su rgery (if given sooner, theres an in-
creased risk of bleed ing) (1).
b. Fond ap arinu x is cleared by the kid ney, and is contrain-
d icated w hen the creatinine clearance is < 30 m L/ m in
Venous Thromboembolism 41

(11). It is also contraind icated in p atients w ho weigh


< 50 kg because of an increased risk of bleeding (11).

2. Indications
Fond aparinux is as effective as LMWH for throm bopro-
p hylaxis after hip and knee su rgery (see Table 3.4) (5).

F. Special Consideration After Hip and Knee


Surgery
Follow ing hip and knee su rgery, there is an increase in
sym p tom atic VTE after p rop hylaxis is term inated and p a-
tients are d ischarged from the hosp ital, and sym p tom atic
VTE is the m ost com m on cause of read m ission after hip
rep lacem ent su rgery (1). These observations p rom p ted the
follow ing recom m end ations (1):

1. After hip and knee su rgery, throm bop rophylaxis shou ld


be continu ed for at least 10 d ays, even after patients are
d ischarged .

2. After hip su rgery, p atients w ith ad d itional risk factors for


VTE (e.g., m alignancy, ad vanced age, prior history of
VTE), shou ld receive p rop hylaxis for a total of 28 to 35
d ays.

III. DIAGNOSTIC APPROACH


Throm bosis in the d eep veins of the legs is often clinically
silent, and becom es ap p arent only w hen a portion of the
throm bu s breaks loose and becom es evid ent as a p u lm onary
em bolus. Therefore, the d iagnostic evaluation of susp ected
VTE u sually involves an evaluation of su spected acu te pu l-
monary em bolism .
42 Preventive Practices in the Critically Ill

TABLE 3.5 Clinical and Laboratory Findings in Patients


with Suspected Pulmonary Embolism
Positive Negative
Findings Predictive Value Predictive Value
Dyspnea 37% 75%
Tachycardia 47% 86%
Tachypnea 48% 75%
Pleuritic chest pain 39% 71%
Hemoptysis 32% 67%
Hypoxemia 34% 70%
Elevated plasma D-dimera 27% 92%
Increased dead space 36% 92%
ventilationb
Pos itive predictive value is the percentage of patients with the finding
who had a pulmonary embolus . It expres s es the likelihood that a pul-
monary embolus is pres ent when the finding is pres ent.
Negative predictive value is the percentage of patients with the finding
who did not have a pulmonary embolus. It expres ses the likelihood that a
pulmonary embolus is not present when the finding is also not present.
a From Reference 14. b From Reference 15. Other data from Reference 12.

A.The Clinical Evaluation


The clinical p resentation of acu te p u lm onary em bolism is
non-sp ecific, and there are no clinical or laboratory find ings
that w ill confirm or exclu d e the p resence of p u lm onary
em bolism w ith certainty (12). The poor p red ictive valu e of
clinical param eters in the d iagnosis of p ulmonary em bolism
is show n in Table 3.5. Tw o of the p aram eters in this table
d eserve m ention: plasm a D-d im er assays and the alveolar
d ead sp ace m easurem ent.

1. Plasma D-Dimer Levels


a. Cross-linked fibrin m onom ers, also called d egrad a-
tion-d im ers or D-dimers, are p rod u cts of clot lysis, and
Venous Thromboembolism 43

p lasm a levels of these D-d im ers are elevated in the


p resence of active throm bosis.
b. Unfortu nately, several cond itions other than throm bo-
sis can be associated w ith elevated p lasm a D-d im er
levels. These inclu d e sep sis, m alignancy, p regnancy,
heart failure, renal failu re, and ad vanced age (13). As
a result, u p to 80% of ICU p atients can have elevated
p lasm a D-d im er levels in the absence of venou s
throm bosis (14).
c. In the ICU, plasm a D-d im er levels m ay be m ore valu -
able for exclu d ing the d iagnosis of VTE. As show n in
Table 3.5, the negative p red ictive valu e of the p lasm a
D-d im er level is 92%, w hich m eans that a norm al
D-d im er level can exclu d e the p resence of VTE w ith
> 90% certainty.
d . The valu e of the D-d im er assay in exclu d ing VTE is
lim ited by the high prevalence of elevated D-d im er
levels in ICU p atients.

2. Alveolar Dead Space


a. One of the m ajor consequ ences of a p u lm onary em bo-
lus is a d ecrease in pulm onary blood flow and an in-
crease in alveolar d ead space ventilation.
b. In p atients w ho present to the em ergency room w ith
su sp ected p u lm onary em bolism , a norm al d ead space
measurem ent (i.e., < 15% of total ventilation) can ex-
clud e the p resence of VTE w ith > 90% certainty (see
the negative pred ictive valu e in Table 3.5) (15).
c. The pred ictive value of the d ead space m easurem ent
has not been stu d ied in ICU patients.
Because the clinical evalu ation of su sp ected pu lm onary
em bolism has poor pred ictive valu e, sp ecialized tests are
requ ired . These tests are includ ed in the flow d iagram in
Figu re 3.1.
44 Preventive Practices in the Critically Ill

1. PROXIMAL LEG VEIN


ULTRAS ONOGRAPHY

Lung Dis e a s e ? Anticoa gula tion

N Y

2. S PIRAL CT
ANGIOGRAM

3. RADIONUCLIDE +
LUNG S CAN

Obs e rve Anticoa gula tion

Low High
Norma l P roba bility Inde te rmina te P roba bility

Obs e rve Anticoa gula tion


S TOP

Ve ntila tor No Ve ntila tor

PULMONARY Go to 2
ANGIOGRAM

FIGURE 3.1. Flow diagram for the evaluation of suspected pulmonary


embolism.

B.Venous Ultrasound
Most p u lm onary em boli are believed to originate from
throm bi located in large, p roxim al leg veins (e.g., fem oral
vein), so the evalu ation of su sp ected p u lm onary em bolism
can begin w ith an evaluation of the leg veins.

1. Reliability of Venous Ultrasound


a. For the d etection of d eep vein throm bosis (DVT) in the
thigh (proxim al DVT), u ltrasou nd has a sensitivity
95%, a specificity 97%, a p ositive pred ictive valu e
Venous Thromboembolism 45

as high as 97%, and a negative p red ictive valu e as high


as 98% (16). These nu mbers ind icate that u ltrasound
has a high d egree of accu racy for the d etection of prox-
im al DVT in the legs.
b. For the d etection of venou s throm bosis below the knee
(calf DVT), u ltrasound has a sensitivity of only 33% to
70% (2). Therefore, u ltrasou nd is not a reliable m ethod
for the d iagnosis of DVT below the knee.

2. When Venous Ultrasound is Unrevealing


a. As many as 30% of patients w ith acu te p u lm onary
em bolism show no evid ence of venous throm bosis in
the legs (17). As a resu lt, a negative venou s u ltrasound
evaluation of the legs d oes not exclu d e the d iagnosis
of p u lm onary em bolu s.
b. When venous u ltrasou nd is u nrevealing, the next step
in the evaluation of p ulm onary em bolism is either spi-
ral com pu ted tom ograp hy (CT) or a rad ionu clid e lu ng
scan (see Figu re 3.1)

C. Radionuclide Lung Scan


Ventilation-p erfu sion lu ng scans are d iagnostic for p u l-
monary em bolism in only 25% to 30% of cases (18). The
p roblem is that the presence of lung d isease w ill p rod uce an
abnorm al scan in about 90% of cases (18). Lu ng scans are
most helpfu l in p atients w ith no und erlying lu ng d isease
(w hich, u nfortu nately, exclu d es m ost ICU p atients). If the
d ecision is m ad e to p roceed w ith a lu ng scan, the resu lts can
be used as follow s (18):

1. A norm al lu ng scan exclu d es the p resence of a p u lm o-


nary em bolu s, w hereas a high-p robability lu ng scan car-
ries a 90% p robability that a p u lm onary em bolu s is pres-
ent.

2. A low -p robability lu ng scan d oes not reliably exclu d e


the presence of a pu lm onary em bolism . H ow ever, w hen
46 Preventive Practices in the Critically Ill

com bined w ith a negative u ltrasou nd evalu ation of the


legs, a low -p robability scan is su fficient reason to stop
the d iagnostic w orku p and observe the p atient.

3. An interm ed iate-p robability or ind eterm inate lu ng scan


has no valu e in pred icting the presence or absence of a
p ulmonary em bolu s. In this situ ation, the op tions in-
clud e spiral CT angiography (see next) or conventional
p ulmonary angiograp hy.

D. Spiral CT Angiography
This techniqu e is m ost valu able in p atients w ith lu ng d isease
(w here lu ng scans are often nond iagnostic), bu t its u se in the
ICU is lim ited by the need to breath-hold d u ring the p roce-
d u re (see below ).

1. Technique
a. In conventional com p u ted tom ograp hy (CT), the d e-
tector is m oved in fixed increm ents to p rod u ce a series
of im ages that ap pear as slices of tissu e. In sp iral
CT, the d etector is continu ou sly rotated around the
p atient to p rod u ce a volu m etric im age.
b. Sp iral CT of the thorax takes 30 second s to com plete,
and there m u st be no lu ng m otion d u ring the p roce-
d u re. This m eans that patients must be able to breath-hold
for 30 seconds to perform a spiral CT scan, and this ex-
clud es patients w ho are ventilator-d ep end ent or are
u nable to follow com mand s.
c. When spiral CT is com bined w ith p eripheral injection
of a contrast agent, the central p u lm onary arteries can
be visu alized . A pu lm onary em bolu s app ears as a fill-
ing d efect.

2. Performance
a. Sp iral CT angiograp hy has a sensitivity of 93% and a
sp ecificity of 97% for d etecting clots in the m ajor p ul-
Venous Thromboembolism 47

monary arteries (19). The sensitivity is only 30% for


d etecting clots in smaller, subsegm ental arteries (19).

E. Pulmonary Angiography
Pu lm onary angiograp hy is the gold stand ard m ethod for
d etecting p u lm onary em boli, bu t is requ ired in few er than
15% of cases of suspected p u lm onary em bolism .

III. ANTITHROMBOTICTHERAPY

A. Anticoagulation
The initial treatm ent of throm boem bolism that is not life-
threatening is anticoagu lation w ith hep arin.

1. Unfractionated Heparin
a. The stand ard treatm ent of VTE is u nfractionated hep -
arin given by continu ou s intravenou s infu sion u sing
w eight-based d osing as show n in Table 3.6 (20).
b. Unfractionated heparin has u np red ictable anticoagu -
lant activity (as d escribed earlier), and anticoagu lant
activity m u st be m onitored u sing the p artial throm bo-
p lastin tim e (PTT). This test is a reflection of Factor IIa
activity, and one of the p rom inent effects of heparin is
inhibition of Factor IIa.

2. Low-Molecular-Weight Heparin (LMWH)


LMWH is as effective as u nfractionated hep arin (21) and
offers som e ad vantages, inclu d ing sim plified d osing and
no need to m onitor anticoagu lant activity (see later).
a. A stand ard LMWH treatm ent for VTE is enoxaparin
given in a d ose of 1 mg/ kg by su bcu taneou s injection
every 12 hours.
48 Preventive Practices in the Critically Ill

b. Becau se LMWH is cleared by the kid neys (see earlier),


u nfractionated hep arin is recom m end ed for p atients
w ith renal failu re (21).
c. The PTT cannot be used to m onitor anticoagulation
w ith LMWH becau se LMWH acts p rim arily to inhibit
Factor Xa, and the PTT is not a reflection of Factor Xa
activity.
d . Since LMWH prod u ces a p red ictable level of antico-
agulation, m onitoring anticoagu lant activity is usu ally
not necessary. Factor Xa activity m u st be m easu red to
d eterm ine the anticoagu lant resp onse to LMWH (20).

TABLE 3.6 Weight-Based Heparin Dosing Regimen


1. Prepare heparin infusion by adding 20,000 IU heparin to 500 mL
diluent (40 IU/mL).
2. Give initial bolus dose of 80 IU/kg and follow with continuous
infusion of 18 IU/kg/hr. (Use actual body weight.)
3. Check PTT 6 hrs. after start of infusion, and adjust heparin dose
as indicated below.

PTT (sec) PTT Ratio Bolus Dose Continuous Infusion


<35 <1.2 80 IU/kg Increase by 4 IU/kg/hr
3545 1.21.5 40 IU/kg Increase by 2 IU/kg/hr
4670 1.52.3
7180 2.33.0 Decrease by 2 IU/kg/hr
>90 >3 Stop infusion for 1 hr then
decrease by 3 IU/kg/hr

4. Check PTT 6 hrs. after each dose adjustment. When in the


desired range (4670 sec), monitor daily.
From Raschke RA, Reilly BM, Guidry J R, et al. The weight-bas ed heparin
dosing nomogram compared with the standard care nomogram. Ann
Intern Med 1993; 119:874.
Venous Thromboembolism 49

3. Warfarin
a. Long-term anticoagu lation w ith w arfarin (cou m ad in)
is started on the first d ay of hep arin therap y. The
u su al starting d ose is 510 m g once d aily. When the
p rothrom bin tim e reaches an international norm alized
ratio (IN R) of 2 to 3 (w hich u su ally takes 3 d ays or
longer), the hep arin can be d iscontinu ed .
b. Anticoagu lation w ith coum ad in is continued for 3 to 6
months, or longer in p atients w ith cancer-related or
recu rrent VTE (21).

B.Thrombolytic Therapy
1. Throm bolytic therap y is reserved for life-threatening
cases of pu lm onary em bolism accom panied by hem od y-
nam ic instability (21,22). Som e recom m end lytic therap y
for hem od ynam ically stable p atients w ith right ventricu -
lar d ysfu nction (23), althou gh the benefits in this situ a-
tion are unproven (21,23).

2. The m ajor p roblem w ith lytic therap y is bleed ing: there is


a 12% incid ence of m ajor bleed ing (22), and a 1% inci-
d ence of intracranial hem orrhage (21,22).

3. All throm bolytic agents are consid ered equ ally effective,
and system ic d ru g ad m inistration is favored over local
infusion into the p u lm onary arteries (21). The tw o d ru g
regim ens show n below are d esigned to achieve rap id clot
lysis.
a. Alteplase: 0.6 m g/ kg over 15 m inu tes (24).
b. Reteplase: 10 Units by bolu s injection and rep eat in 30
minu tes (25).

4. For m ore inform ation on the u se of throm bolytic agents,


see Chap ter 14.
50 Preventive Practices in the Critically Ill

IV. INFERIOR VENA CAVA FILTERS


Filter d evices can be placed in the inferior vena cava (IVC) to
trap thrombi that break loose from leg veins, thu s preventing
pu lmonary em bolization.

A. Indications
1. IVC filters are ind icated for p atients w ith p roxim al DVT
w ho have any of the follow ing (26):
a. A contraind ication to anticoagu lation
b. Pu lm onary em bolization d u ring fu ll anticoagu lation
c. A free-floating throm bu s (i.e., the lead ing ed ge of the
throm bu s is u nattached ).
d . Poor card iop u lmonary reserve (i.e., u nlikely to tolerate
a p u lm onary em bolu s).

2. Th ese filters are in serted p ercu tan eou sly, u su ally


throu gh the internal ju gu lar vein or fem oral vein, and are
p laced below the renal veins, if possible.

B. Efficacy
1. The incid ence of p ost-insertion p u lm onary em bolism is
abou t 5% (27).

2. Major com p lications (e.g., m igration of the filter) occu r in


less than 1% of cases (27). Rem arkably, septicem ia alm ost
never resu lts in seed ing of IVC filters, d esp ite their
intravascu lar location.

REFERENCES
1. Geerts WH , Pineo GF, H eit JA, et al. Prevention of venou s throm -
boem bolism . The Seventh ACCP Conference on Antithrom botic
and Throm bolytic Therap y. Chest 2004; 126(Supp l):338S-400S.
Venous Thromboembolism 51

2. H eit JA. Risk factors for venous throm boem bolism . Clin Chest
Med 2003; 24:1-12.
3. Bick RL, H aas S. Throm bop rophylaxis and throm bosis in m ed -
ical, surgical, trau m a, and obstetric/ gynecologic p atients. H em -
atol Oncol Clin N Am 2003; 17:217-258.
4. Rocha AT, Tapson VF. Venou s throm boem bolism in the intensive
care u nit. Clin Chest Med 2003; 24:103-122.
5. Gold haber SZ, Marpu rgo M, for the WH O/ ISFC Task Force on
Pu lm onary Em bolism . Diagnosis, treatm ent and p revention of
p ulm onary em bolism . JAMA 1992; 268:1727-1733.
6. Wells PS, Lensing AW, H irsh J. Grad u ated com p ression stockings
in the p revention of postop erative venou s throm boem bolism . A
m eta-analysis. Arch Intern Med 1994; 154:6772.
7. H irsch J, Raschke R. H ep arin and low -m olecu lar-w eight hep arin.
The Seventh ACCP Conference on Antithrom botic and Throm -
bolytic Therap y. Chest 2004; 126(Su p p l):188S-203S.
8. Bick RL, Frenkel EP, Walenga J, et al. Unfractionated hep arin, low
m olecu lar w eight heparins, and p entasaccharid e: Basic m echa-
nism of actions, p harm acology and clinical u se. H em atol Oncol
Clin N Am 2005; 19:1-51.
9. Raskob G, H irsch J. Controversies in tim ing of first d ose of anti-
coagulant prop hylaxis against venou s throm boem bolism after
m ajor orthop ed ic surgery. Chest 2003; 124(Su p p l):379S-385S.
10. Bau er KA. N ew pentasaccharid es for p rophylaxis of d eep vein
throm bosis: Pharm acology. Chest 2003; 124(Su p p l):364S-370S.
11. Fon d ap arin u x. Mosbys Dru g Consu lt 2005. Accessed at
w w w.m d consu lt.com on March 6, 2007.
12. H oellerich VL, Wigton RS. Diagnosing pu lm onary em bolism
u sing clinical find ings. Arch Intern Med 1986; 146:1699-1704.
13. Kelly J, Rud d A, Lew is RR, H u nt BJ. Plasm a D-d im ers in the
d iagnosis of venous throm boem bolism . Arch Intern Med 2002;
162:747-756.
14. Kollef MH , Zahid M, Eisenberg PR. Pred ictive value of a rapid
sem iqu antitative D-d im er assay in critically ill p atients w ith su s-
p ected throm boem bolism . Crit Care Med 2000; 28:414-420.
15. Kline JA, Israel EG, Michelson EA, et al. Diagnostic accuracy of
a bed sid e D-d im er assay and alveolar d ead sp ace m easu rem ent
for rap id exclu sion of p u lm on ary em bolism . JAMA 2001;
285:761-768.
16. Tracey JA, Ed low JA. Ultrasound d iagnosis of d eep venou s
throm bosis. Em erg Med Clin N Am 2004; 22:775-796.
52 Preventive Practices in the Critically Ill

17. H u ll RD, H irsh J, Carter CJ, et al. Pu lm onary angiograp hy, ven-
tilation lu ng scanning, and venograp hy for clinically su sp ected
p u lm onary em bolism w ith abnorm al p erfu sion scans. Ann
Intern Med 1983; 98:891899.
18. The PIOPED Investigators. Valu e of the ventilation/ perfu sion
scan in acute pu lm onary em bolism . Resu lts of the prosp ective
investigation of p u lm onary em bolism d iagnosis (PIOPED).
JAMA 1990; 263:2753-2759.
19. Mu llins MD, Becker DM, H agsp eil KD, Philbrick JT. The role of
spiral volu m etric com pu ted tom ography in the d iagnosis of p u l-
m onary em bolism . Arch Intern Med 2000; 160:293-298.
20. Raschke RA, Reilly BM, Gu id ry JR, et al. The w eight-based
hep arin d osing nom ogram com p ared w ith a stand ard care
nom ogram . Ann Intern Med 1993; 119:874881.
21. Bu ller H R, Agnelli G, H u ll RD, et al. Antithrom botic therap y for
venou s throm boem bolic d isease. The Seventh ACCP Conference
on Antithrom botic and Throm bolytic Therapy. Chest 2004; 126
(Sup pl): 401S-428S.
22. Wood KE. Major pu lm onary em bolism . Chest 2002; 121:877-905.
23. Com eraota AJ. The role of fibrinolytic therap y in the treatm ent of
venou s throm boem bolism . Dis Mon 2005; 51:124-134.
24. Gold haber SZ, Agnelli G, Levine MN . Red u ced d ose bolu s
altep lase vs conventional altep lase infu sion for p u lm onary
em bolism throm bolysis: an international m u lticenter rand om -
ized trial: the Bolu s Altep lase Pu lm onary Em bolism Grou p .
Chest 1994; 106:718-724.
25. Tebbe U, Graf A, Kam ke W, et al. H em od ynam ic effects of d ou -
ble bolu s reteplase versus alteplase infusion in m assive p u l-
m onary em bolism . Am H eart J 1999; 138:39-44.
26. Stein PD, Kayali F, Olson RE. Tw enty-one year trend s in the u se
of inferior vena cava filters. Arch Intern Med 2004; 164:1541-1545.
27. Athanasou lis CA, Kaufm an JA, H alp ern EF, et al. Inferior vena
cava filters: review of 26-year single-center clinical exp erience.
Rad iology 2000; 216:54-66.
Chapter 4
VASCULAR CATHETERS
Access to the vascu lar system is m and atory in the care of
critically ill p atients. This chap ter d escribes the basic and
sp ecialty featu res of the catheters that p rovid e this access.

I. BASIC FEATURES

A. Composition and Size


1. Vascu lar catheters are m ad e of p olym ers im p regnated
w ith bariu m or tu ngsten salts to enhance rad iop acity.

2. Catheters d esigned for short-term u se (d ays) are m ad e of


p olyu rethane, a polym er know n for its strength and d u -
rability. Catheters d esigned for p rolonged u se are m ad e
of a silicone p olym er that is m ore flexible and less throm -
bogenic than p olyurethane.

3. The size of vascu lar catheters is exp ressed in term s of


their ou tsid e d iam eter. Size can be exp ressed in a m etric-
based French size or a w ire-based gauge size.
a. The French size is a series of w hole nu m bers that
increases in increm ents of rou ghly 0.33 m illim eters
(e.g., 1 French = 0.33 mm , 2 French = 0.66 m m ).
b. The gau ge size (originally d evelop ed for solid w ires)
has no d efinable relationship to other units of m eas-
u rem ent, and requires a table of reference valu es like
the one in Table 4.1.

53
54 Vascular Access

TABLE 4.1 Size Chart for Vascular Catheters


French Inner Outer
Size Gauge Diameter Diameter
1 27 0.1 mm 0.4 mm
2 23 0.3 mm 0.6 mm
3 20 0.5 mm 0.9 mm
4 18 0.6 mm 1.2 mm
5 16 0.7 mm 1.7 mm
7 13 1.3 mm 2.4 mm
9 11 1.6 mm 3.2 mm
From www.norfolkacces s .com/Catheters .html. Acces s ed on 4/7/2007.

B. Determinants of Flow Rate


1. Flu id flow throu gh rigid tu bes is d efined by the Hagen-
Poisseuille equation:

Q = P (r4 /8L) (4.1)

Q is the stead y-state flow rate.


P is the p ressu re grad ient along the tu be: (P in P ou t).
r is the inner rad iu s of the tu be.
L is the length of the tu be.
is the viscosity of the flu id .

2. Because flow rate varies d irectly w ith the fou rth p ow er


of the rad ius, the radius of a catheter is the principal deter-
minant of flow rate. For exam p le, if the rad iu s of a cath-
eter is d ou bled , the flow rate w ill increase 16-fold :
(2r)4 = 16r.

3. Equ ation 4.1 d em onstrates that rap id infu sion rates are
best achieved w ith catheters that are short and have a
large d iam eter. The role of catheter size in volu m e resu s-
citation is d escribed in Chap ter 10.
Vascular Catheters 55

II.TYPES OF CATHETERS

A. Peripheral Vein Catheters


1. Catheters u sed to cannu late p erip heral veins are short
and narrow (length: 5 7 cm, d iam eter: 18 22 gau ge).

2. These catheters are intend ed only for short-term u se


(hou rs to d ays) becau se the plastic polym ers in the cath-
eters (e.g., p olyethylene) p rovoke a strong inflam m atory
reaction u p on contact w ith blood vessels. Becau se they
are short, these catheters also tend to d islod ge from
blood vessels. The lim ited life sp an of these catheters also
lim its their p opu larity in the care of ICU patients.

B. Central Venous Catheters


Catheters u sed to cannulate the large veins entering the tho-
rax (i.e., internal ju gu lar and subclavian veins) are 15 to
25 cm in length, and are available w ith one, tw o or three
infu sion channels. The d iam eter of central venou s catheters
(CVCs) varies accord ing to the num ber and size of the infu -
sion channels.

1. Multilumen Catheters
Mu ltilu men CVCs are p op u lar in the ICU becau se they
allow m u ltip le infu sions throu gh a single venip u nctu re.
Table 4.2 show s the variety of m u ltilu m en catheter sizes
available from one m anu factu rer (Cook Critical Care).
The m ost popu lar of these is the 7 French trip le-lu m en
catheter, w hich is show n in Figu re 4.1. This catheter is
sm all enou gh to p ass throu gh introd u cer catheters (see
later), and the channels are large enough to p erm it ad e-
qu ate flow rates for m ost p atient care need s.
a. INFECTIOUS RISK. Desp ite the greater nu m ber of infu -
sion channels, m u ltilu m en catheters are not associated
w ith a higher incid ence of catheter-related infections
w hen com p ared to single lu m en catheters (1).
56 Vascular Access

TABLE 4.2 The Variety of Multilumen Central Venous


Catheters
French Cross- Gauge Flow
Size Section Port Size Ratea
Distal 18 52 mL/min
5.0 Mid 23 2 mL/min
Proximal 23 2 mL/min

Distal 16 20 mL/min
7.0 Mid 18 22 mL/min
Proximal 18 24 mL/min

Distal 14 130 mL/min


7.5
Proximal 21 5 mL/min

Distal 14 130 mL/min


9.0 Mid 18 29 mL/min
Proximal 18 31 mL/min

Distal 13 133 mL/min


9.5
Proximal 18 43 mL/min

aThe flow rate of purified water flowing from a height of 100 cm.
From Cook Double and Triple Lumen Quick Reference Guide, available
at www.cookmedical.com. Acces s ed on 4/8/2007.

2. Heparin-Bonded Catheters
Throm bu s form ation has been d ocu m ented on as m any
as one-third of ind w elling CVCs (2). These throm bi cre-
ate a risk of vascu lar occlu sion, pu lm onary em boli, and
catheter-related infection (the infectious risk is d u e to
microorganism s that becom e trap ped and proliferate in
the fibrin m eshw ork of blood clots).
Vascular Catheters 57

a. CVCs are available w ith a hep arin coating to p revent


throm bus form ation. H ow ever, this hep arin coating is
w ashed aw ay by blood flow, and it can be comp letely
lost w ithin a few hou rs after catheter insertion (2).
b. H ep arin bond ing is associated w ith only a sm all (2%)
d ecrease in the incid ence of catheter-related infections
(3). Fu rtherm ore, the hep arin that is w ashed aw ay
from th ese cath eters can cau se h ep arin -in d u ced
throm bocytopenia in su scep tible ind ivid u als (4).
c. H ep arin-bond ed catheters are now com m onp lace.
H ow ever, consid ering that these catheters p rovid e
only lim ited benefit, yet create a risk of heparin-in-
d u ced throm bocytop enia, their p op u larity is u nd e-
served .

3. Antimicrobial-Impregnated Catheters
a. CVCs are available that are coated w ith chlorhexid ine
and silver su lfad iazine (Arrow International, Read ing,
PA) or m inocycline and rifam p in (Cook Critical Care,
Bloom ington, IN ).
b. A single m u lticenter stu d y com p aring both types of
antim icrobial catheters show ed su p erior resu lts w ith
the m inocycline-rifam p in CVCs (5). These catheters
show antim icrobial activity for u p to 4 w eeks, com -
p ared to one w eek for the chlorhexid ine-silver su lfad i-
azine CVCs (6).
c. Antim icrobial-im pregnated CVCs shou ld be consid -
ered if the rate of catheter-related septicem ia in your
ICU is higher than the national average (3.8 to 5.3
infections p er 1,000 catheter-d ays in m ed ical-su rgical
ICUs) (7). They shou ld also be consid ered in neu -
trop enic p atients and bu rn p atients.

C. Introducer Catheters
Large-bore introducer catheters like the one show n in Figu re
4.1 have a d iam eter (8 to 9 French) that is large enou gh to
58 Vascular Access

FIGURE 4.1. A popular sized multilumen central venous catheter and a


large-bore introducer catheter.

allow p assage of central venou s catheters (inclu d ing m u lti-


lum en catheters) and p u lm onary artery catheters. Central
venou s cannu lation u su ally begins w ith insertion of an intro-
d u cer catheter, w hich is left in p lace. N arrow er catheters can
then be inserted and rep laced rep eated ly w ithou t the risks of
a new venip unctu re. (Figu re 7.1 show s a p u lm onary artery
catheter thread ed throu gh an introd u cer catheter). Introd u-
cer catheters can also be u sed as stand -alone infusion d evi-
ces. The large d iam eter of these catheters m akes them w ell
su ited for rap id infu sion rates, w hich can be ad vantageou s
for resuscitation in the bleed ing p atient (see Chap ter 10).

D. Specialty Catheters
1. Hemodialysis Catheters
Short-term hem od ialysis is p erform ed w ith sp ecially d e-
Vascular Catheters 59

signed d ou ble-lu m en catheters like the one show n in


Figu re 4.2 that are placed in the internal ju gu lar vein or
fem oral vein. One lu m en of the catheter carries blood
from the p atient to the d ialysis m em branes, and the
other lum en carries blood back to the p atient. Each
lum en is equivalent in d iam eter to an introd ucer catheter
(8 French or 12 gau ge) to accomm od ate the rap id flow
rates (200 to 300 m L/ m in) requ ired for effective hem o-
d ialysis.

12 Ga

12 Ga

FIGURE 4.2. A large-bore, double-lumen catheter used for short-term


hemodialysis.

2. Pulmonary Artery Catheters


Pu lm onary artery catheters are u sed for hem od ynam ic
assessm ents, and can p rovid e as m any as 16 m easu re-
ments of card iovascu lar fu nction. These catheters are
d escribed in d etail in Chap ter 7 (see Figu re 7.1).
60 Vascular Access

REFERENCES
1. McGee DC, Gould MK. Preventing com p lications of central ve-
nou s catheterization. N Engl J Med 2003; 348:1123-1133.
2. Jacobs BR. Central venou s catheter occlu sion and throm bosis.
Crit Care Clin 2003; Vol. 19:489-514.
3. Marin MG, Lee JC, Sku rnick JH . Prevention of nosocom ial blood -
stream infections: effectiveness of antim icrobial-im p regnated
and heparin-bond ed central venou s catheters. Crit Care Med
2000; 28:3332-3338.
4. Laster JL, N ichols WK, Silver D. Throm bocytopenia associated
w ith hep arin-coated catheters in p atients w ith hep arin-associat-
ed antiplatelet antibod ies. Arch Intern Med 1989; 149:2285-2287.
5. Darou che RO, Raad II, H eard SO, et al. A com p arison of antim i-
crobial-im pregnated central venou s catheters. N Engl J Med
1999; 340:1-8.
6. H anna H , Darouche R, Raad I. N ew approaches for prevention of
intravascular catheter-related infections. Infect Med 2001; 18:38-48.
7. Centers for Disease Control and Prevention. Gu id elines for the
p revention of intravascu lar catheter-related infections. MMWR
2002; 51(N o.RR-10):1-30.
Chapter 5
ESTABLISHING
VENOUS ACCESS
This chap ter p resents som e p ractical gu id elines for the inser-
tion of p eripheral and central venou s catheters, and d e-
scribes the ad verse events that can occu r d u ring catheter
insertion.

I. PREPARING FORVASCULAR CANNULATION

A. Hospital Staff
1. H and w ashing w ith an antim icrobial soap or gel is recom -
mend ed for all vascu lar catheter insertions (see Table
1.2).

2. Sterile gloves are recom m end ed for insertion of central


venou s catheters and arterial catheters. N onsterile d is-
p osable gloves can be u sed for cannu lation of peripher-
al veins as long as the gloved hand s d o not tou ch the
catheter (see Table 1.3).

3. Masks, gow ns, and sterile d rapes are recom m end ed for
insertion of central venous catheters and perip herally-
inserted central catheters (PICCs).

B. Insertion Site
1. The skin arou nd the catheter insertion site shou ld be
d econtam inated w ith an antisep tic agent (see Table 1.1).

61
62 Vascular Catheters

Chlorhexid ine is currently preferred becau se of its pro-


longed activity ( 6 hrs.).

2. If an iod op hor su ch as p ovid one-iod ine is used , the solu -


tion shou ld be left in contact w ith the skin for a few m in-
u tes (see Chap ter 1).

II. CATHETER INSERTION TECHNIQUES

A. Catheter-Over-Needle Technique
Short catheters (5 to 7 cm in length) are inserted into sm all,
su perficial veins u sing a catheter-over-need le d evice like the
one show n in Figu re 5.1. The entire d evice (catheter and
need le) is ad vanced tow ard the target vessel w ith the bevel
of the need le p ointed u p w ard . When the tip of the need le
enters the blood vessel, blood ap p ears in the transp arent
flash cham ber. When this occu rs, the need le is kep t station-
ary and the catheter is ad vanced over the need le and into the
lum en of the blood vessel. The need le is then w ithd raw n and
the catheter is secu red to the skin.

Introduce r Ne e dle

Fla s h
Ca the te r Cha mbe r

Ca p

FIGURE 5.1. A catheter-over-needle device used to cannulate peripheral


veins. Area of magnification shows needle extending beyond the
catheter tip, and the tapered shape of the catheter tip. When the needle
enters the vein, blood is visible in the flash chamber.
Establishing Venous Access 63

B. Guidewire Technique
Long catheters (10 to 25 cm in length) are inserted into d eep-
ly located veins by thread ing the catheter over a gu id ew ire.
This techniqu e (called the Seldinger technique after its
found er) is show n in Figure 5.2. A sm all-bore need le is u sed
to p robe for the target blood vessel. When the tip of the nee-
d le enters the vessel, a long, flexible w ire is p assed throu gh
the need le and into the lum en of the vessel. The need le is
then rem oved over the gu id ew ire, and the catheter is
ad vanced over the gu id ew ire and into the blood vessel. The
guid ew ire is then rem oved and the catheter is secu red to the
skin.

III.VENOUS ACCESS SITES

A.The Upper Extremity


1. Peripheral Veins
The arm s are p referred to the legs for p erip heral vein
cannulation because of ease of access and a low er risk of
throm bosis (1). Becau se the catheters are short and easi-
ly d islod ged , areas of lim ited m ovem ent (e.g., the fore-
arm of the nond om inant hand , aw ay from the w rist and
elbow ) are m ost likely to ensu re su ccessfu l cannu lation.

2. Peripherally-Inserted Central Catheters


a. Long catheters (50 to 60 cm ) are available that can be
inserted into the veins of the antecubital fossa and ad -
vanced into the su p erior vena cava. There is no risk of
p neu m othorax, w hich is the principal ad vantage of
these peripherally-inserted central catheters (PICC).
b. The basilic vein is p referred to the cephalic vein for
PICC placem ent becau se it is slightly larger and ru ns a
shorter cou rse u p the arm (see Figu re 5.3).
64 Vascular Catheters

1. Ins e rt ne e dle

2. Pa s s guidewire through ne e dle

3. Re move ne e dle

4. Pa s s ca the te r ove r guide wire

FIGURE 5.2. The steps involved in guidewire-assisted cannulation of


blood vessels (the Seldinger technique).
Establishing Venous Access 65

c. PICCs can be placed blind ly by ad d ing the length of


the vascu lar segm ents show n in Figu re 5.3. Alternate-
ly, the d istance from the antecu bital fossa to the 3rd
anterior intercostal sp ace on the right (w here the su p e-
rior vena cava enters the right atriu m ) can be m eas-
u red . H ow ever w ithou t flu oroscopy, m alp osition of
PICCs is com m on (2).
d . PICCs offer no ad vantage over other m ethod s of cen-
tral venou s catheterization. Althou gh there is no risk
of p neu m othorax w ith PICCs, the risk of p neu m otho-
rax from central venou s catheterization is sm all (see
later), at least w hen p erform ed by trained p ersonnel.
PICCs are used p rim arily for long-term venou s access
(30 d ays or longer), and they have no role in the care
of critically ill p atients.

B.The Subclavian Vein


1. Anatomy
a. The su bclavian vein is a continu ation of the axillary
vein as it passes over the first rib. It ru ns m ost of its
course along the u nd ersid e of the clavicle and contin-
u es to the thoracic inlet, w here it joins the internal
ju gu lar vein to form the innom inate vein. The conver-
gence of the right and left innom inate veins then form s
the su p erior vena cava.
b. The average d istance from insertion site to the right
atriu m is 14.5 cm and 18.5 cm for right-sid ed and left-
sid ed cannu lations, resp ectively. Subclavian vein cath-
eters should be no longer than 15 cm to avoid p lacing the
catheter tip in the right sid e of the heart (3).

2. Locating the Vessel


a. Id entify the insertion of the sternocleid omastoid m u s-
cle on the clavicle. The su bclavian vein lies just u nd er-
neath the clavicle at this p oint. The vein can be ap-
p roached from above or below the clavicle, and it
66 Vascular Catheters

shou ld be entered w ithin 2 to 3 cm of the insertion site


on the skin.
b. When ad vancing the p robe need le, keep the need le
ju st u nd erneath the clavicle to p revent accid ental
p unctu re of the subclavian artery (w hich ru ns d eep to
the subclavian vein).

3. Benefits and Risks


a. The su bclavian vein is w ell su ited for cannu lation be-
cau se it is a large vessel (d iam eter of 20 mm ) w ith a
p red ictable anatom ic location. Patient tolerance of cen-
tral venou s catheters is highest w ith su bclavian vein
catheters.
b. The m ajor concern w ith su bclavian vein cannu lation is
p neu m othorax from p u nctu re of the lu ng apex. Table
5.1 shows that this is not a common occurrence when the
proced ure is performed by experienced personnel (4,5).
c. Major bleed ing is also u ncom mon (see Table 5.1), and
the p resence of a coagu lop athy d oes not increase the
risk of bleed ing (6,7). The p resence of a coagu lopathy
is not a contraind ication to central venou s cannu lation.

TABLE 5.1 Complications of Large Vein Cannulation


Complication Rates
Subclavian Internal Jugular Femoral
Complication Vein Vein Vein
Arterial Puncture 1 5% 3% 9%*
Major Bleeding 2% 1% 1%
Thrombosis 1% 0 6%*
Pneumothorax 1 3% 1%
Systemic sepsis 1 4% 0 8% 2 5%
From References 4,5,9,10. Rates are expressed as the nearest whole number.
*Indicates a rate that is s ignificantly different from the others
Establishing Venous Access 67

C.The Internal Jugular Vein


1. Anatomy
a. The internal ju gu lar (IJ) vein is located u nd er the ster-
nocleid omastoid mu scle in the neck. It ru ns obliqu ely
along a line d raw n from the p inna of the ear to the
sterno-clavicu lar joint. In the low er region of the neck,
the vein ru ns ju st lateral to the carotid artery, and this
p roxim ity creates a risk of carotid artery p u nctu re.
b. The IJ vein on the right sid e runs a straight course to
the right atriu m , and the d istance involved is abou t 15
cm (see Figu re 5.3). Therefore, catheters u sed to cannu -
late the right IJ vein shou ld be no longer than 15 cm to
avoid ad vancing the catheter into the right sid e of the
heart. (This is the sam e maxim um length recom m end -
ed for su bclavian vein catheters.)

2. Locating the Vessel


Use the right sid e of the neck w hen possible (because of
the straight cou rse to the heart).
a. POSTERIOR APPROACH. Id entify the point w here the
external ju gu lar vein crosses over the lateral ed ge of
the sternocleid omastoid m u scle. The insertion site is
one centim eter su p erior to this p oint. The p robe nee-
d le shou ld be inserted ju st u nd er the belly of the ster-
nocleid om astoid m u scle and ad vanced tow ard the
su p rasternal notch. The vein shou ld be entered 5 to 6
cm from the skin.
b. ANTERIOR APPROACH. At the base of the neck, id enti-
fy a triangu lar area w here the sternocleid om astoid
m u scle sp lits to form the sternal and clavicu lar head s
of the m uscle. The p robe need le shou ld be inserted at
the apex of this triangle and ad vanced tow ard the ipsi-
lateral nipp le at a 45 angle w ith the skin. The vein
shou ld be entered w ithin 5 cm of the skin. This ap -
p roach has a higher risk of carotid artery pu nctu re
than the posterior ap proach.
68 Vascular Catheters

3. Benefits and Risks


Cannulation of the IJ vein has few ad vantages over sub-
clavian vein cannulation.
a. The IJ ap proach w as p op u larized becau se of the as-
sum ption that the site of catheter insertion in the neck
w ou ld elim inate the risk of p neu m othorax. H ow ever,
this is not the case (4,5). In fact, the incidence of pneu-
mothorax is the same with internal jugular vein and subcla-
vian vein cannulation (see Table 5.1). H ow can the lu ng
be p unctu red by a catheter inserted in the neck? One
p ossible answ er is if the lung apex protru d es into the
neck from overinflation d u ring m echanical ventila-
tion.
b. The m ost life-threatening com plication of IJ cannu la-
tion is carotid artery p u nctu re, w hich occu rs d u ring
3% of attem pted IJ cannu lations (see Table 5.1).
c. The only clear ad vantage of IJ cannu lation is anatom -
ic; i.e., the straight cou rse from the right IJ vein to the
right atriu m . For this reason, the right IJ vein is the
p referred site for insertion of pacemaker catheters and
hem od ialysis catheters.

C.The Femoral Vein


1. Anatomy
The fem oral vein is the m ain venou s ou tflow from the
legs. In the u pp er one-third of the thigh, the fem oral vein
ru ns ad jacent to the fem oral artery. Both vessels are locat-
ed in the m ed ial p ortion of the fem oral triangle, w ith the
fem oral vein situ ated ju st med ial to the fem oral artery
(see Figu re 5.4). Both vessels are w ithin a few centimeters
of the skin at the ingu inal crease.

2. Locating the Vessel


a. Ju st below the ingu inal crease, p alpate the fem oral
artery p u lse in the m ed ial one-third of the leg. The
fem oral vein is ju st m ed ial to the palpated pu lse.
Establishing Venous Access 69

Inte rna l Jugula r


6 cm

R. Innomina te
S ubclavia n 2.5 cm
6 cm
L. Innomina te
Axilla ry 6.5 cm
13 cm

Ba s ilic
24 cm

Ce pha lic
38 cm

S upe rior Ve na Cava


7 cm

FIGURE 5.3. The length of venous segments involved in the insertion of


peripherally inserted central catheters (PICCs) and central venous (sub-
clavian and internal jugular vein) catheters. The circle in the third ante-
rior intercostal space marks the junction of the superior vena cava and
right atrium.

Insert the p robe need le w ithin 2 cm of the palpable


p ulse, and you shou ld enter the femoral vein 2 to 4 cm
below the skin.
b. If the fem oral artery p u lse is not p alp able, d raw an
im aginary line from the anterior sup erior iliac crest to
the p u bic tu bercle, and d ivid e the line into three equal
segm ents. The fem oral artery shou ld be ju st u nd er the
ju nction betw een the m id d le and m ed ial segm ents of
the line, and the fem oral vein w ill be 1 to 2 cm m ed ial
to this point. This m ethod has a 90% su ccess rate for
locating the femoral vein (8).
70 Vascular Catheters

3. Benefits and Risks


a. The m ajor benefit of fem oral vein cannu lation is an-
atom ic: i.e., the vein is large, easily located , and far re-
moved from the thorax.
b. The m ajor risks of fem oral vein cannu lation are fem -
oral artery p u nctu re and fem oral vein throm bosis
(4,9). Catheter-related infections d o not occu r more fre-
qu ently w ith fem oral vein catheters w hen comp ared to
internal ju gular and su bclavian vein catheters (see
Table 5.1) (10).
c. Becau se of the enhanced risk for arterial pu nctu re and
venou s throm bosis, femoral vein catheters should be

Inguina l Fe mora l Fe mora l


liga me nt ne rve a rte ry

Fe mora l
ve in

S a rtorius
mus cle
Adductor
longus
mus cle

FIGURE 5.4. The anatomy of the femoral triangle.


Establishing Venous Access 71

u sed only w hen cannu lation of the internal ju gular


and subclavian veins is not possible. Fem oral vein
catheters shou ld be rem oved as soon as p ossible to
lim it the risk of venous throm bosis.

IV. IMMEDIATE CONCERNS

A.Venous Air Embolism


When a vascu lar catheter is ad vanced into the thorax, the
negative intrathoracic p ressu re generated d u ring sponta-
neous breathing can d raw air into the venou s circulation if
the catheter is op en to the atm osp here. The entrained air can
travel to the right sid e of the heart as a venous air embolism
and p rod u ce life-threatening obstru ction in the p u lm onary
circulation (11).

1. Preventive Measures
Air is prevented from entering the venous circu lation
w hen the venou s p ressu re exceed s atm osp heric (zero)
p ressu re. The tw o m aneu vers below are d esigned to in-
crease central venou s pressu re.
a. Placing the patient in the Trend elenbu rg position w ith
the head 15 below the horizontal p lane w ill increase
the venou s pressure in the head and neck regions,
w hich can be ad vantageou s d uring cannulation of the
su bclavian and internal ju gu lar veins. This m aneu ver
is not intend ed for p atients w ho alread y have elevated
venou s p ressu res from card iop u lm onary d isease.
b. When changing connections in a central venou s line,
a tem p orary increase in venou s p ressu re can be a-
chieved by having the p atient hu m au d ibly. This not
only p rod u ces a p ositive intrathoracic p ressu re, it also
allow s you to hear w hen the d esired effect is occu r-
ring.
72 Vascular Catheters

2. Clinical Presentation
a. The earliest clinical m anifestation of venou s air em -
bolism is acu te onset of d ysp nea. H yp otension and
card iac arrest can d evelop rap id ly.
b. Air can pass across a patent foram en ovale and ob-
stru ct the cerebral circu lation, p rod u cing an acu te is-
chem ic stroke.
c. A characteristic m ill w heel m u rm ur can be heard
over the right heart, bu t it can be fleeting.

3. Therapeutic Maneuvers
a. When air entry is first su sp ected , the central venou s
line shou ld be aspirated to rem ove any resid ual air,
and the p atient shou ld be p laced w ith the left sid e
d ow n (so air w ill collect in the right sid e of the heart
instead of the p u lm onary ou tflow tract).
b. In d ire circu m stances, a need le can be inserted throu gh
the chest w all and into the right ventricle to asp irate
the air. To perform this p roced u re, insert a long need le
in the 4th intercostal sp ace ju st to the right of the ster-
nu m and ad vance the need le u nd er the sternu m at a
45 angle until there is blood retu rn.
c. In severe cases of venou s air em bolism , the m ortality
is high d espite the above therapeutic maneu vers.

B. Pneumothorax
Although the risk of pneu mothorax from central venou s can-
nu lation is sm all (see Table 5.1), rou tine chest x-rays are rec-
om m end ed im med iately follow ing all cannu lations (or at-
tem pts) of the su bclavian and internal ju gular veins.

1. Radiographic Detection
a. Postinsertion chest x-rays shou ld be obtained in the
u pright p osition and d u ring exp iration, if p ossible.
Expiration d ecreases the volum e of air in the lu ngs,
Establishing Venous Access 73

bu t not the volu m e of air in the p leural sp ace, so exp i-


ration w ill facilitate the d etection of sm all p neu m otho-
races (12).
b. Upright film s are not alw ays feasible in ICU patients.
If the sup ine p osition is u sed , rem em ber that pleural air
does not collect at the apex of the lung when the patient is in
the supine position (13). In this p osition, p leu ral air
tend s to collect anteriorly and at the base of the lu ng
(see Chap ter 20).

2. Delayed Pneumothorax
a. Pneu m othorax may not be rad iograp hically evid ent
u ntil 24 to 48 hou rs after catheter insertion (14). There-
fore, the absence of a p neu m othorax on an imm ed iate
p ostinsertion chest film d oes not absolu tely exclu d e
this com plication. H ow ever, serial chest x-rays are not
ju stified in asym p tom atic p atients.
b. Delayed pneu m othorax shou ld be a consid eration in
any p atient w ho d evelop s d ysp nea or p rogressive hy-
p oxem ia in the first few d ays after central venou s can-
nu lation.

C. Catheter Position
Chest x-rays are ad vised after all central venous cannu la-
tions to ensu re p rop er catheter p lacem ent.

1. Proper Placement
A p rop erly p laced central venou s catheter shou ld ru n
p arallel to the shad ow of the su perior vena cava, and the
tip of the catheter should be at or slightly above the third
anterior intercostal sp ace (w here the su p erior vena cava
meets the right atriu m ).

2. Tip in the Right Atrium


A catheter tip that extend s below the third right anterior
intercostal space is likely to be in the right sid e of the
74 Vascular Catheters

heart. If the anterior p ortion of the third rib cannot be


visu alized , a catheter tip that extend s below the tracheal
carina (i.e., the d ivision of the trachea into the right and
left m ainstem bronchi) can be used as evid ence of right
heart catheterization. Althou gh card iac p erforation is
rare (15), w ithd raw al of the catheter tip to the app rop ri-
ate location is ad vised .

3. Tip Against the Wall of the Vena Cava


Catheters inserted from the left sid e m u st m ake an acu te
tu rn d ow nw ard w hen they enter the su p erior vena cava
from the left innom inate vein. Catheters that d o not m ake
this tu rn can end u p w ith the tip p ointing d irectly at the
lateral w all of the su p erior vena cava. These catheters can
p erforate the su perior vena cava, and they shou ld either
be w ithd raw n into the innom inate vein or ad vanced fu r-
ther d ow n the vena cava.

REFERENCES
1. Centers for Disease Control and Prevention. Gu id elines for the
p revention of intravascu lar catheter-related infections. MMWR
2002; 51 (N o.RR-10):1-30.
2. H effner JE. A gu id e to the m anagem ent of p erip herally inserted
central catheters. J Crit Illness 2000; 15:165-169.
3. McGee WT, Ackerm an BL, Rou ben LR, et al. Accu rate placem ent
of central venous catheters: a p rosp ective, rand om ized , m u lti-
center trial. Crit Care Med 1993; 21:11181123.
4. Merrer J, DeJonghe B, Golliot F, et al. Com p lications of fem oral
and su bclavian venous catheterization in critically ill patients.
JAMA 2001; 286:700-707.
5. Ru esch S, Wald er B, Tram er M. Com p lications of central venou s
catheters: internal jugu lar versu s subclavian access A system at-
ic review. Crit Care Med 2002; 30:454-460.
6. Fisher N C, Mutim er DJ. Central venou s cannu lation in patients
w ith liver d isease and coagu lop athy a p rosp ective au d it. Inten-
sive Care Med 1999; 25:481-485.
7. Doerfler M, Kau fm an B, Gold enberg A. Central venous catheter
Establishing Venous Access 75

p lacem ent in patients w ith d isord ers of hem ostasis. Chest 1996;
110:185-188.
8. Getzen LC, Pollack EW. Short-term fem oral vein catheterization.
Am J Su rg 1979; 138:875-877.
9. Joynt GM, Kew J, Gom ersall CD, et al. Deep venou s throm bosis
caused by fem oral venous catheters in critically ill ad u lt patients.
Chest 2000; 117:178-183.
10. Deshpand e K, H atem C, Ulrich H , et al. The incid ence of infec-
tious com plications of central venou s catheters at the su bclavian,
internal jugu lar, and fem oral sites in an intensive care unit p op -
u lation. Crit Care Med 2005; 33:13-20.
11. Muth CM, Shank ES. Gas em bolism . N Engl J Med 2000; 342:
476-482.
12. Marino PL. Delayed p neum othorax: a com p lication of su bcla-
vian vein catheterization. J Parenter Enteral N u tr 1985;9:232.
13. Tocino IM, Miller MH , Fairfax WR. Distribution of pneum otho-
rax in the su pine and sem irecu m bent critically ill ad u lt. Am J
Rad iol 1985; 144:901905.
14. Collin GR, Clarke LE. Delayed p neu m othorax: a com p lication of
central venous catheterization. Su rg Rou nd s 1994; 17:589594.
15. McGee WT, Ackerm an BL, Rou ben LR, et al. Accu rate p lacem ent
of central venous catheters: a prosp ective, rand om ized , m u lti-
center trial. Crit Care Med 993; 21:11181123.
Chapter 6
THE INDWELLING
VASCULAR CATHETER
This chap ter d escribes the rou tine care and ad verse conse-
qu ences of ind w elling vascular catheters, w ith em p hasis on
the prevention, d iagnosis, and treatm ent of catheter-related
infections.

I. ROUTINE CATHETER CARE

A. Protective Dressings
Catheter insertion sites are covered as a stand ard antiseptic
measure. Sterile gau ze pad s p rovid e ad equ ate protection in
most instances (1).

1. Adhesive, Semipermeable Dressings


Ad hesive d ressings m ad e of transp arent, sem ip erm eable
p olyu rethane m em branes are very p opu lar. These d ress-
ings partially block the escape of w ater vapor from the
u nd erlying skin, and create a m oist environm ent that is
beneficial for w ound healing.
a. Desp ite their pop u larity, these d ressings d o not red uce
the incid ence of catheter colonization or infection
w hen com p ared to sterile gau ze d ressings (1-3). In fact,
they can increase the risk of infection (2,3) becau se the
m oist environm ent they create favors the grow th of
m icroorganism s.
b. Occlu sive d ressings can be reserved for skin sites that
are close to a sou rce of infectiou s secretions (e.g., a tra-
cheostom y).
77
78 Vascular Access

B. Antimicrobial Ointment
The p ractice of ap p lying antim icrobial gels to the insertion
site of central venou s catheters d oes not red u ce the incid ence
of catheter-related infections (4), and it can p rom ote the d e-
velopm ent of antibiotic-resistant organism s (5). As a resu lt,
the rou tine u se of antim icrobial ointm ents is not recom -
mend ed (1,4).

C. Flushing Catheters
Vascu lar catheters are flu shed at regular intervals to p revent
throm botic occlusion.

1. Heparinized Flushes
a. The stand ard flu sh solu tion is isotonic saline w ith hep -
arin (10 to 1000 U/ m L).
b. Catheters that are u sed interm ittently are filled w ith
hep arinized saline and cap p ed w hen id le. (This is
called a heparin lock becau se the cap that seals the
catheter creates a vacu um that hold s the flu sh solu tion
in p lace.)
c. Arterial catheters are flu shed continu ou sly (3 mL/ hr)
u sing a p ressu rized bag.

2. Alternatives to Heparin
The sm all qu antities of hep arin u sed in flu sh solu tions
can p rom ote hep arin-ind u ced throm bocytop enia (see
Chap ter 31). Alternatives to hep arinized flu shes are
available that elim inate this risk.
a. For flu shing venou s catheters, saline alone is as effec-
tive as hep arinized saline (6).
b. For flu shing arterial catheters, 1.4% sod iu m citrate is a
suitable alternative to hep arinized saline (7).
The Indwelling Vascular Catheter 79

D. Replacing Peripheral Venous Catheters


The concern w ith p rolonged cannu lation of p erip heral veins
is inflamm ation (p hlebitis), not infection. The inflam m ation
is a reaction to the plastic polym ers that m ake up vascular
catheters, and is aggravated by m echanical irritation of the
blood vessel w all.

1. The incid ence of clinically ap p arent p hlebitis increases


significantly after p erip heral vein catheters are left in
p lace longer than 72 to 96 hours (1).

2. Therefore, rep lacem ent of p erip heral vein catheters (u s-


ing a new venip u nctu re site) is recomm end ed every 72 to
96 hou rs (1).

E. Replacing Central Venous Catheters


1. Routine Replacement Not Warranted
Sep ticem ia from central venou s catheters begins to ap -
p ear after catheters have been in p lace for 3 d ays (1).
H ow ever, rep lacing central venou s catheters at regular
intervals d oes not red uce the incid ence of catheter-relat-
ed infections (8). In fact, it increases the risk of catheter-
related m echanical comp lications (4), so the overall risk
(infectiou s and m echanical) is increased (9). Therefore,
rou tine rep lacem ent of central venou s catheters is not
ad vised (1,4).

2. Indications for Catheter Replacement


Catheter replacement is recom m end ed :
a. When there is pu rulent d rainage from the catheter in-
sertion site. Erythema around the catheter insertion
site is not absolu te evid ence of infection (9), and is not
an ind ication for catheter rep lacem ent.
80 Vascular Access

b. When an ind w elling vascu lar catheter is su sp ected as


a sou rce of sep sis and the p atient has a p rosthetic
valve, is im m u nocomp rom ised , or has severe sep sis or
sep tic shock.
c. When a catheter has been placed em ergently, w ithou t
strict asep tic techniqu e, and it can be rep laced safely.
d . When a femoral vein catheter has been in place longer
than 48 hou rs and it can be replaced safely. This w ill
lim it the risk of fem oral vein throm bosis (see Table 5.1).

II.THE OCCLUDED CATHETER


Catheter occlusion is the m ost com m on comp lication of cen-
tral venous cannu lation (11).

A. Sources of Obstruction
1. Throm bosis is the m ost com m on cau se of obstru ction of
central venous catheters (11).

2. Insolu ble p recip itates in the infu sate can accu m u late in
the catheter lu m en and cau se obstru ction. Possible sou r-
ces of this type of obstruction inclu d e d rugs that are in-
solu ble in w ater (e.g., d iazep am , d igoxin, p henytoin, and
trimethop rim -su lfa), p recip itation of inorganic salts (e.g.,
CaPO 4), and lipid resid u es.

3. The lum en of the catheter can also be com promised by


sharp angles and localized ind entations. These u su ally
occu r d u ring catheter insertion.

B. Restoring Catheter Patency


A p rotocol for restoring p atency in obstru cted catheters is
show n in Table 6.1. Since thrombosis is the most common
The Indwelling Vascular Catheter 81

cause of catheter occlusion, the initial attempt to restore pa-


tency should involve an attempt to lyse the occluding thrombus.

TABLE 6.1 Protocol for Restoring Patency in Occluded


Catheters
Drug Preparation
1. Alteplase (tissue plasminogen activator):
Reconstitute 50 mg vial with 50 mL sterile water (1 mg/mL).
2. Prepare 2 mL aliquots and freeze until needed.
Protocol
1. Thaw two aliquots of drug solution. (Drug must be used within
8 hours after thawing.)
2. Draw 2 mL of drug solution (2mg) into a 5 mL syringe and
attach to hub of the occluded catheter.
3. Inject as much volume as possible (up to 2 mL) into the lumen
of the catheter and then cap the hub of the catheter.
4. Leave the drug solution in the catheter lumen for 2 hours.
5. Attempt to flush the catheter with a saline solution. Do not use a
tuberculin syringe to flush occluded catheters (the high pressure
generated by these syringes can fracture the hub of a catheter).
6. If the catheter is still obstructed, repeat steps 1 5.
7. If the catheter remains obstructed, consider using 0.1N HCL
(2 mL) for drug or CaPO4 precipitates, or 70% ethanol (2 mL) for
suspected lipid residue.
8. If the obstruction persists, replace the catheter using a new
venipuncture site.

From References 1215.

1. Thrombotic Occlusion
Local instillation of the throm bolytic agent altep lase (tis-
su e plasm inogen activator), u sing the regim en in Table
6.1, is 90% effective in restoring p atency in catheters w ith
82 Vascular Access

p artial or com plete occlusion (12,13). The total d ru g d ose


in this regim en (up to 4 mg) is too sm all to cau se system ic
throm bolysis.

2. Non-Thrombotic Occlusion
a. Catheter occlu sion that is refractory to throm bolysis
w ill occasionally respond to instillation of 0.1N hyd ro-
chloric acid to p rom ote the solu bility of inorganic salts
and som e m ed ications (14).
b. If lip id resid u es are su sp ected as a cau se of catheter
occlu sion (i.e., in p atients receiving lip id em u lsions for
nu trition), instillation of 70% ethanol (2 m L) can re-
store catheter p atency (15).

3. Replacing an Occluded Catheter


If the obstru ction cannot be relieved and the catheter
mu st be rep laced , a new venip u nctu re site is necessary.
Catheter replacem ent over a guid ew ire is not ad vised
becau se the gu id ew ire can d islod ge the obstru cting m ass
or a throm bu s in the su rrou nd ing vein (see next) and
create a pu lm onary em bolu s.

C.Venous Thrombosis
Throm botic occlu sion of a central venou s catheter can be
accom p anied by throm bosis in the su rrou nd ing vein. This is
most prom inent in the su bclavian and fem oral veins.

1. Subclavian Vein Thrombosis


a. Clinically ap parent thrombosis occu rs in abou t 1% of
p atients w ith subclavian vein catheters (see Table 5.1).
b. The hallm ark of subclavian vein throm bosis is u nilat-
eral arm sw elling (16). The thrombu s can extend prox-
im ally into the sup erior vena cava, bu t com p lete occlu -
sion of the su p erior vena cava w ith the resu ltant supe-
rior vena cava syndrome (sw elling of neck and face, etc.)
is rare (17).
The Indwelling Vascular Catheter 83

c. Sym p tom atic p u lm onary em bolism can occu r, but the


rep orted incid ence varies from zero to 17% (16,18).
d . Ultrasou nd has a low sensitivity and specificity (56%
and 69%, respectively) for the d etection of su bclavian
vein throm bosis (19), and the d iagnosis is often based
on the clinical presentation (i.e., u nilateral arm sw el-
ling). Contrast venograp hy is rarely p erform ed .
e. Treatm ent involves im m ed iate catheter rem oval and
elevation of the affected arm . System ic anticoagu lation
w ith hep arin is p opu lar (16,18), bu t u np roven.

2. Femoral Vein Thrombosis


a. Clinically ap parent throm bosis is reported in 6% of pa-
tients w ith fem oral vein catheters (see Table 5.1).
b. As rep orted in Chap ter 3, venou s u ltrasou nd has a
high (> 90%) sensitivity and sp ecificity for the d etec-
tion of p roxim al d eep vein throm bosis in the leg.
Treatm ent inclu d es im m ed iate catheter rem oval and
hep arin anticoagu lation as d escribed in Chap ter 3.

III. CATHETER-RELATED INFECTIONS


H ospital-acqu ired (nosocom ial) blood stream infections are 2
to 7 tim es m ore frequ ent in ICU p atients than in other hospi-
talized p atients (20), and ind w elling vascu lar catheters are
responsible for over half of these blood stream infections (21).

A. Routes of Infection
The rou tes of infection involving ind w elling vascu lar cath-
eters are d escribed below u sing the correspond ing num bers
show n in Figu re 6.1.

1. Microbes can gain access to the internal lu m en of vascu -


lar catheters throu gh break points in the infu sion system ,
su ch as stop cocks and catheter hu bs.
84 Vascular Access

2. Microbes on the skin can m igrate along the ou ter su rface


of the catheter in the tract created d u ring p ercu taneou s
insertion of the catheter. This is consid ered the m ajor
rou te of catheter-related blood stream infections.

FIGURE 6.1. The routes of catheter-related bloodstream infections.

3. Microbes p resent in circu lating blood can attach to the


intravascu lar portion of an ind w elling catheter. Once
attached , the m icrobes can p roliferate and becom e a sec-
ond ary sou rce of sep ticem ia.

B.Types of Infection
The Centers for Disease Control and Prevention (CDC) has
identified the following types of catheter-related infection (1).

1. Catheter colonization is characterized by the presence of


microbes on the catheter bu t not in the blood stream .

2. Exit-site infection is characterized by d rainage from the


catheter insertion site that grow s a m icroorganism on
cu lture. Blood cu ltures m ay be positive or negative.

3. Catheter-related septicemia is a cond ition w here the same


microorganism s are p resent on the tip of the catheter
and in the blood stream , and the catheter is the p rim ary
sou rce of infection.
The Indwelling Vascular Catheter 85

C. Clinical Features
1. Catheter colonization is asym p tom atic, w hile catheter-
related sep ticem ia is u su ally accom p anied by signs of
system ic inflam m ation (i.e., fever, leu kocytosis, etc.).

2. There are no sp ecific signs of catheter-related sep ticem ia.


The p resence of erythem a arou nd the insertion site is not
p red ictive of sep ticem ia (10), and the p resence of p u ru -
lent d rainage from the insertion site can ind icate exit-site
infection w ithou t septicem ia (1,22).

3 . Catheter-related sep ticem ia is u su ally su sp ected w hen a


p atient w ith a vascu lar catheter in p lace for longer than
48 hou rs has an u nexp lained fever. Confirm ation is based
on the resu lts of app rop riate cu ltures, as d escribed next.

D. Catheter Tip Cultures


The m ost com m on ap p roach to su sp ected catheter-related
sep ticem ia is to com bine a cu ltu re of the catheter tip w ith a
blood cultu re obtained from a p erip heral vein. This m ethod
is d escribed below.

1. The catheter is first rem oved and (u sing sterile tech-


niqu e) a 2 inch segm ent is severed from the d istal end
of the catheter and p laced in a sterile cu ltu rette tu be.
There are 2 m ethod s for cu ltu ring catheter tips.

2. Roll-Plate Method
a. The catheter tip is rolled d irectly over the su rface of a
blood agar p late, and grow th is m easu red as the nu m -
ber of colony-form ing u nits (CFUs) on the p late.
b. The diagnosis of catheter-related septicemia requires
grow th of at least 15 CFUs on the culture plate plus iso-
lation of the same organism from the blood culture (22).
c. This m ethod w ill d etect infection only on the ou ter
su rface of the catheter, w hich exp lains w hy it has a
86 Vascular Access

sensitivity of only 60% for the d etection of catheter-tip


infections (see Table 6.2) (22).

3. Serial Dilution Method


a. The catheter tip is p laced in cu ltu re broth and agitated
vigorou sly to release attached organism s. After serial
d ilu tions, the broth is p laced on a blood agar p late,
and grow th is m easu red as the nu m ber of colony-
form ing u nits (CFUs) on the p late.
b. The d iagnosis of catheter-related sep ticem ia requ ires
grow th of at least 100 CFUs on the cu ltu re p late plus
isolation of the sam e organism from the blood cu ltu re.
c. This m ethod w ill d etect infection on both (ou ter and
inner) surfaces of the catheter, w hich explains w hy the
sensitivity of this method (80%) is higher than the roll-
p late m ethod (see Table 6.2).

TABLE 6.2 Culture Methods for Catheter-Related Septicemia


Catheter Surface
Method Sensitivity
Sampled
Catheter tip culture
Roll-plate method Outer surface 60%
Serial dilution method Outer and inner 80%
surfaces
Quantitative blood cultures
Catheter vs. peripheral blood Inner surface 50%
From Reference 22.

E. Quantitative Blood Cultures


The d isad vantage of catheter tip cu ltu res is the need to re-
move the catheter. Consid ering that as many as 70% of cath-
eters that are rem oved for presu m ed infection are sterile
The Indwelling Vascular Catheter 87

w hen cultu red (22), an alternative cu ltu re m ethod that d oes


not requ ire catheter rem oval is d esirable. The qu antitative
blood cu ltu re techniqu e d escribed below is su ch a m ethod .

1. This method com pares the cu ltu re resu lts from 2 blood
sam p les (10 m L each): one sam p le is d raw n through the
ind w elling catheter, and the other is taken from a p eriph-
eral vein. The sam p les are p laced in sp ecial cu ltu re tu bes
(e.g., Isolator System , Du pont Co.) for transp ort to the
laboratory.

2. Each blood sp ecim en is p rocessed by first isolating the


cells and su spend ing them in a cu ltu re m ed iu m . The cells
are then lysed to release intracellu lar organism s, and the
su p ernatant is p laced on an agar p late and incu bated .
Grow th is m easu red as the nu m ber of colony-form ing
u nits p er m illiliter (CFU/ m L).

3. The d iagnosis of catheter-related sep ticem ia requ ires iso-


lation of the sam e organism in both blood cu ltures p lus
either of the follow ing: grow th of at least 100 CFU/ m L
from the catheter blood or a colony cou nt in catheter
blood that is at least 5 tim es greater than the colony count
in p erip heral blood (see Figu re 6.2).

4. This m ethod w ill d etect infection only on the inner su r-


face of the catheter, and this m ight exp lain the low sensi-
tivity of this m ethod (40 to 50%) for the d etection of
catheter-related infections (see Table 6.2) (22).

F.Which Culture Method is Preferred?


The choice of cu ltu re m ethod is d ictated largely by the feasi-
bility of rem oving the catheter. The criteria for catheter
removal are listed earlier (See also Figu re 6.3).

1. If the catheter shou ld be rem oved , the catheter tip should


be cu ltu red u sing the serial d ilu tion m ethod (w hich is
more sensitive than the roll-plate m ethod ).
88 Vascular Access

FIGURE 6.2. Comparative growth of quantitative blood cultures from a


case of catheter-related septicemia. Catheter Blood is blood withdrawn
through a central venous catheter. Peripheral Blood is blood taken from a
peripheral vein. (From Reference 32).

2. If catheter rep lacem ent is not necessary (e.g., for p atients


w ith isolated fever), or is not easily accom p lished (i.e.,
for tu nneled catheters or lim ited venou s access), the com -
p arative blood cu ltu re method is app rop riate.

G. Empiric Antibiotic Coverage


Em p iric antibiotic coverage is ind icated in m ost cases of su s-
pected catheter-related sep ticem ia.

1. The Microbial Spectrum


The selection of em p iric antibiotics is d ictated by the
microbes m ost likely involved .
a. A su rvey of 112 m ed ical ICUs in the United States re-
vealed the follow ing m icrobial spectrum in prim ary
hosp ital-acqu ired bacterem ias (m ost cau sed by in-
d w elling catheters) (23): Staphylococcus epidermidis
(36%), enterococci (16%), gram -negative aerobic bacil-
li (Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli,
The Indwelling Vascular Catheter 89

etc.) (16%), Staphylococcus aureus (13%), Candida


sp ecies (11%), and other organism s (8%).
b. Abou t half of the infections involve stap hylococci, and
half are from organism s u sually fou nd in the bow el,
includ ing Candida organism s.

2. Recommendations
The initial m anagem ent of su sp ected catheter-related
septicem ia can be cond u cted as show n in Figu re 6.3.

CLINICAL CONDITION
INITIAL MANAGEMENT
Is o late d Feve r
Le ave ca the te r in pla ce a nd draw
pa ire d qua ntita tive blood culture s.
Cons ide r Rx with vanc o myc in
pe nding culture re s ults .

S eve re S e ps is o r
S e ptic S ho ck
Re move ca the te r a nd s ta rt Rx
with vanc o myc in + c e ftazidime
pe nding culture re s ults .

Ne utro pe nia
Re move ca the te r a nd s ta rt Rx
with vanc o myc in + imipe ne m
pe nding culture re s ults .

Pro s the tic Valve


Re move ca the te r a nd s ta rt Rx with
vanc o myc in + amino g lyc o s ide
pe nding culture re s ults .

FIGURE 6.3. Recommendations for the initial management of suspected


catheter-related septicemia. From References 22 and 24.
90 Vascular Access

a. Desp ite concern abou t vancom ycin resistance, this an-


tibiotic is w ell su ited for su sp ected catheter-related in-
fections becau se it is active against staphylococci (in-
clud ing coagulase-negative and methicillin-resistant
strains), and m ost strains of enterococci, w hich togeth-
er accou nt for over 50% of catheter-related infections.
b. Gram -negative coverage w ith ceftazid ime or cefepim e
(for antipseu d om onal activity) can be ad d ed for pa-
tients w ith severe sep sis or sep tic shock.
c. For p atients w ith neu trop enia (neu trop hil count < 500
/ mm 3), a carbap enem (im ip enem or m erop enem) can
be ad d ed to vancom ycin (22,24).
d . For p atients w ith a p rosthetic valve, an am inoglyco-
sid e shou ld be ad d ed to vancom ycin (the tw o agents
can be synergistic for Staph. epidermidis end ocard itis).

H.Treatment of Catheter-Related Septicemia


If the cu ltu re resu lts confirm a catheter-related sep ticem ia,
d irected antibiotic therap y shou ld proceed as d ictated by
the antibiotic su scep tibilities of the isolated microbes. Som e
popu lar organism -sp ecific antibiotic regim ens are show n in
Table 6.3.

1. Catheter Removal
a. Catheters that have been left in p lace shou ld be re-
moved if cu ltures confirm the presence of catheter-
related sep ticem ia. (22).
b. Catheter rem oval is not alw ays necessary if the p atient
show s a favorable resp onse to em p iric antibiotics and
the resp onsible organism is Staph. epidermidis (25).
c. Catheters that are not easily rep laced can som etim es
be treated successfully w ith antibiotic lock therapy (see
next).

2. Antibiotic Lock Therapy


a. When a catheter is not u sed for continu ou s intrave-
The Indwelling Vascular Catheter 91

nou s infu sions, a concentrated antibiotic solu tion


(u su ally 1 to 5 m g/ m L) can be injected into the lu m en
of an infected catheter and left in p lace for hou rs to
d ays (22).
b. This approach is best suited for tu nneled catheters that
have been in place for longer than 2 w eeks because

TABLE 6.3 Popular Antimicrobial Regimens for Catheter-


Related Bloodstream Infections
Organism Antibiotic Regimen
Staphylococci
Methicillin-sensitive Nafcillin or oxacillin (2 g every 4 hrs)
Methicillin-resistant Vancomycin (1 g every 12 hrs)
(Includes most strains
of S. epidermidis)
Enterococci
Ampicillin-sensitive Ampicillin (2 g every 4 6 hrs)
Ampicillin-resistant Vancomycin (1 g every 12 hrs)
Vancomycin-resistant Linezolid (600 mg every 12 hrs)
Gram-negative bacilli
E. coli Imipenem (500 mg every 6 hrs) or
Klebsiella spp Meropenem (1 g every 8 hrs)
Enterobacter spp
P. aeruginosa For P. aeruginosa, some prefer
ceftazidime (2 g every 8 hrs) or an
antipseudomonal penicillin
Candida organisms Fluconazole (6 mg/kg/day) or
capsofungin (70 mg load, then
50 mg daily)
Amphotericin B (0.7 mg/kg/day)
for severe infections
Antibiotic regimens are for uncomplicated infections only.
From the guidelines in References 22 and 30.
92 Vascular Access

these catheters are likely to have an intralu m inal


sou rce of infection (22). The su ccess is lim ited w hen
Candida sp ecies are involved (22).

3. Duration of Therapy
For uncom plicated cases of catheter-related septicem ia,
10 to 14 d ays of antibiotics is recom m end ed , bu t only 5 to
7 d ays is su fficient for m ost cases of Staph. epidermidis
septicem ia (22).

I. Persistent Sepsis
Continued signs of sepsis after a few d ays of antibiotic ther-
ap y can signal one of the follow ing cond itions.

1. Suppurative Thrombosis
Throm bosis su rrou nd ing the catheter tip is a com m on
find ing in catheter-related sep ticem ia (11), and if the
throm bu s becom es infected , it can transform into an in-
travascu lar abscess.
a. Pu ru lent d rainage from the catheter insertion site is
not alw ays p resent in this cond ition (22). Sep tic em -
boli in the lungs is an occasional find ing.
b. Catheter rem oval is essential in this cond ition, and
surgical incision and d rainage is recom m end ed if pe-
ripheral vessels are involved .
c. When this condition involves large central veins, anti-
microbial therapy combined with heparin anticoagula-
tion can produce satisfactory results in 50% of cases (26).

2. Endocarditis
a. Vascu lar catheters are the m ost com m on cau se of no-
socom ial end ocard itis, and Staph. aureus is the m ost
com m on offend ing organism (22). As su ch, all cases of
catheter-related Staph. aureus bacteremia should be
evaluated for end ocard itis (22).
The Indwelling Vascular Catheter 93

b. Transesop hageal u ltrasound is the d iagnostic proce-


d u re of choice for end ocard itis.
c. If end ocard itis is d ocu m ented , catheter rem oval is
mand atory, and antibiotic therap y is continu ed for 4 to
6 w eeks (22).

3. Disseminated Candidiasis
a. Vascu lar catheters are the m ost com mon cau se of d is-
sem inated cand id iasis, and the p red isposing factors
inclu d e abd om inal su rgery, bu rns, organ transplanta-
tion, H IV infection, cancer chem otherap y, long-term
steroid therap y, and broad -sp ectru m antim icrobial
therapy (27).
b. The d iagnosis can be m issed in over 50% of cases
becau se blood cu ltu res are often negative (28). The
clinical m arkers of d issem inated cand id iasis includ e
isolation of Candida organism s in m u ltip le sites, can-
d id uria in the absence of an ind w elling u rethral cath-
eter, and end ophthalm itis.
c. H eavy colonization of the u rine in high-risk patients
(regard less of the presence or absence of an ind w elling
u rethral catheter) is an ind ication to initiate em p iric
antifu ngal therap y (29).
d . End op hthalm itis can occur in u p to one-third of pa-
tients w ith d issem inated cand id iasis (28), and can lead
to p erm anent blind ness. Becau se the consequ ences of
this cond ition can be seriou s, all p atients w ith p ersist-
ent cand id em ia shou ld have a d etailed eye exam (28).
e. The stand ard treatm ent for invasive cand id iasis is am -
p hotericin B (0.7 m g/ kg/ d ay) (30), w hich is available
in a special lipid form ulation (lip osom al am photeri-
cin B, 3 m g/ kg/ d ay) that p rod u ces less nep hrotoxicity
(see Chap ter 44). The antifu ngal agent capsofu ngin
(70 m g load ing d ose, follow ed by 50 m g/ d ay) is equal-
ly effective for invasive cand id iasis (31), and m ay be-
com e the preferred agent because of its safety profile.
94 Vascular Access

Desp ite the choice of antim icrobial agent, satisfactory


outcom es are achieved in only 60 to 70% of cases of
invasive cand id iasis (30).

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174:214-217.
19. Mu stafa BO, Rathbu n SW, Whitsett TL, Raskob GE. Sensitivity
and specificity of ultrasonograp hy in the d iagnosis of u p per ex-
trem ity d eep venous throm bosis. A system atic review. Arch In-
tern Med 2002; 162:401-404.
20. Pittet D, Tarara D, Wenzel RP. N osocom ial blood stream infection
in critically ill patients. JAMA 1994; 271:15981601.
21. Ed gew orthJ, Treacher D, Eykyn S. A 25-year stu d y of nosocom i-
al bacterem ia in an ad u lt intensive care u nit. Crit Care Med 1999;
27:1421-1428.
22. Merm el LA, Farr BM, Sherertz RJ, et al. Gu id elines for the m an-
agem ent of intravascu lar catheter-related infections. Clin Infect
Dis 2001; 32:1249-1272.
23. Richard s M, Ed w ard s J, Cu lver D, Gaynes R. N osocom ial infec-
tions in m ed ical intensive care u nits in the United States. Crit
Care Med 1999; 27:887-892.
24. H u ghes WT, Arm strong D, Bod ey GP, Bow EJ, et al. 2002 guid e-
lines for the u se of antim icrobial agents in neutropenic p atients
w ith cancer. Clin Infect Dis 2002; 34:730-751.
96 Vascular Access

25. Raad I, Davis S, Khan A, et al. Im p act of central venou s catheter


rem oval on the recurrence of catheter-related coagu lase-negative
stap hylococcal bacterem ia. Infect Control H osp Epid em iol 1992;
154:808-816.
26. Verghese A, Wid rich WC, Arbeit RD. Central venou s sep tic
throm bophlebitis: the role of antim icrobial therap y. Med icine
1985; 64:394400.
27. Ostrosky-Zeichner L, Rex JH , Bennett J, Ku llberg B-J. Deeply in-
vasive cand id iasis. Infect Dis Clin N orth Am er 2002; 16:821-835.
28. Caland ra T. Candida infections in the intensive care u nit. Curr
Op in Crit Care 1997; 3:335-341.
29. British Society for Antim icrobial Chem otherapy Working Party.
Managem ent of d eep Candida infection in su rgical and intensive
care u nit p atients. Intensive Care Med 1994; 20:522528.
30. Papp as PG, Rex JH , Sobel JD, et al. Guid elines for the treatm ent
of cand id iasis. Clin Infect Dis 2004; 38:161-189.
31. Mora-Duarte J, Betts R, Rotstein C, et al. Com p arison of cap so-
fu ngin and am photericin B for invasive cand id iasis. N Engl J
Med 2002; 347:2020-2029.
32. Cu rtas S, Tram p osch K. Cultu re m ethod s to evalu ate central
venou s catheter sepsis. N utr Clin Pract 1991; 6:43.
Chapter 7
THE PULMONARY
ARTERY CATHETER
The em ergence of critical care m ed icine as a sp ecialty is
largely the resu lt of tw o innovations: positive-pressure m e-
chanical ventilation and the p u lm onary artery catheter. This
chapter w ill introd uce you to the pulm onary artery catheter
and the inform ation it p rovid es (1-3).

I. THE CATHETER

A.The Principle
The p u lm onary artery (PA) catheter is equ ip p ed w ith an
inflatable balloon that acts like a ru bber raft and allow s the
flow of venous blood to carry the catheter tip through the
right sid e of the heart and ou t into the p u lmonary circu la-
tion. This balloon flotation m ethod makes it p ossible to p er-
form a right heart catheterization at the bed sid e w ithou t flu -
oroscop ic gu id ance.

B. Catheter Design
The basic featu res of a PA catheter are illu strated in Figu re
7.1.

1. The catheter is 110 cm long and has an ou tsid e d iameter


of 2.3 m m (abou t 7 French). There are tw o internal chan-
nels: One ru ns the entire length of the catheter and op ens
at the tip (the d istal or PA lu m en), and the other end s
30 cm from the catheter tip and is u su ally in the right atri-
u m (the p roxim al or RA lu m en).
97
98 Hemodynamic Monitoring

Introduce r Ca the te r

RA Lume n

Infla te d
Ba lloon

PA Lume n
The rmis tor

FIGURE7.1. The basic features of the balloon-flotation pulmonary artery


catheter. Note that the catheter is threaded through a large-bore intro-
ducer catheter (see Chapter 4 for a description of introducer catheters).

2. The tip of the catheter has a sm all balloon (1.5 m L capac-


ity) that is u sed as ju st d escribed . When inflated , the bal-
loon creates a recess for the tip of the catheter that pre-
vents the tip from scrap ing along the vessel w all as the
catheter is ad vanced .

3. The catheter also has a sm all therm istor (i.e., a transd u c-


er that senses changes in tem peratu re) located 4 cm from
the catheter tip . This d evice can m easu re the card iac ou t-
p ut u sing the thermodilution m ethod , w hich is d escribed
later in the chap ter.

II. CATHETER PLACEMENT


The PA catheter is u su ally inserted throu gh a large-bore
The Pulmonary Artery Catheter 99

(9 French) introd ucer catheter that has been placed in the


subclavian or internal ju gu lar vein (see Figu re 7.1). Ju st p rior
to insertion, the d istal lu m en is attached to a p ressu re trans-
d u cer. When the tip of the PA catheter em erges from the
introd u cer catheter, a venou s p ressu re w aveform ap pears.
The balloon is then inflated and the catheter is ad vanced .
The location of the catheter tip is d eterm ined by the p ressu re
tracings record ed from the d istal lu m en, as show n in Figu re
7.2.

1. The su p erior vena cava p ressu re is a nonp u lsatile p res-


su re w ith sm all am p litu d e oscillations. The p ressu re
w aveform is u nchanged after the catheter tip is ad vanced
into the right atriu m . The norm al p ressu re in the sup eri-
or vena cava and right atriu m is 2 to 8 m m H g.

2. When the catheter tip m oves across the tricu sp id valve


and into the right ventricle, a p u lsatile w aveform ap-
p ears. The p eak (systolic) p ressu re is a fu nction of the
strength of right ventricu lar contraction, and the low est
(d iastolic) p ressu re is equ ivalent to the right-atrial p res-
su re. The systolic p ressu re in the right ventricle is nor-
m ally 15 to 30 m m H g.

3. When the catheter m oves across the p u lm onic valve and


into a m ain p ulm onary artery, the p ressu re w ave show s
a su d d en rise in d iastolic p ressu re cau sed by flow resist-
ance in the pu lm onary circu lation. This d iastolic p ressu re
is norm ally 6 to 12 m m H g.

4. As the catheter is ad vanced fu rther into the p u lm onary


circu lation, the pu lsatile w aveform eventu ally d isap -
p ears, leaving a venous-typ e w aveform at the sam e p res-
su re level as the pu lm onary artery d iastolic p ressu re (6 to
12 m m H g). This is the p u lm onary artery occlu sion p res-
su re, also called the pulmonary capillary wedge pressure
(PCWP), or sim p ly the wedge pressure. This p ressu re is a
reflection of the d iastolic filling pressu re of the left ven-
tricle (as exp lained in the next chap ter).
100 Hemodynamic Monitoring

We dge d
P ulmona ry Arte ry
30

20

10
4
0

Right Atrium
30 P ulmona ry Arte ry
3 30
20
20
1
10
10
0
0
Right Ve ntricle
30 2

20

10

FIGURE7.2. The pressure waveforms used to guide proper placement of


pulmonary artery catheters.

5. When the w ed ge p ressu re first becom es evid ent, the bal-


loon at the tip of the catheter shou ld be d eflated . This
should resu lt in a retu rn of the p ulsatile pressu re tracing.
If this occurs, the PA catheter shou ld be left in place w ith
the balloon d eflated .

6. In abou t 25% of PA catheter p lacem ents, the p u lsatile PA


p ressu re never d isap pears as the catheter is ad vanced the
maxim u m d istance along the p u lm onary artery (1,2). If
this occu rs, the p ulm onary artery d iastolic pressu re can
be u sed as a reflection of the w ed ge p ressu re (in the ab-
sence of pu lm onary hyp ertension, the tw o p ressu res
should be equ ivalent).

A.The Balloon
1. The balloon shou ld rem ain d eflated w hile the PA catheter
The Pulmonary Artery Catheter 101

is left in place (su stained balloon inflation can result in


p u lm onary artery ru p tu re or p u lm onary infarction).
Balloon inflation is perm itted only w hen m easu ring the
w ed ge p ressu re.

2. When m easu ring the w ed ge p ressu re, DO N OT fully


inflate the balloon w ith 1.5 m L air all at once (catheters
often m igrate into sm aller p u lm onary arteries, and a
fu lly inflated balloon cou ld result in vessel ru p ture). The
balloon shou ld be slow ly inflated u ntil a w ed ge p ressu re
tracing is obtained .

3. Once the w ed ge pressu re is record ed , the balloon shou ld


be fu lly d eflated . Detaching the syringe from the balloon
injection port w ill help p revent inad vertent balloon infla-
tion w hile the catheter is in p lace.

III.THERMODILUTION

A.The Method
The therm od ilu tion m ethod is illu strated in Figu re 7.3. A
d extrose or saline solution that is cold er than blood is inject-
ed throu gh the p roxim al port of the catheter in the right atri-
u m . The cold flu id m ixes w ith blood in the right heart cham -
bers, and the cooled blood is ejected into the p ulm onary
artery and flow s p ast the therm istor on the d istal end of the
catheter. The therm istor record s the change in blood tem p er-
atu re w ith tim e and send s this inform ation to an electronic
instru m ent that record s and d isplays a tem p eratu retim e
cu rve. The area u nd er this cu rve is inversely p roportional to
the rate of blood flow in the p ulm onary artery. In the ab-
sence of intracard iac shu nts, this flow rate is equ ivalent to
the (average) card iac ou tp u t.
102 Hemodynamic Monitoring

B.Technical Considerations
1. Althou gh the ind icator solu tion is u su ally cooled before
injection (to optim ize the tem peratu re d ifference be-
tw een blood and injectate), room tem p eratu re injectates
p rod u ce reliable m easurem ents in m ost patients (4,5).

2. Serial m easu rem ents are recom mend ed for each card iac
outp u t d eterm ination. Three measu rements are su fficient
if they d iffer by 10% or less, and the card iac ou tp ut is
taken as the average of all m easu rem ents. Serial m eas-
u rem ents that d iffer by m ore than 10% are consid ered
u nreliable (6).

Te mp

Time

The rmis tor


Output
3

P roxima l Port 1
Inje ction

Inje cta te mixe s


with Blood

FIGURE 7.3. The thermodilution method of measuring cardiac output.


The Pulmonary Artery Catheter 103

C.Variability
Therm od ilu tion card iac ou tp u t can vary by as m u ch as 10%
w ithou t any ap p arent change in the clinical cond ition of the
p atient (7). A change in thermodilution cardiac output must ex-
ceed 10% to be considered clinically significant.

D. Confounding Conditions
The follow ing clinical cond itions can affect the accu racy of
card iac ou tp ut m easurem ents.

1. Tricuspid Regurgitation
This cond ition m ay be com m on d u ring p ositive-p ressu re
mechanical ventilation. The regu rgitant flow cau ses the
ind icator fluid to be recycled , prod u cing a prolonged ,
low -am plitud e thermod ilu tion cu rve characteristic of a
low card iac ou tpu t. Therefore, this cond ition resu lts in
falsely low card iac ou tpu t m easu rem ents (8).

2. Intracardiac Shunts
Intracard iac shu nts p rod u ce falsely elevated card iac ou t-
p ut m easu rem ents.
a. In right-to-left shu nts, a p ortion of the injectate flu id
p asses throu gh the shu nt, creating an abbreviated
therm od ilution cu rve sim ilar to the one seen in high
outp u t states.
b. In left-to-right shu nts, the shu nted blood increases the
blood volu m e in the right sid e of the heart, and this
d ilu tes the injectate flu id and p rod u ces an abbreviated
therm od ilution cu rve sim ilar to the one seen in high
outp u t states.

E. Continuous Cardiac Output Measurements


A sp ecialized PA catheter is available (from Baxter Ed w ard s
Critical Care) that can provid ed frequ ent and au tom atic
measurem ents of card iac ou tp u t (9). A thermal filam ent
104 Hemodynamic Monitoring

w rap p ed arou nd a d istal p ortion of the catheter is u sed to


generate low -energy heat p ulses that w arm the surrou nd ing
blood . The change in blood tem p eratu re is then sensed by a
therm istor on the catheter, and the average card iac ou tp ut
over successive 3-m inu te tim e intervals is record ed and d is-
played .

1. This continu ou s therm od ilu tion m ethod p rod u ces


more accu rate card iac ou tp u t m easu rem ents (10) than the
intermittent bolu s-injection method , and it d oes not re-
qu ire the tim e or exp ertise of an op erator.

IV. HEMODYNAMIC PARAMETERS


The PA catheter can p rovid e a w ealth of inform ation abou t
card iovascu lar fu nction and system ic oxygen transp ort. This
section p rovid es a brief d escrip tion of the hem od ynam ic
param eters that can be m easu red or d erived w ith PA cath-
eters. These p arameters are listed in Table 7.1.

A. Cardiovascular Parameters
1. Central Venous Pressure
The p roxim al p ort of the PA catheter m easu res the p res-
su re in the su p erior vena cava, w hich is equ ivalent to the
p ressu re in the right atriu m . This p ressu re is com m only
called the central venous pressure (CVP). In the absence of
a tricu sp id valve abnorm ality, the CVP or right-atrial
p ressu re (RAP) is equ ivalent to the right ventricu lar end -
d iastolic pressure (RVEDP):

CVP = RAP = RVEDP

Because the CVP is equ ivalent to the RVEDP, it is u sed as


a m easu re of right-ventricu lar filling. (See Chap ter 8 for
more inform ation on the CVP).
The Pulmonary Artery Catheter 105

TABLE 7.1 Hemodynamic & Oxygen Transport Parameters


Parameter Abbreviation Normal Range
Central Venous Pressure CVP 2 8 mm Hg
Pulmonary Capillary Wedge PCWP 6 12 mm Hg
Pressure
Cardiac Index CI 2.4 4.0 L/min/m2
Stroke Index SI 40 70 L/m2

Systemic Vascular SVRI 25 30 Wood units


Resistance Index
Pulmonary Vascular PVRI 1 2 Wood units
Resistance Index

Oxygen Delivery DO2 520 570 mL/min/m2


Oxygen Uptake VO2 110 160 mL/min/m2
Oxygen Extraction Ratio O2ER 0.2 0.3
mm Hg per liter per minute per s quare meter.

2. Pulmonary CapillaryWedge Pressure


When the inflated balloon on a PA catheter creates a com -
p lete obstru ction in the involved artery, the p ressu re at
the tip of the PA catheter (w hich is called the pulmonary
capillary wedge pressure or PCWP) is equ ivalent to the
p ressu re in the left atriu m . In the absence of a m itral
valve abnorm ality, the PCWP or left-atrial p ressu re
(LAP) is equ ivalent to the left-ventricu lar end -d iastolic
p ressu re (LVEDP):

PCWP = LAP = LVEDP

Because the PCWP is equ ivalent to the LVEDP, it is used


as a measu re of left-ventricu lar filling. (See Chapter 8 for
a d etailed d escrip tion of the w ed ge p ressu re).
106 Hemodynamic Monitoring

3. Cardiac Index
Card iac ou tpu t varies w ith bod y size, so the convention-
al p ractice is to ad ju st the m easu red card iac ou tp u t for
the size of the patient. The size-d ep end ent changes in
card iac output show a closer correlation w ith changes
in bod y su rface area (BSA) than w ith changes in bod y
w eight, so BSA is u sed as the m easure of bod y size. A
sim p le m ethod for d eterm ining the BSA based on height
(H t) and w eight (Wt) is show n below (11).

BS A (m 2 ) = Ht (c m) + Wt (kg ) 60 / 100 (7.1)

To ad ju st for bod y size, the BSA is d ivid ed into the car-


d iac outpu t (CO). The size-ad ju sted p aram eter is called
the cardiac index (CI), and is exp ressed as L/ m in/ m 2.

CI = CO / BS A (7.2)

The average-sized ad u lt has a BSA of 1.6 to 1.9 m 2, so the


card iac ind ex is norm ally abou t 50 to 60% of the m eas-
ured card iac ou tp ut. The norm al range for CI in ad u lts is
show n in Table 7.1.

4. Stroke Index
The stroke volu m e (the volu m e of blood ejected by the
ventricles d u ring systole) is a reflection of the systolic
p erform ance of the heart, and is su p erior to the card iac
ou tp u t in this regard becau se it is not influ enced by heart
rate. The stroke volum e shou ld be ad ju sted for bod y size,
as in Equation 7.3, by d ivid ing the heart rate (H R) into
the card iac ind ex (CI), not card iac ou tp u t. The size-ad -
justed stroke volu m e, or stroke index (SI), is exp ressed as
mL/ m 2.

S I = CI / HR (7.3)

The norm al range of SI in ad u lts is show n in Table 7.1.


An abnorm ally low SI can be the result of red u ced ven-
The Pulmonary Artery Catheter 107

tricu lar filling (e.g., hyp ovolem ia), im paired contractility


(systolic heart failure), or increased im p ed ance to ven-
tricu lar em p tying (e.g., aortic stenosis).

5. SystemicVascular Resistance Index


The system ic vascu lar resistance (SVR) is trad itionally
calculated as the pressu re d rop across the system ic circu-
lation, or the m ean arterial p ressure minu s the central
venou s p ressu re (MAP CVP) d ivid ed by the card iac
outp u t (CO). These relationship s are show n in Equ ation
7.4 u sing the card iac ind ex (CI) to d erive the size-ad ju st-
ed SVR or systemic vascular resistance index (SVRI).

S VRI = (MAP CVP) / CI (7.4)

The SVRI is exp ressed as Wood u nits (m m H g/ L/ m in


/ m 2), and the norm al range is show n in Table 7.1. A com -
mon p ractice is to m u ltip ly Wood u nits by 80 to express
vascu lar resistance in m ore conventional u nits (d ynes
sec-1 cm -5/ m 2), bu t this p ractice offers no ad vantage (12).
a. CAVEAT. The hyd rau lic resistance in the system ic
circu lation is not a m easu rable entity for a nu m ber of
reasons (e.g., resistance varies in d ifferent tissu es, re-
sistance is flow -d ep end ent, the vessels are com p ressi-
ble and not rigid , etc.). The SV RI is not a true measure of
hydraulic resistance; it m erely d escribes the global rela-
tionship betw een blood pressure and blood flow in the
system ic circu lation.

6. PulmonaryVascular Resistance Index


The p u lm onary vascu lar resistance (PVR) is d erived as
the p ressu re grad ient across the lu ngs, or the m ean p u l-
monary artery pressu re m inus the left-atrial or w ed ge
p ressu re (PAP PCWP) d ivid ed by the card iac outp u t
(CO). These relationship s are show n below u sing the car-
d iac ind ex (CI) to d erive the size-ad justed PVR, or pul-
monary vascular resistance index (PVRI).
108 Hemodynamic Monitoring

PVRI = (PAP PCWP) / CI (7.5)

The PVRI is exp ressed as Wood u nits (m m H g/ L/ m in


/ m 2), and the norm al range is show n in Table 7.1. N ote
that the PVRI is only a sm all fraction of the SVRI, w hich
is a reflection of the low p ressu res in the pu lm onary cir-
cu lation. The PVRI su ffers from the sam e shortcom ing as
the SVRI as a m easu re of hyd rau lic resistance.

B. Oxygen Transport Parameters


There are 3 p aram eters u sed to d efine system ic oxygen trans-
port. These are d escribed in d etail in Chap ter 9, and are p re-
sented only briefly here.

1. Oxygen Delivery
The rate of oxygen transp ort in arterial blood , or oxygen
delivery (DO 2), is d eterm ined by the card iac ou tpu t and
the O 2 content in arterial blood (CaO 2). The equation
below show s the d eterm inants of the size-ad justed DO 2 ,
w hich is exp ressed as m L/ m in/ m 2.

DO2 = CI x (1.34 x Hb x S aO2 ) x 10 (7.6)

The term (1.3 x H b x SaO 2) rep resents the arterial O 2 con-


tent (CaO 2), and is d escribed in m ore d etail in Chap ter 9.
The norm al range for the size-ad ju sted DO 2 is show n in
Table 7.1

2. Oxygen Uptake
Oxygen uptake (VO 2) is the rate at w hich oxygen is taken
u p from the systemic cap illaries into the tissu es. Since
oxygen is not stored in tissu es, the VO 2 is equ ivalent to
the O 2 consu mp tion in the tissu es. The equ ation below
show s the d eterm inants of the size-ad ju sted VO 2, w hich
is expressed as m L/ m in/ m 2.

VO2 = CI x 1.34 x Hb x (S aO2 S vO2 ) x 10 (7.7)


The Pulmonary Artery Catheter 109

(The com ponents of this equ ation are d escribed in Chap-


ter 9). The norm al range for the size-ad ju sted VO 2 is
show n in Table 7.1.

3. Oxygen Extraction Ratio


The oxygen extraction ratio (O 2ER) is the fractional u p -
take of oxygen from the system ic m icrocircu lation, and is
equ ivalent to the ratio of O 2 u ptake to O 2 d elivery.

O2 ER = VO2 / DO2 (7.8)

The norm al O 2ER is 0.2 to 0.3 (see Table 7.1), w hich


means that only 20% to 30% of the oxygen that is d eliv-
ered to the tissues is consu m ed .

V. APPLICATIONS

A. Hemodynamic Profiles
Most hem od ynam ic p roblem s are id entified by noting the
p attern of changes in three hem od ynam ic p aram eters: ven-
tricu lar filling p ressu re (CVP or PCWP), card iac ou tp u t, and
system ic or pu lm onary vascu lar resistance. This is d em on-
strated in Table 7.2 u sing the 3 classic form s of shock: hypo-
volem ic, card iogenic, and vasogenic. Each of these cond i-
tions p rod u ces a d istinct p attern or profile of hem od ynam ic
changes. Since there are 3 p arameters and 3 possible cond i-
tions (low, norm al, or high), there are 33 or 27 p ossible p ro-
files, each rep resenting a d istinct hem od ynam ic cond ition.

B. Oxygen Uptake (VO2)


H em od ynam ic profiles can id entify a hemod ynam ic p rob-
lem , but they provid e no inform ation abou t the imp act of the
p roblem on tissu e oxygenation. The ad d ition of the oxygen
110 Hemodynamic Monitoring

up take (VO 2) to hem od ynam ic p rofiles can help in this


regard . An abnorm ally low VO 2, in the absence of hyp om e-
tabolism , is evid ence of im p aired tissu e oxygenation. There-
fore, if a hem od ynam ic p roblem is associated w ith a low VO 2
(less than 100 m l/ m in/ m 2), the cond ition is p otentially life-
threatening and d eserves im m ed iate attention. (See Chap ter
9 for m ore inform ation on the VO 2).

TABLE 7.2 Hemodynamic Patterns in Different Types


of Shock
Hypovolemic Cardiogenic Vasogenic
Parameter Shock Shock Shock
CVP or PCWP Low High Low
Cardiac Output Low Low High
Systemic Vascular Low High Low
Resistance

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ad u lts and its correlation w ith the Du bois form u la. Crit Care
Med 1989; 17:846847.
12. Bartlett RH . Critical Care Physiology. N ew York: Little Brow n &
Co., 1996: 36.
Chapter 8
CARDIACFILLING
PRESSURES
As m entioned in the last chapter, the central venou s p ressu re
and the p u lm onary artery occlu sion (w ed ge) p ressu re are
the d iastolic filling p ressu res of the right and left ventricles,
respectively (see Table 8.1). This chap ter d escribes how these
p ressu res are m easu red , and highlights the lim itations and
misinterp retations that hau nt these p ressu res (1-3).

I.VENOUS PRESSURES IN THETHORAX

A. Intravascular vs.Transmural Pressure


1. The p ressu re record ed from an ind w elling vascu lar
catheter is the intravascular pressure, w hich is m easu red
relative to atm osp heric (zero reference p oint) p ressure.

2. The p ressu re that d istend s the ventricles and d rives


ed em a fluid into the tissues is the transmural pressure, or
the d ifference betw een intravascu lar and extravascu lar
p ressu res. This is the physiologically im p ortant p ressu re.

3. The intravascu lar and transm u ral p ressu res are equ iva-
lent only w hen the extravascu lar p ressu re is zero. In the
thorax, this norm ally occu rs at the end of exp iration (see
next section).

B. Influence of Thoracic Pressure


Respiratory changes in intrathoracic pressure can be trans-
mitted across the w all of blood vessels in the thorax. This
113
114 Hemodynamic Monitoring

creates phasic changes in intravascular p ressu re sim ilar to


the central venou s p ressu re (CVP) tracing in Figu re 8.1.
Despite these changes in intravascu lar p ressu re, there is lit-
tle or no change in the transm u ral p ressu re (becau se the
changes in thoracic pressure are transm itted across the w all
of the blood vessels). This m eans that resp iratory variations
in the CVP and w ed ge pressures d o not reflect changes in the
card iac filling pressu re (i.e., the transm u ral pressu re).

TABLE 8.1 The Cardiac Filling Pressures


Right Heart Left Heart
Measurement Superior vena Pulmonary artery
cava pressure occlusion pressure
Common Term Central venous pressure Wedge pressure
Equivalent Right atrial pressure, Left atrial pressure,
Pressures Right ventricular end- Left ventricular end-
diastolic pressure diastolic pressure*
Normal Range 2 8 mm Hg 6 12 mm Hg
*Is NOT a meas ure of p ulmonary capillary hydros tatic pres s ure.

1. The End of Expiration


a. In the thorax, intravascu lar p ressu res shou ld be equ iv-
alent to transm u ral p ressu res at the end of exp iration,
w hen the intrathoracic (extravascu lar) p ressu re is at
atm osp heric or zero reference level. Therefore, w hen
resp iratory variations are ap p arent in the CVP or
w ed ge p ressu re tracing, the p ressu re should be m eas-
u red at the end of exp iration.
b. The mean pressure (w hich is often d isplayed by bedside
monitors) should never be used as the CVP or w ed ge
pressure when respiratory variations are present.
Cardiac Filling Pressures 115

2. Positive End-Expiratory Pressure


a. Card iac filling p ressu res record ed at the end of exp ira-
tion w ill be falsely elevated in the p resence of p ositive
end -expiratory pressure (PEEP).
b. When PEEP is app lied d u ring m echanical ventilation,
the p atient shou ld be d isconnected from the ventilator
to m easu re the CVP and w ed ge pressure (4).
c. In the presence of intrinsic PEEP (cau sed by incom -
p lete em ptying of the lu ngs d u ring exhalation), accu -
rate record ings of the CVP and w ed ge p ressu res can be
d ifficult (5). See Chap ter 20 for a m ethod of correcting
the CVP and w ed ge p ressu re m easu rem ents in p a-
tients w ith intrinsic PEEP.

FIGURE8.1. Respiratory variations in the central venous pressure (CVP).


The true cardiac filling pressure (the transmural pressure) is at end-expi-
ration, which corresponds to the peak pressures during spontaneous
breathing, and trough pressures during mechanical ventilation.

C. Spontaneous Variations
In ad d ition to resp iratory variations, the CVP and w ed ge
p ressu res can vary spontaneou sly, w ithout ap p arent cause.
The spontaneou s variation in w ed ge p ressu re is 4 m m H g or
less in 60% of p atients, bu t it can be as high as 7 m m H g (6).
In general, a change in the CV P or wedge pressure should exceed
4 mm Hg to be considered a clinically significant change.
116 Hemodynamic Monitoring

II.THEWEDGE PRESSURE
The p u lm onary artery occlu sion p ressu re (know n as the
wedge pressure) is the m easu rem ent that p rom p ted the intro-
d u ction of the pu lm onary artery catheter in 1970. Desp ite
years of enorm ou s pop ularity (w hich is w aning), the w ed ge
pressu re is often m isinterp reted (3,7-9).

30
a
c
v

20
g
H
Ba lloon
m
Infla tion
m
10

We dge P re s s ure

FIGURE8.2. The transition from a pulsatile pulmonary artery pressure to


a balloon-occlusion (wedge) pressure. The magnified area shows 3 com-
ponents that identify the wedge pressure as a venous pressure.

A.The Wedge Pressure Tracing


1. When the p u lm onary artery (PA) catheter is p rop erly
p ositioned , inflation of the balloon at the d istal end of the
catheter w ill obstru ct flow in the involved artery, and the
p ulsatile p ressu re record ed from the tip of the catheter
w ill d isapp ear (see Figu re 8.2).

2. The nonp u lsatile or w ed ged p ressu re has 3 com p onent


w aves: the a w ave is p rod u ced by left atrial contraction,
the c w ave is p rod u ced by closu re of the m itral valve d u r-
ing isom etric contraction of the left ventricle, and the v
w ave is p rod u ced by contraction of the left ventricle
Cardiac Filling Pressures 117

against a closed m itral valve. These w aves id entify the


w ed ge p ressu re as a venou s (card iac filling) p ressu re.

B.The Principle of the Wedge Pressure


1. The p rincip le of the w ed ge p ressu re is easily exp lained
u sing the hyd rau lic relationship s in the follow ing equa-
tion (see Figu re 8.3):

Pc P LA = Q x R v (8.1)

Where: Pc is the pressure at the tip of the PA catheter


PLA is the pressu re in the left atriu m
Q is the rate of blood flow (card iac ou tp u t)
R v is the resistance to flow in the pu lm onary
veins

2. If the balloon at the d istal end of the PA catheter is inflat-


ed to obstruct flow, the follow ing is p red icted by Equ a-
tion 8.1:
When: Q = 0
Then: Pc PLA = 0
And : Pc = PLA
Thu s, the absence of flow elim inates the p ressu re grad i-
ent betw een the tip of the PA catheter and the left atriu m ,
and this allow s the p ressu re at the tip of the PA catheter
(the w ed ge p ressu re) to be used as a measure of the left
atrial p ressu re.

3. The left atrial p ressu re (the w ed ge p ressu re) w ill be


equ ivalent to the end -d iastolic pressure (the filling pres-
su re) of the left ventricle as long as there is no obstru ction
at the m itral valve orifice.

4. Thu s, the p rinciple of the w ed ge p ressu re m easu rem ent


is to create an obstru ction to flow so that the pressu re at
118 Hemodynamic Monitoring

the tip of the PA catheter can be u sed as a su rrogate m eas-


u re of the left ventricu lar filling p ressure.

C. Checking for Accuracy


The follow ing factors can be u sed to d eterm ine if the w ed ge
pressu re is an accurate reflection of the p ressu re in the left
atriu m .

1. Catheter Tip Position


a. The tip of the PA catheter m ust be in a lung region
w here capillary (venous) pressu re exceed s alveolar
pressure (if not, the pressure at the tip of the PA catheter
w ill reflect the alveolar pressu re). This correspond s to
the most d ependent lung region (see Figure 8.3).

- -

FIGURE 8.3. The principle of the wedge pressure measurement. When


flow ceases because of balloon inflation (Q = 0), the pulsatile arterial
pressure (Pa ) is lost, and the pressure at the catheter tip (Pc) is the same
as the pressure in the left atrium (PLA ). This occurs only in the most
dependent lung zone, where the capillary pressure (Pc) exceeds the alve-
olar pressure (PA ).
Cardiac Filling Pressures 119

b. The lu ng regions w here cap illary p ressu re exceed s al-


veolar p ressu re are u su ally below the level of the left
atriu m . Therefore, the tip of the PA catheter shou ld be
located below the level of the left atriu m (3). Confirm -
ing this location requ ires a lateral chest x-ray (w hich is
not a com m on practice).

2. RespiratoryVariations
Prom inent respiratory variations in the w ed ge pressu re
tracing ind icates that the w ed ge p ressu re is a reflection of
alveolar pressu re m ore than left atrial p ressu re. In this
situ ation, the w ed ge p ressu re shou ld be m easu red at the
end of exp iration, w hen the alveolar pressu re is norm al-
ly zero.

3. Wedged Blood PO2


As m any as 50% of the non-pu lsatile p ressu res p rod u ced
by balloon inflation are d am p ed p u lm onary artery pres-
su res and not tru e w ed ge (i.e., venou s) p ressu res (10).
Aspiration of blood from the catheter tip d uring balloon
inflation can help to id entify a tru e w ed ge p ressu re.
a. A tru e w ed ge p ressu re w ill have a w ed ged blood
PO 2 that is at least 20 m m H g higher than the arterial
PO 2 (10). This ind icates that the blood sam p led is from
the pulm onary capillaries.

D.Wedge vs. Capillary Hydrostatic Pressure


1. The p ressu re at the tip of the PA catheter m easu red d u r-
ing balloon inflation is often u sed as a m easure of the
hyd rostatic pressu re in the p u lm onary cap illaries. The
p roblem here is that the w ed ge p ressure is m easu red in
the absence of flow. W hen the balloon is deflated and blood
flow resumes, the pressure at the tip of the PA catheter (the cap-
illary hydrostatic pressure) will increase relative to the left-
atrial (wedge) pressure (this is the p ressu re grad ient that
d rives blood flow from the p u lm onary cap illaries to the
120 Hemodynamic Monitoring

left atriu m ) (11). This is exp ressed below u sing Equ ation
8.1 and su bstitu ting the p u lm onary cap illary w ed ge
p ressu re (PCWP) for the left atrial p ressu re (PLA ).

Pc PCWP = Q x R v (8.2)

If: Q x Rv > 0
Then: P c PCWP > 0
And : P c > PCWP

2. The d iscrep ancy betw een the cap illary hyd rostatic p res-
su re and the w ed ge p ressu re is p artly d eterm ined by the
resistance to flow in the pu lm onary veins. This may be
exaggerated in critically ill patients because cond itions
that p rom ote venoconstriction (e.g., hyp oxia, end otox-
em ia, ARDS) are com m on in these p atients (12). There-
fore, the cap illary hyd rostatic p ressu re m ay be signifi-
cantly higher than the w ed ge pressure in critically ill pa-
tients.

3. Becau se the cap illary hyd rostatic p ressu re is higher than


the w ed ge pressu re, a normal wedge pressure does not
exclude the diagnosis of cardiogenic pulmonary edema.

III. RELIABILITY

A. Pressure vs.Volume
1. Accord ing to the Frank Starling Law of the Heart, the vol-
u m e in the ventricles at the end of d iastole is the p rinci-
p al factor that governs the strength of card iac contraction
(13). Therefore, the im p ortant m easu re of card iac filling is
ventricu lar end -d iastolic volu m e.

2. End -d iastolic volu m e is not easy to m easu re, so the ven-


tricu lar end -d iastolic p ressu re (as m easu red by the CVP
Cardiac Filling Pressures 121

and w ed ge p ressu re) is u sed as the clinical measu re of


card iac filling.

3. Unfortu nately, the CVP and w ed ge p ressu res show an


inconsistent relationship to the end -d iastolic volum e
(14,15), as d em onstrated in Figu re 8.4. N ote that only half
of the w ed ge p ressu re m easu rem ents are w ithin the nor-
mal range (the shad ed area) even thou gh the stu d y in-
clud ed only healthy su bjects.
4. Observations like those in Figu re 8.4 ind icate that isolated
measurements of cardiac filling pressures are unreliable as
measures of cardiac filling. Trend s in card iac filling p res-
su res m ay be more reliable than single m easurem ents.

90
r = 0.04
)
2
70
m

L
m
(
I
V
D
E
V
L
50

0 5 10 15
P CWP (mm Hg)

FIGURE 8.4 The relationship between the pulmonary capillary wedge


pressure (PCWP) and the left-ventricular end-diastolic volume index
(LVEDVI) in 12 normal subjects. The shaded area represents the normal
range for PCWP, and the r value is the correlation coefficient. From
Reference 15.
122 Hemodynamic Monitoring

B.Ventricular Compliance
1. Card iac filling p ressu res are d eterm ined not only by end -
d iastolic volu m e, bu t also by the d istensibility (com pli-
ance) of the ventricles. Therefore, the p oor correlation
betw een the card iac filling p ressu res and end -d iastolic
volu m e m ay be d u e to variations in ventricu lar com p li-
ance.

2. Ventricu lar com p liance d escribes the relationship be-


tw een changes in end -d iastolic volu m e (EDV) and end -
d iastolic p ressu re (EDP):

Co mplianc e = EDV / EDP (8.3)

a. A d ecrease in ventricu lar com p liance is associated


w ith a greater change in EDP for a given change in
EDV. In this situ ation, (w hich m ay be com m on in ICU
p atients), card iac filling pressu res w ill overestim ate
card iac filling (EDV).
b. If ventricular com p liance is constant, changes in the
EDP shou ld have a constant relationship to changes in
the EDV. Therefore, changes in the card iac filling p res-
su res m ight p rovid e m ore inform ation abou t card iac
filling than isolated m easu rem ents.

REFERENCES
1. Magd er S. Central venous p ressu re: A usefu l but not so sim p le
m easu rem ent. Crit Care Med 2006; 34:2224-2227.
2. Pinsky MR. H em od ynam ic m onitoring in the intensive care u nit.
Clin Chest Med 2003; 24:549-560.
3. OQu in R, Marini JJ. Pu lm onary artery occlusion p ressu re: clini-
cal p hysiology, m easu rem ent, and interp retation. Am Rev Resp ir
Dis 1983; 128:319326.
4. Pinsky M, Vincent J-L, De Sm et J-M. Estim ating left ventricu lar
filling p ressu re d u ring p ositive end -exp iratory p ressu re in hu -
m ans. Am Rev Respir Dis 1991; 143:2531.
Cardiac Filling Pressures 123

5. Tebou l J-L, Pinsky MR, Mercat A, et al. Estim ating card iac filling
p ressu re in m echanically ventilated p atients w ith hyp erinflation.
Crit Care Med 2000; 28:3631-3636.
6. N em ens EJ, Wood s SL. N orm al flu ctu ations in pu lm onary artery
and pulm onary capillary w ed ge pressures in acu tely ill patients.
H eart Lu ng 1982; 11:393398.
7. Jacka MJ, Cohen MM, To T, et al. Pu lm onary artery occlu sion
p ressu re estim ation: H ow confid ent are anesthesiologists. Crit
Care Med 2002; 30:1197-1203.
8. N ad eau S, N oble WH . Misinterp retation of pressu re m easure-
m ents from the p ulm onary artery catheter. Can Anesth Soc J
1986; 33:352363.
9. Kom and ina KH , Schenk DA, LaVeau P, et al. Interobserver vari-
ability in the interpretation of p ulm onary artery catheter pres-
su re tracings. Chest 1991; 100:16471654.
10. Morris AH , Chapm an RH . Wed ge pressu re confirm ation by as-
p iration of pu lm onary capillary blood . Crit Care Med 1985;
13:756759.
11. Cop e DK, Grim bert F, Dow ney JM, et al. Pu lm onary cap illary
p ressu re: a review. Crit Care Med 1992; 20:10431056.
12. Kloess T, Birkenhau er U, Kottler B. Pu lm onary pressu reflow
relationship and peripheral oxygen su p ply in ARDS d u e to bac-
terial sepsis. Second Vienna Shock Foru m , 1989:175180.
13. Opie LH . Mechanism s of card iac contraction and relaxation. In
Brau nw ald E, Zip es DP, Libby P (ed s). H eart d isease: A textbook
of card iovascu lar m ed icine. 6th ed ., Philad elp hia: W.B. Sau nd ers,
2001:443-478.
14. Diebel LN , Wilson RF, Tagett MG, Kline RA. End -d iastolic vol-
u m e. A better ind icator of p reload in the critically ill. Arch Su rg
1992; 127:817822.
15. Kum ar A, Anel R, Bu nnell E, et al. Pu lm onary artery occlu sion
p ressu re and central venou s pressure fail to p red ict ventricular
filling volum e, card iac p erform ance, or the response to volu m e
infu sion in norm al su bjects. Crit Care Med 2004; 32:691-699.
Chapter 9
SYSTEMIC
OXYGENATION
One of the sem inal goals of p atient care in the ICU is to
maintain ad equ ate tissu e oxygenation. This chapter d e-
scribes the p aram eters u sed to m onitor system ic oxygen
transport and how they are u sed to evalu ate tissu e oxygena-
tion.

I. SYSTEMIC OXYGEN TRANSPORT


There are fou r p aram eters u sed to evalu ate system ic O 2
transp ort: the concentration of O 2 in blood , the rate of O 2
transport in arterial blood , the rate of O 2 u ptake into tissues,
and the extent of hem oglobin d esatu ration in cap illary
blood .

A. Oxygen Content of Blood


The concentration of O 2 in blood (called the O2 content) is the
sum m ed contribution of the O 2 that is bou nd to hem oglobin
and the O 2 that is d issolved in p lasm a.

1. Hemoglobin-Bound O2

HbO2 = 1.34 x Hb x S O2 (9.1)

a. H bO 2 is the concentration of hemoglobin-bound O 2


(m L O 2 per 100 m L w hole blood ).
b. H b is the hem oglobin concentration in blood
(grams per 100 m L blood ).

125
126 Hemodynamic Monitoring

c. 1.34 is the O 2 bind ing capacity of hemoglobin (1.34 mL


O 2 per gram Hb).
d . SO 2 is the O 2 saturation of hemoglobin, which is ex-
pressed as the ratio of oxygenated Hb to total Hb
(SO 2 = HbO 2/ total Hb). SO 2 should be expressed as a dec-
imal rather than a percentage (e.g., 0.9 instead of 90%).
Equ ation 9.1 states that, w hen H b is fu lly satu rated w ith
oxygen (SO 2 = 1), each gram of H b bind s 1.34 m L O 2.

2. Dissolved O2 (m L O 2/ 100 m L blood )


Dis s o lve d O2 = 0.003 x PO2 (9.2)

a. PO 2 is the p artial p ressu re of O 2 in blood (m m H g).


b. 0.003 is the solu bility coefficient of O 2 in plasm a at
normal bod y tem perature This num ber represents the
volum e of oxygen (m L) that w ill d issolve in 100 m L
plasm a for each 1 m m H g increm ent in the PO 2 (m L
O 2/ 100 m L blood / m m H g).
Equ ation 9.2 d em onstrates that oxygen is relatively insolu-
ble in plasma. For exam p le, if the arterial PO 2 of blood is
100 m m H g, each 100 m L of blood contains only 0.3 m L
of d issolved O 2 (or one liter of blood w ill contain only
3 m L of d issolved O 2).

3. Total O2 Content (m L O 2/ 100 m L blood )

O2 Co nte nt = (1.34 x Hb x S O2 ) + (0.003 x PO2 ) (9.3)

Table 9.1 show s the norm al concentrations of O 2 (bou nd ,


d issolved , and total O 2) in arterial and venou s blood .
N ote that the contribu tion of d issolved O 2 is very sm all.
Becau se d issolved O 2 is su ch a sm all fraction of total O 2
in blood , the O2 content of blood is considered equivalent to
the Hb-bound fraction.
O2 Co nte nt = 1.34 x Hb x S O2 (9.4)
Systemic Oxygenation 127

TABLE 9.1 Normal Levels of Oxygen in Arterial and


Venous Blood1
Parameter Arterial Blood Venous Blood
PO2 90 mm Hg 40 mm Hg
O2 Saturation of Hb 0.98 0.73
HbO2 19.7 mL/dL 14.7 mL/dL
Dissolved O2 0.3 mL/dL 0.1 mL/L
Total O2 content 20 mL/dL 14.8 mL/dL
Blood volume2 1.25 L 3.75 L
Volume of O2 250 mL 555 mL
1 Values s hown are for a body temperature of 37C and a hemoglo-
bin concentration of 15 g/dL (150 g/L) in blood.
2 Volume es timates are bas ed on a total blood volume (TBV) of 5

liters , an arterial blood volume that is 25% of TBV, and a venous


blood volume that is 75% of TBV.
Abbreviations : Hb = hemoglobin, HbO2 = hemoglobin-bound O2 ,
PO2 = partial pres s ure of O2 , dL = deciliter (100 mL).

B. Oxygen Delivery (DO2)


The rate of O 2 transport in arterial blood is known as O2 delivery
(DO 2).

DO2 = Q x CaO2 x 10 (9.5)

a. DO 2 is the delivery rate of O 2 in arterial blood (mL/ min).


b. Q is card iac ou tp u t (L/ m in).
c. CaO 2 is the O 2 content of arterial blood (mL/ 100m L).
d . The m u ltip lier of 10 is u sed to convert the CaO 2 from
m L/ 100 m L to m L/ L, w hich allow s the DO 2 to be ex-
p ressed as m L/ m in.
If the CaO 2 is broken d ow n into its com ponents (1.34 x
H b x SaO 2), w here SaO 2 is the oxyhemoglobin satu ration
128 Hemodynamic Monitoring

in arterial blood , the DO 2 equ ation can be rew ritten as:


DO2 = Q x (1.34 x Hb x S aO2 ) x 10 (9.6)

Table 9.2 show s the norm al range of DO 2 in ad u lts. The


size-ad ju sted valu es are d eterm ined u sing the bod y su r-
face area in m eters squ ared , as d escribed in Chap ter 7
(see Equ ation 7.1).

TABLE 9.2 Normal Ranges for Oxygen Transport Parameters


Size-Adjusted
Parameter Absolute Range Range1
Cardiac Output 56 L/min 2.44.0 L/min/m2
O2 Delivery 9001100 mL/min 520570 mL/min/m2
O2 Uptake 200270 mL/min 110160 mL/min/m2
O2 Extraction Ratio 0.200.30
1 Size-adjus ted
values repres ent the abs olute values divided by the
patients body s urface area (BSA) in s quare meters (m 2 ).

C. Oxygen Uptake (VO2)


The rate at w hich O 2 m oves ou t of the cap illaries and into the
tissu es is called the O2 uptake (VO 2). Becau se O 2 is not stored
in tissues in significant qu antities, the VO 2 is also a measu re
of the O2 consumption of the tissu es. The VO 2 can be calcu lat-
ed or m easu red d irectly.

1. Calculated VO2
The u p take of any su bstance into a tissu e bed is a reflec-
tion of 2 variables: the rate of blood flow through the tis-
su e bed , and the d ecrease in concentration of the sub-
stance from arterial to venou s blood . When O 2 is the su b-
stance, this relationship can be stated as follow s:

VO2 = Q x (CaO2 CvO2 ) x 10 (9.7)


Systemic Oxygenation 129

a. VO 2 is the rate of O 2 u p take into tissues (m L/ m in).


b. Q is the card iac ou tput (L/ m in).
c. CaO 2 CvO 2 is the d ifference in oxygen content be-
tw een arterial and venou s blood .
d . The m u ltip lier of 10 is need ed for the sam e reason as
exp lained for the DO 2.
CaO 2 and CvO 2 share a com m on term (1.34 x H b), so
Equ ation 9.7 can be rew ritten as:

VO2 = Q x (1.34 x Hb) x (S aO2 S vO2 ) x 10 (9.8)

w here SaO 2 SvO 2 is the d ifference in oxyhem oglobin


satu ration betw een arterial and m ixed venou s (p u l-
m onary artery) blood . The d eterm inants of VO 2 in this
equ ation are all m easu rable qu antities (a p u lm onary ar-
tery catheter is need ed to m easure card iac ou tput and
SvO 2, as d escribed in Chap ter 7).

2. Measured VO2
The VO 2 can be m easu red as the rate of O 2 u ptake from
the lungs.
VO2 = VE x (FIO2 FEO2 ) (9.9)

a. VO 2 is the rate of O 2 u p take from the lu ngs (m L/ m in).


b. VE is the volum e of gas that is exhaled per m inu te
(L/ m in).
c. FIO 2 and FEO 2 represent the fractional concentration
of O 2 in inhaled and exhaled gas, resp ectively.
The VO 2 can be m easu red at the bed sid e w ith a sp ecial-
ized d evice that is equipped w ith an oxygen sensor.

3. Calculated vs. Measured VO2


The m easu red VO 2 is superior to the calculated VO 2 for
the follow ing reasons:
a. The calcu lated VO 2 has a greater variability becau se it
involves fou r m easurem ents (Q, H b, SaO 2, SvO 2), and
130 Hemodynamic Monitoring

each of these m easu rem ents has its ow n variability


(see Table 9.3) (14).
b. The calculated VO 2 is less accu rate as a m easu re of
w hole-bod y VO 2 because it d oes not inclu d e the VO 2 of
the lu ngs. Althou gh the lu ngs norm ally contribu te
only 5% or less to the w hole-bod y VO 2, this contribu -
tion can increase to 20% or m ore w hen there is inflam -
m ation in the lu ngs (e.g., p neu m onia or ARDS). (5).
The norm al VO 2 in a resting ad u lt is show n in Table 9.2.
N ote that the VO 2 is only a sm all fraction of the DO 2. This
is exp lained in the next section.

TABLE 9.3 Variability of Calculated and Measured VO2


Parameter Variability
Thermodilution Cardiac Output 10%
Hemoglobin Concentration 2%
Arterial O2 Saturation (SaO2) 2%
Mixed Venous O2 Saturation (SvO2) 5%
Calculated VO2 19%
Measured VO2 5%
From References 14.

D. Oxygen Extraction
The ratio of O 2 up take to O 2 d elivery is called the oxygen ex-
traction ratio (O 2ER).

O2 ER = VO2 / DO2 (9.10)

(This ratio can be multiplied by 100 and expressed as a


percentage.) Since the VO 2 and DO 2 share common terms
(Q x 1.34 x Hb x 10), Equation 9.10 can be expressed as follow s:

O2 ER = (S aO2 S vO2 ) / S aO2 (9.11)


Systemic Oxygenation 131

When the SaO 2 is close to 1.0 (w hich is u su ally the case), the
O 2ER is rou ghly equ ivalent to SaO 2 SvO 2:

O2 ER S aO2 S vO2 (9.12)

The O 2ER is norm ally abou t 0.25 (range = 0.2 0.3), as show n
in Table 9.2. This m eans that only 25% of the oxygen delivered
to the systemic capillaries is taken up into the tissues. Althou gh
O 2 extraction is norm ally low, it can increase w hen O 2 d eliv-
ery is im p aired , as exp lained in the next section.

II. CONTROL OF OXYGEN UPTAKE

A.The Role of O2 Extraction


The oxygen transp ort system op erates to m aintain a constant
flow of oxygen into the tissu es (a constant VO 2) in the face of
changes in oxygen su pply (varying DO 2). This behavior is
mad e possible by the ability of O 2 extraction to ad ju st to
changes in O 2 d elivery (6). The control system for VO 2 can be
d escribed by rearranging Equ ation 9.10 to m ake VO 2 the
d ep end ent variable:

VO2 = DO2 x O2 ER (9.13)

Thu s, the VO 2 w ill rem ain constant if changes in O 2 d elivery


are accom p anied by equ ivalent and recip rocal changes in O 2
extraction. H ow ever, if the O 2 extraction rem ains fixed , chan-
ges in DO 2 w ill be accom p anied by equ ivalent changes in
VO 2. The ability of O 2 extraction to ad ju st to changes in DO 2
therefore d eterm ines the tend ency of VO 2 to rem ain constant
in the face of changes in DO 2.

A.The DO2 VO2 Relationship


The resp onse to a p rogressive d ecrease in O 2 d elivery is illu s-
132 Hemodynamic Monitoring

trated in the graph in Figu re 9.1 (The equ ation at the top of
the figu re is sim ilar to Equ ation 9.13, bu t the SaO 2 SvO 2 d if-
ference is u sed as the O 2ER.) At the p oint ind icating a nor-
m al DO 2, the arterial O 2 satu ration (SaO 2) is 98%, the m ixed
venou s O 2 satu ration (SvO 2) is 73%, and the O 2 extraction
(SaO 2 SvO 2) is 25%. As the DO 2 d ecreases (m oving left
along the horizontal axis of the grap h), the VO 2 rem ains con-
stant u ntil a p oint is reached w here the SvO 2 has d ecreased
to 50% and the correspond ing O 2 extraction (SaO 2 SvO 2)
has increased to 48%. This is the m axim u m O 2 extraction that
can be achieved in resp onse to d ecreases in O 2 d elivery.
When O 2 extraction is m axim al, fu rther d ecreases in DO 2 w ill
result in equivalent d ecreases in VO 2. When this occu rs, the
VO 2 is referred to as being supply-dependent, w hich m eans
that the rate of aerobic m etabolism is lim ited by the supply
of oxygen. This cond ition is know n as dysoxia, and it is ac-
com panied by lactate accu m u lation (from anaerobic glycoly-
sis) and im paired cell fu nction.

1. Critical DO2
The DO 2 at w hich the VO 2 becom es supply-d epend ent
is called the critical oxygen delivery (critical DO 2). It is
the low est DO 2 that is capable of fully su pporting aerobic
m etabolism . Althou gh im p ortant concep tu ally, the criti-
cal DO 2 has little clinical valu e for the follow ing reasons:
a. The critical DO 2 has varied w id ely in stu d ies of criti-
cally ill p atients (68), and thu s it is not p ossible to p re-
d ict the critical DO 2 in any ind ivid u al p atient.
b. The DO 2 VO 2 cu rve d oes not alw ays have a d istinct
point that m arks the transition to a su pp ly-d ep end ent
VO 2 (9).
Althou gh it is not p ossible to id entify the critical DO 2 in
each p atient, you can avoid the critical DO 2 in m ost
patients by m aintaining the DO 2 at a rate that is at least
fou r tim es higher than the VO 2.
Systemic Oxygenation 133

VO 2 = DO 2 x (S a O 2 S vO 2 )

S a O 2 = 98% S a O 2 = 98%
S vO 2 = 50% S vO 2 = 73%

VO 2
a
xi
o
ys

Ma xima l
D

Norma l
O 2 Extra ction

?
DO 2

FIGURE 9.1. Graph showing the effects of a progressive decrease in sys-


temic O 2 delivery (DO 2) on whole-body O 2 uptake (VO 2), and the O 2
saturation of hemoglobin in arterial blood (SaO 2) and mixed venous
blood (SvO2).

III.TISSUE OXYGENATION
It is not p ossible to m easu re tissu e PO 2 d irectly. Instead , the
oxygen transp ort variables and blood lactate levels are u sed
to evalu ate tissue oxygenation. Table 9.4 show s the m arkers
of threatened or im p aired tissu e oxygenation.

TABLE 9.4 Clinical Markers of Threatened or Impaired


Tissue Oxygenation
I. Oxygen Transport Variables
1. VO2 < 100 mL/min/m2 (when not due to hypometabolism).
2. (SaO2 SvO2) 50%
3. SvO2 50%
II. Lactate Concentration in Blood
1. > 2 mEq/L is abnormal.
2. > 4 mEq/L has prognostic implications.
134 Hemodynamic Monitoring

A. Oxygen Transport Parameters


1. Oxygen Uptake (VO2)
a. The ad equ acy of tissu e oxygenation is d eterm ined by
the balance betw een the m etabolic requ irem ent for O 2
(MRO 2) and the tissu e oxygen su p p ly (VO 2).
b. N orm ally, the VO 2 is closely m atched to the MRO 2, and
aerobic m etabolism continu es u nim p ed ed .
c. If the VO 2 falls below the MRO 2, a portion of m etabo-
lism w ill be carried ou t anaerobically. Therefore, an
abnorm ally low VO 2 (< 100 m L/ m in/ m 2), in the ab-
sence of hyp om etabolism (w hich is not com m on in
ICU p atients), is evid ence of inad equ ate tissu e oxy-
genation.
2. Oxygen Extraction (SaO2 SvO2)
a. The grap h in Figu re 9.1 show s that in cond itions
w here oxygen d elivery is red u ced (e.g., anem ia, hy-
p oxem ia, or low card iac ou tp u t), an increase in O 2
extraction to 50% is the m axim u m ad ju stm ent p ossible
to m aintain tissue oxygenation.
b. Therefore, an O 2 extraction (SaO 2 SvO 2) that is at or
near 50% ind icates that tissu e oxygenation is either
im paired or is on the verge of im p airm ent.
c. Consistent w ith this reasoning, an O 2 extraction of
50% has been su ggested as a transfusion trigger to
prom p t the transfu sion of erythrocytes to correct ane-
mia (10).

3. Venous O2 Saturation (SvO2)


a. As m entioned earlier, the SvO 2 can be u sed as a su rro-
gate measu re of O 2 extraction if the SaO 2 is close to
100%.
b. Accord ing to the graph in Figu re 9.1, a d ecrease in
SvO 2 to 50% occu rs w hen O 2 extraction is m axim al.
c. Therefore, an SvO 2 of 50% can be u sed as a su rrogate
m arker of m axim u m O 2 extraction.
Systemic Oxygenation 135

d . The SvO 2 is trad itionally m easu red in m ixed venou s


(p u lm onary artery) blood , bu t su p erior vena cava
blood (from a central venou s catheter) can be a su it-
able alternative (10). H ow ever, m u ltip le m easu re-
m ents of the central venou s SvO 2 m u st be averaged to
gain close agreem ent w ith the SvO 2 in m ixed venou s
blood (11).

B. Blood Lactate
The accu m u lation of lactate in blood is the m ost w id ely u sed
marker of inad equ ate tissu e oxygenation. Lactate can be
measured in w hole blood or p lasm a (12), and concentrations
above 2 m Eq/ L are consid ered abnorm al. Increasing the
threshold to 4 m Eq/ L m ay be m ore ap p rop riate for p red ict-
ing su rvival (12).

1. Other Sources of Lactate


a. Unfortu nately, lactate accu m ulation in blood is not
sp ecific for im paired tissu e oxygenation.
b. Other sou rces of hyp erlactatem ia in ICU p atients
includ e hep atic insufficiency (w hich im pairs lactate
clearance), thiamine d eficiency (w hich inhibits p yru-
vate entry into mitochond ria), severe sep sis (sam e
mechanism as thiam ine d eficiency), and intracellu lar
alkalosis (w hich stimu lates glycolysis) (13,14).
2. Severe Sepsis
a. The p red om inant cau se of lactate accu m u lation in
severe sep sis ap p ears to be cytokine-m ed iated inhibi-
tion of p yru vate d ehyd rogenase, an enzym e involved
in p yru vate transp ort into m itochond ria (15). The
resu lt is p yru vate accu m u lation in the cell cytop lasm
and su bsequ ent conversion to lactate.
b. The absence of anaerobic cond itions in sep sis is su p-
p orted by a stu d y show ing that PO 2 levels in m u scle
are elevated in p atients w ith severe sepsis (16).
c. Thu s, elevation of blood lactate d oes not ap p ear to be
136 Hemodynamic Monitoring

a u sefu l m arker of im p aired tissu e oxygenation in


severe sep sis.
d . There is a strong correlation betw een hyp erlactatem ia
and m ortality in severe sep sis (12,17), p articu larly
w hen 4 m Eq/ L is u sed as the threshold for lactate ele-
vation (12). Therefore, elevated blood lactate levels
have p rognostic im plications in severe sepsis.
See Chap ter 23 for m ore inform ation on lactate accu m u -
lation in blood .

REFERENCES
1. Sasse SA, Chen PA, Berry RB, et al. Variability of card iac ou tp u t
over tim e in m ed ical intensive care unit patients. Chest 1994;
22:225-232.
2. N oll ML, Fountain RL, Duncan CA, et al. Flu ctu ations in m ixed
venou s oxygen satu ration in critically ill m ed ical p atients: a p ilot
stu d y. Am J Crit Care 1992; 3:102-106.
3. Bartlett RH , Dechert RE. Oxygen kinetics: Pitfalls in clinical
research. J Crit Care 1990; 5:77-80.
4. Schneew eiss B, Drum l W, Graninger W, et al. Assessm ent of oxy-
gen-consum ption by u se of reverse Fick-p rincip le and ind irect
calorim etry in critically ill p atients. Clin N u tr 1989; 8:8993.
5. Jolliet P, Thorens JB, N icod L, et al. Relationship betw een p u l-
m onary oxygen consu m p tion, lu ng inflam m ation, and calcu lat-
ed venous ad m ixtu re in p atients w ith acu te lu ng inju ry. Intensive
Care Med 1996; 22:277-285.
6. Leach RM, Treacher DF. The relationship betw een oxygen d eliv-
ery and consu m ption. Dis Mon 1994; 30:301-368.
7. Shoem aker WC. Oxygen transp ort and oxygen m etabolism in
shock and critical illness. Crit Care Clin 1996; 12:939-969.
8. Ronco J, Fenw ick J, Tw eed ale M, et al. Id entification of the criti-
cal oxygen d elivery for anaerobic m etabolism in critically ill sep -
tic and nonsep tic hum ans. JAMA 1993; 270:1724-1730.
9. Lebarsky DA, Sm ith LR, Slad en RN , et al. Defining the relation-
ship of oxygen d elivery and consu m ption: u se of biological sys-
tem m od els. J Su rg Res 1995; 58:503-508.
Systemic Oxygenation 137

10. Levy PS, Chavez RP, Crystal GJ, et al. Oxygen extraction ratio: a
valid ind icator of transfu sion need in lim ited coronary vascu lar
reserve? J Trau m a 1992; 32:769774.
11. Du eck MH , Kilm ek M, Ap penrod t S, et al. Trend s bu t not ind i-
vid u al valu es of central venou s oxygen satu ration agree w ith
m ixed venou s oxygen satu ration d u ring varying hem od ynam ic
cond itions. Anesthesiology 2005; 103:249-257.
12. Ad u en J, Bernstein WK, Khastgir T, et al. The use and clinical
im p ortance of a su bstrate-sp ecific electrod e for rap id d eterm ina-
tion of blood lactate concentrations. JAMA 1994; 272:16781685.
13. Du ke T. Dysoxia and lactate. Arch Dis Child 1999; 81:343-350.
14. Mizock BA, Falk JL. Lactic acid osis in critical illness. Crit Care
Med 1992; 20:8093.
15. Cu rtis SE, Cain SM. Regional and system ic oxygen d elivery/
u ptake relations and lactate flu x in hyp erd ynam ic, end otoxin-
treated d ogs. Am Rev Resp ir Dis 1992; 145:348354.
16. Sair M, Etherington PJ, Winlove CP, et al. Tissu e oxygenation and
p erfusion in patients w ith system ic sep sis. Crit Care Med 2001;
29:1343.
17. Bakker J, Coffernils M, Leon M, et al. Blood lactate levels are
su perior to oxygen-d erived variables in pred icting ou tcom e in
septic shock. Chest 1991; 99:956962.
Chapter 10
HEMORRHAGE AND
HYPOVOLEMIA
The circu latory system op erates w ith a relatively sm all vol-
u m e and a volu m e-sensitive pu mp . This is an energy effi-
cient d esign, bu t it su ffers from a lim ited tolerance to acu te
blood loss. Loss of less than 50% of the blood volu m e can be
fatal, w hereas m ajor organs like the lu ngs, liver, and kid neys
can lose as m u ch as 75% of their fu nctional m ass w ithout a
fatal ou tcom e. Becau se of the lim ited tolerance to blood loss,
su ccessfu l m anagem ent of the bleed ing p atient requ ires
p rom pt intervention to halt bleed ing and rep lace volu m e
d eficits.

I. BODY FLUIDS AND BLOOD LOSS

A. Distribution of Body Fluids


Table 10.1 show s the volu m e of bod y flu id s for ad u lt m en
and w om en exp ressed in relation to lean bod y w eight in
kilogram s. N ote the follow ing:

1. Total bod y w ater in liters is equ ivalent to 60% of the lean


bod y w eight (600 m L/ kg) in m ales, and 50% of the lean
bod y w eight (500 m L/ kg) in fem ales.

2. Blood volu me (66 m L/ kg in m ales, and 60 m L/ kg in


fem ales) is only a sm all fraction (11 to 12%) of the total
bod y w ater. The m eager d istribu tion of bod y fluid s in the
vascu lar com partment is an im p ortant factor in the lim it-
ed tolerance to blood loss.

139
140 Disorders of Circulatory Flow

3. Plasm a volu m e rep resents abou t abou t one qu arter of the


volu m e of extracellu lar flu id (interstitial flu id p lu s p las-
ma). This relationship is imp ortant for u nd erstand ing the
effects of colloid and crystalloid resu scitation flu id s
(d escribed later in the chapter).

TABLE 10.1 Body Fluid Volumes in Adult Men & Women


Men Women
Fluid mL/kg 75 kg mL/kg 60 kg
Total Body Water 600 45 L 500 30 L
Interstitial Fluid 120 9L 100 6L
Whole Blood 66 5L 60 3.6 L
Plasma 40 3L 36 2.2 L
All weights are lean body weight.
Average body weight (lean) for an adult male and female.
From American Ass ociation of Blood Banks Technical Manual. 10th ed.
Arlington, VA, American As sociation of Blood Banks , 1990: 650.

B. Severity of Blood Loss


The follow ing classification system is based the severity of
acu te blood loss (1).

1. Class I
a. Loss of 15% or less of the blood volume (or 10 mL/ kg).
b. The volum e loss in this instance is fu lly rep laced by in-
terstitial flu id shifts (transcap illary refill) so that blood
volum e is m aintained , and clinical find ings are m ini-
m al or absent.

2. Class II
a. Loss of 15 30% of the blood volume (or 10 20 mL/ kg).
b. This represents the com p ensated p hase of hyp ovo-
Hemorrhage and Hypovolemia 141

lem ia. Blood volu m e is red u ced , bu t blood p ressu re


is m aintained by system ic vasoconstriction. Postural
changes in pu lse and blood pressure m ay be evid ent,
bu t not consistently (see later). Urine ou tp u t can fall to
20 or 30 m L/ hr, and sp lanchnic flow m ay be com p ro-
mised .

3. Class III
a. Loss of 30 45% of the blood volume (or 20 30 m L/ kg).
b. This m arks the onset of d ecom p ensated hyp ovolem ia
or hypovolemic shock, w ith hypotension, oligu ria (u rine
outp u t < 15 m L/ hr), d ep ressed m entation, and lactate
accu m u lation in the blood (> 2 m Eq/ L).

4. Class IV
a. Loss of m ore than 45% of the blood volu me (or > 30
mL/ kg).
b. This cond ition can be irreversible and fatal. H yp oten-
sion and oligu ria can be p rofou nd (e.g., u rine ou tp ut
< 5 m L/ hr) and refractory to volum e replacem ent.
Blood lactate levels are typ ically greater than 4 to 6
mEq/ L.
This classification system can be used to d eterm ine the
replacem ent volum e in ind ivid u al p atients w ith acu te
blood loss (see later).

II. CLINICAL EVALUATION

The clinical evalu ation of acu te blood loss is lim ited in accu -
racy, as d escribed next.

A.Vital Signs
The sensitivity of vital signs for d etecting blood loss is p oor,
as show n in Table 10.2 (2).
142 Disorders of Circulatory Flow

1. Contrary to popular belief, supine tachycard ia (> 90 bpm)


is absent in a majority of patients w ith acute blood loss,
regard less of severity.

2. Sup ine hyp otension (systolic p ressu re < 90 m m H g) ap -


p ears only in ad vanced stages of blood loss, w hen vol-
u m e d eficits exceed 30% of blood volu m e (abou t 1.5 liters
or m ore in an average-sized ad u lt).

3. Postural Changes
a. To record p ostu ral changes in p u lse and blood p res-
su re, the position shou ld change from su pine to stand -
ing (not sitting), and at least one m inu te shou ld elapse
before m easu rem ents are obtained (2).
b. A significant p ostu ral change is d efined as an increase
in pu lse rate of at least 30 bp m or a d ecrease in systolic
p ressu re of at least 20 m m H g (2).
c. The most sensitive test is the p ostural p ulse increm ent,
w hich can becom e evid ent after 15 20% loss of blood
volu m e (abou t 750 1,000 m L in an average-sized
ad u lt).
d . In general, orthostatic vital signs ad d little to the eval-
u ation of hyp ovolem ia.

B. Hemoglobin and Hematocrit


1. Acu te hem orrhage involves loss of w hole blood , w hich is
not expected to alter the blood hem oglobin concentration
or hem atocrit. This exp lains w hy there is a p oor correla-
tion betw een blood volu m e d eficits and hem oglobin or
hem atocrit in acute hem orrhage (3).

2. A d rop in hem oglobin and hem atocrit in the early hou rs


after acu te hem orrhage is a reflection of volu m e resu sci-
tation w ith crystalloid or colloid flu id s, (w hich exp and s
the p lasm a volu m e and cau ses a d ilu tional d ecrease in
the hemoglobin and hem atocrit) (4).
Hemorrhage and Hypovolemia 143

3. For the reasons stated above, the hem oglobin and hem a-
tocrit shou ld N EVER be u sed to evalu ate acu te blood
loss.

TABLE 10.2 Sensitivity of Vital Signs in Detecting


Acute Blood Loss
Reported Sensitivities
Moderate Loss Severe Loss
(450 630 mL) (630 1150 mL)
Supine Tachycardia 0 42% 5 24%
Supine Hypotension 0 50% 21 47%
Postural Pulse Incrementa 6 48% 91 100%
Postural Hypotensionb
Age < 65 yrs 6 12%
Age 65 yrs 14 40%
aIncreas e in puls e rate 30 beats /min on s tanding.
b Decreas e in s ys tolic pres s ure > 20 mm Hg on s tanding.
Combined res ults of 9 clinical s tudies . From Reference 2.

C. Invasive Hemodynamics
1. Cardiac Filling Pressures
a. Card iac filling p ressu res show a p oor correlation w ith
ventricu lar end -d iastolic volu m e (see Chap ter 8, Fig-
u re 8.4), and they d o not pred ict resp onsiveness to vol-
u m e infu sion (5).
b. H yp ovolem ia is associated w ith a d ecrease in ventric-
u lar d istensibility (com p liance) (6), w hich m eans that
card iac filling pressu res w ill overestim ate the intravas-
cu lar volu m e in hypovolem ic p atients.
c. Changes in card iac filling p ressu res in resp onse to vol-
u m e infu sion are consid ered more m eaningfu l than
144 Disorders of Circulatory Flow

single m easu rem ents. It is believed that rapid infu sion


of 500 m L isotonic saline w ill not raise the card iac fill-
ing pressures m ore than 2 m m H g in hyp ovolem ic p a-
tients (7), bu t the valid ity of this belief is u np roven.

2. Systemic Oxygen Transport


(See Chap ter 9 for a d escrip tion of the O 2 transport p a-
rameters). H yp ovolem ia is accom p anied by a d ecreased
card iac ou tp ut and an associated d ecrease in systemic O 2
d elivery (DO 2). The effect of this d ecline in DO 2 on the
system ic O 2 u ptake (VO 2) can help to d istingu ish com -
p ensated hypovolemia from hypovolem ic shock.
a. In com pensated hyp ovolemia, the VO 2 w ill rem ain
normal (110160 m L/ m in/ m 2) becau se O 2 extraction
has increased to com pensate for the d ecrease in DO 2.
b. In hypovolem ic shock, the VO 2 falls below norm al
(< 100 m L/ m in/ m 2) becau se O 2 extraction has reached
its m axim u m level (ap p roxim ately 50%) and cannot
increase fu rther in resp onse to the d eclining DO 2.
These DO 2-VO 2 relationships are d em onstrated in Fig-
ure 9.1.

D. Acid-Base Parameters
The arterial base d eficit and blood lactate level can p rovid e
inform ation abou t the effects of hypovolem ia on tissu e oxy-
genation.

1. Arterial Base Deficit


a. The base d eficit is the am ou nt (in m illim oles) of base
need ed to titrate one liter of w hole blood to a pH of
7.40 (at a tem p eratu re of 37C and a PCO 2 of 40 m m
H g). Becau se base d eficit is m easu red w hen the PCO 2
is norm al, it is a m easure of non-respiratory acid -base
d isturbances. In the hyp ovolem ic p atient, an elevated
base d eficit is a m arker of global tissu e acid osis from
Hemorrhage and Hypovolemia 145

im p aired oxygenation (8).


b. Most blood gas analyzers d etem ine the base d eficit
rou tinely (u sing a PCO 2/ H CO 3 nom ogram ), and the
resu lts are inclu d ed in the blood gas rep ort. The base
d eficit can also be calcu lated u sing Equ ation 10.1 (9),
w here BD is base d eficit in m m ol/ L, H b is the hem o-
globin concentration in blood , and H CO 3 is the seru m
bicarbonate concentration.

BD = [(1 0.014 Hb) x HCO3 ] 24


+ [(9.5 + 1.63 Hb) x (pH 7.4)] (10.1)

c. The norm al range for base d eficit is +2 to -2 m m ol/ L.


Increases in base d eficit are classified as m ild (-2 to -5
mm ol/ L), m od erate (-6 to -14 m m ol/ L), and severe
( -15 m m ol/ L).
d . In the bleed ing p atient, there is a d irect correlation be-
tw een the m agnitu d e of increase in base d eficit and the
extent of blood loss (10). Correction of the base d eficit
w ithin hou rs after volu m e resu scitation is associated
w ith a favorable ou tcom e, w hile p ersistent elevations
in base d eficit can be a sign of im pend ing m u ltiorgan
failu re (10).

2. Blood Lactate
a. As d escribed in Chap ter 9, hyp erlactatemia (blood lac-
tate > 2 m Eq/ L) can be a sign of a global shift to anaer-
obic m etabolism .
b. When com pared w ith the base d eficit, elevations in
blood lactate show a closer correlation w ith both the
magnitu d e of blood loss (11), and the likelihood of a
fatal ou tcome (11,12).

III.VOLUME INFUSION
The m ortality in hypovolem ic shock is d irectly related to the
146 Disorders of Circulatory Flow

magnitu d e and d uration of hypoperfu sion of the vital or-


gans (1). This m eans that the rate of volu m e rep lacem ent can
have an im p act on ou tcom e in hyp ovolem ic shock. This sec-
tion d escribes the factors that influ ence the infu sion rate of
resu scitation flu id s.

A. Catheter Size
1. There is a tend ency to cannu late the large central veins to
achieve m ore rap id infu sion rates. H ow ever, the rate of
volume infusion is determined by the dimensions of the vascu-
lar catheter, not the size of the vein.

2. The influ ence of catheter size on infu sion rate is d efined


by the H agen-Poisseu ille equ ation, w hich is d escribed in
Chapter 4 (see Equation 4.1) and is show n below.

Q = P (r4 /8L) (10.2)

Accord ing to this equ ation, stead y flow (Q) throu gh a


catheter is d irectly related to the d riving pressu re (P)
for flow and the fourth pow er of the rad iu s (r) of the
catheter, and is inversely related to the length (L) of the
catheter and the viscosity () of the infusate.

3. Equ ation 10.2 p red icts that flow throu gh central venous
catheters (w hich are at 6 8 inches in length) w ill be m u ch
slow er than flow throu gh p erip heral vein catheters
(w hich are 2 inches in length) if the d iam eter of the infu -
sion channels is equ ivalent.

4. The influ ence of catheter length on infu sion rate is d e-


monstrated in Figu re 10.1 (13). Using catheters of equ al
d iam eter (16 gauge), flow in the 2-inch catheter is abou t
50% higher than flow in the 5.5-inch catheter, and is m ore
than tw ice the flow rate in the 12-inch catheter. Therefore,
for rapid volume resuscitation, cannulation of peripheral veins
with short catheters is preferred to cannulation of large central
veins with long catheters.
Hemorrhage and Hypovolemia 147

5. Introducer Catheters
Volu m e resu scitation of traum a victim s m ay requ ire flow
rates in excess of 5 L/ m in (14). Becau se flow increases
w ith the fou rth p ow er of the rad ius of a catheter, very
rap id flow rates are best achieved w ith large-bore cath-
eters like the introducer catheters d escribed in Chap ter 4
(see Figu re 4.1). These catheters are norm ally u sed as
cond u its for p u lm onary artery catheters, but they can be
u sed as stand -alone infu sion d evices.
a. Gravity-d riven flow throu gh introd u cer catheters can
reach 15 m L/ sec, w hich is only slightly less than the
gravity-d riven flow rate (18 m L/ sec) through stan-
d ard (3 m m d iam eter) intravenou s tu bing (15).
b. The sid e infusion port on the hu b of introd ucer cath-
eters (see Figu re 4.1) has a flow cap acity that is only
25% of the flow cap acity of the catheter (15). There-
fore, the sid e port on these catheters shou ld not be
u sed for rap id volu me infu sion.

S hort Ca the te rs
200

Flow Ra te
(mL /min) Long Ca the te rs
100

0
Dia me te r 14 ga 16 ga 16 ga 16 ga
Le ngth 2 in 2 in 5.5 in 12 in

FIGURE 10.1. The influence of catheter size on the gravity-driven flow


rate of water. Catheter dimensions are indicated below the horizontal
axis of the graph. (From Reference 13).
148 Disorders of Circulatory Flow

B.Type of Resuscitation Fluid


1. Types of Fluid
There are three typ es of resu scitation flu id :
a. Fluid s that contain red blood cells; i.e., w hole blood
and erythrocyte concentrates or p acked cells. Whole
blood is rarely available for resu scitation, and p acked
cells are u sed to increase the oxygen carrying cap acity
of blood .
b. Fluid s that contain large m olecules w ith lim ited m ove-
m ent ou t of the blood stream . These are called colloid
flu id s, and they are d esigned to exp and the p lasm a
volum e. Com m on colloid flu id s includ e albu m in solu-
tions, hetastarch, and the d extrans.
c. Flu id s that contain electrolytes and other sm all m ole-
cu les that m ove freely ou t of the blood stream . These
are called crystalloid flu id s, and they are u sed to ex-
p and the extracellu lar volum e. The m ost notable crys-
talloid fluid s are the saline (sod ium chlorid e) solu tions
and Ringer s solu tions.
2. Flow Characteristics
a. The tend ency for a flu id to flow is d eterm ined by its
viscosity (see Equ ation 10.2), and the viscosity of re-
su scitation flu id s is a fu nction of cell d ensity.
b. The influ ence of cell d ensity on the infu sion rate of
resu scitation flu id s is show n in Figu re 10.2 (16). The
albu m in solu tion flow s as read ily as w ater becau se it
has no cells and has a viscosity com parable to w ater.
Whole blood flow s less rap id ly than the cell-free flu -
id s, and the concentrated erythrocyte p rep aration
(p acked RBCs) has the slow est flow rate.
c. The infu sion rate of p acked RBCs is enhanced by
increasing the d riving pressu re w ith an inflatable cu ff
w rap p ed around the blood bag, and also by ad d ing an
equ al volum e of isotonic saline to red u ce the viscosity
of the infu sate.
Hemorrhage and Hypovolemia 149

IV. RESUSCITATION STRATEGIES


The u ltim ate goal of volu m e resu scitation for acu te blood
loss is to m aintain oxygen u p take (VO 2) into tissu es and sus-
tain aerobic m etabolism . The strategies u sed to m aintain VO 2
are id entified by the d eterm inants of VO 2 in Equ ation 10.3.
(This equation is d escribed in d etail in Chapter 9.)

VO2 = Q x Hb x 1.34 x (S aO2 S vO2 ) x 10 (10.3)

Acu te blood loss affects tw o com ponents of this equ ation:


card iac ou tp ut (Q) and hem oglobin concentration in blood
(H b). Therefore, prom oting card iac ou tp u t and correcting
hem oglobin d eficits are the tw o goals of resu scitation for
acu te blood loss.

A. Promoting Cardiac Output


The consequ ences of a low card iac ou tp u t are far m ore

Ca the te r Dime ns ions


100 dia me te r: 16 ga
le ngth: 2 in

Flow Ra te
(mL/min)
50

0
Wa te r 5% Whole Pa cke d
Albumin Blood RBCs

FIGURE 10.2. Comparative infusion rates of erythrocyte-containing and


cell-free resuscitation fluids. Catheter size and driving pressure are the
same for all infusions. (From Reference 16).
150 Disorders of Circulatory Flow

threatening than the consequ ences of anem ia, so the first pri-
ority in the bleeding patient is to support cardiac output.

1. The Trendelenburg Position


a. The Trend elenbu rg p osition (legs elevated 45 above
the horizontal p lane and head d ow n 15 below the
horizontal plane) is a p opu lar au totransfu sion m a-
neu ver that is believed to prom ote card iac ou tpu t by
shifting blood from the legs to m ore central veins to
au gm ent venous retu rn. H ow ever, these presumed ef-
fects have not been demonstrated in experimental studies.
b. Stud ies have show n that the Trend elenbu rg p osition
d oes not increase central blood volum e (17,18), and
d oes not increase card iac output in hyp ovolem ic pa-
tients (19).
c..Becau se there is no p roof of efficacy, the Trend elenburg
p osition is not ad vised for the m anagem ent of hypov-
olem ia. It is axiom atic that the appropriate treatment of
hypovolemia is volume replacement.

2. Efficacy of Resuscitation Fluids


The ability of each typ e of resu scitation flu id to au gm ent
card iac ou tp u t is show n in Figu re 10.3 (20). The follow -
ing resu lts d eserve m ention:
a. A colloid flu id (d extran-40) is the m ost effective resu s-
citation fluid for au gmenting card iac ou tp u t. On a vol-
u m e-to-volu m e basis, the colloid flu id is abou t tw ice
as effective as w hole blood , six tim es m ore effective
than p acked cells, and eight tim es more effective than
the crystalloid flu id (lactated Ringer s).
b. The limited ability of blood (particularly packed RBCs)
to au gm ent card iac outpu t is d ue to the viscosity effects
of erythrocytes. Some stud ies have show n that packed
RBCs can actually decrease card iac output (21).
If au gm enting card iac ou tp u t is the first p riority in acu te
hem orrhage, the resu lts in Figu re 10.3 ind icate that blood
Hemorrhage and Hypovolemia 151

is not the fluid of choice for early volume resuscitation in acute


blood loss.

3. Colloid vs. Crystalloid Resuscitation


a. The marked d ifference in the ability of colloid and
crystalloid fluid s to au gm ent card iac ou tp u t, as d em -
onstrated in Figu re 10.3, is d u e to d ifferences in vol-
u m e d istribu tion.
b. Crystalloid flu id s are d istribu ted evenly in the extra-
cellu lar flu id and , becau se p lasm a represents only 25%
of the extracellular fluid , only 25% of the infused volume
of crystalloid fluids will remain in the vascular space and
expand the plasma volume (22).
c. Colloid fluid s are prim arily restricted to the p lasm a

1.0

Cl
(L/min /m 2 )

0.5

0
Pa cke d Whole Ringe r's 10%
RBCs Blood La cta te Dextra n-40
(2 U) (1 U) (1 L) (500 mL)

Blood P roducts As a nguinous Fluids

FIGURE 10.3. Graph showing the change in cardiac index (CI) follow-
ing a one-hour infusion of the specified resuscitation fluids. The volume
of whole blood (1 unit = 450 mL) packed RBCs (2 units = 500 mL) and
dextran-40 (500 mL) is equivalent, while the volume of Ringers lactate
(1 Liter) is twice that of the other fluids. (From Reference 20).
152 Disorders of Circulatory Flow

becau se these flu id s contain large m olecu les that d o


not read ily move into the interstitial flu id . A t least 75%
of the infused volume of colloid fluids will remain in the vas-
cular space and expand the plasma volume in the first few
hou rs after infu sion (22).
d . Thu s, colloid flu id s are m ore effective for au gmenting
card iac ou tpu t becau se they are m ore effective for au g-
menting plasm a volu m e.
e. Crystalloid flu id s can achieve the sam e au gm entation
of p lasm a volu m e and card iac ou tp u t as seen w ith col-
loid flu id s, bu t the infu sion volu m e m u st be at least
three tim es greater than that of colloid flu id s.
Colloid and crystalloid resuscitation is d escribed in d e-
tail in the next chap ter.

B.The Resuscitation Volume


The volu m e of colloid or crystalloid flu id need ed to rep lace
volu m e d eficits can be estim ated in ind ivid u al p atients u sing
the follow ing tw o-step app roach.

1. Estim ate the volu m e d eficit by m atching the p atients


cond ition as closely as p ossible to one the four stages of
p rogressive blood loss d escribed earlier in the chap ter.
The corresp ond ing volu me d eficits are as follow s: Class I
= 5 m L/ kg, Class II = 15 m L/ kg, Class III = 25 m L/ kg,
Class IV = 35 m L/ kg (these valu es are m id w ay betw een
the range of valu es show n earlier). Remem ber to u se
id eal bod y w eight.

2. The resu scitation volu m e (VInfuse) is then d eterm ined as


the volu m e d eficit (VLost) d ivid ed by the fraction of the
infu sed volu m e that is retained in the p lasm a. The latter
variable is the ratio of the increm ent in plasm a volum e to
the infused volum e (Vplasm a / VInfuse), and can be called the
plasma retention ratio.

VInfus e = VLo s t / Plas ma Re te ntio n Ratio (10.4)


Hemorrhage and Hypovolemia 153

For colloid flu id s, at least 75% of the infu sed volu m e w ill
remain in the p lasm a, so the p lasm a retention ratio is
0.75. For crystalloid flu id s, only 25% of the infu sed vol-
u m e is retained in p lasm a, so the p lasm a retention ratio
is 0.25.

3. Example
Assu m e that an ad ult m ale w ith an id eal bod y w eight of
70 kg p resents w ith acu te GI hem orrhage, and the physi-
cal exam show s only a p ostural increase in pu lse rate of
35 bpm . The latter find ing m akes this a Class II hem or-
rhage w ith an estim ated volu me loss of 15 m L/ kg, so the
volu m e loss in this p atient is 15 x 70 =1,050 m L. If a crys-
talloid flu id is u sed for volu m e resu scitation, the resu sci-
tation volu m e is 1,050/ 0.25 = 4,200 mL. If a colloid fluid
is used , the m inim u m resu scitation volu m e is 1,050/ 0.75
=1,400 m L. Therefore, resu scitation w ith a crystalloid flu -
id requ ires at least 3 tim es m ore volu m e than resu scita-
tion w ith a colloid flu id .

C. Correcting Anemia
After volu m e d eficits are replaced and card iac outpu t is re-
stored , attention can be d irected to correcting hem oglobin
d eficits. The u se of RBC transfusions to correct anemia is
d escribed in Chap ter 30.

D. End-Points of Resuscitation

1. Traditional End-Points
a. The trad itional end -p oints of volu m e resu scitation are
norm alization of blood p ressu re and u rine ou tpu t.
b. As m any as 85% of p atients w ith hyp ovolem ic shock
w ill have continu ed evid ence of im p aired tissu e oxy-
genation after the blood pressure and urine output
retu rn to normal (23).
154 Disorders of Circulatory Flow

c. Therefore, norm alization of blood pressu re and u rine


outp u t shou ld not m ark the end of resu scitation, but
shou ld be follow ed by an evalu ation of system ic oxy-
genation.

2. Systemic Oxygenation
a. The clinical m easu res listed below are u sed as ind irect
evid ence of ad equ ate tissu e oxygenation (see Chapter
9), and thu s they can also be u sed as end -points of vol-
u m e resu scitation in hypovolem ic shock.
Oxygen u ptake (VO 2) > 100 m L/ min/ m 2
Arterial base d eficit > 2 m m ol
Seru m lactate < 2 m Eq/ L

b. The goal is to reach these end -p oints w ithin 24 hours


of the onset of hypovolem ic shock (23). Unfortu nately,
this is not alw ays p ossible, and the m ore p rolonged
the circulatory shock, the greater the risk of a fatal ou t-
come. In one stu d y of trau m a victim s (24), there w ere
no m ortalities w hen blood lactate levels returned to
norm al w ithin 24 hou rs, bu t the m ortality rate rose to
85% w hen hyp erlactatem ia p ersisted for longer than
48 hours.

REFERENCES
1. Falk JL, OBrien JF, Kerr R. Flu id resu scitation in trau m atic hem -
orrhagic shock. Crit Care Clin 1992; 8:323-340.
2. McGee S, Abernathy WB, Sim el DL. Is this patient hyp ovolem ic.
JAMA 1999; 281:1022-1029.
3. Cord ts PR, LaMorte WW, Fisher JB, et al. Poor p red ictive valu e
of hem atocrit and hem od ynam ic param eters for erythrocyte
d eficits after extensive vascu lar operations. Su rg Gynecol Obstet
1992; 175:243248.
4. Stam ler KD. Effect of crystalloid infu sion on hem atocrit in non-
bleed ing patients, w ith ap plications to clinical traum atology.
Ann Em erg Med 1989; 18:747749.
Hemorrhage and Hypovolemia 155

5. Kum ar A, Anel R, Bu nnell E, et al. Pu lm onary artery occlu sion


p ressu re and central venou s pressure fail to p red ict ventricular
filling volu m es, card iac perform ance, or the resp onse to volu m e
infu sion in norm al su bjects. Crit Care Med 2004; 32:691-699.
6. Walley KR, Cooper DJ. Diastolic stiffness im p airs left ventricular
fu nction d u ring hypovolem ic shock in pigs. Am J Physiol 1991;
260:H 702712.
7. Barbeito A, Mark JB. Arterial and central venou s p ressu re m oni-
toring. Anesthesiol Clin 2006; 24:717-735.
8. Kincaid EH , Miller PR, Mered ith JW, et al. Elevated arterial base
d eficit in trau m a p atients: a m arker of im p aired oxygen u tiliza-
tion. J Am Coll Su rg 1998; 187:384-392.
9. Land ow L. Letter to the ed itor. J Trau m a 1994; 37:870-871.
10. Davis JW, Shackford SR, Mackersie RC, H oyt DB. Base d eficit as
a gu id e to volu m e resu scitation. J Traum a 1998; 28:1464-1467.
11. Moom ey CB Jr, Melton SM, Croce MA, et al. Prognostic valu e of
blood lactate, base d eficit, and oxygen-d erived variables in an
LD 50 m od el of penetrating traum a. Crit Care Med 1999; 27:154-
161.
12. H usain FA, Martin MJ, Mu llenix PS, et al. Seru m lactate and base
d eficit as pred ictors of m ortality and m orbid ity. Am J Su rg 2003;
185:485-491.
13. Mateer JR, Thom p son BM, Ap raham ian C, Darin JC. Rap id flu id
resu scitation w ith central venous catheters. Ann Em erg Med
1983; 12:149152.
14. Bu chman TG, Menker JB, Lip sett PA. Strategies for trau m a resu s-
citation. Su rg Gynecol Obstet 1991; 172:812.
15. H ym an SA, Sm ith DW, England R, et al. Pulm onary artery
catheter introd ucers: Do the com ponent parts affect flow rate?
Anesth Analg 1991; 73:573575.
16. Du la DJ, Mu ller A, Donovan JW. Flow rate variance of com m on-
ly u sed IV infusion techniqu es. J Trau m a 1981; 21:480482.
17. Bivins H G, Knopp R, d os Santos PAL. Blood volu m e d istribu tion
in the Trend elenburg p osition. Ann Em erg Med 1985; 14:641643.
18. Gaffney FA, Bastian BC, Thal ER, Atkins JM. Passive leg raising
d oes not prod uce a significant autotransfu sion effect. J Trau m a
1982; 22:190193.
19. Sing R, OH ara D, Saw yer MJ, Marino PL. Trend elenburg p osi-
tion and oxygen transp ort in hyp ovolem ic ad u lts. Ann Em erg
Med 1994; 23:564568.
156 Disorders of Circulatory Flow

20. Shoem aker WC. Relationship of oxygen transp ort patterns to the
p athophysiology and therap y of shock states. Intensive Care
Med 1987; 213:230243.
21. Marik PE, Sibbald WJ. Effect of stored -blood transfu sion on oxy-
gen d elivery in p atients w ith sep sis. JAMA 1993; 269:30243029.
22. Im m A, Carlson RW. Fluid resu scitation in circu latory shock. Crit
Care Clin 1993; 9:313333. .
23. Tisherm an SA, Barie P, Bokhari F, et al. Clinical p ractice gu id e-
line: End p oints of resuscitation. Winston-Salem (N C): Eastern
Association for Su rgery of Trau m a, 2003. Available at
w w w.east.org/ tp g/ end points.p d f (accessed 6/ 18/ 07)
24. Abram son D, Scalea TM, H itchcock R, et al. Lactate clearance
and su rvival follow ing inju ry. J Trau m a 1993; 35:584-589.
Chapter 11
COLLOID AND
CRYSTALLOID
RESUSCITATION
Intravenou s flu id s are classified as crystalloid or colloid flu -
id s. This chap ter d escribes the com p arative featu res of each
type of flu id , and the ind ivid u al flu id s available for clinical
u se. A brief d escrip tion of hyp ertonic flu id resu scitation is
includ ed at the end of the chap ter.

I. CRYSTALLOID FLUIDS
Crystalloid fluid s are electrolyte solutions that contain only
sm all m olecu les cap able of u nrestricted m ovem ent betw een
p lasm a and interstitial flu id . The p rincip al ingred ient in
crystalloid flu id s is the inorganic salt sod iu m chlorid e
(w hich takes ad vantage of sod iu m s role as the principal sol-
u te in extracellu lar flu id ).

A. Crystalloid Distribution
1. Crystalloid flu id s are d istribu ted u niform ly in the extra-
cellu lar flu id . Since the interstitial flu id rep resents abou t
75% of the extracellu lar flu id (exclu d ing bone), then 75%
of infu sed crystalloid flu id s w ill be d istribu ted in the
interstitial fluid .

2. The tend ency for crystalloid flu id s to d istribu te m ore in


the interstitial flu id than in p lasm a is d em onstrated in
Figu re 11.1. In this case, infu sion of one liter of 0.9% sod i-

157
158 Disorders of Circulatory Flow

u m chlorid e (isotonic saline) ad d s of 275 m L to the p las-


ma, and 825 m L to the interstitial flu id (1). The total vol-
u m e increm ent (1,100 m L) is m ore than the volu m e in-
fu sed because isotonic saline is slightly hypertonic to in-
terstitial flu id , and w ill d raw w ater ou t of cells.

1000

Incre a s e
in 500
P la s ma Volume

0.9% 5% 7.5%
(mL) 0 D5 W NaCl Albumin NaCl
(1L) (1L) (1L) (250 mL)

Incre a s e 500
in
Inte rs titia l Volume

1000

FIGURE 11.1. The effects of selected colloid and crystalloid fluids on the
plasma volume and interstitial fluid volume. The infusion volume for
each fluid is shown in parentheses. (From Reference 1).

B. Isotonic Saline
The classic crystalloid flu id is 0.9% sod iu m chlorid e (0.9%
N aCL), w hich is also called isotonic saline (even thou gh it is
not isotonic to p lasm a) or norm al saline (even though it is
not a one-norm al solu tion) .

1. Composition
When com p ared to plasma (see Table 11.1) isotonic saline
has a higher sod iu m concentration (154 vs. 140 m Eq/ L),
Colloid and Crystalloid Resuscitation 159

a m uch higher chlorid e concentration (154 vs. 103 m Eq


/ L), a m uch low er p H (5.7 vs. 7.4) and a slightly higher
osm olality (308 vs. 290 m Osm / L). The chlorid e d iffer-
ence has significance, as d escribed next.
2. Adverse Effects
Large volum e infu sions of isotonic saline can prod u ce a
hyperchloremic metabolic acidosis (2). The cu lprit is the ex-
cess chlorid e in isotonic saline, w hich w ill p rom ote renal
bicarbonate excretion. This cond ition has no ad verse con-
sequ ences, but it can create confu sion in the resu scitation
of d iabetic ketoacid osis, as exp lained in Chap ter 23.

C. Lactated Ringers Solution


Ringer s solu tion w as introd u ced in 1880 as a calciu m -con-
taining flu id that cou ld p rom ote card iac contraction in frog
heart prep arations. It w as later ad op ted for clinical u se, and
lactate w as ad d ed as a bu ffer in 1930.
1. Composition
a. Ringer s solu tions contain p otassiu m and calciu m in
concentrations that ap p roxim ate the free (ionized )
concentrations in p lasma. The ad d ition of these cations
requ ires a red u ction in sod iu m concentration for elec-
trical neu trality, and the resu ltant sod iu m concentra-
tion is low er than in isotonic saline or p lasm a (see
Table 11.1).
b. The ad d ition of lactate (28 m Eq/ L) requ ires a d rop in
chlorid e concentration, and the resu ltant chlorid e con-
centration (109 m Eq/ L) is close to that of p lasm a (103
mEq/ L). This elim inates the risk of hyp erchlorem ic
metabolic acid osis observed after large-volum e infu -
sions of isotonic saline.
2. Adverse Effects
a. The calciu m in Ringer s solu tions can bind to d ru gs
(e.g., am photericin, am p icillin, thiop ental) and red u ce
160 Disorders of Circulatory Flow

TABLE 11.1 Comparative Features of Crystalloid Fluids


and Plasma
mEq/L
Osmolality
Fluid Na Cl K Ca Mg Buffers pH (mOsm/L)
Plasma 140 103 4 5 2 HCO3 7.4 290
0.9% NaCl 154 154 5.7 308
Ringers 130 109 4 3 Lactate 6.4 273
Lactate
7.5% NaCl* 1283 1283 5.7 2567
Normosol
Plasma-Lyte 140
Isolyte } 98 5 3
Acetate &
Gluconate
7.4 295

*From Stapczyns ki J S et al. Emerg Med Rep 1994; 15:245.


Is olyte als o contains phos phate (1 mEq/L).

efficacy (3). These d ru gs shou ld not be m ixed w ith


Ringer s solu tions.
b. The calciu m in Ringer s can also bind to the citrated
anticoagu lant in blood p rod u cts. This inactivates the
anticoagu lant and p rom otes clot form ation in d onor
blood . Accord ing to the Am erican Association of
Blood Banks, Ringers solutions are contraindicated as a
diluent for red blood cell transfusions (4).

D. Normal pH Fluids
1. Three crystalloid flu id s (N orm osol, Isolyte, and Plasm a-
Lyte) contain both acetate and glu conate bu ffers to a-
chieve a p H of 7.4 (see Table 11.1). All three flu id s con-
tain p otassiu m (5 m Eq/ L) and m agnesiu m (3 m Eq/ L),
w hile Isolyte also contains p hosp hate (1 m Eq/ L).
Colloid and Crystalloid Resuscitation 161

2. These fluid s are not p op u lar, bu t they have been recom -


mend ed as preferable to isotonic saline for w ashing or
d ilu ting salvaged red blood cells (5).

II. DEXTROSE SOLUTIONS

A. Protein-Sparing Effect
1. Dextrose w as originally ad d ed to intravenou s flu id s as a
nu trient. One gram of d extrose p rovid es 3.4 kilocalories
(kcal) w hen fu lly m etabolized , so a 5% d extrose solu tion
(50 gram s p er liter) p rovid es 170 kcal p er liter.

2. Daily infu sion of 3 liters of a 5% d extrose (D 5) solu tion


provid es abou t 500 kcal p er d ay, w hich is enou gh non-
protein calories to lim it the breakd ow n of end ogenou s
proteins to m eet d aily caloric requ irem ents. This protein-
sparing effect is responsible for the early p opu larity of
d extrose-containing flu id s.

3. The cu rrent availability of enteral and p arenteral nu tri-


tion regim ens obviates the need for 5% d extrose solu -
tions as a sou rce of calories.

B.Volume Effects
1. The ad d ition of d extrose to an intravenou s flu id d oes not
enhance the p erform ance of the flu id for volu m e resu sci-
tation becau se the d extrose is taken u p by cells and m e-
tabolized .

2. The p oor p erform ance of 5% d extrose-in-w ater (D 5W) as


a resu scitation flu id is show n in Figu re 11.1. In this case,
infu sion of one liter of D 5W is associated w ith a m inim al
(abou t 100 m L) increm ent in plasm a volu m e.
162 Disorders of Circulatory Flow

3. N ote in Figu re 11.1 that the com bined increm ents in plas-
ma volu m e (100 m L) and interstitial fluid volu me (250
mL) are far less than the volu m e infu sed . The volu m e d if-
ference (650 m L) is the resu lt of flu id m ovem ent into
cells, w hich m eans that D 5W expands the intracellular vol-
ume (w hich is not a d esirable effect).

C. Adverse Effects
1. Enhanced Lactate Production
In healthy subjects, only 5% of glu cose metabolism lead s
to lactate prod uction, bu t in critically ill p atients w ith tis-
su e hyp op erfusion, as m u ch as 85% of glu cose m etabo-
lism is d iverted to lactate p rod u ction (6). Thu s w hen tis-
su e oxygenation is im paired , glu cose is a sou rce of m eta-
bolic acid prod u ction m ore than m etabolic energy pro-
d u ction.

2. Hyperglycemia
a. H yp erglycem ia has several u nd esirable effects in criti-
cally ill patients, inclu d ing im m u nosu p p ression (7),
aggravation of ischem ic brain inju ry (8), and increased
mortality (9,10).
b. Clinical stu d ies have show n im p roved su rvival in ICU
p atients w hen there is a p rotocol for strict glycem ic
control w ith insu lin infu sions (9,10). The m echanism
for this effect is not know n.
Because 5% d extrose solu tions offer no benefit, and can
be harm fu l, the routine u se of these solu tions shou ld be
aband oned .

III. COLLOID FLUIDS


The behavior of colloid flu id s is d eterm ined by an osm otic
force that is d escribed briefly in the next section.
Colloid and Crystalloid Resuscitation 163

A. Colloid Osmotic Pressure


1. Colloid flu id s contain large m olecu les that d o not read i-
ly m ove ou t of the vascular comp artm ent. These m ole-
cu les create an osm otic p ressu re called the colloid osmotic
pressure that favors the retention of w ater in the vascular
com p artm ent.

2. The follow ing relationship id entifies the role of the col-


loid osm otic p ressure in cap illary flu id exchange.

Q (P c COP) (11.1)

a. Q is the flow rate across the cap illaries.


b. P c is the hyd rostatic pressu re in the cap illaries.
c. COP is the colloid osm otic p ressu re of p lasm a. This
pressu re is created by p lasm a p roteins (mostly albu -
min), and the norm al range is 20 25 m m H g.

3. The tw o p ressu res (P c and COP) act in opp osition: P c fa-


vors the m ovem ent of flu id ou t of the cap illaries, and
COP favors m ovem ent into the cap illaries.

4. Colloid flu id s that are u sed to rep lace volu m e losses have
a COP that is equ ivalent to the COP of p lasm a. This helps
to retain m ost of the infu sed volu m e in the p lasm a.

5. Som e colloid flu id s have a COP that is m u ch higher than


the COP of p lasm a: these flu id s are u sed to d raw intersti-
tial fluid into the p lasm a.

B.Volume Effects
1. The effect of colloid flu id resu scitation on p lasma and
interstitial fluid volu m es is show n in Figu re 11.1 The col-
loid flu id in this case is a 5% albu m in solution, w hich has
a COP (20 m m H g) that is equ ivalent to the COP of plas-
ma. Infu sion of one liter of this solu tion ad d s 700 m L to
the plasm a and 300 m L to the interstitial flu id .
164 Disorders of Circulatory Flow

2. Com p aring the effects of the colloid and crystalloid flu id


on p lasm a volu m e in Figu re 11.1 reveals that the colloid
fluid is about three times more effective than the crystalloid
fluid for increasing the plasma volume (1,11 13).

3. Colloid flu id s d iffer in their ability to increase the p lasm a


volum e, and this d ifference is a function of the COP of
each flu id . This is d emonstrated in Table 11.2, w hich
show s that flu id s w ith a higher COP p rod u ce greater
increm ents in plasm a volu me.

TABLE 11.2 Comparative Features of Colloid Fluids


Colloid
Osmotic Plasma Volume Duration
Fluid Pressure Infused Volume of Effect
25% Albumin 70 mm Hg 4.0 5.0 12 h
10% Dextran-40 40 mm Hg 1.0 1.5 6h
6% Hetastarch 30 mm Hg 1.0 1.3 24 h
5% Albumin 20 mm Hg 0.7 1.3 12 h
From References 1,1113,17.

C. Albumin Solutions
Albu m in solutions are heat-treated p reparations of hum an
seru m album in that are available as a 5% solu tion (50 g/ L)
and a 25% solu tion (250 g/ L) in isotonic saline.

1. Volume Effects
a. The 5% albu m in solu tion has an album in concentra-
tion (5 g/ d L) and a COP (20 m m H g) that are equ iva-
lent to p lasm a. This solution is given in aliquots of
250 mL, and the acute volume effect (70% retention in plas-
ma, as shown in Figure 11.1) is lost after 12 hours (1,11).
Colloid and Crystalloid Resuscitation 165

b. The 25% albu m in solu tion has a COP (70 m m H g) that


is about three times higher than the COP of plasm a.
As a resu lt, 25% albu m in d raw s flu id from the intersti-
tial space, and the increm ent in p lasm a volu m e can be
four to five tim es greater than the volu m e infu sed (see
Table 11.2). This colloid flu id is given in sm all aliqu ots
(50 m L) to shift interstitial flu id into the p lasm a in con-
d itions w here hypovolem ia is associated w ith ed em a
(e.g., hyp oalbum inem ia). It is not ap p rop riate for re-
p lacing volum e losses.

2. Safety
Early claim s of increased mortality attribu ted to albu min
infusions (14) have not been corroborated in m ore recent
stu d ies (15). In ad d ition, there is evid ence of red u ced
morbid ity w hen album in is u sed instead of crystalloid
fluid s (16).

D. Hydroxyethyl Starch
H yd roxyethyl starch (hetastarch) is a synthetic starch poly-
mer that is available as a 6% solu tion in isotonic saline. There
are 3 p rep arations based on m olecu lar w eight (high MW,
med iu m MW, and low MW), bu t only the high MW p rep ara-
tion is available in the United States (17).

1. Volume Effects
Overall, 6% hetastarch is consid ered equ ivalent to 5%
albu m in as a p lasm a volu m e exp and er (even thou gh the
COP is higher, and the increm ent in p lasm a volu m e is
slightly greater, as show n in Table 11.2).

2. Side Effects
a. H igh MW hetastarch can cau se a bleed ing tend ency
d u e to d ecreased levels of Factor VIII and von Wille-
brand factor, and imp aired p latelet ad hesiveness (17,
18). This effect becom es pronounced w hen m ore than
1.5 L hetastarch is infu sed w ithin a 24 hr p eriod (17).
166 Disorders of Circulatory Flow

Overt bleed ing is inconsistent. This sid e effect is not


seen w ith low MW hetastarch (18).
b. Serum am ylase levels are elevated (2 to 3 tim es nor-
mal) for one w eek after hetastarch infu sion (the am y-
lase cleaves hetastarch prior to clearance by the kid -
neys) (17), and this cou ld be m isinterp reted as ind icat-
ing p ancreatitis.
3. Clinical Role
Hetastarch is a less costly alternative to 5% albumin (see
Table 11.3), but the resuscitation volume should be less
than 1,500 mL d aily to avoid a troublesome coagulopathy.

E.The Dextrans
The d extrans are glu cose p olym ers p rep ared as 10% d ex-
tran-40 and 6% d extran-70, each w ith a d ifferent m olecu lar
w eight. Both p rep arations u se isotonic saline as the d ilu ent.

1. Volume Effects
Both d extran p rep arations have a COP of 40 m m H g, and
cau se a greater increase in p lasm a volu m e than 5% albu -
min or 6% hetastarch (see Table 11.2). Dextran-70 m ay be
p referred becau se the d u ration of action (12 hou rs) is
longer than that of d extran-40 (6 hours) (11).
2. Side Effects
a. Dextrans p rod u ce a d ose-related bleed ing tend ency
that involves im paired p latelet aggregation, d ecreased
levels of Factor VIII and von Willebrand factor, and
enhanced fibrinolysis (18). These effects are m inim al
w hen the d extran d ose is lim ited to 20 m L/ kg d aily.
b. Dextrans coat the su rface of red blood cells and can in-
terfere w ith the ability to cross-m atch blood . Red cell
p rep arations m u st be w ashed to elim inate this prob-
lem . Dextrans also increase the erythrocyte sed im enta-
tion rate as a resu lt of their interactions w ith red blood
cells (19).
Colloid and Crystalloid Resuscitation 167

c. Dextrans have been im plicated as a cau se of acute re-


nal failu re (19), bu t a cau sal link is u np roven.

3. Clinical Role
The d extrans have fallen ou t of favor becau se of their
sid e effects.

TABLE 11.3 Cost Comparison for Resuscitation Fluids


Fluid Manufacturer Unit Size AWP
Crystalloid Fluids
Isotonic Saline Hospira 1,000 mL $1.46
Lactated Ringers Hospira 1,000 mL $1.48
Colloid Fluids
5% Albumin Bayer 250 mL $30.63
25% Albumin Bayer 50 mL $30.63
6% Hetastarch Abbott 500 mL $27.63
6% Dextran-70 Hospira 500 mL $14.96
Average wholes ale price lis ted in 2005 Redbook. Montvale, NJ ,
Thoms on PDR, 2005.

IV. COLLOIDS vs. CRYSTALLOIDS


There is a longstand ing d ebate concerning the typ e of flu id
(crystalloid or colloid ) that is m ost app ropriate for volum e
resuscitation.

A. Colloid Fluids
1. Pros
The m ajor p oint in favor of colloid flu id s is their effec-
tiveness in exp and ing the p lasm a volu m e. Colloid fluid s
168 Disorders of Circulatory Flow

w ill achieve a given increm ent in p lasm a volu m e w ith


only one-qu arter to one-third the volu m e requ ired of
crystalloid flu id s. Since the goal of volu m e resu scitation
is to su p p ort the intravascu lar volum e, colloid flu id s are
the logical choice over crystalloid flu id s

2. Cons
The m ajor argu m ent against colloid flu id s is the exp ense
(see Table 11.3) and the lack of a d ocu m ented su rvival
benefit to ju stify the expense. The bu lk of evid ence show s
no d ifference in m ortality in patients w ho are resu scitat-
ed w ith colloid or crystalloid flu id s (15,20).

B. Crystalloid Fluids

1. Pros
The p rop onents of crystalloid resu scitation claim that
crystalloid fluid s can achieve the sam e increm ent in plas-
ma volum e as colloid fluid s (if enou gh crystalloid fluid is
infused ) bu t at a m uch low er cost.

2. Cons
The m ajor argu m ent against crystalloid flu id s is their
p oor p erform ance as p lasm a volu m e exp and ers. The prin-
cipal effect of crystalloid infusions is to expand the interstitial
fluid volume, not the plasma volume.

C. Preferences
Instead of selecting one typ e of flu id for all occasions, it
seem s m ore reasonable to select the m ost ap p rop riate flu id
for the clinical cond ition. For examp le, a crystalloid flu id is
more ap propriate for a patient w ith hyp ovolem ia d u e to
d ehyd ration (w here there is a uniform loss of extracellu lar
fluid ), w hereas a colloid flu id is m ore ap p ropriate for a pa-
tient w ith life-threatening hyp ovolem ia d u e to hem orrhage.
Colloid and Crystalloid Resuscitation 169

V. HYPERTONIC RESUSCITATION
Volu m e resuscitation w ith 7.5% N aCL (hypertonic saline),
w hich has an osm olality abou t 8.5 tim es greater than that of
p lasm a (see Table 11.1), is being investigated as a m ethod of
sm all-volum e resu scitation.

A.Volume Effects
1. As show n in Figu re 11.1, the increm ent in p lasm a volu m e
follow ing infu sion of 250 m L of 7.5% N aCL is abou t tw ice
the infu sed volu m e. The sam e increm ent in p lasm a vol-
u m e w ould require infu sion of 2 liters of isotonic saline
(or eight tim es the volu me of hyp ertonic saline).

2. Figu re 11.1 also show s 7.5% N aCL p rod u ces an increase


in extracellu lar fluid volu m e (1,235 m L) that is 4 to 5
times greater than the infu sed volu m e (250 m L). The
ad d itional volu m e com es from intracellu lar flu id that
moves ou t of cells and into the extracellu lar space. This
highlights one of the feared consequ ences of hypertonic
resu scitation: i.e., cell d ehyd ration.

B. Clinical Role?
1. Sm all-volu m e resu scitation w ith hyp ertonic saline has
p otential benefits in the follow ing clinical situ ations:
a. In trau m a victim s w ith hyp otension and closed head
injuries (to lim it the severity of cerebral ed em a) .
b. In cases of acu te hem orrhage from a vascular inju ry (to
lim it blood loss through the inju red vessel u ntil the in-
ju ry can be su rgically rep aired ).
c. In p atients w ith su barachnoid hem orrhage, a com bi-
nation of hyp ertonic saline in 6% hetastarch has been
su ccessful in red ucing intracranial p ressu re (21).
170 Disorders of Circulatory Flow

2. At the p resent time, there are no firm ind ications for hy-
p ertonic saline over m ore trad itional resu scitation flu id s.

REFERENCES
1. Im m A, Carlson RW. Fluid resu scitation in circulatory shock. Crit
Care Clin 1993; 9:313-333.
2. Scheingraber S, Rehm M, Schm isch C, Finsterer U. Rapid saline
infu sion p rod u ces hyp erchlorem ic acid osis in p atients u nd ergo-
ing gynecologic su rgery. Anesthesiology 1999; 90:1265-1270.
3. Griffith CA. The fam ily of Ringer s solu tions. J N atl Intravenou s
Ther Assoc 1986; 9:480483.
4. Am erican Association of Blood Banks Technical Manual. 10th ed .
Arlington, VA: Am erican Association of Blood Banks, 1990:368.
5. H alpern N A, Alicea M, Seabrook B, et al. Isolyte S, a p hysiologic
m u ltielectrolyte solu tion, is preferable to norm al saline to w ash
cell saver salvaged blood : conclu sions from a prosp ective, ran-
d om ized stu d y in a canine m od el. Crit Care Med 1997; 12:2031-
2038.
6. Gunther B, Jauch W, Hartl W, et al. Low-dose glucose infusion in
patients who have undergone surgery. Arch Surg 1987; 122:765771.
7. Tu rina M, Fry D, Polk H C, Jr. Acu te hyperglycem ia and the in-
nate im m une system : Clinical, cellu lar, and m olecu lar asp ects.
Crit Care Med 2005; 33:1624-1633.
8. Sieber FE, Traystm an RJ. Special issu es: glu cose and the brain.
Crit Care Med 1992; 20:104114.
9. Van Den Berghe G, Wou ters P, Weekers F, et al. Intensive insu lin
therapy in critically ill patients. N Engl J Med 2001; 345:1359-
1367.
10. Finney SJ, Zekveld C, Elia A, Evans TW. Glu cose control and
m ortality in critically ill p atients. JAMA 2003; 290: 2041-2047.
11. Griffel MI, Kau fm an BS. Pharm acology of colloid s and crystal-
loid s. Crit Care Clin 1992; 8:235254.
12. Kaminski MV, Haase TJ. Albumin and colloid osmotic pressure:
implications for fluid resuscitation. Crit Care Clin 1992; 8:311322.
13. Su tin KM, Ru skin KJ, Kau fm an BS. Intravenou s flu id therapy in
neu rologic injury. Crit Care Clin 1992; 8:367408.
Colloid and Crystalloid Resuscitation 171

14. Cochrane Inju ries Grou p Album in Review ers. H u m an albu m in


ad m inistration in critically ill patients: System atic review of ran-
d om ized , controlled trials. Br Med J 1998; 317:235-240.
15. SAFE Stu d y Investigators. A com p arison of albu m in and saline
for fluid resu scitation in the Intensive Care Unit. N Engl J Med
2004; 350:2247-2256.
16. Vincent J-L, N avickis RJ, Wilkes MM. Morbid ity in hosp italized
p atients receiving hum an seru m albu m in: A m eta-analysis of
rand om ized , controlled trials. Crit Care Med 2004; 32:2029-2038.
17. Treib J, Baron JF, Grau er MT, Strauss RG. An international view
of hyd roxyethyl starches. Intensive Care Med 1999; 25:258-268.
18. d e Jonge E, Levi M. Effects of d ifferent plasm a su bstitu tes on
blood coagu lation: A com p arative review. Crit Care Med 2001;
29:1261-1267.
19. N earm an H S, H erm an ML. Toxic effects of colloid s in the inten-
sive care u nit. Crit Care Clin 1991; 7:713723.
20. Choi PT, Yip G, Quinonez LG, et al. Crystalloid s vs. colloid s in
flu id resu scitation: A system atic review. Crit Care Med 1999; 27:
200-210.
21. Bentsen G, Breivik H , Lu nd ar T, Stubhau g A. H yp ertonic saline
(7.2%) in 6% hyd roxyethyl starch red u ces intracranial pressu re
and im proves hem od ynam ics in a placebo-controlled stud y in-
volving stable patients w ith subarachnoid hem orrhage. Crit Care
Med 2006; 34:2912-2917.
Chapter 12
ACUTE
HEART FAILURE( S)
Acu te, d ecom p ensated heart failu re is the lead ing cause of
hospital ad m issions for ad u lts over the age of 65 (1). H eart
failu re is not a single entity, bu t can be classified accord ing to
the sid e of the heart that is involved (right-sid ed and left-
sid ed heart failu re) and the p ortion of the card iac cycle that
is affected (d iastolic and systolic heart failu re). This chapter
d escribes the d iagnosis and m anagem ent of these heart fail-
u re(s) in the ICU.

I. HEMODYNAMIC ALTERATIONS

A. Progressive Heart Failure


The influ ence of p rogressive heart failu re on card iac p er-
form ance is show n in Figu re 12.1. Changes in card iac per-
form ance occu r in 3 d istinct stages (as ind icated by the cir-
cled nu mbers in Figure 12.1):

1. The earliest stage of heart failu re is characterized by an


isolated increase in ventricular end -d iastolic pressure
(the w ed ge pressu re in Figu re 12.1). The stroke volum e
and card iac ou tpu t are m aintained , bu t at the exp ense of
venou s congestion.

2. The next stage is characterized by a d ecrease in stroke


volu m e and a corresp ond ing increase in heart rate. The
tachycard ia offsets the red u ction in stroke volu m e, so the
card iac ou tpu t rem ains unchanged .

173
174 Disorders of Circulatory Flow

3. The final stage is characterized by a stead y d ecline in car-


d iac ou tput and an accelerated rise in the w ed ge pres-
su re. (N ote the blu nted heart rate resp onse, w hich is re-
sp onsible for the d rop in card iac ou tp u t). These changes
mark the onset of decompensated heart failure. If left u n-
checked , the stead y d ecline in card iac ou tp ut w ill even-
tu ally lead to hyp op erfu sion of the vital organs and is-
chem ic tissu e injury: a cond ition know n as cardiogenic
shock.

4. The changes in card iac p erform ance in p rogressive heart


failu re are su m m arized in Table 12.1. The follow ing
p oints d eserve m ention:
a. Becau se the card iac ou tp u t d oes not d ecline u ntil the
later stages of heart failu re, card iac ou tp u t m onitoring
is not a sensitive m ethod of d etecting heart failure

FIGURE 12.1. Serial changes in measures of cardiac performance in a


patent who developed rapidly progressive heart failure in the immedi-
ate postoperative period.
Acute Heart Failure(s) 175

b. The op tim al measu re of card iac p erform ance for the


d etection of card iac pum p failu re is the relationship
betw een end -d iastolic p ressure and stroke volu m e. An
increase in end -d iastolic pressu re w ithout a correspon-
d ing rise in stroke volu m e is the earliest sign of pu m p
failu re (see Table 12.1).

TABLE 12.1 Cardiac Performance in Progressive Heart Failure


Cardiac Pump Failure
Performance
Measure Mild Moderate Advanced
End-Diastolic Pressure High High High
Stroke Volume Normal Low Low
Cardiac Output Normal Normal Low

B. Systolic vs. Diastolic Heart Failure


1. The Entities
a. H eart failu re is classically d escribed as failu re of car-
d iac contraction d u ring systole. This cond ition is now
know n as systolic heart failure.
b. Systolic fu nction is norm al in 40 to 50% of new ly-d iag-
nosed cases of heart failu re (1). In these cases, the heart
failu re is d ue to a d ecrease in ventricu lar d istensibility
d u ring d iastole. This cond ition is know n as diastolic
heart failure (2). Com m on cau ses of d iastolic heart fail-
u re in ICU patients inclu d e ventricu lar hypertrop hy,
myocard ial ischem ia (stu nned m yocard iu m ), and pos-
itive-pressu re m echanical ventilation.

2. Pressure-Volume Curves
The pressure volu m e relationship s in Figu re 12.2 w ill be
u sed to p oint ou t the sim ilarities and d ifferences betw een
systolic and d iastolic heart failu re.
176 Disorders of Circulatory Flow

FIGURE12.2. Graphs showing the effects of heart failure on pressure-vol-


ume relationships during systole (upper curves) and diastole (lower
curves). Left heart failure is associated with an increase in end-diastolic
pressure, and this is associated with an increased end-diastolic volume in
systolic failure and a decreased end-diastolic volume in diastolic failure.

a. The cu rves at the top of Figu re 12.2 d em onstrate that


heart failure is associated w ith an increased end -d ias-
tolic p ressu re (EDP) and a d ecreased stroke volu m e.
These changes occu r in both typ es of heart failu re, as
ind icated in Table 12.2.
b. The low er set of cu rves in Figu re 12.2 show the pres-
su revolu m e relationship s d uring d iastole in both
typ es of heart failu re. N ote that in systolic heart fail-
u re, the increased EDP is associated w ith an increase in
end -d iastolic volum e (EDV), w hile in d iastolic heart
failu re, the increased EDP is associated w ith a d ecrease
in EDV. Therefore, end-diastolic volume, not end-diastolic
pressure, is the parameter that distinguishes diastolic from
systolic heart failure (see Table 12.2).
Acute Heart Failure(s) 177

c. Unfortu nately, end -d iastolic volu m e is not easily m ea-


su red at the bed sid e, bu t there is another m easure that
has d iscrim inatory value (see next).

TABLE 12.2 Features of Diastolic & Systolic Heart Failure


Diastolic Systolic
Parameter Failure Failure
End-Diastolic Pressure High High
Stroke Volume Low Low

End-Diastolic Volume Low High


Ejection Fraction Normal Low
Note that only the parameters below the dotted line can dis tinguis h
between the two types of heart failure.

3. Ventricular Ejection Fraction


a. The ventricular ejection fraction (EF) expresses the stroke
volume (SV) as a fraction of the end -d iastolic volum e
(EDV):

EF = S V/ EDV (12.1)

The EF p rovid es a m easu re of card iac contractile


strength d u ring d iastole.
b. The EF is norm al in patients w ith d iastolic heart fail-
u re, and red u ced in p atients w ith systolic heart failu re.
The norm al ejection fraction of each ventricle is show n
below :
Ejection Fraction (EF) N ormal Range
Right Ventricle 0.50-0.55
Left Ventricle 0.40-0.50
c. Card iac u ltrasou nd can be u sed to m easu re EF at
the bed sid e. Transthoracic u ltrasou nd can be used to
measure the EF of the left ventricle (2,3), and trans-
esophageal ultrasound can be used to measure the EF of
178 Disorders of Circulatory Flow

the right ventricle (4). A sp ecialized pu lm onary artery


catheter is also available that can monitor the EF of the
right ventricle (see next section).

C. Right Heart Failure


1. Right heart failu re is m ore com m on than su sp ected in the
ICU (5), bu t it m ay be clinically ap p arent only in the later
stages of illness.

2. Right heart failu re is u sually systolic failu re, and thus is


associated w ith an increased end -d iastolic volu m e and a
d ecreased ejection fraction.

3. The central venou s p ressu re (CVP) is norm al in abou t


one-third of cases of right heart failu re (6). The CVP be-
gins to rise only w hen right ventricu lar d ilatation has
reached a p oint w here it is im p ed ed by the p ericard iu m
(6). This d iffers from left heart failu re, w here the pu lm o-
nary cap illary w ed ge pressure (PCWP) rises early in the
course of illness (see Figu re 12.1).

4. A sp ecialized p u lm onary artery catheter is available that


can m easu re the end -d iastolic volu m e and ejection frac-
tion of the right ventricle (see Reference 7 for a d escrip-
tion of this catheter). Transesop hageal u ltrasou nd can
also be used to m easu re right ventricu lar EF, as m en-
tioned earlier.

II. B-TYPE NATRIURETIC PEPTIDE


Brain-type (B-type) natriuretic pep tid e (BN P) is a horm one
that is released by the ventricu lar m yocard iu m in resp onse
to volu m e and p ressu re overload . Plasm a levels of BN P
increase in d irect relation to increases in ventricular end -
d iastolic volu m e and end -d iastolic pressure (both right-
sid ed and left-sid ed ), and the rise in BN P p rod u ces both
vasod ilation and an increase in renal sod iu m excretion (8).
Acute Heart Failure(s) 179

A. Diagnostic Value
1. In p atients w ho p resent to the em ergency room w ith
d yspnea of unknow n etiology, a plasm a BN P > 100 pico-
grams/ m illiliter (pg/ m L) w ill id entify heart failure al-
most 90% of the time (9).

2. Plasm a BN P levels also show a d irect correlation w ith the


severity of heart failu re (8), w hich m eans that p lasm a
BN P levels m ay be u sefu l for evaluating treatm ent re-
sp onses and selecting end -p oints of m anagem ent.

3. Plasm a BN P levels are also influ enced by gend er, age,


and renal fu nction. The levels are 50% higher in fem ales
than in m ales, and levels in both sexes can trip le in ad -
vanced age (> 75 years) (8). H ow ever, these factors d o not
raise the BN P levels above the 100 pg/ m L threshold for
the d iagnosis of heart failu re.

4. Renal insu fficiency increases p lasma BN P levels becau se


BN P is cleared by the kid neys, and plasm a levels can ex-
ceed the 100 pg/ mL threshold if there is associated vol-
u m e overload (10).

B. Any Role in the ICU?


1. Plasma BNP has been studied primarily in the emergency
room setting. Few studies have been performed in the ICU.

2. It is u nlikely that p lasm a BN P w ill rep lace m ore trad i-


tional m ethod s of evalu ating heart failu re in the ICU, but
BN P levels could prove u seful for m onitoring the re-
sp onse to treatm ent.

III. MANAGEMENT STRATEGIES


The m anagem ent of heart failu re d escribed here is intend ed
only for the ICU environm ent becau se the treatm ents are
180 Disorders of Circulatory Flow

based on invasive hem od ynam ic m easu rements rather than


sym ptom s, and the d ru gs that are u sed are given by contin-
u ou s intravenou s infu sion. Table 12.3 contains a list of the
d ru gs and the recom m end ed d ose rates. (These d rugs are
p resented in m uch m ore d etail in Chap ter 45.)

TABLE 12.3 Drugs Used to Manage Acute Heart Failure


Drug Dose Range Principal Actions
Dobutamine 315 g/kg/min Positive inotropic effect and
systemic vasodilatation
Dopamine 13 g/kg/min Renal vasodilatation and
natriuresis
310 g/kg/min Positive inotropic effect and
systemic vasodilatation
>10 g/kg/min Systemic vasoconstriction
Milrinone 50 g/kg bolus, then Positive inotropic effect and
0.25 1 g/kg/min lusitropic effect, and
systemic vasodilatation
Nitroglycerin 150 g/min Venous vasodilatation
>50 g/min Arterial vasodilatation
Nitroprusside 0.32 g/kg/min Systemic vasodilatation

A. Left-Sided Systolic Heart Failure


Contractile failu re involving the left ventricle is the proto-
type m od el of heart failu re, and the one for w hich m ost treat-
ments are d esigned . The treatm ents d escribed here are for
d ecom pensated heart failu re, w hich corresp ond s to the p oint
on the low er cu rve in Figu re 12.3. The goal of therap y is to
move the point to the left and u pw ard (as ind icated by the
arrow ). The treatm ents are organized accord ing to the cond i-
tion of the p atients blood p ressu re (i.e., high, norm al, or
low ).
Acute Heart Failure(s) 181

Inotrope s
3 Norma l or
Va s odila tors

Diure s is
x
2
e
)
P ulmona ry
d
2
m
n
I
Ede ma
/
n
c
i
a
m
i
d
/
L
r
a
(
1 Optima l
C
He a rt
Filling
Fa ilure
P re s s ure

0
0 10 20 30

P ulmona ry Ca pilla ry We dge P re s s ure (mm Hg)

FIGURE 12.3. Cardiac performance curves for the normal and failing left
ventricle. The point on the lower curve represents decompensated heart
failure.

1. High Blood Pressure


Decom p ensated heart failu re w ith elevated blood p res-
su re is a fam iliar cond ition in the early p eriod after car-
d iopu lm onary bypass surgery.
Profile: H igh PCWP/ Low CO/ H igh BP
Treatment: Vasod ilator therap y w ith nitropru ssid e or ni-
troglycerin. If the PCWP remains above 20 mm
H g, ad d d iuretic therap y w ith fu rosem id e.
a. Vasod ilator d rugs like nitropru ssid e and nitroglycerin
w ill d ilate both arteries and veins, and the overall ef-
fect w ill be a red u ction in blood p ressu re, an increase
in card iac ou tp ut, and a d ecrease in the w ed ge p res-
su re (11).
b. N itroprussid e is a m ore effective vasod ilator than ni-
troglycerin, bu t d ru g safety is a concern. The m ajor
p roblem w ith nitrop ru ssid e is cyanide toxicity, w hich is
182 Disorders of Circulatory Flow

d escribed in Chap ter 45. N itroprussid e is also not ad -


vised in patients w ith ischemic heart d isease because
the d rug can prod uce a coronary steal synd rome (12).
c. N itroglycerin is a safer alternative to nitrop ru ssid e.
Low infu sion rates (< 50 g/ m in) w ill d ilate veins se-
lectively (w hich can red u ce card iac outpu t fu rther),
and d ose rates in excess of 50 g/ m in are u su ally re-
qu ired to prod u ce effective arterial vasod ilation. The
major d raw back w ith nitroglycerin infusions is the d e-
velopm ent of tolerance, w hich can ap p ear after 16 to
24 hou rs (12).
d . Diu retic therapy w ith furosem id e is ind icated only if
vasod ilator therap y d oes not red u ce the w ed ge p res-
su re below 20 m m H g. (The effects of d iu retic therap y
are d escribed later in the chap ter).
e. The w ed ge p ressu re shou ld be kep t ju st u nd er 20 m m
H g becau se this is the highest pressu re that w ill au g-
ment card iac output w ithou t prod u cing pulm onary e-
d em a. This is show n in Figu re 12.3 as the highest p oint
on the low er cu rve that d oes not enter the hatched
(p u lm onary ed em a) region.

2. Normal Blood Pressure


This is the u su al p resentation of heart failu re cau sed by
non-hyp ertensive heart d isease (e.g., ischem ic heart d is-
ease).
Profile: H igh PCWP/ Low CO/ N orm al BP
Treatment: Inodilator therapy with dobutamine or milri-
none, or vasod ilator therapy w ith nitroglyc-
erin. If the PCWP d oes not d rop below <20
mm Hg, add diuretic therapy w ith furosemide.
a. Dobu tam ine and m ilrinone are called inodilators be-
cau se they have both p ositive inotrop ic and vasod ila-
tor actions (13,14). Dobu tam ine is a -recep tor agonist,
w hile m ilrinone is a p hosp hod iesterase inhibitor. Both
d ru gs au gm ent card iac ou tp u t and red u ce ventricu lar
Acute Heart Failure(s) 183

filling pressures. Blood pressure is u su ally unaffected


in the u sual d oses, bu t d obu tam ine can increase blood
p ressu re, and m ilrinone can p rom ote hyp otension.
b. Because d obutam ine can increase m yocard ial oxygen
(becau se of its p ositive inotrop ic actions), vasod ilator
therapy (e.g., nitroglycerin) has been recom m end ed as
a safer alternative to d obu tam ine in p atients w ith is-
chem ic heart d isease (13,14).
c. Milrinone is p referred to d obu tam ine in p atients re-
ceiving -blocker d ru gs becau se its efficacy is ind e-
p end ent of -recep tors.
d . Diu retic therap y has the sam e role in this situ ation as
it d id for hypertensive heart failu re: i.e., it is reserved
for cases w here the w ed ge p ressu re rem ains above 20
mm H g d espite inod ilator or vasod ilator therapy.

3. Low Blood Pressure


Decom p ensated heart failu re accom p anied by hyp oten-
sion is the sine qua non of card iogenic shock., and requires
p rom p t intervention.
Profile: H igh PCWP/ Low CO/ Low BP
Treatment: Dopam ine in vasoconstrictor d oses. Consider
a mechanical assist device in patients with coro-
nary artery disease and a correctable lesion.
a. H em od ynam ic d ru gs are notoriou sly u nsu ccessfu l in
card iogenic shock, and the m ortality rate continu es to
be is as high as 80% (15).
b. Increasing blood pressure (to a m ean pressu re of
60 m m H g) is a p riority, and d op am ine is a p op u lar
choice becau se it acts as a vasop ressor in high d oses
(> 10 g/ kg/ m in) and retains som e p ositive inotrop ic
actions associated w ith low er d oses (5 t o 10 g/ kg
/ min) (12-14). H ow ever, low card iac ou tp u t states are
accomp anied by system ic vasoconstriction, and vaso-
p ressor d rugs can further aggravate tissu e hypoperfu -
sion.
184 Disorders of Circulatory Flow

c. Mechanical card iac su p p ort is ind icated if m yocard ial


fu nction is expected to imp rove spontaneously (as oc-
cu rs in the early period follow ing card iopulm onary
byp ass surgery), or w hen a corrective p roced u re (e.g.,
angiop lasty) is planned . A d escrip tion of the su p p ort
d evices is beyond the scope of this text.

4. Limited Role for Diuretics


a. Diu retics shou ld be u sed cau tiou sly in acu te heart fail-
u re because intravenous furosemide can cause a 15 to 20%
drop in cardiac output in this situation (16,17). The ex-
p ected effect of d iu resis in d ecom p ensated heart fail-
u re is show n by the arrow in Figu re 12.3.
b. Dru gs that au gm ent card iac ou tp u t shou ld alw ays be
given p riority over d iu retics in acute heart failu re. In
fact, if card iac outp u t can be restored , the stimu lu s to
retain salt and w ater w ill be elim inated , and d iu retics
w ill not be necessary.

5. Furosemide by Continuous Infusion


a. Critically ill p atients can have an attenu ated resp onse
to furosem id e (18), p ossibly as a resu lt of red u ced
transp ort p roteins and chlorid e d ep letion (fu rosem id e
acts by inhibiting chlorid e reabsorp tion in the Loop of
H enle).
b. Becau se the d iu retic effect of furosem id e is closely re-
lated to its u rinary excretion rate (19), continu ous in-
fu sion of the d ru g w ill prod u ce a m ore vigorous d i-
u resis than bolu s injection.
c. INDICATION. Continu ou s fu rosem id e infu sion shou ld
be consid ered w hen an 80 mg IV bolu s d ose of furo-
sem id e fails to p rod u ce m ore than 2 liters of u rine ou t-
p ut in the ensu ing fou r hou rs.
d . DOSAGE. Start w ith 100 m g fu rosemid e as an IV bolus,
and im m ed iately follow w ith a continu ou s infu sion of
fu rosemid e at 40 m g/ hr. Dou ble the d ose rate every 12
Acute Heart Failure(s) 185

hours if need ed to achieve a u rine outpu t of at least


100 m L/ h. The d ose rate shou ld not exceed 170 m g/ hr
(20).

6. Nesiritide
a. N esiritid e (N atrecor) is a recom binant hu man B-typ e
natriu retic peptid e that acts as a system ic vasod ilator
to au gm ent card iac ou tp u t.
b. DOSAGE. Give initial bolu s of 2 g/ kg and follow w ith
a continu ou s infu sion at 0.01 g/ kg/ min. This d ose
rate can be increased 0.01 g/ kg/ m in every 3 hou rs to
a m axim u m d ose of 0.03 g/ kg/ m in (21).
c. Clinical stu d ies show that nesiritid e offers no ad van-
tage over trad itional vasod ilators su ch as nitroglycerin
(21). In fact, there is a rep ort of increased short-term
(30 d ay) m ortality attribu ted to nesiritid e (22), w hich
p rom p ted an FDA safety alert abou t the d ru g.

B. Left-Sided Diastolic Heart Failure


The p revalence of d iastolic d ysfu nction in acu te heart failu re
is not know n, but heart failu re associated w ith left ventricu -
lar hypertrophy or acute myocard ial ischem ia is probably
d iastolic failure. There is no general agreem ent abou t the op-
timal treatm ent of d iastolic heart failu re (3), bu t the follow -
ing recom m end ations seem valid .

1. Becau se systolic fu nction is norm al or only m ild ly im -


p aired in d iastolic heart failure, positive inotropic agents
have no role in the treatment of diastolic heart failure.

2. Becau se ventricu lar filling is im p aired in d iastolic heart


failu re, diuretic therapy is counterproductive in diastolic heart
failure.

3. Vasod ilator therapy is ap p ropriate for d iastolic failu re re-


su lting from hyp ertension-ind u ced left ventricu lar hy-
186 Disorders of Circulatory Flow

p ertrop hy. Som e vasod ilator agents, su ch as nitroglycerin


and m ilrinone, can p romote ventricular relaxation d ur-
ing d iastole (3,14), and these lusitropic effects are w ell-su it-
ed for d iastolic heart failu re.

C. Right Heart Failure


The therap eu tic strategies below are m eant for cases of p ri-
mary right heart failu re and not for patients w ith right heart
failu re second ary to lu ng d isease. The pu lmonary cap illary
w ed ge pressure (PCWP) and right ventricular end -d iastolic
volume (RVEDV) are used as the focal points of management.
(The RVEDV can be measured w ith a specialized PA catheter
as d escribed p reviou sly).

1. If PCWP is below 15 mm Hg, infuse volume until the PCWP


or CVP increases by 5 mm Hg or either one reaches 20 mm
Hg (6).

2. If the RVEDV is less than 140 m L/ m 2, infu se volu m e u n-


til the RVEDV reaches 140 mL/ m 2 (23).

3. If PCWP is above 15 m m H g or the RVEDV is 140 m L/ m 2


or higher, infu se d obutam ine, beginning at a rate of 5
g/ kg/ m inu te (24,25).

4. In the presence of AV dissociation or complete heart block,


institute sequential A-V pacing and avoid ventricular pacing
(3).
The response to volum e infu sion m ust be carefu lly m oni-
tored in right heart failure becau se excessive volu m e can
overd istend the right ventricle, cau sing the interventricu lar
septum to bu lge into the left ventricular cavity and im pair
left ventricu lar filling. This p rocess w hereby the right ventri-
cle can influ ence the fu nction of the left ventricle is called
interventricu lar interd ep end ence.
Acute Heart Failure(s) 187

REFERENCES
1. N iem inen MS, H arjola V-P. Definition and etiology of acute heart
failu re synd rom es. Am J Card iol 2005; 96(Su p pl):5G-10G.
2. Zile MR, Baicu CF, Gaasch WH . Diastolic heart failu re. Abnor-
m alities in active relaxation and p assive stiffness of the left ven-
tricle. N Engl J Med 2004; 350:1953-1959.
3. Aurigem m a GP, Gaasch WH . Diastolic heart failu re. N Engl J
Med 2004; 351:1097-1015.
4. Numi Y, Haki M, Ishiguro Y, et al. Determination of right ventricu-
lar function by transesophageal echocardiography: Impact of proxi-
mal right coronary artery stenosis. J Clin Anesthesia 2004; 16:104-110.
5. H u rford WE, Zapol WM. The right ventricle and critical illness:
a review of anatom y, p hysiology, and clinical evalu ation of its
fu nction. Intensive Care Med 1988; 14:448457.
6. Isner JM. Right ventricu lar m yocard ial infarction. JAMA 1988;
259:712718.
7. Vincent JL, Thirion M, Brim iou lle S, et al. Therm od ilu tion m eas-
u rem ent of right ventricu lar ejection fraction w ith a m od ified
p ulm onary artery catheter. Intensive Care Med 1986; 12:33-38.
8. Maisel AS, Wanner EC. Measu ring BN P levels in the d iagnosis
and treatm ent of CH F. J Crit Illness 2002; 17:434-442.
9. Maisel AS, Krishnasw am y P, N om ak RM, et al. Rap id m easure-
m ent of B-type natriuretic peptid e in the em ergency d iagnosis of
heart failure. N Engl J Med 2002; 347:161-167.
10. Takam i Y, H orio T, Iw ashim a Y, et al. Diagnostic and p rognostic
valu e of p lasm a bran natriu retic p ep tid e in non-d ialysis-d ep end -
ent CRF. Am J Kid ney Dis 2004; 44:420-428.
11. Stough WG, OConnor CM, Gheorghiad e M. Overview of cu r-
rent noninod ilator therap ies for acu te heart failu re synd rom es.
Am J Card iol 2005; 96(Su p pl):41G-46G.
12. The Task Force on Acu te H eart failu re of the European Society
of Card iology. Gu id elines on the d iagnosis and treatm ent of
heart failure. Eu ropean Society of Card iology Web Site. Available
at w w w.escard io.org.
13. Bayram M, De Luca L, Massie B, Gheorghiade M. Reassessment of
dobutamine, dopamine, and milrinone in the management of acute
heart failure synd romes. Am J Cardiol 2005; 96(Suppl): 47G-58G.
188 Disorders of Circulatory Flow

14. Chatterjee K, De Marco T. Role of nonglycosidic inotropic agents:


indications, ethics, and limitations. Med Clin N Am 2003; 87:391-418.
15. Sam uels LE, Darze ES. Managem ent of acute card iogenic shock.
Card iol Clin 2003; 21:43-49.
16. Kiely J, Kelly DT, Taylor DR, Pitt B. The role of fu rosem id e in the
treatm ent of left ventricular d ysfu nction associated w ith acute
m yocard ial infarction. Circu lation 1973; 58:581587.
17. Mond H , H u nt D, Slom an G. H aem od ynam ic effects of fru se-
m id e in p atients su sp ected of having acu te m yocard ial infarc-
tion. Br H eart J 1974; 36:4453.
18. Brater DC. Resistance to loop d iu retics: w hy it hap pens and w hat
to d o about it. Dru gs 1985; 30:427-443.
19. van Meyel JJM, Smits P, Russell FGM, et al. Diu retic efficiency of
fu rosemid e d u ring continu ous ad ministration versus bolus injec-
tion in healthy volunteers. Clin Pharm acol Ther 1992; 51:440444.
20. H ow ard PA, Du nn MI. Aggressive d iu resis for severe heart fail-
u re in the eld erly. Chest 2001; 119:807-810.
21. Vasod ilation in the Managem ent of Acute CH F (VMAC) Inves-
tigators. Intravenous nesiritid e vs nitroglycerin for treatm ent of
d ecom p ensated congestive heart failure. JAMA 2002; 287:1531-
1540.
22. Sackner-Bernstein JD, Kow alski M, Fox M, Aaronson K. Short-
term risk of d eath after treatm ent w ith nesiritid e for d ecom pen-
sated heart Failure. JAMA 2005; 293:1900-1905.
23. Reuse C, Vincent JL, Pinsky MR. Measu rem ent of right ventricu -
lar volu m es d u ring flu id challenge. Chest 1990; 98:1450-1454.
24. Vincent RL, Reu se C, Kahn RJ. Effects on right ventricular fu nc-
tion of a change from d op am ine to d obu tam ine in critically ill
p atients. Crit Care Med 1988; 16:659662.
25. DellItalia LJ, Starling MR, Blu m hard t R, et al. Com p arative ef-
fects of volum e load ing, d obu tam ine and nitropru ssid e in p a-
tients w ith p red om inant right ventricu lar infarction. Circu lation
1986; 72:13271335.
Chapter 13
CARDIAC ARREST
Card iac arrest is m anaged w ith a variety of interventions
know n in total as cardiopulmonary resuscitation or CPR. Since
few er than 10% of card iac arrest victim s survive the experi-
ence (1), CPR can hard ly be called effective, yet it is u niver-
sally em braced as a stand ard of care. This chap ter p resents
the essential featu res of CPR as d escribed in the m ost recent
guid elines on the subject (2).

I. BASIC LIFE SUPPORT


Basic life support involves 3 d irectives: establish and maintain
patency of the upper airw ays, provid e ventilation through
periodic lung inflations, and promote circulation w ith chest
compressions (3).

A. Airway Patency
1. Airw ay patency is a concern for all u nconscious p atients.

2. The orop haryngeal airw ay, an S-shaped d evice that is


p assed over the tongu e and into the p harynx, is easily
p laced and can p revent a flaccid tongu e from occlu d ing
the orop harynx.

3. Translaryngeal intu bation shou ld be the p referred meth-


od for m aintaining airw ay p atency in the hosp ital set-
ting, w here trained personnel are available.

B.Ventilation
1. Ventilation in BLS m eans p eriod ic lu ng inflations w ith
self-inflating ventilating bags that are attached to a
face m ask or end otracheal tu be.
189
190 Disorders of Circulatory Flow

2. The recom m end ed rate of lu ng inflations is 8 to 10 per


minute, and it is not necessary to d eliver the inflations
betw een chest com pressions.

3. The inflation volu m es shou ld be ju st enou gh to p rod u ce


a rise in the chest w all, and the inflation tim e shou ld not
exceed one second to allow tim e for the lungs to em pty.

4. Excessive Ventilation
a. There is a tend ency to overventilate p atients d u ring
CPR, w hich can be cou nterp rod u ctive. In one su rvey
of CPR techniqu es, the rate of lu ng inflations w as
20/ min (d ouble the recom m end ed rate) in 60% of the
resu scitations (4).
b. The p roblem w ith rap id breathing and large inflation
volu m es is the inability of the lu ngs to fu lly em p ty
d u ring exhalation. The retained air creates a p ositive
end -expiratory pressure (called intrinsic PEEP), and
this p ressu re can red u ce card iac ou tp u t by im p ed ing
venou s retu rn and restricting ventricu lar d istension
d u ring d iastole. This w ill only ad d to the high m ortal-
ity in this situation (5).
c. To avoid excessive ventilation d u ring CPR, it is im per-
ative to keep the rate of lu ng inflations at 8 10/ m in-
u te. Inflation volu m es can be red u ced by u sing one
hand to com press the ventilating bag. The cap acity of
these bags is abou t 1,600 m L, w hich is abou t three
tim es greater than the tid al volu m e of an average-
sized ad u lt (abou t 7 m L/ kg, or 500 m L in a 70 kg
su bject). One-hand ed com p ression w ill exp el a volum e
of about 800 m L, w hich is closer to the norm al tid al
volu m e than com p letely em p tying the bag w ith tw o-
hand ed comp ression.

C. Chest Compressions
1. Chest com p ressions shou ld be d elivered over the m id -
Cardiac Arrest 191

sternu m w ith the elbow s locked and the arm s straight.


Each com p ression is a thru st d elivered throu gh the heel
of the hand s (one on top of the other) to d ep ress the ster-
nu m 1.5 to 2 inches. When the com p ression is released ,
the sternu m shou ld be allow ed to recoil com p letely be-
fore the next com pression.

2. The rate of chest com pressions shou ld be at least 100 per


minute, and a com p ression-ventilation ratio of 30:2 is rec-
om m end ed (3).

3. It is im portant to avoid u nnecessary interru ptions in


chest com p ressions. One su rvey of CPR revealed that in-
terru p tions in chest com p ressions accou nted for one-
qu arter of the total resu scitation tim e (4).

II. ADVANCED LIFE SUPPORT


Ad vanced life supp ort (also called ad vanced card iac life
su p p ort or ACLS) inclu d es m easu res for ventilatory su p p ort
(intu bation and m echanical ventilation), hem od ynam ic su p -
p ort (d ru gs) and card iac rhythm su p port (d efibrillation).
This section d escribes the u se of these su p p ort m easu res in
the m anagem ent of pu lseless card iac arrest. This inform ation
is inclu d ed in the flow d iagram s in Figu re 13.1 and 13.2.

A. Defibrillation
Direct-cu rrent (DC) card ioversion is the treatm ent of choice
for ventricu lar tachycard ia (V-Tach) and ventricu lar fibrilla-
tion (V-Fib), and it is the only treatment m od ality that has
had an im p act on su rvival from card iac arrest.

1. Timing
a. The su rvival benefit of electrical card ioversion is a
fu nction of the tim e elapsed from onset of card iac ar-
192 Disorders of Circulatory Flow

V-TACH/V-FIB
1 Give 1 s ho ck:
Monopha s ic: 360 joule s
AED: device -s pe cific
Bipha s ic: device -s pe cific or 200 joule s
Re s ume CPR im m e d ia te ly afte r s ho ck.

No
2 Che ck rhythm: is it s ho ckable ?

{ {
Ye s
If puls e le s s,
go to
Re pe at Box 1
Box 1A in
Figure 13.2

If IV/IO ava ila ble, give va s opre s s or during CP R (be fore or a fte r
the s hock):
Epine phrine : 1 mg IV/IO, a nd re pe a t eve ry 3 5 min if ne e de d
Vas o pre s s in: May give one dos e (40 Units IV/IO) to re pla ce
firs t or s e cond dos e of e pine phrine.

No
Che ck rhythm: is it s ho ckable ?

{ {
Ye s
If puls e le s s,
Re pe at Box 1 go to
Box 1A in
Figure 13.2

Cons ide r a ntia rrhythmics during CP R (be fore or a fte r the s hock):
Amio daro ne : 300 mg IV/IO a nd cons ide r a nothe r 150 mg
OR
Lido c aine : 1 1.5 mg/kg IV/IO, the n 0.5 0.75 mg/kg if ne e de d
(ma x dos e = 3 mg/kg). Us e only a s a s e cond-line a ge nt.
OR
Mag ne s ium: 1 2 gra ms IV/IO for tors a de s de pointe s

FIGURE 13.1. Flow diagram for the management of pulseless cardiac


arrest due to ventricular tachycardia (V-Tach) and ventricular fibrillation
(V-Fib). Adapted from Reference 8.
Cardiac Arrest 193

AS YS TOLE / PEA
1A Whe n IV/IO ava ila ble, give va s opre s s or during CP R:
Epine phrine : 1 mg IV/IO, a nd re pe a t eve ry 3 5 min if ne e de d.
Vas o pre s s in: May give one dos e (40 Units IV/IO) to
re pla ce firs t or s e cond dos e of e pine phrine.
Cons ide r Atro pine (1 mg IV/IO) for a s ys tole or s low P EA ra te.
Re pe a t eve ry 3 5 min if ne e de d to a tota l of 3 dos e s.

No
Che ck rhythm: is it s ho ckable ?

Ye s { Re pe a t Box 1A
{
if s till puls e le s s

Give 1 s ho ck:
Monopha s ic: 360 joule s
AED: device -s pe cific
Bipha s ic: device -s pe cific or 200 joule s
Re s ume CPR im m e d ia te ly afte r s ho ck.

{ Go to Box 2
in Figure 13.1 {
FIGURE 13.2. Flow diagram for the management of cardiac arrest due to
asystole or pulseless electrical activity (PEA). Adapted from Reference 8.

rest to the first electric shock (6,7). This is d em onstrat-


ed in Figu re 13.3. N ote that 40% of p atients su rvived
w hen the first shock w as d elivered 5 m inu tes after the
arrest, w hile only 10% of p atients su rvived if d efibril-
lation w as d elayed for 20 m inutes.
b. For out-of-hosp ital card iac arrests w hen the response
time exceed s 5 m inu tes, a brief p eriod of CPR (1.5 to 3
minu tes) is recomm end ed prior to the initial cou nter-
shock. This recom m end ation is based on evid ence that
chest com pressions can enhance the response to elec-
trical card ioversion (1).
194 Disorders of Circulatory Flow

2. Technical Considerations
The effectiveness of electric cou ntershocks d ep end s on
the typ e of w aveform d elivered . N ew er d efibrillators d e-
liver biphasic shocks, w hich are effective at low er energy
levels than the m onophasic shocks u sed by old er d efibril-
lators.
a. The recom m end ed energy level for the first shock is
200 jou les for bip hasic shocks (u nless otherw ise speci-
fied by the d efibrillator m anu factu rer) and 360 jou les
for m onop hasic shocks (11).
b. If the first shock is ineffective, tw o ad d itional shocks
can be attem p ted (d ont forget to p erform CPR be-
tw een successive shocks). There is no evid ence that in-
creasing the energy levels in su ccessive shocks is m ore
effective than m aintaining the energy level of the ini-
tial shock.

50
N = 1,667

40
)
%
30
(
s
r
o
v
vi
r
20
u
S
10

0
5 10 15 20
Time to De fibrilla tion (min)

FIGURE13.3. The relationship between survival rate and time to defibril-


lation in patients with ventricular fibrillation. N = number of subjects
studied. (From Reference 7).
Cardiac Arrest 195

3. Automated External Defibrillators


Autom ated external d efibrillators (AEDs) are d esigned
to operate w ith m inim al hu m an inp u t (6).
a. The AED has 2 electrod e p ad s: one is placed on the
right anterior chest w all, and the other is p laced on the
left lateral chest w all.
b. Sensors in the pad s act like precord ial lead s to record
the card iac rhythm . The AED analyzes the rhythm and
then d isplays a prom pt ind icating if d efibrillation is
ap p ropriate. The op erator d oes not see the card iac
rhythm. If d efibrillation is ind icated , the op erator sim -
p ly presses a bu tton to d eliver the shock. The m achine
au tom atically selects the strength of the p u lse.
c. After the shock is d elivered , the m achine w ill again
analyze the card iac rhythm and d eterm ine if a second
shock is necessary. This sequence can continu e until
three shocks are d elivered .
d . AEDs have been u sed p rim arily for card iac arrests that
occu r ou tsid e the hosp ital, bu t they are also available
in m ost hosp itals as w ell. The ability to d eliver rap id
DC card ioversion w ithout introd ucing hum an error
shou ld m ake AEDs pop u lar in all settings.

B. Routes of Drug Administration


1. Intravenous Route
a. The intravenou s rou te is p referred for d ru g d elivery
d u ring CPR, and peripheral veins are preferred to central
veins because cannu lation of perip heral veins d oes not
requ ire interru p tion of CPR (8).
b. Drugs given via peripheral veins should alw ays be in-
jected as a bolus, follow ed by a 20 mL bolus of an intra-
venous fluid (8). The extremity should be elevated for
10 to 20 second s to facilitate d rug d elivery to the heart.
c. If the initial d ru g injection is u nsu ccessfu l, central
venou s cannulation can be perform ed for su bsequent
196 Disorders of Circulatory Flow

d ru g ad m inistration. This latter m aneu ver red u ces the


transit tim e for d ru gs to reach the heart by 1 to 2 m in-
u tes (8).
2. Alternate Routes
a. When venou s access is not read ily available, d ru gs can
be d elivered by p u nctu ring a m arrow cavity (u su ally
in the sternum ) or injecting the d rug into the u pper
airw ays.
b. The intraosseous (IO) route is preferred to the airway route
becau se d rug absorp tion from the airw ays is erratic
(8). H ow ever, the airw ays rou te continu es to be a p op-
u lar alternative in ad u lts.
3. The Endotracheal Route
a. The d ru gs that can be given via the end otracheal rou te
are atropine, epinep hrine, vasop ressin, and lid ocaine.
b. The end otracheal d ose of each d ru g should be 2 to 2.5
times the recom m end ed intravenou s d ose (8).
c. All d ru gs injected into the airw ays shou ld be d ilu ted
in 5 to 10 m L of w ater or isotonic saline. Water m ay be
the p referred d ilu ent becau se of enhanced d ru g ab-
sorption (8).

C. Vasopressor Drugs
Vasopressor d rugs are recom m end ed for m ost cases of p ulse-
less card iac arrest (see Figu res 13.1 and 13.2).

1. Epinephrine
a. Ep inep hrine, w hich is a -recep tor agonist in low d o-
ses and an -receptor agonist in high d oses, is the tra-
d itional vasop ressor u sed in card iac arrest.
b. The recom m end ed d ose is 1 m g (10 m L of a 1:10,000
solu tion) as a bolus injection (IV/ IO), rep eated every 3
to 5 m inu tes if necessary (see Table 13.1).
c. End otracheal ep inephrine (u su al d ose is 2 to 2.5 m g)
is not ad vised because poor absorption can result in
Cardiac Arrest 197

p rom inent -recep tor stim u lation and u nw anted car-


d iac stimu lation (8).

2. Vasopressin
a. Vasop ressin is a nonad renergic vasoconstrictor that
can be u sed in a single bolu s d ose of 40 Units (IV/ IO)
to rep lace the first or second d ose of ep inep hrine.

TABLE 13.1 Cardiopulmonary Resuscitation Drugs


Drug Dosage (IV or IO) Indications
Vasopressors
Epinephrine 1 mg first dose and Asystole, PEA, and shock-
repeat every 35 min resistant V-Fib or V-Tach
if needed
Vasopressin 40 U as a single dose Can replace the first or
2nd dose of epinephrine
Antiarrhythmic Agents
Amiodarone 300 mg first dose, V-Fib or V-Tach that is
then 150 mg once refractory to defibrillation
if needed and vasopressors
Lidocaine 11.5 mg/kg first dose, Alternative to amiodarone
then 0.5 0.75 mg/kg
to a total of 3 doses
or 3 mg/kg
Magnesium 12 g over 5 minutes Torsades de pointes
associated with a
prolonged QT interval
Atropine 1 mg first dose and Bradyarrhythmias, or as
repeat every 35 min an adjunct to vasopressors
if needed to a total for asystole and slow-rate
of 3 doses PEA

From Reference 8.
Abbreviations : IV = intravenous , V-Fib = ventricular fibrillation,
V-Tach = ventricular tachycardia, PEA = puls eles s electrical activity.
198 Disorders of Circulatory Flow

b. The u se of vasopressin has tw o p otential benefits: (1)


vasopressin acts as a cerebral vasod ilator, and (2) there
is no risk of unw anted card iac stim u lation from epi-
nep hrine. The d isad vantage of vasopressin is its ac-
tions as a coronary artery vasoconstrictor (8).
c. Several clinical trials have show n no survival benefit
when vasopressin is substituted for epinephrine (9).

D. Antiarrhythmic Agents
1. Amiodarone
a. Am iod arone is recom m end ed for cases of V-Fib and
p ulseless V-Tach that are refractory to d efibrillation
and vasopressor d ru gs (8,10).
b. The initial d ose is 300 m g (IV/ IO), follow ed by a sec-
ond d ose of 150 m g if need ed .
c. Amiod arone can p rod uce hyp otension and brad ycar-
d ia (10), bu t these effects have been m inim ized by a
new aqu eou s form u lation that d oes not contain vaso-
active solvents (8).

2. Lidocaine
a. Lid ocaine has been the trad itional antiarrhythmic a-
gent u sed for shock-resistant V-Fib and V-Tach. H ow -
ever, becau se am iod arone seem s to prod u ce better re-
su lts for short-term su rvival (11), lid ocaine is now re-
com m end ed only as a second -line agent (8).
b. The recom mend ed d osage of lid ocaine is 11.5 m g/ kg
(IV/ IO) initially, then 0.5 0.75 m g/ kg every 5 to
10 m inu tes if need ed to a m axim u m of 3 d oses or
3 m g/ kg.

3. Magnesium
a. Intravenous magnesium is effective in terminating poly-
morphic V-Tach (also called torsades de pointes) asso-
ciated with a prolonged QT interval (see Chapter 15).
Cardiac Arrest 199

b. The recom m end ed d ose of m agnesiu m is 12 gram s


(IV/ IO) infu sed over 5 m inu tes (8).

4. Atropine
a. Atrop ine is an anticholinergic agent that is recom -
mend ed as an ad ju nct to vasopressor therapy for car-
d iac arrest associated w ith asystole or slow -rate p u lse-
less electrical activity (see Figu re 13.2). The recom -
mend ed d ose is 1 m g (IV/ IO), w hich can be rep eated
every 3 to 5 m inu tes to a total d ose of 3 m g (the d ose
that p rod u ces com plete vagal blockad e) (8).

III. MONITORING DURING CPR


The goal of the resu scitation effort is to restore circu latory
flow. Since it is not p ossible to d irectly m easu re blood flow
(global or regional) d u ring CPR, ind irect or su rrogate m eas-
u res of blood flow are u sed . These m easu rem ents, w hich are
d escribed below, are lim ited and som etimes m islead ing.

A. Arterial Pulse and Pressure


Despite their popu larity, the arterial pu lse and p ressure are
not reliable m arkers of circu latory blood flow. This is d em -
onstrated in Figu re 13.4, w hich show s the effect of chest
com pressions on the arterial pressure and central venou s
p ressu re in a patient w ith asystole. If the arterial blood p res-
sure is consid ered in isolation, the size of the p ressu re pu lse
(50 m m H g) w ou ld be interp reted as ind icating that the chest
com pressions are successful in prom oting systemic blood
flow. H ow ever, the central venou s p ressu re is rou ghly the
sam e m agnitu d e as the arterial p ressu re, ind icating that there
is no pressure gradient for systemic blood flow. Therefore, the
arterial p ressu re in this case is u nlikely to be associated w ith
a significant rate of blood flow.
200 Disorders of Circulatory Flow

FIGURE13.4. The influence of chest compressions on arterial and central


venous pressure tracings in a patient with asystolic cardiac arrest. Al-
though there is a systolic pressure of 50 mm Hg, the central venous pres-
sure is equivalent, so there is no pressure gradient to drive systemic
blood flow.

1. Mean Arterial Pressure


Desp ite the fact that blood p ressu re is an u nreliable
marker of blood flow d u ring CPR, a p opu lar goal of re-
su scitation is a m ean arterial p ressu re of 60 mm H g,
w hich is consid ered the m inim u m p ressu re need ed for
ad equ ate cerebral blood flow.

2. Coronary Perfusion Pressure


a. The p ressu re grad ient that d rives coronary blood flow,
w hich is called the coronary perfusion pressure (CPP) is
the d ifference betw een the aortic d iastolic p ressu re
and the right-atrial p ressu re.
b. Clinical stu d ies have show n that a CPP 15 m m H g
d u ring CPR is associated w ith a su ccessfu l ou tcom e
(12,13).
c. When CPR is p erform ed on a patient w ith ind w elling
arterial and central venou s catheters, the CPP can be
Cardiac Arrest 201

estim ated by using the p eripheral arterial d iastolic


p ressu re as a su bstitu te for the aortic d iastolic p res-
su re.

B. End-Tidal PCO2
The excretion of carbon d ioxid e in exhaled gas is a d irect
fu nction of pu lm onary blood flow, and the p artial p ressu re
of CO 2 in end -expiratory gas (the end -tid al PCO 2) can be
used as an ind irect ind icator of card iac ou tp u t d u ring CPR
(16,18-20). The end -tid al PCO 2 is easily m easu red at the bed -
sid e w ith infrared sensing d evices called cap nom eters that
are connected to an artificial airw ay (i.e., a tracheal tu be).
a. An increase in end -tid al PCO 2 d u ring CPR is an ind i-
cation that the resuscitation effort is su ccessfu l in pro-
moting card iac ou tpu t.
b. Clinical stud ies have show n that an increase in end -
tid al PCO 2 d u ring CPR is p red ictive of a su ccessfu l

30
S urvivors
(N = 16)
20
End-Tida l
P co 2
(mm Hg)
Nons urvivors
10
(N = 74)

0
Initia l Afte r 20 min

FIGURE 13.5. Changes in end-tidal PCO 2 during CPR in survivors and


nonsurvivors of cardiac arrest due to pulseless electrical activity. Data
points represent the mean end-tidal PCO 2 for each group. (From
Reference 15).
202 Disorders of Circulatory Flow

outcom e (12,14,15). This is d em onstrated in Figu re


13.5. N ote that the end -tid al PCO 2 increased (from 12
to 31 m m H g) after 20 m inu tes of CPR in the su rvivors,
w hile the end -tid al PCO 2 d ecreased d u ring CPR in
nonsu rvivors.
c. A threshold of 10 m m H g for end -tid al PCO 2 can be
u sed to p red ict ou tcom e: i.e., when end-tidal PCO2 does
not rise above 10 mm Hg during CPR, the resuscitative ef-
fort is unlikely to be successful.

C.Venous Blood Gases


During CPR, arterial blood gas analysis often reveals a respi-
ratory alkalosis (ind icating op erator-ind u ced hyp erventila-
tion), w hile venou s blood gas analysis often reveals a m eta-
bolic acid osis (ind icating system ic hyp op erfu sion) (16,17).
Therefore, venous blood gas analysis is m ore ap p rop riate for
evaluating tissu e p erfusion d u ring CPR.

IV. POST-RESUSCITATION CONCERNS


The im m ed iate goal of CPR is to restore sp ontaneou s circu -
lation, bu t this d oes not ensu re a satisfactory recovery. This
section d escribes som e concerns in the p ost-resu scitation
managem ent that w ill help to optim ize the recovery from
card iac arrest.

A. Fever Suppression
1. Anim al stu d ies show that ischem ic brain inju ry is aggra-
vated by increased bod y tem p eratu re (18), and clinical
stu d ies show that increased bod y tem p eratu re after CPR
is associated w ith an u nfavorable neurologic ou tcom e
(19). These stud ies su ggest that it is w ise to avoid in-
creased bod y temp eratu re follow ing card iac arrest.

2. Acetam inophen (1015 m g/ kg p er d ose, 3 to 4 tim es a


d ay) can be u sed for antip yresis. This d ru g m u st be given
Cardiac Arrest 203

enterally, and shou ld not be given to p atients w ith hepat-


ic d ysfu nction.

3. Cooling blankets are problematic becau se they can in-


d uce shivering (w hich increases bod y temperature) and
can provoke vasospasm in d iseased coronary arteries (20).

TABLE 13.2 Induced Hypothermia after Cardiac Arrest


Eligible Patients
Patients with out-of-hospital cardiac arrest due to V-Fib or V-Tach
who remain comatose after return of spontaneous circulation
Inclusion Criteria
All of the following criteria must be satisfied:
a. Cardiac arrest is cardiac in origin
b. Body temperature is not reduced
c. Patient is hemodynamically stable
d. Patient is intubated and on a ventilator
Methodology
1. Cooling should begin within 1 to 2 hours after CPR.
2. Use cooling blamket to achieve a body temperature of 32C to
34C (89.6F to 93.2F).
3. Use sedation and neuromuscular blockade to avoid shivering.
4. Watch for hyperkalemia and hyperglycemia during hypothermia
5. Maintain hypothermia for 1224 hours, and then allow passive
rewarming.
From References 21 and 22.

B.Therapeutic Hypothermia
1. Ind u ced hypothermia has been show n to improve neuro-
logic outcom e in patients w ho rem ain com atose after ou t-
of-hospital card iac arrest d ue to V-Fib or V-Tach (21,22).

2. The eligibility criteria for p ost-CPR hyp otherm ia are


listed in Table 13.2, along w ith im p ortant aspects of the
method ology.
204 Disorders of Circulatory Flow

a. The target bod y tem p eratu re is 32C to 34C (89.6F to


93.2F), and this shou ld be m aintained for no less than
12 hou rs and no longer than 24 hou rs (21).
b. External cooling can p rovoke shivering, w hich is
cou n terp rod u ctive for th e reason s stated earlier.
Therefore, shivering shou ld be su p p ressed by ad m in-
istering a neu rom u scu lar blocker (e.g., atracu riu m ).
c. H ypotherm ia is associated w ith hyperkalem ia (u su al-
ly m ild ) and hyp erglycem ia (27), so vigilance for these
changes is w arranted .

C. Glycemic Control
1. H yp erglycem ia follow ing card iac arrest is associated
w ith a p oor neu rologic ou tcom e (23).

2. There are no stu d ies to show that aggressive m anage-


ment of hyp erglycemia im p roves neu rologic ou tcom e af-
ter card iac arrest, bu t this p ractice has been show n to re-
d uce m orbid ity and m ortality in ICU p atients (24).

3. Based on these observations, the recent American H eart


Association Guid elines for CPR recom m end avoid ing
hyp erglycem ia in the p ost-resu scitation p eriod (25). This
goal is accom plished by using insulin infusions w hen
necessary, and avoid ing d extrose-containing intravenou s
solu tions w hen possible. Carefu l monitoring of blood
glucose is necessary d u ring insulin infusions becau se hy-
p oglycem ia can also be inju riou s to the central nervous
system .

D. Predicting Neurologic Outcome


In p atients w ho d o not aw aken im m ed iately after CPR, the
single m ost im p ortant concern is the likelihood of neu rolog-
ic recovery. The follow ing clinical factors w ill help to p red ict
the likelihood of a satisfactory neu rologic recovery.
Cardiac Arrest 205

1. Duration of Coma
a. Failu re to regain consciou sness after CPR has p rognos-
tic significance if the com a p ersists for longer than 4 to
6 hou rs.
b. Few er than 15% of p atients w ill recover fully if their
com a persists for longer than 4 to 6 hou rs after card iac
arrest (26).
c. If a p atient is not aw ake 24 hou rs after a card iac arrest,
there is only a 10% chance of satisfactory neu rologic
recovery (26).
d . A Glasgow Com a Score less than 5 p oints (see Chap -
ter 40) on the third d ay follow ing card iac arrest w ill
id entify patients w ith little or no chance of neu rologic
recovery (27).

2. Other Prognostic Signs


A review of 11 stu d ies involving p atients w ho d id not
aw aken im m ed iately after CPR id entified fou r clinical
signs that act as ind ep end ent p red ictors of d eath or p oor
neu rologic recovery after card iac arrest (28).
a. N o corneal reflex.
b. N o pupillary light reflex.
c. N o w ithd raw al to p ain.
d . N o m otor response.
The presence of any of these signs 24 hou rs after card iac
arrest carries a p oor p rognosis for neu rologic recovery.

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206 Disorders of Circulatory Flow

lation, 2005; 112(Su ppl).


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58IV-66.
9. Aung K, H tay T. Vasop ressin for card iac arrest: a system atic re-
view and m eta-analysis. Arch Intern Med 2005; 165:1724.
10. Kud enchuk PJ, Cobb LA, Cop ass MK, et al. Am iod arone for ou t-
of-hospital card iac arrest d u e to ventricu lar fibrillation. N Engl J
Med 1999; 341:871878.
11. Dorian P, Cass D, Schw artz B, et al. Am iod arone as com p ared to
lid ocaine for shock-resistant ventricular fibrillation. N Engl J
Med 2002; 346:884890.
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d iopu lm onary resuscitation. JAMA 1990; 263:11061113.
14. Falk JL, Rackow EC, Weil MH . End -tid al carbon d ioxid e concen-
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15. Wayne MA, Levine RL, Miller CC. Use of end-tidal carbon dioxide
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Cardiac Arrest 207

16. Weil MH , Rackow EC, Trevino R. Difference in acid base state


betw een venou s and arterial blood d u ring card iop ulm onary
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18. H ickey RW, Kochanek PM, Ferim er H , et al. Ind u ced hyp erther-
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20. N obel EG, Gang P, Gord on JB, et al. Dilation of norm al and con-
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21. The H ypotherm ia After Card iac Arrest Stu d y grou p. Mild thera-
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22. Bernard SA, Gray TW, Buist MD, et al. Treatm ent of com atose
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therm ia. N Engl J Med 2002; 346:557563.
23. Calle PA, Bu ylaert WA, Vanhau te OA. Glycem ia in the p ost-
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Chapter 14
ACUTE CORONARY
SYNDROMES
The m anagem ent of p atients w ith acu te coronary synd rom es
requ ires tim ely interventions (often w ithin hou rs after the
onset of sym ptom s). These interventions are d escribed here
u sing inform ation from gu id elines listed in the bibliograp hy
at the end of the chap ter (1-3).

I. THE CORONARY SYNDROMES

A. Definitions
A cute coronary syndromes (ACS) are characterized by the su d -
d en onset of coronary insufficiency as a result of throm botic
occlu sion of one or m ore coronary arteries. The follow ing
cond itions are id entified :

1. ST-segm ent elevation m yocard ial infarction (STEMI),


cau sed by com plete and sustained coronary occlusion.

2. N on-ST-segm ent elevation m yocard ial infarction (non-


STEMI) and unstable angina (UA), w hich are cau sed by
p artial coronary occlu sion or transient occlu sion w ith
sp ontaneou s revascu larization.

B. Pathogenesis
The sem inal event in all these cond itions is throm bu s form a-
tion in one or m ore coronary arteries. The inciting event is
ru pture of an atherosclerotic plaqu e, w hich exp oses the
blood to throm bogenic lip id s and lead s to activation of
209
210 Critical Care Cardiology

platelets and clotting factors. The trigger for p laqu e d isru p -


tion is not know n, bu t liqu efaction cau sed by local inflam -
mation and inflam m atory m ed iators is believed to be in-
volved .

II. ROUTINE MEASURES


The rou tine m easu res u sed for all p atients w ith ACS are
show n in Figu re 14.1. These m easu res shou ld be initiated
im m ed iately after ACS is su spected .

A. Relieving Chest Pain


1. Nitroglycerin
a. N itroglycerin (0.4 m g su blingu al tablets or aerosol
sp ray) is given for u p to three d oses (each 5 m inu tes
ap art) to relieve chest p ain. If the chest p ain p ersists
after 3 d oses of nitroglycerin, im m ed iate ad m inistra-
tion of m orp hine is ind icated .
b. Intravenou s infu sion of nitroglycerin is recom m end ed
for patients w ith recu rrent chest pain d ue to unstable
angina. The initial d ose rate is 5 10 g/ m in, and this
can be increased by 5 10 g/ m in every 5 m inu tes
u ntil pain relief is achieved . (See Chap ter 45 for a nitro-
glycerin d ose chart.)
c. N itroglycerin is N OT ad vised in p atients w ho have
taken a nitric oxid e synthetase inhibitor or p hosp hod i-
esterase inhibitor for erectile d ysfunction w ithin the
p ast 24 hours (becau se of the risk for hyp otension).

2. Morphine
Morp hine is the d ru g of choice for chest p ain that is re-
fractory to nitroglycerin.
a. The initial d ose is 5 m g given by slow intravenou s
Acute Coronary Syndromes 211

p ush (e.g., 1 m g/ m inu te), and this can be rep eated


every 5 to 10 m inu tes if necessary. Pain relief can be
su stained w ith a morphine infu sion (1 5 m g/ hr).
b. Morphine m ay cau se a d ecrease in blood p ressu re,
w hich is p rim arily d u e to red u ced sym p athetic nerv-
ous system activity. This u su ally requ ires no interven-

ROUTINE MEAS URE


S P ECIFIC RECOMMENDATIONS

Re lieve Che s t Pain


S ta rt with nitro g lyc e rin (0.4 mg s ublingua l
ta ble ts or a e ros ol s pray).
If no re lie f a fte r 3 dos e s, us e mo rphine
(5 mg IV eve ry 5 to 10 min a s ne e de d).

Antiplate le t The rapy


Us e chewa ble as pirin (162 to 325 mg initia l
dos e, the n 75 to 162 mg da ily).
For a lte rna tive Rx, us e clo pido g re l (300 mg
initia l dos e, the n 75 mg da ily).

ACE Inhibitio n
Us e ora l the ra py only with a ny ACE inhibitor a nd
s ta rt a t a re duce d dos e to minimize the ris k of
hypote ns ion.
S a mple re gime n: ora l lis ino pril a t 5 mg on day 1,
5 mg on day 2, 10 mg on day 3, the n 10 mg da ily.

-Re c e pto r Blo ckade


Us e ora l the ra py unle s s ACS a ccompa nie d by
high BP or ta chya rrhythmia . Ca n us e me to pro lo l:
s ta rt with IV dos e of 2.5 to 5 mg a nd re pe a t
eve ry 5 min if ne e de d to tota l dos e of 10 mg.
At 15 min a fte r la s t IV dos e, s ta rt ora l Rx with
50 mg eve ry 6 hrs for 48 hrs, the n 100 mg BID.

FIGURE 14.1 Routine measures for the early management of acute


coronary syndromes. Abbreviation: ACE = angiotensin-converting-
enzyme.
212 Critical Care Cardiology

tion. A d rop in blood p ressu re to hypotensive levels


u su ally ind icates hyp ovolem ia, and can be corrected
by volu m e infu sion (2). Pressor agents shou ld N EVER
be u sed to correct m orp hine-ind u ced d ecreases in
blood p ressu re.

B. Antiplatelet Therapy

1. Aspirin
Aspirin causes irreversible inhibition of platelet aggrega-
tion by inhibiting thromboxane prod uction (4), and re-
d uces short-term (30 d ay) mortality in ACS by 2 to 3% (5).
a. Chew able aspirin in a d ose of 162 to 325 mg shou ld be
given to all p atients w ith su sp ected ACS w ho have not
taken asp irin p rior to p resentation. N on-enteric-coated
aspirin is preferred because of enhanced buccal ab-
sorp tion.
b. The initial d ose shou ld be follow ed by a d aily d ose of
75 to 162 m g, w hich is continu ed ind efinitely.

2. Thienopyridines
The thienop yrid ines irreversibly block su rface recep tors
involved in ADP-ind u ced p latelet aggregation (4). This
mechanism of action d iffers from that of aspirin, so the
antip latelet effects of asp irin and the thienop yrid ines can
be ad d itive.
a. There are 2 d ru gs in this class: clopidogrel (Plavix)
and ticlodipine (Ticlid ). Clop id ogrel seem s to be pre-
ferred becau se of few er sid e effects (4).
b. The recom mend ed d ose of clop id ogrel in ACS is 300
m g initially, follow ed by 75 m g d aily (2).
c. Clop id ogrel has been u sed as a su bstitu te for asp irin.
H ow ever, com bined therap y w ith clop id ogrel and
aspirin in ACS is associated w ith a low er m ortality
than that seen w ith asp irin therap y alone (6).
Acute Coronary Syndromes 213

C. -Receptor Blockade
Beta-recep tor blockad e is recom m end ed for all patients w ith
ACS excep t those w ith contraind ications (e.g., brad ycard ia)
and those w ith cocaine-ind u ced m yocard ial infarction (be-
cau se of the risk of coronary vasospasm from u nopposed
-recep tor activity) (7).
a. Oral therapy is su itable for m ost cases of ACS. Intra-
venou s therap y is m ore ap p rop riate for p atients w ith
hyp ertension or tachyarrhythm ias.
b. The agents used m ost often are atenolol (Tenorm in)
and metoprolol (Lop ressor), w hich are selective 1-
recep tor antagonists. The oral and intravenou s d osing
regim ens for m etop rolol are show n below (8).
Oral regimen: Start w ith intravenou s m etop rolol d ose
of 2.5 to 5 m g and rep eat every 5 m inu tes if need -
ed to a total d ose of 10 m g. Fifteen m inu tes after
the last IV d ose, start oral therap y w ith 50 mg
every 6 hou rs for 48 hou rs, then 100 m g BID.
IV regimen: Ad d 5 m g m etop rolol to 50 m L D 5W and
infu se over 15 to 30 m inu tes. Repeat every 6
hou rs.

D. Angiotensin-Converting-Enzyme Inhibition
Angiotensin-converting-enzym e (ACE) inhibitors red u ce
card iac w ork, and m ay also have an inhibitory effect on the
card iac rem od eling that contribu tes to p ost-MI heart failu re.

1. ACE inhibitors are recom m end ed for all p atients w ith


acu te MI, but they p rovid e the m ost benefit in the follow -
ing cond itions (9):
a. Anterior MI
b. Acu te MI w ith left ventricu lar d ysfu nction (LV ejection
fraction < 0.40) or symp tomatic left heart failu re.
c. Acu te MI w ith tachycard ia.
214 Critical Care Cardiology

2. Contraind ications to ACE inhibitors inclu d e hyp oten-


sion, seru m creatinine > 2.5 m g/ d L, and bilateral renal
artery stenosis.

3. Any ACE inhibitor can be u sed , and the first d ose should
be given w ithin 24 hou rs after sym p tom onset (2). One
effective ACE inhibitor regim en is show n in Figu re 14.1
(10). Oral therap y only is recom m end ed , to m inimize the
risk of hyp otension.

4. Angiotensin-recep tor blockers (ARBs) are consid ered as


a su itable alternative to ACE inhibitors in p atients w ith
acu te MI com p licated by LV d ysfunction or heart failu re
(2). One su ccessfu l ARB regim en is oral valsartan given
in a d ose of 20 m g initially, follow ed by a grad u al in-
crease to 160 m g tw ice d aily by the end of the hosp ital-
ization (11).

III. REPERFUSION THERAPY


Reperfu sion therap y is d esigned to alleviate throm botic ob-
stru ction and restore p atency in occlu d ed coronary arteries.
There are tw o ap p roaches to rep erfu sion: p harm acologic
(u sing throm bolytic agents) and m echanical (u sing balloon
angiop lasty).

A.Thrombolytic Therapy
1. Indications
Patients are cand id ates for throm bolytic therap y w hen
all of the follow ing cond itions are satisfied .
a. Onset of chest p ain betw een 30 m inu tes and 12 hours
p rior to presentation.
b. 12-lead ECG show s ST elevation of at least 0.1 m V
(1 m m ) in tw o contiguou s lead s, or a new left bu nd le
branch block.
c. Coronary angiop lasty not im m ed iately available.
Acute Coronary Syndromes 215

d . N o hypotension or evid ence of heart failu re.


e. N o contraind ication to throm bolytic therapy (see Table
14.1).
Recent gu id elines (2) inclu d e tru e p osterior MI as an in-
d ication for throm bolytic therap y if treatm ent is started
w ithin 12 hou rs of sym p tom onset. This cond ition should
be su sp ected w hen the ECG show s ST-segm ent d ep res-
sion w ith u pright T w aves in lead s V1 throu gh V4 (12).

TABLE 14.1 Contraindications to Thrombolytic Therapy


Absolute Contraindications
Active bleeding other than menses
Malignant intracranial neoplasm (primary or metastatic)
Cerebrovascular anomaly (e.g., AVmalformation)
Suspected aortic dissection
Ischemic stroke within 3 months (but not within 3 hours)
Prior history of intracranial hemorrhage
Significant closed-head or facial trauma within 3 months
Relative Contraindications
Systolic BP >180 mm Hg or diastolic BP >110 mm Hg
Active bleeding within the past 4 weeks
Noncompressible vascular punctures
Major surgery within the past 3 weeks
Traumatic or prolonged (>10 min) CPR
Ischemic stroke over 3 months ago
Dementia
Active peptic ulcer disease
Pregnancy
Ongoing therapy with anticoagulants
From Reference 2.

2. Timing
The su rvival benefit of throm bolytic therap y is greatest
216 Critical Care Cardiology

w hen therap y is initiated in the first few hou rs after


the onset of chest p ain. Thereafter, the su rvival benefit
d eclines stead ily w ith time and is eventu ally lost 12
hou rs after sym p tom onset. To ensu re tim ely initiation of
throm bolytic therapy, em ergency room s in the United
States have ad op ted the follow ing gu id elines (2):
a. When a patient w ith su d d en onset of chest p ain enters
the em ergency room , a 12-lead ECG shou ld be p er-
form ed and interpreted w ithin 10 m inu tes (d oor-to-
ECG tim e <10 m inu tes).
b. Throm bolytic therapy, if ind icated , should be started
w ithin 30 m inu tes after the p atient enters the em er-
gency room (d oor-to-need le time <30 minu tes).

TABLE 14.2 Thrombolytic Agents


Agent Dose Comments
Streptokinase 1.5 million Units IV Less effective and more
(SK) over 60 min frequent side effects
than alteplase
Alteplase 15 mg IVbolus, Most frequently used
(tPA) + 0.75 mg/kg over 30 min lytic agent
+ 0.5 mg/kg over 60 min
(90 min total)
Reteplase 10 Units as IVbolus and Bolus doses are easier
(rPA) and repeat in 30 min to give and produce
more rapid clot lysis
than tPA
Tenecteplase IVbolus of: Most clot-specific and
(TNK) 30 mg for BW< 60 kg rapidly acting lytic agent
35 mg for BW= 6069 kg Easiest to use because
40 mg for BW= 7079 kg of single bolus dose
45 mg for BW= 8089 kg
50 mg for BW90 kg
Acute Coronary Syndromes 217

3. Fibrinolytic Agents
The available fibrinolytic agents and recom m end ed d os-
ing regim ens for acu te MI are show n in Table 14.2. All of
these agents act by converting p lasm inogen to p lasm in,
w hich then breaks fibrin strand s into sm aller su bu nits.
Strep tokinase acts on circu lating p lasm inogen and p ro-
d u ces a system ic lytic state, w hile the other agents act
only on fibrin-bou nd p lasminogen and p rod u ce clot-spe-
cific lysis. This d istinction (clot-sp ecific versu s system ic
lysis), how ever, has little clinical relevance.
a. Streptokinase w as the first throm bolytic agent that
show ed a su rvival benefit in acu te MI. The p op ularity
of this agent has w aned over the years, in p art becau se
of trou blesom e sid e effects. Strep tokinase is a bacterial
p rotein and acts as an antigen to p rom ote fever (20 to
40% of cases), allergic reactions (5% of cases), and ac-
cu m u lation of neu tralizing antibod ies (w ith rep eated
u se) (13).
b. Alteplase (tissu e p lasm inogen activator or tPA) p ro-
vid es a greater su rvival benefit than strep tokinase (14)
and has few er sid e effects. It is cu rrently the favored
lytic agent for reperfu sion therap y, bu t its p op u larity
is being challenged by new er lytic agents cap able of
m ore rapid clot lysis.
c. Reteplase (rPA) is a m olecu lar variant of tPA that is
given as tw o bolu s d oses 30 m inu tes ap art (see Table
14.3). Despite m ore rap id clot lysis (15), reteplase d oes
not p rod u ce better ou tcom es than alteplase (16).
d . Tenecteplase (TN K-tPA) is another variant of tPA that
is given as a single bolus. Clot lysis occurs in less time
than w ith the other lytic agents (17), bu t the m ortality
rate is no d ifferent than w ith other lytic agents (18).
Exclud ing streptokinase, there is no clear favorite am ong
the throm bolytic agents in term s of p rom oting su rvival
in STEMI. H ow ever, bolus therapy with reteplase or tenecte-
218 Critical Care Cardiology

plase should probably be favored because of the m ore rapid


clot lysis (w hich is d esirable even if survival is u naffect-
ed ) and the sim p lified d osing regim ens.

4. Bleeding
a. The bleed ing tend ency that hau nts throm bolytic ther-
ap y is the resu lt of system ic fibrinolysis w ith d ep letion
of circu lating fibrinogen levels.
b. Intracerebral hem orrhage is the m ost feared com p lica-
tion of throm bolytic therapy, and occu rs in 0.5 to 1% of
cases (17). Altep lase, retep lase, and tenectep lase share
the sam e risk for this seriou s com p lication.
c. Troublesom e bleed ing elsew here (i.e., that requ ires
blood rep lacement) occu rs in 5 to 15% of p atients, re-
gard less of the lytic agent used (19).
d . The hem ostatic d efect prod u ced by fibrinolytic agents
can be partially corrected by cryoprecipitate ad m inis-
tration (10 to 15 bags) to raise the seru m fibrinogen
level to 1 g/ L (19). If bleed ing p ersists, fresh frozen
p lasm a (u p to 6 u nits) w ill elevate fibrinogen levels
fu rther, and w ill p rovid e volu m e rep lacem ent as w ell.
e. Antifibrinolytic agents such as epsilon-am inocaproic
acid (5 gram s infu sed over 15 to 30 m inu tes) shou ld be
reserved only for the m ost seriou s and refractory cases
of bleed ing becau se these agents can p rom ote w id e-
sp read throm bosis (19).

5. Reocclusion
Reocclu sion (occu rring w ithin d ays) is reported in about
one of every fou r p atients w ho receive throm bolytic ther-
ap y (2,17). Thrombin released d u ring clot d issolu tion is
believed to be the cu lp rit. This risk of reocclu sion has
p rom pted the u se of antithrom botic therap y w ith hep-
arin and antip latelet agents after su ccessfu l clot lysis.
This ad ju nctive therap y is d escribed later in the chapter.
Acute Coronary Syndromes 219

B. Coronary Angioplasty
The u se of balloon-tip p ed catheters to op en occlu d ed arter-
ies w as ad ap ted for u se in the coronary arteries in 1977, and
this m ethod of percutaneous coronary angioplasty is now the pre-
ferred method of reperfusion in acute coronary syndromes.

1. Angioplasty vs. Lytic Therapy


Several clinical trials have com p ared coronary angiop las-
ty and throm bolytic therap y in p atients w ith STEMI w ho
p resent w ithin 12 hou rs of sym ptom onset. The p ooled
resu lts show a significant red u ction in both m ortality rate
and reinfarction rate w hen angiop lasty is u sed instead of
throm bolytic therap y. For every 100 patients treated with
angioplasty instead of thrombolytic therapy, there are 2 fewer
deaths and 4 fewer (non-fatal) reinfarctions (20).

2. Timing
Clinical trials in patients w ith STEMI have show n that
the su rvival benefit of angiop lasty falls significantly
w hen the proced u re is d elayed for m ore than 2 hou rs
after the patient arrives at the hospital (21). This observa-
tion has prompted the recommend ation that no more than
90 minutes should elapse from the time the patient arrives in the
emergency room and the time the angioplasty is performed (2).

3. Interhospital Transfer
Less than 25% of hospitals in the United States (and less
than 10% of the hosp itals in Eu rop e) have the cap ability
to p erform coronary angioplasty. One p otential rem ed y
for this situ ation is tim ely interhosp ital transfer of
p atients. Clinical stu d ies have show n that interhosp ital
transfer for coronary angioplasty, if com p leted in one to
tw o hours, can retain the su rvival benefit of angioplasty
(2,22). The follow ing recom m end ations have been pro-
p osed for hospitals w ithou t angiop lasty cap ability (2):
220 Critical Care Cardiology

a. If the sym p tom d u ration is less than 3 hou rs, throm -


bolytic therap y is recom m end ed (becau se lytic therapy
is m ost effective in this tim e p eriod ) u nless interhosp i-
tal transfer w ill not d elay rep erfu sion therap y by m ore
than one hou r.
b. If the sym ptom d u ration is longer than 3 hou rs, inter-
hosp ital transfer for angiop lasty is recom m end ed . The
total d oor-to-balloon tim e, inclu d ing the transfer tim e,
shou ld be close to 90 m inu tes to achieve the optim al
benefit of angiop lasty.

IV. ADJUNCTS TO REPERFUSION THERAPY


Antithrom botic therapy w ith antiplatelet agents and heparin
has a p roven benefit w hen u sed alone or in com bination
w ith reperfusion therap y. When u sed in com bination, anti-
throm botic therap y red u ces the risk of reocclu sion and rein-
farction.

A. Heparin
1. Which Heparin for Which Condition
The follow ing is a su m m ary of the ACC/ AH A recom -
mend ations for the use of u nfractionated heparin (UFH )
and low -m olecu lar-w eight hep arin (LMWH ) in acu te
coronary synd rom es (2,3). (See Chap ter 3 for a d escrip -
tion of the d ifferent hep arin p rep arations).
a. LMWH is p referred to UFH for p atients w ith u nstable
angina (UA) and non-ST-segm ent elevation m yocar-
d ial infarction (non-STEMI) (3,23).
b. UFH and LMWH are consid ered equivalent in pa-
tients w ith ST-segment elevation m yocard ial infarction
(STEMI) w ho d o not receive rep erfusion therap y (2).
c. Desp ite p romising resu lts w ith LMWH (24), UFH is
recom m end ed for patients w ith STEMI w ho u nd ergo
angiop lasty or throm bolytic therap y (2).
Acute Coronary Syndromes 221

2. Dosing Regimens
The ACC/ AH A recom m end ations for hep arin d osing
in acu te coronary synd rom es are show n below (1-3).
Enoxaparin is used as the LMWH because this agent has
been stu d ied m ost in clinical trials.
Enoxaparin: Start w ith an intravenou s bolu s of 40 m g and
follow w ith su bcu taneou s injections of 1 m g/ kg
tw ice d aily for 5 d ays (3). Red u ce the d ose in p a-
tients w ith renal insu fficiency u sing the gu id elines
in Table 14.3.
UFH: Start w ith an intravenou s bolu s of 60 70 Units/ kg,
and follow w ith an infu sion of 12 15 Units/ kg/ hr.
Use the low est d oses (bolu s d ose of 60 Units/ kg and
infu sion rate of 12 Units/ kg/ hr) w hen UFH is com -
bined w ith throm bolytic therap y and u se a larger
bolu s d ose (70 to 100 Units/ kg) w hen UFH is com -
bined w ith angiop lasty. Measu re the activated par-
tial throm bop lastin tim e (aPTT) 3 hou rs after start-
ing the infu sion, and ad ju st the infu sion rate to
m aintain the aPTT at 1.5 to 2 tim es control (3).

TABLE 14.3 Enoxaparin Dosage Based on Renal Function


GFR SC Dose GFR SC Dose
(mL/min) (mg/kg q 12h) (mL/min) (mg/kg q 12h)
80 1.0 40 49 0.6
70 79 0.9 30 39 0.5
60 69 0.8 20 29 0.4
50 59 0.7 10 19 0.3
GFR (mL/min) = (140 age) x wt (kg)/ 72 x s erum creatinine (mg/dL)
For females , multiply GFR by 0.5.
From Green B. et al. Dos ing Strategy for enoxaparin in patients with renal
impairment presenting with acute coronary syndromes. Br J Clin
Pharmacol 2004; 59:281.
222 Critical Care Cardiology

B. Aspirin
When used in com bination w ith fibrinolytic agents, asp irin
red uces the rate of reinfarction. The d osing regim en for as-
pirin is d escribed earlier in the chap ter.

C. Platelet Glycoprotein Inhibitors


When p latelets are activated , specialized glycop roteins on
the p latelet su rface (called IIb/ IIIa recep tors) change config-
uration and begin to bind fibrinogen. Fibrinogen bind ing to
ad jacent p latelets then prom otes p latelet aggregation. A class
of d ru gs know n as platelet glycoprotein (IIb/IIIa) inhibitors can
bind to the IIb/ IIIa recep tors on p latelets and p revent the
bind ing of fibrinogen. The final resu lt is inhibition of p latelet
aggregation. Because the IIb/ IIIa receptors are the final com -
mon pathw ay for platelet aggregation, the IIb/ IIIa inhibitors
are the m ost p ow erfu l antip latelet agents available.

1. Drug Preparations
The p latelet glycop rotein inhibitors available for clinical
u se are inclu d ed in Table 14.4, along w ith the d osing reg-
im en for each.
a. Abciximab (try to p ronou nce it!) is a m onoclonal anti-
bod y and is the m ost expensive. m ost p otent, and
longest-acting d ru g in the grou p . The bleed ing tim e
can take 12 hou rs to norm alize after d iscontinu ing this
d ru g (4). This p rolonged activity is a d isad vantage
w hen em ergency coronary byp ass su rgery is requ ired .
b. Eptifibatide (a synthetic p ep tid e) and tirofiban (a
tyrosine d erivative) are short-acting agents that are
cleared by the kid neys. After d iscontinu ing these
d ru gs, bleed ing tim es retu rn to norm al in 15 m inu tes
(for ep tifibatid e) to 4 hou rs (for tirofiban) (4).
c. Dose ad ju stm ents are recom m end ed for the short-act-
ing agents in patients w ith renal insufficiency (see
Table 14.4). Abcixim ab is cleared by the reticu loend o-
Acute Coronary Syndromes 223

thelial system and d oes not requ ire d ose ad ju stm ents
in renal failu re.

TABLE 14.4 Platelet Glycoprotein (IIb/IIIa) Inhibitors


Commercial
Agent Preparation Dosing Regimen
Abciximab ReoPro 0.25 mg/kg as IVbolus followed
by infusion of 0.125 g/kg/min
(maximum 10 g/min)
Eptifibatide Integrilin 180 g/kg as IVbolus followed
by infusion of 2 g/kg/min for
up to 96 hours
For serum creatinine of 24
mg/dL, first reduce dose to
130 g/kg and reduce infusion
rate to 0.5 g/kg/min
Tirofiban Aggrastat 0.4 g/kg/min for 30 minutes
followed by infusion of
0.1 g/kg/min
For creatinine clearance
<30 mL/min, reduce both dose
rates by 50%.
Manufacturers recommendation.

2. Indications
Platelet glycoprotein inhibitors are p rim arily u sed in pa-
tients w ith u nstable angina (UA) and non-ST-elevation
myocard ial infarction (non-STEMI) w hen the follow ing
cond itions are p resent (3):
a. When coronary angiop lasty is p lanned in the next 24
to 48 hou rs.
b. When there is evidence of continuing myocardial ischemia.
c. When there are risk factors for recu rrent ischem ic
224 Critical Care Cardiology

events, su ch as age > 75 years, heart failu re, new or


w orsening m itral regurgitation, m arked ly elevated
card iac trop onin levels, and card iogenic shock (3).
The greatest benefit occu rs w hen these agents are u sed in
conju nction w ith angiop lasty (1-3,23), and abcixim ab is
used only w hen angiop lasty is p erform ed . These d rugs
are also gaining pop ularity in p atients w ith STEMI, and
are u su ally given in com bination w ith angiop lasty or
throm bolytic therap y (2,3).

3. Adverse Effects
Abnorm al bleed ing is, of cou rse, the m ajor concern w ith
p latelet glycop rotein inhibitors.
a. Mu cocu taneous bleed ing is the m ost com m on sid e
effect, but the true incid ence is d ifficu lt to ascertain
becau se these d ru gs are often given in com bination
w ith asp irin and hep arin. Intracranial hem orrhage has
not been rep orted in association w ith these d ru gs.
b. Throm bocytop enia is rep orted in 2% of p atients w ho
receive abcixim ab, and is m ore com m on w ith rep eated
u se of the d ru g (23).

4. Contraindications
a. Active bleed ing is an absolu te contraind ication to
p latelet glycop rotein inhibitors.
b. Relative contraind ications includ e major su rgery w ith-
in the p ast 3 m onths, stroke in the p ast 6 m onths, sys-
tolic p ressu re > 180 m m H g or d iastolic p ressu re > 110
mm H g, and severe throm bocytop enia (23).

V. EARLY COMPLICATIONS

A. Mechanical Complications
Mechanical comp lications are u su ally the resu lt of transmu -
ral MI. All are seriou s, and all requ ire p rom p t action.
Acute Coronary Syndromes 225

1. A cute mitral regurgitation is the resu lt of p ap illary m u scle


ru p tu re, and presents w ith the su d d en onset of p u lm o-
nary ed em a and the characteristic holosystolic m urm u r
rad iating to the axilla. The p u lmonary artery occlu sion
p ressu re m ay reveal p rominent V w aves, bu t this can be
a nonsp ecific find ing. The d iagnosis is confirm ed by
echocard iography, and arterial vasod ilators (e.g., hy-
d ralazine) are often need ed to relieve p u lm onary ed em a
p end ing su rgery. The m ortality rate is 70% w ithou t su r-
gery and 40% w ith su rgery (24).

2. Ventricular septal rupture can d evelop at any tim e in the


first 5 d ays after an acu te MI. The d iagnosis can be elu -
sive w ithou t card iac u ltrasou nd . There is a step-u p in O 2
satu ration from the right atriu m to the p u lm onary artery,
bu t this is rarely m easu red . The initial m anagem ent in-
volves vasod ilator (e.g., nitroglycerin) infu sions com -
bined w ith m echanical su p port (the intraaortic balloon
p um p) if need ed . The m ortality rate is 90% w ithou t su r-
gery and 20 to 50% w ith su rgery (2).

3. Ventricular free wall rupture occu rs in u p to 6% of cases of


STEMI, and is m ore com m on w ith anterior MI, fibrino-
lytic or steroid therap y, and ad vanced age (2). Early m an-
ifestations includ e recu rrence of chest p ains and new ST-
segm ent abnormalities on the ECG. Accu m u lation of
blood in the p ericard iu m often lead s to rap id d eteriora-
tion and card iovascu lar collap se from p ericard ial tam -
p onad e. Diagnosis is m ad e by card iac u ltrasou nd (if tim e
p erm its), and p rom p t p ericard iocentesis com bined w ith
aggressive volu m e resu scitation is requ ired for hem od y-
nam ic su pp ort. Im m ed iate su rgery is the only cou rse of
action, bu t few er than half of the p atients su rvive d esp ite
su rgery (2).

B. Arrhythmias
Card iac rhythm d istu rbances are com m on after acu te MI,
and this topic is covered in d etail in the next chap ter.
226 Critical Care Cardiology

C. Cardiac Pump Failure


Abou t 15% of cases of acu te MI are accom panied by card iac
pu m p failu re and card iogenic shock (24). The m anagem ent
involves hemod ynam ic su pport (usually w ith intraaortic
balloon cou nterp u lsation) follow ed by rep erfu sion u sing
coronary angioplasty or coronary byp ass su rgery. The m or-
tality rate in card iogenic shock is high (60 to 80%) (25),
d espite our best efforts.
1. Hemodynamic Support
The goal of hem od ynam ic su p p ort in this situ ation is to
au gm ent card iac ou tp u t w ithou t increasing m yocard ial
oxygen consu m ption. Table 14.5 show s the effects of d if-
ferent types of hem od ynam ic su pport on the d eterm i-
nants of m yocard ial O 2 consum p tion (p reload , contractil-
ity, afterload , and heart rate) in d ecom p ensated heart
failu re and card iogenic shock. As ind icated by th e net
effect on m yocard ial O 2 consu m p tion, vasod ilator ther-
ap y is su p erior to d obu tam ine in heart failu re, and the

TABLE 14.5 Hemodynamic Support and Myocardial


Oxygen Consumption
Heart Failure Cardiogenic Shock
Parameter Vasodilators Dobutamine IABP Dopamine
Preload
Contractility
Afterload
Heart Rate

Net effect on
myocardial VO2
IABP = Intraaortic balloon pump; VO 2 = oxygen cons umption.
Acute Coronary Syndromes 227

intraaortic balloon pu m p (IABP) is su perior to d opam ine


in card iogenic shock. (See Chapter 12 for m ore inform a-
tion on the treatm ent of card iac p u m p failure).
2. Reperfusion Therapy
a. The ACC/ AH A gu id elines recom m end coronary an-
giop lasty w hen card iogenic shock ap p ears w ithin 36
hours of acute MI and w hen the angioplasty can be
p erform ed w ithin 18 hou rs of the onset of shock (2).
b. Coronary artery byp ass su rgery is consid ered if the
card iac catheterization reveals m ultivessel d isease that
is not su itable for angiop lasty, or the obstru ction in-
volves the left m ain coronary artery (2).

VI. ACUTE AORTIC DISSECTION


Aortic d issection is inclu d ed in this chap ter becau se the clin-
ical presentation can be m istaken as an acute coronary syn-
d rom e, and a m issed d iagnosis can be fatal.

A. Chest Pain
1. Chest p ain is the m ost comm on com p laint in acu te aortic
d issection. The p ain is often sharp , and is d escribed as
rip ping or tearing in abou t 50% of cases (26). Rad ia-
tion to the jaw s and arm s is uncom m on.

2. The chest pain in aortic d issection can subside spontaneous-


ly for hou rs to d ays (26,27), and this is a sou rce of m issed
d iagnoses. The recurrence of pain after a pain-free inter-
val is often a sign of im p end ing aortic ru p tu re.

B. Clinical Findings
1. H yp ertension and aortic insu fficiency are each p resent in
abou t 50% of cases, and hyp otension is reported in 25%
of cases (26,27).
228 Critical Care Cardiology

2. Dissection can cau se obstru ction of the left su bclavian


artery lead ing to blood p ressu re d ifferences in the arm s.
H ow ever, this find ing is absent in u p to 85% of cases (27).

3. Med iastinal w id ening is evid ent on rou tine chest x-rays


in 60% of p atients w ith aortic d issection. This finding nei-
ther confirms nor excludes the presence of aortic dissection.

C. Diagnosis
1. The diagnosis requires one of four imaging modalities (28):
a. Magnetic resonance im aging (MRI): sensitivity and
sp ecificity 98%.
b. Contrast-enhanced com p u ted tom ograp hy: sensitivity
94%, sp ecificity 87%.
c. Transesophageal echocard iography: sensitivity 98%,
sp ecificity 77%.
d . Aortograp hy: sensitivity 88%, sp ecificity 94%.

2. MRI is the d iagnostic m od ality of choice for aortic d issec-


tion. CT angiography and transesophageal u ltrasou nd
are high-yield alternatives to MRI.

D. Management
1. Acu te d issection in the ascend ing thoracic aorta is a su r-
gical em ergency.

2. Prom p t control of hyp ertension is w arranted p rior to su r-


gery to red u ce the risk of aortic ru p tu re. The blood p res-
su re red u ction shou ld not be accom p anied by an increase
in card iac outpu t because increased flow rates in the aorta
w ill create shear forces that promote further d issection.

3. The d ru g regim ens show n in Table 14.6 w ill red u ce blood


p ressu re w ithou t increasing card iac outp u t (26,27). One
regim en u ses a vasod ilator (nitrop ru ssid e) infu sion com -
Acute Coronary Syndromes 229

bined w ith a -blocker (esm olol) infu sion. The -blocker


is given first to prevent the vasod ilator-ind uced increase
in card iac ou tpu t. Esm olol is u sed as the -blocker be-
cause it has a short d u ration of action (9 m inu tes) and
thu s is easy to titrate. Single-d ru g therap y w ith labetalol,
a com bined - and -recep tor antagonist, w ill p rod u ce
the sam e resu lt.

TABLE 14.6 Treating Hypertension in Aortic Dissection


Combined therapy with -blocker and vasodilator:
Start with esmolol: 500 g/kg bolus and follow with 50 g/kg/min.
Increase infusion by 25 g/kg/min every 5 min
until heart rate 6080 bpm.
Maximum dose rate is 200 g/kg/min.
Add nitroprusside: Start infusion at 0.2 g/kg/min and titrate
upward to desired effect.
See the nitroprusside dosage chart in
Chapter 45.
Monotherapy with combined - receptor antagonist:
Labetalol: 20 mg IVover 2 min, then infuse 12 mg/min
to desired effect and stop infusion.
Maximum cumulative dose is 300 mg.

REFERENCES
1. 2005 Am erican H eart Association Gu id elines for Card iop u lm o-
nary Resuscitation and Em ergency Card iovascu lar Care. Part 8:
Stabilization of the patient w ith acu te coronary synd rom es.
Circu lation 2005; 112(Su pp l I):IV89-IV110.
2. Antman EM, Anbe DT, Arm strong PW, et al. ACC/ AH A gu id e-
lines for the m anagem ent of patients w ith ST-elevation myocar-
d ial infarction executive sum mary: a rep ort of the American
College of Card iology/ American H eart Association Task Force
230 Critical Care Cardiology

on Practice Guid elines (Writing Comm ittee to Revise the 1999


Guid elines for the Management of Patients w ith Acu te Myocar-
d ial Infarction). Circulation 2004; 110:588-636.
3. Brau nw ald E, Antm an EM, Beasley JW, et al. ACC/ AH A 2002
gu id eline u pd ate for the m anagem ent of p atients w ith u nstable
angina and non-ST-segm ent m yocard ial infarction su m m ary
article: a rep ort of the Am erican College of Card iology/ Am eri-
can H eart Association Task Force on Practice Gu id elines (Com -
m ittee on the Managem ent of Patients w ith Unstable Angina).
J Am Coll Card iol 2002; 40:1366-1374.
4. Patrono C, Coller B, Fitzgerald G, et al. Platelet-active d ru gs: The
relationships am ong d ose, effectiveness, and sid e effects. Chest
2004; 126:234S-264S.
5. ISIS-2 (Second International Stu d y of Infarct Su rvival) Collabo-
rative Grou p. Rand om ized trial of intravenou s strep tokinase,
oral aspirin, both, or neither am ong 17,187 cases of su sp ected
acute m yocard ial infarction: ISIS-2. Lancet 1988; 2:349-360.
6. Clopid ogrel in Unstable Angina to Prevent Recurrent Events
Trial Investigators. Effects of clop id ogrel in ad d ition to aspirin in
p atients w ith acu te coronary synd rom es w ithou t ST-segm ent ele-
vation. N Engl J Med 2001; 345:494-502.
7. Kloner RA, H ale S. Unraveling the com p lex effects of cocaine on
the heart. Circu lation 1993; 87:1046-47.
8. Metoprolol su ccinate and m etop rolol tartrate. In: McEvoy GK,
ed . AH FS d ru g inform ation, 2001. Bethesd a, MD: Am erican
Society for H ealth System Pharm acists, 2001:1622-1629.
9. ACE Inhibitor Myocard ial Infarction Collaborative Grou p. In-
d ications for ACE inhibitors in the early treatm ent of acu te
m yocard ial infarction: system atic overview of ind ivid u al d ata
from 100,000 p atients in rand om ized trials. Circulation 1998;
97:2202-2212.
10. Gru ppo Italiano per lo Stu d io d ella Sopravvivenza nellinfarto
Miocard ico (GISSI). GISSI-3: effects of lisinop ril and transd erm al
glyceryl trinitrate singly and together on 6-w eek m ortality and
ventricular fu nction after acu te m yocard ial infarction. Lancet
1994; 343:1115-1122.
11. Pfeffer MA, McMurray JJ, Velazqu ez EJ, et al, for the Valsartan in
Acute Myocard ial Infarction Trial Investigators. Valsartan, cap to-
p ril, or both in m yocard ial infarction com p licated by heart fail-
u re, left ventricular d ysfunction, or both. N Engl J Med 2003;
349:1893-1906.
Acute Coronary Syndromes 231

12. Bod en WE, Kleiger RE, Gibson RS, et al. Electrocard iograp hic
evolu tion of posterior acu te m yocard ial infarction: im p ortance of
early precord ial ST-segm ent d ep ression. Am J Card iol 1987; 59:
782-787.
13. Gu id ry JR, Raschke R, Morku nas AR. Anticoagu lants and throm -
bolytics. In: Blu m er JL, Bond GR, ed s. Toxic effects of d ru gs in the
ICU. Critical care clinics. Vol. 7. Philad elp hia: WB Sau nd ers,
1991; 533554.
14. GUSTO Investigators. An international rand om ized trial com -
p aring four throm bolytic strategies for acu te m yocard ial infarc-
tion. N Engl J Med 1993; 329:673682.
15. Sm alling RW, Bod e C, Kalbfleisch J, et al. More rap id , com p lete,
and stable coronary throm bolysis w ith bolus ad m inistration of
reteplase com pared w ith altep lase infu sion in acute m yocard ial
infarction. Circu lation 1995; 91:2725-2732.
16. GUSTO-III Investigators. An international, m u lticenter, rand om -
ized com parison of retep lase w ith altep lase for acu te m yocard ial
infarction. N Engl J Med 1997; 337:1118-1123.
17. Llevad ot J, Giugliano RP, Antm an EM. Bolu s fibrinolytic therap y
in acu te m yocard ial infarction. JAMA 2001; 286:442-449.
18. Assessm ent of the Safety and Efficacy of a N ew Throm bolytic
(ASSEN T-2) Investigators. Single-bolu s tenectep lase com p ared
w ith front-load ed altep lase in acu te m yocard ial infarction.
Lancet 1999; 354:716-722.
19. Young GP, H offm an JR. Throm bolytic therapy. Em erg Med Clin
1995; 13:735759.
20. Keeley EC, Bou ra JA, Grines CL. Prim ary angiop lasty versu s
intravenou s throm bolytic therap y for acu te m yocard ial infarc-
tion: a quantitative review of 23 rand om ized trials. Lancet 2003;
361:13-20.
21. Cannon CP, Gibson CM, Lam brew CT, et al. Relationship of
sym ptom onset to balloon tim e and d oor-to-balloon tim e w ith
m ortality in p atients u nd ergoing angiop lasty for acu te m yocar-
d ial infarction. JAMA 2000; 283:2941-2947.
22. And ersen H R, N ielsen TT, Rasm u ssen K, et al. for the DAN AMI-
2 Investigators. A com p arison of coronary angiop lasty w ith fibri-
nolytic therapy in acute m yocard ial infarction. N Engl J Med
2003; 349:733-742.
23. Bhatt DL, Topol EJ. Current role of platelet glycoprotein IIb/ IIIa
inhibitors in acute coronary syndromes. JAMA 2000; 284:1549-1558.
232 Critical Care Cardiology

24. Thom p son CR, Bu ller CE, Sleep er LA, et al. Card iogenic shock
d u e to acu te severe m itral regu rgitation com p licating acu te m yo-
card ial infarction: a report from the SH OCK trial registry. J Am
Coll Card iol 2000; 36:1104-1109.
25. Sam uels LF, Darze ES. Managem ent of acu te card iogenic shock.
Card iol Clin 2003; 21:43-49.
26. Khan IA, N air CK. Clinical, d iagnostic, and m anagem ent p er-
spectives of aortic d issection. Chest 2002; 122:311-328.
27. Knau t AL, Cleveland JC. Aortic em ergencies. Em erg Med Clin N
Am 2003; 21:817-845.
28. Zegel H G, Chm ielew ski S, Freim an DB. The im aging evalu ation
of thoracic aortic d issection. Ap pl Rad iol 1995; (Ju ne):1525.
Chapter 15
TACHYCARDIAS
This chap ter d escribes the d iagnosis and m anagem ent of
rap id rhythm d istu rbances u sing clinical p ractice gu id elines
d eveloped by consensu s grou ps in the United States and
Eu rope (see References 13).

I. DIAGNOSTIC APPROACH
The d iagnostic ap p roach to tachycard ias (heart rate > 100
beats/ m inu te) can be organized as show n in Figu re 15.1.
This ap p roach is based on selected com p onents of the elec-
trocard iogram , inclu d ing 1) the d u ration of the QRS com -
p lex, 2) the u niform ity of the R-R intervals, and 3) the p attern
of atrial activity.

A. QRS Duration
1. A norm al QRS d u ration ( 0.12 second ) id entifies tachy-
card ias that originate above the AV cond uction system .
These narrow QRS complex tachycardias (also called su p ra-
ventricu lar tachycard ias) inclu d e sinu s tachycard ia, atri-
al tachycard ias, AV nod al re-entrant tachycard ia (a typ e
of paroxysm al su praventricu lar tachycard ia), atrial flut-
ter and atrial fibrillation (see Figu re 15.1).

2. A p rolonged QRS d u ration (> 0.12 second s) is m ost often


the resu lt of a tachycard ia that originates below the AV
cond u ction system ; i.e., ventricu lar tachycard ia (VT). Oc-
casionally, a w id e QRS com p lex tachycard ia is the resu lt
of a su p raventricu lar tachycard ia (SVT) w ith p rolonged
cond u ction throu gh the AV nod e.

233
234 Critical Care Cardiology

He art Rate > 100 bpm

(QRS 0.12 s e c) (QRS > 0.12 s e c)

Narrow QRS Co mple x Wide QRS Co mplex


Tac hyc ardias Tac hyc ardias
1. S inus ta chyca rdia 1. Ve ntricula r ta chyca rdia
2. Atria l ta chyca rdia 2. S uprave ntricula r ta chyca rdia
3. AV noda l re -e ntra nt ta chyca rdia (S VT) with prolonge d AV
4. Atria l flutte r or fibrilla tion conduction

Irre gula r
Uniform Irre gula r R-R
R-R inte rva ls R-R inte rva ls inte rva ls

1. Sinus tachycardia 1. Multifoca l a tria l S VT with


2. AV noda l ta chyca rdia (MAT) prolonge d
re -e ntra nt 2. Atria l fibrilla tion (AF) AV conduction
ta chyca rdia
(AVNRT) AV dis s ocia tion
3. Atria l flutte r or fus ion be a ts

Eva lua te Atria l Activity Ve ntricula r


ta chyca rdia
S inus ta ch: uniform p wave s
AVNRT: no p wave s
A.flutte r: s awtooth wave s
MAT: multiple p wave morphologie s
AF: fibrilla tory wave s

FIGURE 15.1. Flow diagram for the evaluation of tachycardias using


selected criteria from the electrocardiogram.

B. Uniformity of the R-R intervals


The regu larity of the card iac rhythm is d eterm ined by the
Tachycardias 235

d istance betw een R w aves (the R-R interval) in a series of


consecutive heart beats. (A regu lar rhythm w ill p rod u ce R-R
intervals that are u niform in length from beat to beat). The
d iagnostic im plications of uniform and non-uniform R-R
intervals is show n in Figu re 15.1, and is su m m arized below.

1. Narrow QRS Complex Tachycardias


a. If the R-R interval is u niform (ind icating a regu lar
rhythm ), the p ossible rhythm s inclu d e sinu s tachycar-
d ia, AV nod al re-entrant tachycard ia, and atrial flu tter.
b. If the R-R interval is non-u niform (ind icating an irreg-
u lar rhythm ), the most likely rhythm s are mu ltifocal
atrial tachycard ia and atrial fibrillation.

2. Wide QRS Complex Tachycardias


a. A u niform R-R interval d oes not help to d istingu ish
ventricu lar tachycard ia from an SVT w ith p rolonged
AV cond u ction. In this situ ation, look for AV d issocia-
tion or fusion beats, w hich are evid ence of ventricular
tachycard ia (these ECG find ings are d escribed later in
the chap ter)
b. An irregu lar R-R interval is evid ence of an SVT w ith
p rolonged AV cond u ction.

C. Atrial Activity
The p attern of atrial activity can be very u sefu l in id entifying
the cau se of a narrow QRS com p lex tachycard ia, as ind icat-
ed at the bottom of Figu re 15.1.

1. For a narrow QRS com p lex tachycard ia w ith a regu lar


rhythm :
a. The p resence of u niform p w aves and a fixed PR inter-
val is evid ence of a sinu s tachycard ia.
b. The absence of p w aves is evid ence of an AV nod al re-
entrant tachycard ia (see Figu re 15.2).
c. The presence of sawtooth waves is evidence of atrial flutter.
236 Critical Care Cardiology

1 sec

FIGURE 15.2 AV nodal re-entrant tachycardia, a type of paroxysmal


supraventricular tachycardia (PSVT). Note the absence of p waves,
which are hidden in the QRS complexes.

2. For a narrow QRS com p lex tachycard ia w ith an irregular


rhythm (see Figu re 15.3):
a. The p resence of m u ltip le p w ave m orp hologies is evi-
d ence of m ultifocal atrial tachycard ia.
b. The p resence of fibrillatory w aves is evid ence of atrial
fibrillation.

FIGURE 15.3. Narrow QRS complex tachycardias with an irregular


rhythm. Panel A is a multifocal atrial tachycardia (note the multiple p
wave morphologies and variable PR intervals) and panel B is atrial fib-
rillation. (From the CD ROM provided with Critical care nursing: A
holistic approach. Philadelphia: Lippincott Williams & Wilkins, 2005.)
Tachycardias 237

II. ATRIAL FIBRILLATION


Atrial fibrillation (AF) is the m ost p revalent card iac arrhyth-
mia, affecting abou t 1% of the ad u lt p opu lation (3).

A. Predisposing Factors
1. Most p atients w ith AF are eld erly (m ed ian age 75 years)
and have u nd erlying heart d isease. Abou t 15% are
younger (< 60 yrs) and have no com orbid cond itions (3).
This latter cond ition is know n as lone atrial fibrillation.

2. H yp erthyroid ism is consid ered the m ajor extracard iac


sou rce of AF, but the im p ortance of this cond ition m ay be
overestim ated . In one su rvey of nu rsing hom e resid ents
w ith AF, not a single case of hyp erthyroid ism w as d is-
covered (4).

3. AF is very com m on in the first 3 to 4 d ays after card iac


su rgery. The incid ence is 30% follow ing coronary artery
byp ass su rgery and 60% follow ing valve surgery (5). The
etiology is u nclear, bu t 90% of cases convert sponta-
neou sly to sinu s rhythm w ithin 2 m onths (3).

B. Adverse Consequences
1. Cardiac Performance
a. The principal threat from AF is im paired ventricular
filling. The contributing factors are loss of atrial con-
tractions (w hich normally contribu te 25% of the ven-
tricular end -d iastolic volume) and a rapid heart rate
(w hich red uces d iastolic filling time). Diastolic d ys-
function (e.g., from left ventricular hypertrophy) mag-
nifies the d eleteriou s effects of AF on ventricu lar filling.
b. Card iac stroke ou tp u t w ill d ecrease in resp onse to the
change in ventricu lar filling, bu t the m agnitu d e of
change w ill d ep end on several factors (e.g., the pres-
ence and severity of systolic d ysfu nction).
238 Critical Care Cardiology

2. Atrial Thrombosis
Throm bu s form ation in the left atriu m can be app arent 72
hours after the onset of AF (7). These throm bi can (and
d o) break loose and enter the cerebral circu lation to pro-
d u ce em bolic stroke. The managem ent issu es related to
atrial throm bosis in AF are d escribed later in the chapter.

C. DC Cardioversion
Direct-current (DC) card ioversion, w hich is a p ainfu l and
anxiety-p rovoking experience for aw ake p atients, should be
reserved only for cases of AF w ith severe hem od ynam ic
com prom ise (hypotension or acu te p u lm onary ed em a). The
follow ing p rotocol has p roven successful in 90% of card io-
version attem pts (3):

1. Prem ed ication w ith an op iate (m orp hine or fentanyl) is


ad vised , and w ill p rovid e both analgesia and sed ation.

2. The DC shocks should be synchronized to the R w ave of


the QRS complex to avoid electrical stimulation d uring
the vulnerable period of ventricular repolarization, w hich
usually coincid es w ith the peak of the T w ave (3).

3. If the d efibrillator is an old er mod el that d elivers m ono-


p hasic shocks, begin w ith 200 jou les (J) for atrial fibrilla-
tion and 50 J for atrial flu tter. If ad d itional shocks are
need ed , increase the energy level by 100 J for each shock
u ntil a m axim u m strength of 400 J is reached .

4. For biphasic shocks (the w aveform used by new er mod el


d efibrillators), follow the protocol for monop hasic shocks
bu t d ecrease the energy of each shock by 50%.

D. Pharmacologic Cardioversion
1. Indications
Acu te card ioversion w ith an antiarrhythm ic agent is
Tachycardias 239

ap p rop riate for first episodes of A F that are less than 48


hours in duration and are not associated with hemodynamic
compromise. Su ccessfu l card ioversion in this situ ation w ill
avoid the need for long-term anticoagu lation. The d eci-
sion to attem p t card ioversion m u st be w eighed against
the fact that 50% of cases of new -onset AF convert sp on-
taneou sly to sinu s rhythm in the first 72 hou rs (6).

2. Drug Regimen
The m ost su ccessfu l antiarrhythm ic agent for acu te ter-
mination of AF is ibutilide (see d ose recom m end ation in
Table 15.1). Su ccessful card ioversion is achieved in over
50% of cases, and 80% of the resp onses occur w ithin 30
minutes of d ru g ad m inistration (7). The only risk associ-
ated w ith ibu tilid e is torsad es d e p ointes (d escribed la-
ter), w hich is rep orted in 4% of cases (7).

E. Acute Rate Control


When there is no im m ed iate threat to life, the m anagem ent
of AF is d irected at slow ing the heart rate to a target level of
60 to 80 bp m (3). This is accom p lished w ith the d ru g regi-
mens show n in Table 15.1. The d ru gs in this table share the
ability to slow imp u lse transm ission throu gh the AV nod e.

1. Diltiazem
a. Diltiazem is a calciu m -channel blocker that achieves
satisfactory rate control in 85% of patients with A F (8).
The acu te resp onse d issip ates in 1 3 hou rs, so a con-
tinu ou s infu sion (5 to 15 m g/ hr) is recom m end ed to
maintain rate control.
b. Diltiazem has negative inotropic actions, bu t is gener-
ally safe to u se in patients w ith systolic heart failu re (3).
2. -Blocker s
a. -Blockers are p referred for rate control w hen AF is
associated w ith hyp erad renergic states (e.g., after car-
d iac su rgery).
240 Critical Care Cardiology

TABLE 15.1 Acute Pharmacotherapy of Atrial Fibrillation


Drug Dose Regimen Comments
Cardioversion
Ibutilide 1 mg IVover 10 min Successful cardioversion
and repeat once if in 50% of cases, usually
needed. within 30 min.
Acute Rate Control
Diltiazem 0.25 mg/kg IVover Effective rate control in
2 min, then 0.35 mg/kg 85% of patients.
15 min later if needed. Safe to use in patients
Follow with infusion of with heart failure.
515 mg/hr for 24 hr.
Esmalol 500 g/kg IVover Ultra-short-acting
1 min, then infuse at -blocker that permits
50 g/kg/min. Increase rapid dose titration.
dose rate by 25 g/kg/min
every 5 min if needed to
maximum of 200 g/kg/min.
Metoprolol 2.55 mg IVover 2 min. Bolus dosing regimen
Repeat every 1015 min not optimal for precise
if needed to total of 3 rate control.
doses.
Amiodarone 300 mg IVover 15 min, A suitable alternative for
then 45 mg/hr for 24 hr. patients who do not
tolerate more effective
rate-reducing drugs.

From Reference 3. Amiodarone dos e regimen from Reference 17.

b. The -blockers w ith p roven efficacy in AF inclu d e


esmolol and metoprolol. Esm olol is p referred for
acu te rate control becau se it is u ltrashort-acting
(seru m half-life of 9 m inu tes) and the d ose rate can be
titrated rapid ly to m aintain the d esired heart rate (9).
Tachycardias 241

3. Amiodarone
a. When given as recom m end ed in Table 15.1, am iod a-
rone w ill p rod uce satisfactory rate red u ction in 75% of
p atients w ith AF (10).
b. Amiod arone is less effective than d iltiazem , bu t it pro-
d u ces less card iac d epression and hypotension than
d iltiazem (10). This creates a p ossible niche for am io-
d arone in p atients w ho d o not tolerate d iltiazem .
c. The ad verse effects of intravenou s am iod arone inclu d e
hyp otension (15%), infu sion phlebitis (15%), brad ycar-
d ia (5%), and elevated liver enzym es (3%) (7,11).
d . There are several potential d ru g interactions because
am iod arone is m etabolized by the cytochrom e P450
enzym e system in the liver. The interactions w ith d i-
goxin and w arfarin (blood levels increased by am io-
d arone) are m ost relevant in the ICU (11).

F. Antithrombotic Therapy
The risk of atrial throm bosis and su bsequ ent em bolic stroke
is one of the m ajor concerns in patients w ith AF.

1. Risk Categories
There are 3 risk categories for em bolic stroke (high, m od -
erate, and low risk), and Table 15.2 show s the clinical
characteristics for each category, along w ith the thera-
p eu tic recom m end ations.
a. For patients in the high risk category, the incid ence of
em bolic stroke is 6% per year w ithou t treatment, and
3% p er year w ith cou m ad in anticoagu lation to achieve
an IN R of 2 to 3. (12)
b. Patients in the m od erate-risk category have a 2% an-
nu al incid ence of em bolic stroke (w hich is low er than
the incid ence rep orted d u ring anticoagu lation therapy
w ith cou m ad in). Antiplatelet therap y w ith asp irin (325
m g d aily) is recom m end ed for these patients.
242 Critical Care Cardiology

c. Patients w ith lone atrial fibrillation (i.e., AF w ithout


com orbid cond itions in a p atient younger than 60 yrs
of age) have the sam e risk of em bolic stroke as the gen-
eral popu lation, so antithrom botic therap y is not re-
qu ired in these patients.

2. Cardioversion
For card ioversion of AF that is less than 48 hou rs in d u ra-
tion, the risk of embolism w ith card ioversion is low
(< 1%), so anticoagu lation is not need ed p rior to card io-
version (3). When the d u ration of AF exceed s 48 hours,
the risk of em bolization w ith card ioversion is abou t 6%,
and anticoagu lation is recom m end ed for 3 w eeks before
card ioversion is attem p ted .

TABLE 15.2 Antithrombotic Therapy &Risk of Embolic Stroke


High Risk
I. Oral Anticoagulation (INR= 2 3)
Age > 75 yrs
Age 60 yrs plus diabetes or coronary artery disease
Heart failure with LVejection fraction < 0.35
Heart failure with hypertension or thyrotoxicosis
Prosthetic heart valves (mechanical or tissue)
Rheumatic mitral valve disease
Prior thromboembolism
Moderate Risk
II. Antiplatelet Therapy (Aspirin, 325 mg daily)
Age < 60 yrs with heart disease, but no risk factors
Age 60 yrs with no risk factors
Low Risk
III. No Therapy Required
Age <60 yrs and no heart disease (Lone AF)
Ris kfactors include heart failure, LV ejection fraction <0.35. and a
his tory of hypertens ion.
Tachycardias 243

G.WolffParkinsonWhite (WPW) Syndrome


1. The WPW synd rom e (short PR interval and d elta w aves
before the QRS) is characterized by recu rrent su p raven-
tricu lar tachycard ias that originate from an accessory (re-
entrant) p athw ay in the AV cond uction system (2). One
of these tachycard ias is atrial fibrillation.

2. In cases of A F associated with W PW syndrome, calcium-chan-


nel blockers and digoxin are contraindicated because these
d ru gs can parad oxically accelerate the ventricular rate
(by blocking the w rong pathw ay).

3. The treatm ent of choice for this typ e of tachycard ia is


electrical card ioversion or card ioversion w ith procain-
am id e. (The p rocainam id e d osing regim en is: 100 m g IV
over 2 m inu tes, then u p to 25 m g/ m in IV to a m axim u m
of one gram in the first hour, then 2 to 6 m g/ m in.)

III. MULTIFOCAL ATRIALTACHYCARDIA

A. Features
Mu ltifocal atrial tachycard ia (MAT) is a narrow QRS tachy-
card ia w ith an irregu lar rhythm , and is characterized by
mu ltiple p w ave m orp hologies and a variable PR interval
(see Figu re 15.3). It is seen m ost often in the eld erly (average
age = 70), and over half of the cases occu r in patients w ith
chronic lu ng d isease (13).

B. Acute Management
MAT can be d ifficu lt to manage, bu t the follow ing m easu res
can be effective.

1. Start w ith intravenou s magnesium: m ix 2 gram s MgSO 4


in 50 m L saline and infu se over 15 m inu tes, then m ix 6
244 Critical Care Cardiology

gram s MgSO 4 in 500 m L saline and infu se over 6 hours


(14). This regim en has been su ccessfu l in converting
MAT to sinu s rhythm in 88% of attemp ts, even w hen
serum magnesium levels are norm al. The m echanism is
unclear, bu t the actions of m agnesiu m as a calciu m -chan-
nel blocker m ay be resp onsible.

2. Correct hyp omagnesem ia and hypokalem ia if p resent. If


these electrolyte d isord ers co-exist, the m agnesiu m d efi-
ciency m ust be corrected before p otassiu m replacem ent
is started . (The reason for this is exp lained in Chap ter 28).
Use the follow ing replacem ent p rotocol: 2 m g MgSO 4 (in
50 m L saline) IV over 15 m inu tes, then 40 mg potassium
IV over 1 hou r.

3. If the above m easu res are ineffective, give IV metoprolol


(a -blocker) as d irected in Table 15.1. This regimen has
been su ccessfu l in converting MAT to sinu s rhythm in as
many as 80% of attem pts (13).
a. If m etoprolol cannot be given safely (e.g., p atient has
reactive airw ays d isease), give verapamil (a calciu m -
channel blocker) in a d ose of 7 150 m g/ kg IV over 2
m inu tes (3). Verap am il converts MAT to sinu s rhythm
in less than 50% of cases, bu t it can also slow the ven-
tricu lar rate. Watch for hyp otension, w hich is a com-
m on sid e effect of verap am il.

IV. PAROXYSMAL SUPRAVENTRICULAR


TACHYCARDIA

A. Features
1. Paroxysmal su p raventricu lar tachycard ia (PSVT) is a
narrow QRS com plex tachycard ia w ith a regu lar rhythm
and an abru pt onset.
Tachycardias 245

2. The sou rce of these arrhythm ias is an accessory pathway


that cond ucts im pulses at a d ifferent speed than the nor-
m al cond u ction pathw ays. The d ifference in cond u ction
velocities allow s an im pulse traveling d ow n one path-
w ay (antegrad e transm ission) to travel u p the other path-
w ay (retrograd e transm ission). This circu itou s transm is-
sion of im pu lses creates a self-su staining re-entrant tachy-
cardia. The trigger is an ectopic impulse that travels through
one of the pathways.

3. There are 5 d ifferent typ es of PSVT, each w ith a d ifferent


location for the accessory p athw ay. The m ost com m on is
AV nodal re-entrant tachycardia, w here the accessory path-
w ay is in the AV nod e.

B. AV Nodal Re-entrant Tachycardia


1. Features
a. AV nod al re-entrant tachycard ia (AVN RT) is a narrow
QRS com p lex tachycard ia w ith a regu lar rhythm and a
rate betw een 140 and 220 bp m . It d iffers from sinus
tachycard ia in that the onset is abru p t and there are no
d iscernible p w aves on the ECG (see Figu re 15.2).
b. This arrhythm ia is typ ically seen in relatively you ng
ad u lts w ith no com orbid cond itions w ho com p lain of
the su d d en onset of p alp itations, d ysp nea, and chest
p ains.

2. Adenosine
a. Ad enosine is an end ogenou s p u rine nu cleotid e that
briefly d ep resses activity in the sinus and AV nod es.
When given by rap id intravenous injection, ad enosine
term inates AV re-entrant tachycard ias in over 90% of
cases (15). The effect is u su ally app arent w ithin 30 sec-
ond s, and the AV block lasts only 1 2 m inu tes.
b. A sum m ary of the clinical u se of ad enosine is p resent-
ed in Table 15.3
246 Critical Care Cardiology

c. N ote that perip heral veins are preferred for ad enosine


injection. This is based on rep orts show ing that ad eno-
sine injection (in stand ard d oses) throu gh central ve-
nous catheters can provoke brief period s of card iac
stand still (16). If a central venou s catheter is u sed for
ad enosine injection, the d ose m u st be red u ced by 50%.
d . Sid e effects are com m on after ad enosine injection, bu t
most d isappear rap id ly becau se of ad enosines u ltra-
short d uration of action. One of the trou blesom e sid e
effects is bronchoconstriction in asthm atic subjects
(17), w hich is w hy ad enosine shou ld N OT be u sed in
p atients w ith asthm a.

TABLE 15.3 Adenosine for AVNodal Re-entrant Tachycardia


I. Injection site:
Use a peripheral vein for drug injection if possible.
If a central vein is used, reduce adenosine dose by 50%.
II. Dosing Regimen:
1. Give 6 mg by rapid injection and follow with 20 mL saline
flush.
2. If no response after 2 min, give a second dose of 12 mg.
3. The 12 mg dose can be repeated once if necessary.
III. Transient Reactions:
Facial flushing (50%)
Sinus bradycardia, AVblock (50%)
Dyspnea (35%)
Chest pain (20%)
Nausea, headache, dizziness (5 10%)
IV. Drug Interactions:
Theophylline antagonizes the actions of adenosine.
Adenosine effect is enhanced by -blockers, calcium-channel
blockers, and dipyridamole. (Reduce adenosine dose 50%).
V. Contraindications: Asthma, AVblock, sick sinus syndrome
AV = atrioventricular. From References 15 17.
Tachycardias 247

3. Calcium-Channel Blockers
In u ncom m on cases w here ad enosine is ineffective or not
tolerated , calcium -channel blockers can be u sed to term i-
nate AVN RT. One recom m end ed d ru g regim en is show n
below (18):

Diltiazem: 0.25 m g/ kg IV over 2 m inu tes. If no resp onse,


give 0.35 m g/ kg over 2 minu tes. After conversion to
sinu s rhythm , infuse at 5 15 m g/ hr for 24 hou rs.

It is very im p ortant to ru le ou t Wolff-Parkinson-White


(WPW) synd rom e as a cause of the PSVT before giving
calciu m-channel blockers becau se of the potential for
these d ru gs to increase the ventricu lar rate in tachycar-
d ias associated w ith WPW (see earlier in the chapter).

V.VENTRICULAR TACHYCARDIA
Ventricu lar tachycard ia (VT) is a w id e QRS com plex tachy-
card ia that has an abru p t onset, a regu lar rhythm , and a rate
above 100 bpm . VT that lasts longer than 30 second s (su s-
tained VT) is a p otentially life-threatening arrhythm ia that
requ ires p rom p t attention.

A.VT versus SVT


VT can be d ifficult to d istinguish from an SVT w ith pro-
longed cond u ction throu gh the AV nod e. This is d em onstrat-
ed in Figu re 15.4 The tracing in the u p p er p anel show s a
w id e QRS com plex tachycard ia that looks like VT. The trac-
ing in the low er panel show s spontaneous conversion to si-
nu s rhythm . N ote that the QRS com p lex rem ains u nchanged
after the arrhythm ia is term inated , revealing an u nd erlying
bu nd le branch block. Thu s, the app arent VT in the u pp er
p anel is actu ally a paroxysm al SVT w ith a p re-existing bun-
d le branch block.
248 Critical Care Cardiology

FIGURE15.4. An apparent VT (upper panel) that is actually an SVT with


aberrant (prolonged) AV conduction. The correct diagnosis is evident
only when spontaneous conversion to sinus rhythm (in the lower panel)
reveals a pre-existing bundle branch block. (Tracings courtesy of Dr.
Richard M. Greenberg, M.D.).

1. Evidence of VT
The p resence of either of the follow ing ECG abnorm ali-
ties is evid ence that the rhythm d istu rbance is VT.
a. AV DISSOCIATION. The atria and ventricles beat inde-
pend ently in VT, so the lack of a fixed relationship
betw een P w aves and QRS complexes is evid ence of VT.
b. FUSION BEATS. A fu sion beat is an irregu larly-shap ed
QRS com p lex that ju st preced es the onset of VT. These
com p lexes are the resu lt of retrograd e transm ission of
a ventricular ectop ic im p u lse that m erges (fu ses) w ith
a norm al QRS com p lex. The p resence of a fu sion beat
is therefore evid ence of ventricu lar ectopic activity.

2. Primary Heart Disease


A sim plified approach to d istingu ishing VT from SVT
w ith aberrant cond u ction is to consid er the p resence or
Tachycardias 249

absence of heart d isease.


a. VT is the cau se of 95% of w id e com p lex tachycard ias
in p atients w ith p rim ary heart d isease (19).
b. Therefore, a wide QRS complex tachycardia in any patient
with primary heart disease should be treated as V T.

B. Acute Management
The m anagem ent of p atients w ith a w id e QRS com p lex
tachycard ia can p roceed as follow s. This ap p roach is organ-
ized in a flow d iagram in Figu re 15.5.

WIDE QRS COMPLEX TACHYCARDIA


WITH UNIFORM MORPHOLOGY

Is the patie nt s table ?

N Y

1 IMMEDIATE CARDIOVERS ION


1. Us e s ynchronize d s hocks.
Are yo u s ure the rhythm is VT?
2. S ta rt a t 100 J.
3. Re pe a t if ne e de d a nd a dd 100 J
to e a ch s ucce s s ive s hock.

Y N

2 INTRAVENOUS AMIODARONE
1. Give 150 mg IV ove r 10 min. 3 INTRAVENOUS ADENOS INE
2. Follow with 1 mg/min infus ion
for 6 hours, the n 0.5 mg/min 1. S ta rt with 6 mg IV pus h.
infus ion for 18 hours. 2. If no re s pons e in 2 min,
3. Additiona l dos e s of 150 mg IV give 12 mg IV pus h.
ca n be give n eve ry 10 min a s 3. If no re s pons e in 2 min,
ne e de d. give 12 mg IV pus h.
4. Ma ximum da ily dos e is 2.2 g. 4. If no re s pons e, go to box #2.

FIGURE 15.5. Flow diagram for the acute management of patients with
wide QRS complex tachycardias. (From Reference 1).
250 Critical Care Cardiology

1. If there is evid ence of hem od ynam ic com p rom ise, initiate


DC card ioversion im m ed iately w ith an initial shock of
100 J, follow ed by rep etitive shocks of 200, 300, and 360 J,
if necessary. This is necessary regard less of w hether the
rhythm is VT or SVT w ith aberrant cond u ction.

2. If there is no evid ence of hem od ynam ic com prom ise and


the d iagnosis of VT is certain, start intravenou s amio-
darone to term inate the arrhythm ia (see Figu re 15.5 for
the am iod arone d osing regim en) (1).

3. If there is no evid ence of hem od ynam ic com prom ise and


the d iagnosis of VT is u ncertain, intravenous adenosine can
help to unmask a paroxysmal SV T. Ad enosine w ill not ter-
minate VT, bu t it w ill abru p tly term inate m ost cases of
p aroxysm al SVT. If the arrhythm ia p ersists after ad eno-
sine, VT is the likely d iagnosis, and intravenou s am io-
d arone is ind icated to term inate the rhythm .

4. Lidocaine can be u sed to term inate VT in p atients w ho


d o not tolerate am iod arone. The initial d ose is 1 to 1.5
mg/ kg by bolu s injection. After 5 m inu tes, a second d ose
of 0.5 to 0.75 m g/ kg can be given if need ed . A m ainte-
nance infu sion of 2 to 4 m g/ m in can be u sed for contin-
u ed arrhythmia su p pression. Lid ocaine infu sions shou ld
not extend beyond 6 to 12 hou rs becau se p rolonged infu -
sions can p rod u ce an excitatory neu rotoxic synd rom e.

VI. TORSADES DE POINTES

A. General Features
1. Torsad es d e p ointes (tw isting arou nd the p oints) is a
p olym orp hic VT that is associated w ith a p rolonged QT
interval (20). The nam e d erives from the ap p earance of
the QRS com p lexes as tw isting arou nd the isoelectric line
of the ECG (see Figu re 15.6).
Tachycardias 251

FIGURE15.6. Torsades de pointes, a polymorphic ventricular tachycardia


that appears to be twisting around the isoelectric line of the ECG.
(Tracing courtesy of Dr. Richard M. Greenberg, M.D.).

2. Polym orp hic VT w ith a norm al QT interval is not tor-


sad es d e p ointes, and is sim p ly called p olym orp hic VT.

3. Measuring the QT Interval


The QT interval is u sually m easu red in lim b lead II, and
mu st be corrected for the heart rate. The rate-corrected
QT interval (QTc) is equ ivalent to the m easu red QT inter-
val d ivid ed by the squ are root of the R-R interval (21).

QTc = QT/ " ww


RR (15.1)

A prolonged QT interval is defined as a QTc > 0.44 seconds.

B. Etiologies
Torsad es d e pointes can be congenital (id iopathic) or ac-
qu ired . The acqu ired form is cau sed by a variety of d rugs
and electrolyte d isord ers that p rolong the QT interval.

1. The d ru gs that can trigger this arrhythm ia are listed in


Table 15.4 (22,23).

2. The electrolyte d isord ers that m ay be resp onsible are


hyp okalem ia, hyp om agnesem ia, or hyp ocalcem ia (20).

C. Management
The m anagem ent of p olym orp hic VT w ith a norm al QT
252 Critical Care Cardiology

interval is the sam e as d escribed for m onom orphic VT (i.e.,


am iod arone). The m anagem ent of torsad es d e p ointes d e-
pend s on w hether the QT p rolongation is congenital or ac-
qu ired .

1. The congenital form is managed w ith ventricular pacing


to raise the heart rate above 100 bpm. The increased rate
shortens the QT interval and red uces the tend ency for VT.

2. The acqu ired form is treated as follow s:


a. Use intravenou s m agnesiu m (Mg ++) for acu te m anage-
m ent: Start w ith 2 gram s Mg ++ (as MgSO 4) injected
over one m inu te, and rep eat 10 m inu tes later if need -
ed . Follow w ith a continu ou s infu sion of 1 gram Mg ++
p er hou r for the next 6 hou rs.
b. Id entify and d iscontinue any d ru gs that prolong the
QT interval.
c. Id entify and correct any relevant electrolyte abnorm al-
ities. Mg ++ d eficiency is the p rincip al concern here,
particu larly since hypokalem ia and hyp ocalcem ia can
be the result of an u nd erlying Mg ++ d eficiency. (For
more inform ation on Mg ++ d eficiency, see Chap ter 28).

TABLE 15.4 Drugs That Can Trigger Torsades de Pointes


Anti- Anti-
Antiarrhythmics microbials psychotics Others

IA {
Quinidine
Procainamide
Clarithromycin Chlorpromazine Cisapride
Erythromycin Haloperidol Droperidol
Flecainide Gatifloxacin Thioridazine Methadone

III {
Ibutilide
Sotalol
Levofloxacin
Pentamidine
From References 22,23.
Tachycardias 253

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19. Akhtar M, Shenasa M, Jazayeri M, et al. Wid e QRS com p lex
tachycard ia. Ann Intern Med 1988; 109:905912.
20. Vu km ir RB. Torsad es d e p ointes: a review. Am J Em erg Med
1991; 9:250262.
21. Garson A Jr. H ow to m easure the QT interval: w hat is norm al?
Am J Card iol 1993; 72:14B16B.
22. Frothingham R. Rates of torsad es d e pointes associated w ith ci-
p rofloxacin, oflaxacin, levofloxacin, gatifloxacin, and m oxiflox-
acin. Pharm acotherapy 2001; 21:14681472.
23. Rod en DM. Dru g-ind u ced p rolongation of the QT interval. N
Engl J Med 2004; 350:10131022.
Chapter 16
ACUTE RESPIRATORY
DISTRESS SYNDROME
The cond ition d escribed in this chap ter, w hich has the non-
d escript nam e acute respiratory distress syndrome (ARDS), is
the lead ing cau se of acu te resp iratory failu re, and is charac-
terized by w id esp read inflam m ation in the lu ngs, often ac-
com panied by inflam m atory inju ry in other organs (13).

I. FEATURES

A. Pathogenesis
1. ARDS is a d iffu se inflam m atory p rocess that involves
both lu ngs.

2. The p rocess u su ally begins w ith activation of circu lating


neu trop hils, w hich ad here to the end otheliu m of the pu l-
monary cap illaries. The neu trop hils then release the con-
tents of their cytop lasm ic granu les, w hich d am ages the
end otheliu m and prod uces a leaky-capillary type of exu -
d ation into the lung parenchym a.

3. N eu trop hils cross the cap illary end otheliu m and p ro-
d u ce an inflamm atory inju ry of the lu ng parenchym a,
and this tissu e d am age p rom otes fu rther inflam m ation,
creating a viciou s cycle that lead s to progressive respira-
tory insu fficiency.

B. Predisposing Conditions
A variety of cond itions p red isp ose to ARDS, and the m ost
notable are listed in Table 16.1.
255
256 Common Pulmonary Disorders

1. The m ost comm on pred isp osing cond itions are those that
trigger a system ic inflam m atory response (i.e., fever and
leu kocytosis). The m ost com m on of these is the sepsis syn-
drome, w hich is a local or blood stream infection associat-
ed w ith a system ic inflam m atory resp onse. The incid ence
of ARDS in the sep sis synd rom e is as high as 40% (4).

TABLE 16.1 Predisposing Conditions for ARDS


1. Conditions associated with a systemic inflammatory response
(fever, leukocytosis):
a. Sepsis syndrome
b. Endotoxemia
c. Extensive tissue injury
d. Cardiopulmonary bypass
2. Local conditions in the lungs:
a. Gastric acid aspiration
b. Pneumonia
c. Pulmonary contusion
d. Ventilator-induced lung injury
3. Embolism syndromes:
a. Fat embolism syndrome
b. Amniotic fluid embolism
4. Miscellaneous conditions:
a. Blood transfusions
b. Drugs
c. Pancreatitis
d. Intracranial hypertension.

2. If the p red isposing cond itions are com bined , the inci-
d ence of ARDS is abou t 25%, and the p resence of ARDS
increases the m ortality rate threefold (4).
Acute Respiratory Distress Syndrome 257

C. Clinical Manifestations
1. The earliest signs of ARDS inclu d e tachyp nea and p ro-
gressive hypoxem ia, w hich is often refractory to su p ple-
mental oxygen. Fever is comm on and may be p resent
from a pred isposing cond ition.

2. The chest x-ray can be u nrevealing in the first few hou rs


of the illness. H ow ever by 24 hou rs after sym p tom onset,
the chest x-ray reveals bilateral p u lm onary infiltrates (see
Figu re 16.1).

3. Progressive hyp oxem ia lead ing to d ep end ence on m ech-


anical ventilation often occu rs in the first 48 hou rs of the
illness.

FIGURE 16.1. Portable chest x-ray from a patient with ARDS. The infil-
trates appear to be distributed uniformly throughout both lower lung
fields. The actual location of the infiltrates in ARDS is shown in Figure 16.2.
258 Common Pulmonary Disorders

II. DIAGNOSIS

A. Diagnostic Criteria
1 The d iagnosis of ARDS requ ires all of the cond itions list-
ed in Table 16.2 (5). N ote the term acute lung injury (ALI),
w hich is a less severe form of ARDS.

2. The cond itions m ost often confu sed w ith ARDS are mul-
tilobar pneumonia and cardiogenic pulmonary edema. Multi-
lobar p neu m onia can be ind istingu ishable from ARDS
based on the d iagnostic criteria in Table 16.2, and card io-
genic p u lm onary ed em a can be m istaken as ARDS be-
cau se of the lim itations of the w ed ge p ressu re m easu re-
m ent (see next).

TABLE 16.2 Diagnostic Criteria for ARDS and ALI


1. Acute onset
2. Presence of a predisposing condition
3. Bilateral infiltrates on chest x-ray
4. PaO2/FIO2 < 200 mm Hg for ARDS
PaO2/FI O2 = 200 300 mm Hg for ALI
5. Pulmonary artery occlusion pressure 18 mm Hg or no clinical
evidence of left heart failure.

B. ARDS vs. Hydrostatic Pulmonary Edema


The clinical p resentation of ARDS and hyd rostatic (card io-
genic) p u lm onary ed em a can be ind istingu ishable, and the
pu lm onary artery occlu sion p ressu re (know n as the wedge
pressure and d escribed in Chap ter 8) is consid ered a valu able
measurement for d ifferentiating betw een the 2 cond itions.
As ind icated in Table 16.2, a w ed ge p ressu re 18 m m H g is
consid ered evid ence of ARDS, and a w ed ge p ressu re above
Acute Respiratory Distress Syndrome 259

18 m m H g is consid ered evid ence of hyd rostatic p ulm onary


ed em a. The p roblem here is that the w ed ge p ressu re is not a
measure of capillary hyd rostatic pressure (see next).

1. Pitfalls of the Wedge Pressure


a. As d escribed in Chap ter 8, the w ed ge p ressu re is a
measure of left atrial p ressu re, and the p u lm onary cap-
illary hyd rostatic pressure is higher than the left atrial
p ressu re (if the 2 p ressures w ere equ ivalent, there
w ou ld be no p ressu re grad ient for flow in the p u lm o-
nary veins).
b. The w ed ge pressu re w ill therefore u nd erestim ate the
actu al capillary hyd rostatic p ressure. In cond itions
w here the p u lmonary venou s resistance is elevated
(e.g., d uring m echanical ventilation), the w ed ge p res-
su re m ay be consid erably low er than the cap illary
hyd rostatic p ressu re. This m eans that a wedge pressure
18 mm Hg does not exclude the possibility of hydrostatic
pulmonary edema.

2. Bronchoalveolar Lavage
Althou gh rarely u sed , bronchoalveolar lavage is a reli-
able test for d istingu ishing ARDS from hyd rostatic p u l-
monary ed em a. This p roced ure is p erform ed at the bed -
sid e u sing a flexible bronchoscop e that is ad vanced into
one of the involved lu ng segm ents. Once in p lace, the
lu ng segm ent is lavaged w ith isotonic saline. The lavage
fluid is then analyzed for neutrophil d ensity and protein
concentration.
a. In p u lm onary ed em a, neu trop hils w ill m ake u p less
than 5% of the cells recovered in lu ng lavage flu id ,
w hereas in ARDS, as m any as 80% of the recovered
cells are neu trophils (6).
b. Inflam m atory exu d ates are rich in p roteinaceou s m ate-
rial, and lu ng lavage flu id in ARDS is sim ilarly rich in
p rotein. When the p rotein concentration in lung la-
vage flu id is expressed as a fraction of the p lasm a p ro-
260 Common Pulmonary Disorders

tein concentration, the follow ing criteria can be applied


(7):

lavage p rotein/ p lasm a protein < 0.5 = hyd rostatic ed em a


lavage p rotein/ p lasm a protein > 0.7 = ARDS

III. MANAGEMENT
Since ARDS w as first d escribed in 1967, only one therapeu -
tic m anip u lation has p roven effective in im p roving su rvival
in ARDS: i.e., the u se of red u ced inflation volu mes d u ring
mechanical ventilation. This is not really a sp ecific therap y
for ARDS, bu t is a lessening of the harm fu l effects of m ech-
anical ventilation on the lu ngs.

A.Ventilator-Induced Lung Injury


Since the introd u ction of p ositive-p ressu re m echanical venti-
lation, large inflation volu m es (tid al volu mes) have been
used to red u ce the tend ency for atelectasis d u ring m echani-
cal ventilation.

1. The stand ard tid al volu mes d u ring m echanical ventila-


tion are 10 to 15 m L p er kg bod y w eight, w hich are abou t
tw ice the size of norm al tid al volu m es record ed d u ring
qu iet breathing (6 to 7 m L/ kg).

2. In patients w ith ARDS, the large inflation volu m es are


d elivered into lu ngs that have a m arked red u ction in
fu nctional volum e. The d ecreased fu nctional volu m e in
ARDS is evid ent in Figu re 16.2. N ote that the lu ng con-
solid ation is confined to the p osterior or d ep end ent lu ng
regions. The relatively sm all region of u ninvolved lu ng
in the anterior portion of the thorax is the region w here
the inflation volu m es from the ventilator are d istribu ted .
Acute Respiratory Distress Syndrome 261

Re duc e d
Lung
Capac ity

Infla mma tory Infla mma tory


Infiltra te Infiltra te
Pos te rior Pos te rior

FIGURE 16.2 CT images of lung slices in a patient with ARDS. Lung


capacity is reduced by the consolidation in the posterior lung regions,
and the bulk of mechanical ventilation is delivered to the uninvolved
lung regions in the anterior thorax. (CT images digitally retouched.
From Rouby J-J, et al. Crit Care Med 2003; 31(Suppl):S285-S295.)

3. Becau se the fu nctional lu ng volu m e in ARDS is m ark-


ed ly red u ced , the large inflation volu m es d elivered by
mechanical ventilation cause overd istension and ru p-
tu re of the d istal airsp aces. This volum e-related inju ry is
know n as volutrauma. (Pressu re-related lu ng inju ry is
called barotrauma).

4. Volu trau m a p rod u ces stress-fractu res in the alveolar cap -


illary interface, and this lead s to infiltration of the d istal
airsp aces w ith an inflam m atory cells and p roteinaceou s
material. The resu lting clinical cond ition is called ventila-
tor-induced lung injury, and the p athologic changes look
strikingly sim ilar to ARDS (8).

5. The d am aging effects of m echanical ventilation m ay not


be confined to the lu ngs; i.e., inflam m atory m ed iators
that accu m u late in the lu ngs in resp onse to volu trau m a
could enter the system ic circu lation and travel to d istant
organs to p rod u ce w id esp read inflam m atory inju ry and
mu ltiorgan d ysfu nction (9).
262 Common Pulmonary Disorders

B. Low-Volume Ventilation
To red uce the risk of ventilator-ind u ced lu ng inju ry, a new
strategy has been ad op ted for m echanical ventilation in
ARDS that u ses red uced tid al volu m es (6 m L/ kg instead of
the u su al 10 to 15 m L/ kg). Som e clinical trials have show n
a su rvival benefit associated w ith low -volu m e ventilation in
ARDS (10,11).

1. Protocol
a. A p rotocol for low -volu m e ventilation in ARDS is
show n in Table 16.3. This p rotocol has 3 objectives: (1)
maintain a tid al volu m e no higher than 6 m L/ kg, (2)
keep the end -insp iratory p lateau p ressure below 30 cm
H 2O (this pressure is d escribed in Chap ter 18), and (3)
avoid severe respiratory acid osis.
b. N ote that the tid al volu m es in this p rotocol are based
on predicted body weight (w hich is the w eight that best
corresp ond s to normal lu ng volu m es).

2. Permissive Hypercapnia
One of the consequ ences of low -volu m e ventilation is
red u ced CO 2 elim ination, w hich can lead to hyp ercap nia
and resp iratory acid osis. Allow ing hypercap nia to p ersist
in favor of m aintaining low -volu m e ventilation is know n
as permissive hypercapnia (12).
a. Clinical trials of p erm issive hyp ercap nia have show n
that arterial PCO 2 levels of 60 to 70 m m H g and arteri-
al pH levels of 7.2 to 7.25 are safe for m ost p atients
(13). The p rotocol in Table 16.3 is d esigned to keep the
arterial p H above 7.15, bu t the p referred arterial p H is
7.30 to 7.45.
b. Carbon d ioxid e is a p ow erfu l resp iratory stim u lant,
and even m ild d egrees of hyp ercap nia can lead to in-
creases in respiratory rate that interfere w ith effective
mechanical ventilation. If this occu rs, neu rom u scu lar
paralysis m ay be necessary.
Acute Respiratory Distress Syndrome 263

TABLE 16.3 Protocol for Low-Volume Ventilation in ARDS


I. First Stage:
1. Calculate patients predicted body weight (PBW).
Males: PBW = 50 + [2.3 x (height in inches 60)]
Females: PBW = 45.5 + [2.3 x (height in inches 60)]
2. Set initial tidal volume (VT) at 8 mL/kg PBW.
3. Add positive end-expiratory pressure (PEEP) of 5 7 cm H2O.
4. Reduce VT by 1 mL/kg every 2 hours until VT = 6 mL/kg.
5. Adjust FIO2 to achieve SaO2 90%.
II. Second Stage:
1. When VT = 6 mL/kg, measure plateau pressure (Ppl).
2. If Ppl > 30 cm H2O, decrease VT in 1 mL/kg increments until
Ppl < 30 cm H2O or VT = 4 mL/kg.
III. Third Stage:
1. Monitor arterial blood gases for respiratory acidosis.
2. If pH = 7.15 7.30, increase respiratory rate (RR) until
pH >7.30 or RR = 35 bpm.
3. If pH < 7.15, increase RR to 35 bpm. If pH still < 7.15,
increase VT in 1 mL/kg increments until pH >7.15.
IV. Optimal Goals:
VT = 6 mL/kg, Ppl < 30 cm H2O, pH = 7.30 7.45
Adapted from the protocol developed by ARDS Network, available
at www.ards net.org/s tudies /arma.

3. Positive End-Expiratory Pressure (PEEP)


Low -volu me ventilation is often accom panied by col-
lap se of term inal airw ays at the end of exp iration and re-
opening of the airw ays d u ring lu ng inflation. This repet-
itive op ening and closing of term inal airw ays can itself
be a sou rce of lung inju ry (p ossibly by creating shear
forces that d amage the airw ay ep itheliu m ) (14). This
p roblem can be corrected (at least p artially) by u sing p os-
itive end -expiratory pressure (PEEP) to red u ce the ten-
264 Common Pulmonary Disorders

d ency for airw ay collap se at end -exp iration. (PEEP is


d escribed in Chap ter 20.)
a. The u se of low -level PEEP (5 7 cm H 2O) is a stand ard
practice d u ring low -volu me ventilation. There is no
ad d ed benefit from higher levels of PEEP (for p revent-
ing airw ays collap se) (15).
b. H igher levels of PEEP can be u sed , if necessary, to re-
d u ce the fractional concentration of inhaled oxygen
(FIO 2) to safe levels. PEEP op ens d istal airsp aces (alve-
olar recru itm ent), and this effect im p roves arterial oxy-
genation and allow s a red uction in the FIO 2. When an
FIO 2 > 60% is need ed to maintain an SaO 2 90% (or
88% if a p u lse oxim eter is u sed to m easu re SaO 2),
PEEP is ad d ed in increm ents of 2 4 cm H 2O u ntil the
FIO 2 can be red uced below 60%. (The risk of p ulm o-
nary oxygen toxicity is consid ered m inim al w hen the
FIO 2 is below 60%).

C. Fluid Management
Fluid m anagem ent in ARDS is usually aim ed at red ucing ex-
travascu lar lu ng w ater w ith d iu retics. While this ap p roach
has show n m od est benefits in clinical m easures like lung
com pliance, gas exchange, and length of tim e on the ventila-
tor, there is little evid ence of a consistent su rvival benefit
(16,17). The follow ing are som e p roblems w ith d iu retic ther-
ap y in ARDS that d eserve m ention.

1. Problems with Diuretic Therapy in ARDS


a. The first problem w ith d iuretic therap y in ARDS is the
natu re of the lu ng infiltration. Diuretics are u sed to re-
d u ce w atery ed em a flu id . H ow ever, the lung infiltration
in A RDS is an inflammatory process, and diuretics dont
reduce inflammation.
b. The second problem w ith d iuretic therap y in ARDS is
the risk for hem od ynam ic com p rom ise. Most p atients
w ith ARDS are receiving p ositive-p ressu re m echanical
Acute Respiratory Distress Syndrome 265

ventilation, and venou s p ressu res m u st be higher than


norm al to exceed the positive intrathoracic pressu res
and m aintain venou s retu rn to the heart. Diu retic ther-
ap y can com p rom ise venou s retu rn to the heart, and
the resu lting d ecrease in card iac ou tp u t w ill ad versely
affect system ic oxygen transp ort. H em od ynam ic m on-
itoring w ith a pu lm onary artery catheter can provid e
valu able inform ation if aggressive d iu retic therap y is
p lanned .

B. Blood Transfusions
1. The trad itional p ractice of transfu sing RBCs to m aintain
a hem oglobin of 10 gm / d L has no d ocu m ented benefit in
ICU p atients, inclu d ing ventilator-d ep end ent p atients
(18). A low er transfusion threshold of 7 gm / d L has p ro-
ven safe in ICU p atients, excep t p ossibly p atients w ith
active coronary artery d isease (19).

2. Consid ering that blood transfu sions can cause ARDS, and
that this comp lication m ay be m uch m ore com m on than
recognized (20), it is w ise to avoid RBC transfu sions
w henever possible in p atients w ith ARDS.

3. See Chap ter 30 for m ore inform ation on anem ia and


blood transfu sions in the ICU.

C. Pharmacotherapy
1. Steroids
H igh-d ose steroid therap y has no effect on ARDS w hen
given w ithin 24 hou rs of the onset of illness (21). H ow -
ever w hen steroid s are given later in the cou rse of illness,
d u ring the fibrinop roliferative phase that begins 7 14
d ays after the onset of illness, there is a d efinite su rvival
benefit (22). One of the su ccessfu l regim ens involves
methylp red nisolone in a d ose of 2 to 3 m g/ kg/ d ay.
266 Common Pulmonary Disorders

2. Failed Therapies
Several attem p ted therap ies for ARDS have failed to
show a su rvival benefit. The failed therap ies inclu d e su r-
factant (in ad u lts), nitric oxid e, p entoxyp hylline, liso-
p hylline, ibup rofen, p rostagland in E1, ketoconazole, and
N -acetylcysteine (16,17).

D. Misdirected Therapy?
Attem pts at treating ARDS have been d irected prim arily at
the lu ngs, bu t a m ajority of d eaths in p atients w ith ARDS are
the resu lt of m u ltiorgan failu re rather than respiratory
(2325). The relationship betw een m ortality and m u ltiorgan
failu re in ARDS is show n in Figu re 16.3 (24,25). N ote the
stead y rise in m ortality rate as the nu m ber of organ failu res
increases. This relationship su ggests that the therap eu tic

100 Nine Hos pita ls (N = 201)

One Hos pita l (N = 80)


80
)
%
60
(
y
t
i
l
a
t
r
o
40
M
20

0
Lungs +2 +4

Orga ns Fa ile d

FIGURE 16.3. Mortality rate in ARDS as a function of number of organs


failed. Data from References 24 and 25.
Acute Respiratory Distress Syndrome 267

ap p roach to ARDS shou ld be d irected aw ay from the lu ngs


and tow ard a m ore system ic inflamm atory d isord er if there
is to be a su rvival benefit.

REFERENCES
1 Ware LB, Matthay MA. The acute resp iratory d istress synd rom e.
N Engl J Med 2000; 342:1334-1349.
2. Abraham E, Matthay MA, Dinarello C, et al. Consensu s confer-
ence d efinitions for sepsis, sep tic shock, acu te lu ng inju ry and
acu te resp iratory d istress synd rom e: Tim e for a reevalu ation. Crit
Care Med 2000; 28:232235.
3. The Fou rth Margaux Conference on Critical Illness. Acute lu ng
injuryund erstand ing m echanism s of inju ry and repair. Crit
Care Med 2003; 31(Sup pl):S183S337.
4. H u d son LD, Milberg JA, Anard i D, Mau nd er RJ. Clinical risks for
d evelopm ent of the acu te resp iratory d istress synd rom e. Am Rev
Resp ir Crit Care Med 1995; 151:293301.
5 Bernard GR, Artigas A, Brigham KL, et al. The Am erican
Eu ropean Consensus Conference on ARDS: d efinitions, m echa-
nism s, relevant ou tcom es, and clinical trial coord ination. Am
Rev Respir Crit Care Med 1994; 149:818824.
6. Idell S, Cohen AB. Bronchoalveolar lavage in patients with the adult
respiratory distress syndrome. Clin Chest Med 1985; 6:459471.
7. Sp ru ng CL, Long WM, Marcial EH , et al. Distribution of proteins
in pulm onary ed em a. The value of fractional concentrations. Am
Rev Respir Dis 1987;136:957963.
8. Dreyfu ss D, Saum on G. Ventilator-ind u ced lu ng inju ry. Am J
Resp ir Crit Care Med 1998; 157:294323.
9. Ranieri VM, Giunta F, Suter P, Slu tsky AS. Mechanical ventilation
as a m ed iator of m ultisystem organ failure in acu te respiratory
d istress synd rom e. JAMA 2000; 284:4344.
10. Fan E, N eed ham DM, Stew art TE. Ventilator m anagem ent of
acu te lu ng inju ry and acu te resp iratory d istress synd rom e.
JAMA 2005; 294:28892896.
11. The Acute Respiratory Distress Synd rom e N etw ork. Ventilation
w ith low er tid al volu m es as com p ared w ith trad itional tid al vol-
u m es for acute lu ng inju ry and the acute resp iratory d istress syn-
d rom e. N Engl J Med 2000; 342:13011308.
268 Common Pulmonary Disorders

12. Bid aniA, Tzouanakis AE, Card enas VJ, Zw ischenberger JB. Per-
m issive hyp ercap nia in acute resp iratory failure. JAMA 1994;
272:957962.
13. H ickling KG, Walsh J, H end erson S, et al. Low m ortality rate in
ad u lt resp iratory d istress synd rom e u sing low -volu m e, p ressu re-
lim ited ventilation w ith p erm issive hyp ercap nia: A p rosp ective
stu d y. Crit Care Med 1994; 22:15681578.
14. Mu sced ere JG, Mullen JBM, Gan K, et al. Tid al ventilation at low
airw ay pressures can au gm ent lu ng injury. Am J Resp ir Crit Care
Med 1994; 149:13271334.
15. The N ational H eart, Lung, and Blood Institu te ARDS Clinical
N etw ork. H igher versus low er positive end -expiratory p ressu res
in p atients w ith acute resp iratory d istress synd rom e, N Engl J
Med 2004; 351:327336.
16. Brow er RG, Ware LB, Berthiau m e Y, Matthay MA. Treatm ent of
ARDS. Chest 2001; 120:13471367.
17. McIntyre RC Jr, Pu lid o EJ, Bensard DD, et al. Thirty years of clin-
ical trials in acu te respiratory d istress synd rom e. Crit Care Med
2000; 28:33143331.
18. H ebert PC, Blajchm an MA, Cook DJ, et al. Do blood transfu sions
im prove outcom es related to m echanical ventilation? Chest 2001;
119:18501857.
19. H ebert PC, Yetisir E, Martin C, et al. Is a low transfusion thresh-
old safe in critically ill p atients w ith card iovascular d isease. Crit
Care Med 2001; 29:227234.
20. Good nou gh LT. Risks of blood transfu sion. Crit Care Med 2003;
31(Sup pl):S678S686.
21. Bernard GR, Lu ce JM, Sp rung CL, et al. H igh-d ose corticos-
teroid s in patients w ith ad u lt respiratory d istress synd rom e. N
Engl J Med 1987; 317:15651570.
22. Med u ri GU, Chinn A. Fibrinoproliferation in late ad ult respirato-
ry d istress synd rom e. Chest 1994; 105(Su pp l):127S129S.
23. Montgom ery AB, Stager MA, Carrico J, H u d son LD. Cau ses of
m ortality in p atients w ith the ad u lt resp iratory d istress syn-
d rom e. Am Rev Resp ir Dis 1985; 132:485489.
24. Bartlett RH , Morris AH , Fairley B, et al. A prosp ective stu d y of
acute hypoxic resp iratory failure. Chest 1986; 89:684689.
25. Gillespie DJ, Marsh H MM, Divertie MB, Mead ow s JA III. Clinical
outcom e of respiratory failu re in patients requiring prolonged
(> 24 hou rs) m echanical ventilation. Chest 1986; 90:364369.
Chapter 17
ASTHMA AND COPD
IN THE ICU
This chap ter d escribes the m anagem ent of p atients w ith
acu te exacerbations of asthma and chronic obstru ctive p u l-
monary d isease (COPD). The focu s here is on the u se of
p harm acologic agents to relieve airw ays obstruction. The
p rinciples of m echanical ventilation are d escribed in the next
section of the book.

I. ACUTE EXACERBATION OF ASTHMA

A. Peak Expiratory Flow Rate


The m anagem ent of acu te asthm a requ ires an assessm ent of
the severity of airflow obstru ction, bu t the physical exam ina-
tion is u nreliable in this regard (1). The peak expiratory flow
rate (PEFR) is an objective m easu re of airflow obstru ction
that is easily obtained at the bed sid e.

1. The PEFR is the greatest flow velocity that can be gener-


ated d u ring a forced exhalation from total lu ng cap acity
(i.e., w hen the lungs are fu lly inflated ). The m easu rem ent
is obtained w ith a hand -held d evice (called a peak flow
meter) that the patient exhales into. A series of 3 m easu re-
ments shou ld be obtained , if p ossible, and the highest
valu e is taken as the PEFR.

2 The PEFR is an effort-d ep end ent m easu rem ent, and is


reliable only w hen the p atient gives a m axim u m exp ira-
tory effort. Patients w ho are in resp iratory d istress m ay
be unable to p erform this m aneu ver.
269
270 Common Pulmonary Disorders

3. Figure 17.1 show s the norm al PEFR for ad u lt men and


w om en (2). As ind icated , the PEFR varies w ith age, gen-
d er, and height. For m en, PEFR read ings u p to 100 L/ m in
below p red icted are consid ered w ithin norm al lim its. For
w om en, the equ ivalent figu re is 85 L/ m in.

680

660

640

620

600

580

560

540

520
)
500
n
i
m
He ig ht
/
L
480 (Me n)
(
R
F
460 75 in
E
72 in
P
440 69 in
66 in
420 63 in

400

380

360 He ig ht
(Wo me n)
340
72 in
69 in
320 66 in
63 in
300 60 in
15 20 25 30 35 40 45 50 55 60 65 70 75 80 85
Ag e (Ye ars )

FIGURE 17.1 Normal peak expiratory flow rates (PEFR) for adult men
and women. Adapted from Reference 2 for the Mini-Wright Peak Flow
Meter.
Asthma and COPD in the ICU 271

4. The PEFR can be u sed in acu te asthm a as show n in


Figu re 17.2 (3,4).
a. PEFR > 70% of norm al valu es ind icates m inim al or no
airflow obstru ction.
b. PEFR = 50 70% of norm al valu es ind icates m od erate
airflow obstru ction.
c. PEFR < 50% of norm al valu es ind icates severe airflow
obstru ction.

B. Aerosol Drug Therapy


The d ru gs used to relieve airflow obstru ction (i.e., bron-
chod ilators) are d elivered as inhaled aerosols. This m od e of
d elivery is m ore effective than oral or intravenous therapy
(5,6), and has few er sid e effects. Tw o d evices are u sed to gen-
erate bronchod ilator aerosols: nebu lizers and m etered -d ose
inhalers.

1. Nebulizers
Sm all-volu m e nebulizers u se a reservoir volu me of 3 to 6
mL (d ru g p lu s saline d ilu ent). A narrow cap illary tu be is
su bm erged in the solu tion and a rap id ly flow ing stream
of gas is p assed over the open end of the tu be. This gas
jet creates a viscou s d rag that d raw s the d ru g solu tion u p
the cap illary tube. When the solu tion reaches the gas jet,
it is pu lverized to form an aerosol sp ray, w hich is then
inhaled by the p atient. The reservoir volu m e is comp lete-
ly aerosolized in less than 10 m inutes.

2. Metered-Dose Inhalers
The m etered -d ose inhaler (MDI) op erates like a can of
hair sp ray. The d evice has a p ressu rized canister that con-
tains a d ru g solu tion w ith a boiling p oint below room
tem p eratu re. When the canister is squ eezed betw een the
thu m b and fingers, a valve op ens that releases a fixed
volu m e of the d ru g solu tion. The liqu id im med iately
vaporizes w hen it em erges from the canister, and a liqu id
272 Common Pulmonary Disorders

p ropellant in the solu tion creates a high-velocity sp ray.


a. The high velocity of MDI sp rays is p roblem atic be-
cau se m ost of the aerosol sp ray im p acts on the p oste-
rior w all of the orop harynx and is not inhaled . The
velocity of the spray can be red uced by u sing a spacer
d evice to increase the d istance betw een the MDI and

INITIAL AS S ES S MENT OF ACUTE AS THMA

PEFR > 50% PEFR < 50%


Inha le d 2 -a gonis t by MDI or Inha le d 2 -a gonis t + a nticholine rgic
ne bulize r eve ry 20 min. x 3 by ne bulize r eve ry 20 min. x 3
Ora l s te roids if no imme dia te or continuous ly for 1 hour
re s pons e or if pa tie nt on Ora l or IV s te roids
chronic s te roid Rx

S eve re Re s pirato ry Dis tre s s


Intuba tion a nd me cha nica l ve ntila tion
REPEAT AS S ES S MENT Ne bulize d 2 -a gonis t + a nticholine rgic
IV corticos te roid

Admit to ICU

PEFR 50 80% pre dic te d PEFR < 50 % pre dic te d


Inha le d 2 -a gonis t eve ry 60 min. Inha le d 2 -a gonis t + a nticholine rgic
Ora l or IV corticos te roid by ne bulize r continuous ly for 1 hour
Continue tre a tme nt 13 hours IV corticos te roid

PEFR 70% PEFR 50% but < 70% PEFR <50%


P CO 2 42 mm Hg

Dis c harg e Ho me Admit to


Ho s pital
Admit to ICU

FIGURE 17.2 Protocol for the management of acute exacerbation of asth-


ma. Adapted from Reference 3. PEFR = peak expiratory flow rate.
Asthma and COPD in the ICU 273

mou th. Sp acer d evices (w hich are u su ally cham bers


that hold several sp rays from an MDI) shou ld be u sed
rou tinely to im prove lu ng d ep osition of MDI sp rays.

3. Nebulizer vs. MDI


The d ose of bronchod ilators d elivered by nebu lizers is
far greater than the d ose d elivered by MDIs, but the
bronchod ilator response is the sam e. This is d em onstrat-
ed in Figu re 17.3 (7). Becau se MDIs are equ ivalent to neb-
u lizer treatm ents bu t are less labor intensive (i.e., d o not
requ ire a resp iratory therap ist to ad m inister), M DIs are
favored over nebulizers for bronchodilator therapy (d ont for-
get to u se a spacer w ith the MDI).

C. -Receptor Agonists
The favored bronchod ilators in asthm a are d ru gs that stim u -
late -ad renergic recep tors in bronchial sm ooth m u scle ( 2
subtyp e) to promote sm ooth m u scle relaxation (8). Short-act-
ing agents are preferred for acute therapy becau se they can
be given m ore frequ ently. The m ost p op u lar short-acting 2-
agonist is albuterol. When inhaled as an aerosol, albuterol
p rod uces an effect w ithin 5 m inu tes, and it lasts 2 5 hours
(8). The d ose of aerosolized albu terol in acu te asthm a is
show n in Table 17.1.

1. Intermittent vs. Continuous Aerosol Therapy


For acute exacerbation of asthm a, albu terol can be given
as a series of interm ittent aerosol treatm ents (u sing a neb-
u lizer or MDI) every 20 m inu tes, or as a single continu -
ous nebu lizer treatm ent (see Table 17.1 for the d oses).
Most stu d ies show no d ifference in efficacy betw een the
tw o regim ens (9). Continu ou s aerosol therapy is favored
by many becau se it is easier to ad m inister.
2. Parenteral Therapy
For the rare asthm atic patient w ho d oes not tolerate
bronchod ilator aerosols (u sually becau se of excessive
274 Common Pulmonary Disorders

60

50
d
e
Ne bulize r
t
R
c
i
F
d
E
e
r
P
P
MDI with S pa ce r
%
12

30
Be fore 1s t Tre a tme nt 2nd Tre a tme nt

FIGURE 17.3 Bronchodilator response to albuterol delivered by nebuliz-


er (2.5 mg per treatment) and metered-dose inhaler (M DI) (0.4 mg per
treatment) in patients with acute exacerbation of asthma. PEFR = peak
expiratory flow rate. Adapted from Reference 7.

coughing), the follow ing regimens are effective (1):


a. Epinephrine: 0.3 0.5 m g by su bcu taneou s injection
every 20 m inutes x 3, or
b. Terbutaline: 0.25 m g by su bcu taneou s injection every
20 m inu tes x 3.

3. Side Effects
H igh-d ose aerosol therapy w ith 2-agonists can prod u ce
a nu m ber of sid e effects, inclu d ing tachycard ia, trem ors,
hyperglycem ia, hyp okalem ia, hyp om agnesem ia, and hy-
pophosp hatem ia (8,10,11). Card iac ischem ia is rare (11).

C. Anticholinergic Agents
1.Anticholinergic agents are less effective than 2-agonists
in asthm a, and are u sed only in in com bination w ith 2-
agonists (see Figu re 17.2) (3,4,12).
Asthma and COPD in the ICU 275

2. The only anticholinergic agent approved for clinical use is


ipatropium bromide, a d erivative of atropine that blocks
muscarinic receptors in the airw ays. The aerosol d ose of
ipatrop iu m in acu te asthm a is show n in Table 17.1.

TABLE 17.1 Drug Therapy for Acute Exacerbation of Asthma


Drug Preparation Dose Comments
Short-Acting 2-Receptor Agonist
Albuterol nebulizer 2.5 5 mg every Dilute albuterol
solution (5 mg/mL) 20 min x3 doses, solution to final
or 10 15 mg/hr volume of 5 mL
continuously, then and deliver at gas
2.5 10 mg every flows of 6 8 L/min.
14 hrs as needed.
Albuterol by MDI 4 8 puffs every As effective as
(90 g/puff) 20 min up to 4 hrs, nebulizer Rx. MDI
then every 1 4 hrs should be used
as needed. with spacer device.
Anticholinergic Agent
Ipatropium bromide 0.5 mg every Can mix in same
nebulizer solution 20 min for 3 doses, nebulizer as
(0.25 mg/mL) then every 24 hrs albuterol. Should
as needed. not be used alone as
first-line therapy.
Ipatropium bromide 4 8 puffs as needed. MDI delivery has not
by MDI (18 g/puff) been studied in
acute asthma.
Corticosteroids
Methylprednisolone 120180 mg/day No difference in effi-
(IV), or prednisone in 3 or 4 divided cacy between IVand
(oral) doses for 48 hrs, oral Rx. Onset of
then 6080 mg/day effect takes several
until PEFR 70% of hours.
predicted.
From Reference 3. Drug dos es are for adults only.
276 Common Pulmonary Disorders

3. System ic absorp tion of aerosolized ip atrop iu m is m ini-


mal, so there is little risk of anticholinergic sid e effects;
i.e., tachycard ia, d ry m ou th, blurred vision, and urinary
retention.

D. Corticosteroids
Steroid s are recom m end ed for all p atients w ith acu te asthm a
(see Figu re 17.2). The steroid p rep arations u sed most often
are methylprednisolone (for intravenou s therap y) and
prednisone (for oral therap y), and the recom m end ed d oses
are show n in Table 17.1. The follow ing p oints abou t steroid
therap y d eserve m ention.

1. There is no d ifference in efficacy betw een oral and intra-


venou s steroid s (13).

2. The beneficial effects of steroid s may not be ap p arent


u ntil 12 hou rs after therap y is started (13).

3. There is no clearly d efined d ose-resp onse cu rve for ste-


roid s, w hich m eans that higher d oses of steroid s are not
su p erior to low er d oses (13).

4. A 10-d ay course of steroid s can be stop p ed abru p tly


w ithou t a tap ering d ose (14).

5. A myopathy has been rep orted in ventilator-d ep end ent


asthm atic p atients treated w ith high-d ose steroid s and
neurom u scular blocking agents (15).
a. Unlike the trad itional steroid m yopathy, w hich is char-
acterized by p roxim al m uscle w eakness, this m yop-
athy involves both p roximal and d istal m u scles, and is
often associated w ith rhabd om yolysis. The mu scle
w eakness can ham p er w eaning from m echanical ven-
tilation.
b. Once the d isord er is su sp ected , rap id tap er of the p ar-
alyzing agents and steroid s is ad vised .
Asthma and COPD in the ICU 277

c. The m u scle w eakness can be p rolonged , bu t the d isor-


d er is u su ally reversible.

E. Other Considerations
The follow ing are som e im p ortant consid erations for the
managem ent of acute asthm a in the em ergency d epartm ent:

1. Su p p lem ental oxygen is not necessary if the arterial O 2


satu ration measured by p u lse oxim etry is 92% or higher.

2. Chest x-rays are not necessary u nless there is su sp icion of


a cond ition other than asthm a (e.g., p neum onia).

3. Arterial blood gases are not necessary u nless the patient


is in extremis, is cyanotic, or is refractory to initial bron-
chod ilator therapy.

4. Antibiotics are not necessary u nless there is evid ence of a


treatable infection.

II. ACUTE EXACERBATIONS OF COPD


Acu te exacerbations of COPD (i.e., chronic bronchitis and
em physem a) are responsible for abou t half a m illion hospi-
tal ad m issions yearly in the United States, and half of these
are ICU ad m issions (16).

A. Bronchodilator Therapy
1. Short-acting 2-agonists like albu terol are u sed rou tinely
in acute exacerbation of COPD. The u su al d ose is 2.5
5 m g via nebu lizer or 2 p u ffs by MDI every 4 to 6 hours.

2. Unlike the case in asthm a, aerosolized ip atrop iu m bro-


m id e can be u sed alone as a bronchod ilator in acu te exac-
278 Common Pulmonary Disorders

erbations of COPD (17,18). The u su al d ose is 0.5 m g by


nebulizer or 2 to 4 p uffs by MDI every 4 to 6 hours. The
com m on practice is to com bine ipatropiu m w ith 2-ago-
nist therap y, but som e stu d ies d o not su p p ort this p rac-
tice (18).

B. Corticosteroids
A short cou rse (2 w eeks) of corticosteroid therapy is recom -
mend ed for all patients w ith acu te exacerbation of COPD
(16-18). One exam p le of an effective 2-w eek steroid regim en
is show n below (19).
M ethylprednisolone: 125 m g IV every 6 hrs on d ays 1 3,
Prednisone: 60 m g once d aily on d ays 4 7,
40 m g once d aily on d ays 8 11,
20 m g once d aily on d ays 12 15.

C. Antibiotic Therapy
1. Infection in the airw ays is believed to be the inciting
event in 80% of cases of acu te exacerbation of COPD, and
bacteria are isolated in at least half of the cases (20). The
infections are usually polymicrobial, and the most frequent
treatable isolates are Chlamydia pneumoniae, Hemophilus in-
fluenza, and Streptococcus pneumoniae.

2. Desp ite the p revalence of airw ay infection, the benefit of


antim icrobial therap y in acu te exacerbation of COPD has
been d ifficu lt to p rove. The m ost recent evid ence u sing
p ooled d ata from 11 clinical trials ind icates that antim i-
crobial therap y is beneficial in p atients w ho are at risk for
a p oor ou tcom e (18).

3. Antibiotic therapy in acu te exacerbation of COPD is not


based on spu tum cultu res, bu t rather on the risk for a
poor ou tcome. Recommend ations for antibiotic therapy
based on risk assessment are show n in Table 17.2.
Asthma and COPD in the ICU 279

4. The op tim al d u ration of antim icrobial therap y is not


know n: the com m on practice is to continu e therapy for at
least 7 d ays.

TABLE 17.2 Antibiotic Therapy for Acute Exacerbation


of COPD Based on Risk Assessment
I. Risk Assessment
Answer the following questions:

Yes No
1. Is the FEV1 less than 50% of predicted?
2. Does the patient have cardiac disease or other
significant comorbid conditions?
3. Has the patient had 3 or more exacerbations in
the previous 12 months?
If the answer is YES to at least one of these questions, the patient
is considered to be high-risk for an unfavorable outcome.
II. Antibiotic Selection
High Risk Patients: Amoxicillin-clavulanate or a newer
fluoroquinolone (gatifloxacin, levofloxacin,
or moxifloxacin)
Low Risk Patients: Doxycycline, a second-generation cephalo-
sporin (e.g., cefuroxime) or a newer macro-
lide (azithromycin or clarithromycin)
From Reference 20. FEV1 = Forced expiratory volume in 1 s econd.

D. Oxygen Therapy
In patients w ith COPD and chronic hyp ercap nia, inhalation
of high concentrations of oxygen can aggravate the hyp er-
cap nia (21). To minim ize this risk, the concentration of in-
haled O 2 shou ld be ju st enou gh to keep the arterial oxyhem o-
globin satu ration (SaO 2) at 88 90%. There is no evid ence
that raising the SaO 2 above this level w ill fu rther enhance tis-
su e oxygenation.
280 Common Pulmonary Disorders

REFERENCES
1. Shim CS, William s MH . Evalu ation of the severity of asthm a:
p atients versu s physicians. Am J Med 1980; 68:1113.
2. N u nn AJ, Gregg I. N ew regression equ ations for p red icting peak
exp iratory flow in ad u lts. Br Med J 1989; 298:10681070.
3. N ational Asthm a Ed u cation and Prevention Program Expert
Panel Rep ort 2. Gu id elines for the d iagnosis and m anagem ent of
asthm a. N IH Pu blication N o. 97-4051, Ju ly, 1997.
4. N ational Asthm a Ed u cation and Prevention Program Expert
Panel Report: Gu id elines for the d iagnosis and m anagem ent of
asthm a. Up d ate on selected top ics, 2002. N IH Pu blication N o. 02-
5074, Ju ne, 2003.
5. Shim C, William s MH . Bronchial response to oral versu s aerosol
m etap roterenol in asthm a. Ann Intern Med 1980; 93:428431.
6. Salm eron S, Brochard L. Mal H , et al. N ebu lized versu s intra-
venou s albu terol in hypercap nic acu te asthm a. Am J Respir Crit
Care Med 1994; 149:14661470.
7. Id ris AH , McDerm ott MF, Raucci JC, et al. Em ergency d epartment
treatment of severe asthm a: Metered -dose inhaler plus hold ing
cham ber is equivalent in effectiveness to nebu lizer. Chest 1993;
103:665672.
8. Du tta EJ, Li JTC. -agonists. Med Clin N Am 2002; 86:9911008.
9 . Rod rigo GJ, Rod rigo C. Continuous vs. interm ittent beta-agonists
in the treatm ent of acu te ad u lt asthma: A systematic review w ith
m eta-analyses. Chest 2002; 122:19821987.
10. Truw it JD. Toxic effect of bronchod ilators. Crit Care Clin 1991;
7:639657.
11. Bod enham er J, Bergstrom R, Brow n D, et al. Frequ ently nebu -
lized beta-agonists for asthm a: Effects on seru m electrolytes. Ann
Em erg Med 1992; 21:13371342.
12. Rod rigo G, Rod rigo C. The role of anticholinergics in acu te asth-
m a treatm ent. An evid ence-based evalu ation. Chest 2002; 121:
19771987.
13. Rod rigo G, Rod rigo C. Corticosteroid s in the em ergency d ep art-
m ent therapy of acu te ad u lt asthm a. An evid ence-based evalu a-
tion. Chest 1999; 116:285295.
14. Cyd u lka RK, Em erm an CL. A pilot stu d y of steroid therap y after
em ergency d ep artm ent treatm ent of acu te asthm a: Is a tap er
need ed ? J Em erg Med 1998; 16:1519.
Asthma and COPD in the ICU 281

15. Griffin D, Fairm an N , Cou rsin D, et al. Acu te m yopathy d u ring


treatm ent of statu s asthm aticu s w ith corticosteroid s and
steroid al m uscle relaxants. Chest 1992; 102:510514.
16. Stoller JK. Acu te exacerbations of chronic obstru ctive p ulm onary
d isease. N Engl J Med 2002; 346:988994.
17. Snow V, Lascher S, Mottu r-Pilson C, for the Joint Exp ert Panel on
COPD of the Am erican College of Chest Physicians and the
Am erican College of Physicians-Am erican Society of Internal
Med icine. The evid ence base for m anagem ent of acute exacerba-
tions of COPD. Chest 2001; 119:11851189.
18. McCrory DC, Brow n C, Gelfand SE, Bach PB. Managem ent of
acu te exacerbations of COPD. A su m m ary and ap p raisal of p u b-
lished evid ence. Chest 2001; 119:11901209.
19. N iew oehner DE, Erbland ML, Deu pree RH , et al. Effect of sys-
tem ic glucocorticoid s on exacerbations of chronic obstructive
p ulm onary d isease. N Engl J Med 1999; 340:19411947.
20. Sethi S. Acute exacerbations of COPD: A m u ltip ronged ap -
p roach. J Respir Dis 2002; 23:217225.
21. Cam pbell EJM. The J. Bu rns Am berson Lectu re. The m anage-
m ent of acu te resp iratory failu re in chronic bronchitis and em -
p hysem a. Am Rev Resp ir Dis 1967; 96:626639.
Chapter 18
BASICS OF
MECHANICAL
VENTILATION
Patient care in any ICU requ ires a w orking know led ge of
mechanical ventilation. Mu ch of this is learned by repeated
exposu re to ventilators at the bed sid e, bu t the inform ation in
the next few chap ters can serve as a starting p oint.

I. POSITIVE-PRESSUREVENTILATION

A. Pressure-Volume Relationships
1. During m echanical ventilation, the ventilator creates a
p ositive p ressu re that p ushes air into the lu ngs. This in-
flation pressure is transm itted into the thorax to create a
p ositive intrathoracic p ressu re.

2. The inflation pressu re is influenced by the volume that is


d elivered (the inflation volume) and the mechanical prop-
erties of the lu ngs. This is d em onstrated in Figu re 18.1.
N ote the follow ing:
a. The inflation p ressu re increases as the inflation vol-
u m e increases.
b. In cond itions of increased airw ays resistance and re-
d u ced lu ng com p liance, the inflation p ressu re is high-
er at any given inflation volu m e (i.e., the cu rve is shift-
ed to the left).

3. The inflation p ressu re is rou ghly equ ivalent to the intra-


283
284 Mechanical Ventilation

thoracic p ressu re. Therefore, Figu re 18.1 show s that the


influence of mechanical ventilation on intrathoracic pressure is
determined by the volume delivered and the mechanical prop-
erties of the lungs.

60

Incre a s e d Airway Re s is ta nce


)
or Re duce d Lung Complia nce
O
2
H
40
m
c
(
e
r
u
s
s
e
r
P
v= k
n
20
o
i
t
p =k
a
l
f
Norma l Lungs
n
I
0

0 500 1,000
Infla tion Volume (mL)

FIGURE 18.1 Pressure-volume relationships during positive-pressure


mechanical ventilation. The vertical arrow (v = k) represents volume-
cycled ventilation, and the horizontal arrow (p = k) represents pressure-
cycled ventilation.

B. Pressure vs. Volume Control


1. A mechanical breath can be term inated at a preset pres-
sure (pressure-cycled ventilation) or a preset volume (vol-
ume-cycled ventilation).

2. During p ressu re-cycled ventilation, the inflation volum e


varies w ith changes in the m echanical p rop erties of the
lu ngs. This is show n by the horizontal arrow in Figu re
Basics of Mechanical Ventilation 285

18.1; i.e., w hen lu ng m echanics are abnorm al, the infla-


tion volu m e d ecreases.

3. During volum e-cycled ventilation, the inflation volu m e


is constant regard less of the m echanical prop erties of the
lu ngs. This is show n by the vertical arrow in Figu re 18.1;
i.e., w hen lu ng m echanics are abnorm al, the ventilator
d evelops higher inflation p ressu res to d eliver the preset
volu m e.

4. Volume-cycled ventilation is favored because of the ability


to maintain a constant inflation volum e d espite changes in
the mechanical properties of the lungs (w hich can occur
frequently in ventilator-d epend ent patients). How ever,
intrathoracic pressures can reach very high levels during
volume-cycled ventilation (p articu larly w hen the lu ngs
are noncom pliant), and this can ad versely affect the car-
d iac ou tpu t (see next).

C. Cardiac Performance
Positive-p ressu re ventilation can influ ence both ventricu lar
filling and ventricular emp tying (1).

1. Ventricular Filling
Positive-pressu re lu ng inflation can red u ce ventricu lar
filling by the follow ing m echanism s:
a. Positive intrathoracic p ressu re im p ed es venou s retu rn
by red ucing the pressu re grad ient for venous inflow
into the thorax.
b. Positive pressu re exerted on the outer surface of the
heart red u ces card iac d istensibility, and this can re-
d u ce ventricu lar filling d u ring d iastole.

2. Ventricular Emptying
Positive intrathoracic pressu re can facilitate ventricu lar
em p tying by red u cing the transm u ral p ressu re that mu st
be d evelop ed by the ventricle to eject the stroke volu m e.
286 Mechanical Ventilation

(The positive intrathoracic pressure acts like a hand that


squeezes the ventricles d u ring systole).

40
Airway P re s s ure

cm H2 O 20

130

110

mm Hg
90

70

FIGURE 18.2 Respiratory variation in blood pressure. The positive-pres-


sure lung inflation (depicted in the upper graph) is associated with a
transient rise in blood pressure, reflecting an increase in cardiac stroke
output.

3. Cardiac Output
The effect of m echanical ventilation on card iac stroke
ou tp u t w ill d ep end on w hich of the tw o effects on car-
d iac perform ance (a d ecrease in ventricu lar filling or an
increase in ventricu lar em ptying) is pred om inant.
a. In cond itions w here the intrathoracic p ressu re exceed s
the central venou s p ressu re (e.g., hypovolem ia), the
p red om inant effect of m echanical ventilation is to re-
d u ce ventricu lar filling and thereby d ecrease card iac
stroke outp ut.
b. When ventricu lar filling is ad equ ate, the p red ominant
effect of m echanical ventilation is to enhance ventricu-
Basics of Mechanical Ventilation 287

lar em ptying and thereby increase card iac stroke out-


p ut.
c. The effect of mechanical ventilation on card iac ou tpu t
can be inferred from the respiratory variations in blood
pressure. When cardiac stroke output is increased, there
is an increase in blood pressure associated w ith each
lung inflation, as demonstrated in Figure 18.2. When
card iac stroke output is d ecreased , each lung inflation
prod uces a decrease in blood pressure.

II. INITIATING MECHANICALVENTILATION


A.Tracheal Intubation
Positive-p ressu re ventilation requ ires tracheal intu bation
w ith sp ecialized endotracheal tubes that have an inflatable bal-
loon (called a cu ff) at the d istal end to prevent air from es-
cap ing arou nd the tu be d u ring lu ng inflation.

1. End otracheal tu bes are sized accord ing to their internal


d iam eter, w hich varies from 5 to 10 m m (in ad u lts). Tu be
sizes of 7 or 8 (i.e., internal d iam eters of 7 or 8 m m ) are
recom m end ed for ad u lts. Sm aller sized (narrow er) tu bes
create an obstru ction to air flow, w hile larger-sized (w id -
er) tu bes increase the risk of laryngeal d am age.

2. Intubation of the trachea is accom p lished by inserting the


end otracheal tu be throu gh the nose or m ou th and ad -
vancing the tu be throu gh the larynx and into the trachea.
The nasal route is reserved for elective intu bations in
aw ake p atients.

3. Once the end otracheal tu be is in p lace, the balloon at the


d istal end of the tu be is inflated (w ith an air-filled sy-
ringe) u ntil there is no evid ence of an air leak (i.e., no
au d ible sound s of air escaping ou t throu gh the mou th
w hen the lu ngs are m anu ally inflated ).
288 Mechanical Ventilation

4. To verify tu be p lacem ent in the trachea, exhaled CO 2 is


m easu red w ith a d isp osable, colorim etric CO 2 d etector
(Easy Cap II, N ellcor, Pleasantville, CA). If the exhaled
CO 2 is above 0.5% (w hich p rod u ces a tan or yellow color
on the CO 2 d etector), the tu be is in the trachea (2). A low -
er concentration of exhaled CO 2 ind icates that the tu be is
in the esop hagu s, and shou ld be rem oved im m ed iately.

5. Listening for breath sou nd s w hen air is forced throu gh


the end otracheal tu be is an u nreliable m ethod for d istin-
guishing betw een tracheal and esop hageal intu bation (3).

6. Once tracheal intu bation is verified , a p ortable chest x-


ray shou ld be obtained to d etermine the location of the
tip of the tu be. The tu be is p rop erly p laced w hen the tip
is located 3 to 5 cm above the tracheal carina (w ith the
head in a neu tral p osition) (4).

B. Low-Volume Ventilation
Follow ing su ccessfu l tracheal intu bation, m echanical venti-
lation can proceed accord ing to the protocol show n in Table
18.1. This p rotocol w as d eveloped for p atients w ith acu te
respiratory d istress synd rom e (ARDS), and it is d escribed in
d etail in Chap ter 16 (see Table 16.3).

1. Low -volume ventilation is d esigned to red uce the risk of


ventilator-induced lung injury (5), a cond ition characterized
by overd istension and ru pture of alveoli in nond iseased
lu ng segm ents. This cond ition is caused by inflation vol-
umes that are too large for the volume of nond iseased
lu ng, w here m ost of the inflation volu m e is d istribu ted .
This cond ition is d escribed in Chapter 16 (section III-A).

2. The inflation volu m e (also called tidal volume) in low -vol-


u m e ventilation is 6 m L/ kg, w hich is abou t half the tra-
d itional inflation volu m e (10 to 12 m L/ kg). N ote that the
predicted body weight is u sed to d eterm ine the tid al vol-
u m e. Pred icted bod y w eight is the p referred m easu re of
Basics of Mechanical Ventilation 289

TABLE 18.1 Protocol for Initiating Low-Volume Ventilation


Step 1: Initial Ventilator Settings
1. Select assist-control mode of ventilation with NO ventilator sighs
2. Set initial tidal volume (VT) at 8 mL/kg using the patients
predicted body weight (PBW).
Males: PBW = 50 + [2.3 x (height in inches 60)]
Females: PBW = 45.5 + [2.3 x (height in inches 60)]
3. Set respiratory rate (RR) at 1214 breaths.
4. Add positive end-expiratory pressure (PEEP) of 57 cm H2O.
5. Set inspired O2 concentration (FIO2) at 100%.
Step 2: Volume Reduction
1. Reduce VT by 1 mL/kg every 2 hrs until VT is 6 mL/kg.
2. When VT is 6 mL/kg, measure end-inspiratory plateau
pressure (Ppl).
3. If Ppl > 30 cm H2O, decrease VT in 1 mL/kg increments until
Ppl < 30 cm H2O or VT = 4 mL/kg.
Step 3: Adjustments for Respiratory Acidosis
1. Measure arterial blood gases for evidence of acute respiratory
acidosis. If present, proceed as follows.
2. If arterial pH is 7.15 7.30, increase RR until pH >7.30 or
RR = 35 bpm.
3. If arterial pH < 7.15, increase RR to 35 bpm. If pH still < 7.15,
increase VT in 1 mL/kg increments until pH >7.15.
Step 4: Achieving a Non-Toxic FIO2
1. Decrease FIO2 in 1020% increments until the FIO2 < 60% or
the SaO2 = 80% (by pulse oximetry).
2. If the FIO2 remains > 60%, add PEEP in increments of 23 cm
H2O until the FIO2 < 60% and the SaO2 88%.

Adapted from the protocol for low volume ventilation in ARDS (s ee


Table 16.3).

bod y size becau se it is closely associated w ith norm al


lu ng volu m es.
290 Mechanical Ventilation

3. The u se of low -level p ositive end -exp iratory p ressu re


(PEEP) is a stand ard p ractice d u ring low -volum e ventila-
tion, and is u sed to cou nteract the tend ency for sm all air-
w ays to collap se at end -exp iration w hen inflation vol-
u m es are red u ced (6).

4. The end -insp iratory p lateau p ressu re (d escribed later in


the chap ter), w hich is the elastic recoil p ressu re of the
lu ngs and thorax, is kep t below 30 cm H 2O becau se a
large clinical stu d y show ed that this cond ition w as asso-
ciated w ith imp roved outcom es d u ring low -volum e ven-
tilation (7).

5. The CO 2 is allow ed to rise d u ring low -volum e ventilation


(a cond ition know n as permissive hypercapnia), but the ar-
terial p H is not allow ed to d rop below 7.15.

6. To reduce the risk of pulmonary oxygen toxicity, the frac-


tional concentration of inspired oxygen (FIO 2) should be
kept below 60% in all patients who breathe supplemental
oxygen for more than 48 hours. Additional PEEP can be
used to achieve this goal if necessary (The actions of PEEP
to improve arterial oxygenation are described in Chapter 19).

III. MONITORING LUNG MECHANICS

A. Mechanical Properties of the Lungs


1. The m echanical p rop erties of the lu ngs inclu d e the resist-
ance to flow in the airw ays and the elastic recoil force of
the lung p arenchym a.

2. The elastic recoil of the lu ngs is m easu red as compliance,


w hich is a m easu re of the d istensibility of the lu ngs (i.e.,
a d ecrease in lu ng com p liance ind icates a d ecrease in
lu ng d istensibility).
Basics of Mechanical Ventilation 291

P roxima l Pe a k
Airway P re s s ure
P re s s ure
P la te a u
P re s s ure

Infla tion Infla tion Hold Exha la tion

FIGURE18.3 Airway pressure profile during an inflation-hold maneuver.

A. Proximal Airway Pressures


The p roxim al airw ay p ressu res d ep icted in Figu re 18.3 can
be used to evalu ate the m echanical p rop erties of the lu ngs
d u ring m echanical ventilation (8,9).

1. Peak Pressure
The p eak p ressu re at the end of insp iration (Ppeak) varies
in the sam e d irection as changes in airw ays resistance,
and varies in the opp osite d irection to changes in lu ng
com pliance (see Table 18.2).
a. When the inflation volu m e is constant, an increase in
Ppeak ind icates either an increase in airw ay resistance, a
d ecrease in lu ng com p liance, or both.

2. Plateau Pressure
If the inflation volu m e is held in the lu ngs by occlu d ing
the exp iratory lim b of the ventilator tu bing, the p roxim al
airw ay p ressu re d ecreases initially and then reaches a
292 Mechanical Ventilation

stead y level (see Figu re 18.3). This inflation-hold p res-


su re is called the plateau pressure.
a. The p lateau pressu re (Pplateau ) varies in the op p osite d i-
rection to changes in lu ng com pliance; i.e., an increase
in Pplateau ind icates a d ecrease in lu ng com p liance.
b. Becau se Pplateau is obtained in the absence of airflow, it
is not influenced by changes in airw ay resistance (see
Table 18.2).
c. Becau se airw ays resistance influences only peak pres-
sure, the pressure d ifference (Ppeak Pplateau ) is a m easu re
of changes in airw ay resistance (see Table 18.2).

TABLE 18.2 Influence of Abnormal Lung Mechanics on


Proximal Airway Pressures
Abnormal Changes in Proximal Airway Pressures
Condition Ppeak Pplateau (Ppeak PPlateau)
Decreased lung Increased Increased No Change
compliance
Increased airway Increased No Change Increased
resistance

3. Summary
a. Changes in lu ng com p liance are d etected by changes
in Pplateau .
b. Changes in airw ay resistance are d etected by changes
in (Ppeak Pplateau ).
CAVEAT. Since airw ays pressu res are m easu red relative to
atm osp heric p ressu re, they are transthoracic pressures, and
are influ enced by cond itions in the chest w all as w ell as
the lu ngs. This can be an im portant consid eration for the
evalu ation of comp liance; i.e., contraction of the chest
w all muscles can red u ce the compliance of the chest w all,
and this can be misinterpreted as a d ecrease in lu ng com-
Basics of Mechanical Ventilation 293

pliance. Thu s, the term thoracic compliance is a m ore accu -


rate d escrip tion of this p aram eter.

B. Practical Applications
The follow ing are tw o situ ations w here interp retation of
p roxim al airw ay p ressu res can be u sefu l.

1. Bedside Evaluation of Respiratory Distress


The flow d iagram in Figu re 18.4 d emonstrates how the
p roxim al airw ay p ressu res can be used to evalu ate a ven-
tilator-d ep end ent p atient w ho d evelop s su d d en onset of
resp iratory d eterioration.
a. If the peak pressu re is increased bu t the p lateau pres-
su re is u nchanged , the p roblem is an increase in air-
w ays resistance. In this situ ation, the m ajor concerns
are obstru ction of the tracheal tu be, airw ay obstru ction
from secretions, and acu te bronchosp asm . Therefore,
im m ed iate interventions shou ld inclu d e airw ays su c-
tioning to clear secretions and an aerosolized broncho-
d ilator treatm ent.
b. If the peak and plateau pressures are both increased ,
the p roblem is a d ecrease in thoracic com p liance. In
this situ ation, the m ajor concerns in the lungs are pneu -
m othorax, lobar atelectasis, acu te p ulmonary ed ema,
w orsening pneu monia, and progression of ARDS. The
ap p rop riate interventions in this situ ation inclu d e au s-
cu ltation of the lu ngs (d im inished breath sou nd s can
be a sign of pneum othorax or lobar atelectasis) and a
STAT chest x-ray (all of the cond itions just m entioned
should be app arent on a chest x-ray).
c. If the p eak p ressu re is d ecreased , the p roblem m ay be
a cu ff leak that allow s p art of the inflation volu m e to
escap e from the lu ngs. A su d d en d rop in p eak p ressu re
can also be the resu lt of a hyp erventilating p atient w ho
is generating enou gh negative intrathoracic p ressu re
to d ecrease the peak airw ay p ressu re.
294 Mechanical Ventilation

2. Bronchodilator Responsiveness
The p roxim al airw ay p ressu res can be u sed to evalu ate
resp onsiveness to aerosolized bronchod ilators d u ring
mechanical ventilation.
a. A favorable bronchod ilator resp onse shou ld be accom -
p anied by a d ecrease in Ppeak w ith no change in Pplateau ;
i.e., a d ecrease in (Ppeak Pplateau ).

ACUTE RES PIRATORY


DETERIORATION

PEAK INS PIRATORY


PRES S URE

(De cre a s e d) (Incre a s e d) (No Cha nge )

Air Le a k PLATEAU P ulmona ry Embolus


Hype rve ntila tion PRES S URE Extra thora cic P roce s s

(No Cha nge ) (Incre a s e )

AIRWAY OBS TRUCTION DECREAS ED COMP LIANCE


As pira tion Abdomina l Dis te ns ion
Bronchos pa s m As ynchronous Bre a thing
S e cre tions Ate le cta s is
Tra che a l Tube Auto-P EEP
Obs truction P ne umothora x
P ulmona ry Ede ma

FIGURE18.4. Flow diagram showing how the peak and plateau pressures
can be used to identify the likely cause(s) of acute respiratory problems.
Basics of Mechanical Ventilation 295

C.Thoracic Compliance
The com p liance of the lu ngs and chest w all (thoracic com p li-
ance) can be d eterm ined as the ratio of the tid al volu m e (VT)
to the elastic recoil p ressu re m easured at end -insp iration
(i.e., Pplateau ).

Cs tat = VT /P plate au (18.1)

Since the p lateau p ressu re is m easu red in the absence of air-


flow, the resu lting com pliance is referred to as static com -
p liance (C stat).

1. Expected Range of Values


In an intu bated p atient w ithou t lu ng d isease (e.g., a d ru g
overd ose), a tid al volu m e (VT) of 500 m L shou ld be asso-
ciated w ith a p lateau p ressu re no higher than 10 cm H 2O.
The thoracic comp liance in this situ ation is: 500 m L 10
cm H 2O = 50 m L/ cm H 2O.
a. Thoracic compliance is normally 5080 mL/ cm H 2O (8).
b. In patients w ith stiff lu ngs d u e to severe infiltrative
lu ng d isease, thoracic com p liance is red u ced to 10 20
m L/ cm H 2O (10).

D. Inspiratory Resistance
The p ressu re d ifference (Ppeak Pplateau ) is the p ressu re grad ient
need ed to overcom e resistance to airflow d u ring lu ng infla-
tion. Therefore, the resistance to flow d u ring insp iration
(Rinsp ) can be d eterm ined u sing the (Ppeak Pplateau ) and the in-
sp iratory flow rate (Q insp ) generated by the ventilator.

Rins p = (P pe ak P plate au ) / Q ins p (18.2)

The Rinsp is a m easu re of the su m m ed resistances of the con-


nector tu bing, the end otracheal tu be, and the airw ays, and is
often called the total inspiratory resistance.
296 Mechanical Ventilation

1. Expected Range of Values


For ventilator-d epend ent patients w ho have no card io-
p ulmonary d isease, the follow ing m easu rem ents are typ-
ical: insp iratory flow rate = 60 L/ m in (1 L/ sec), p eak
p ressu re = 20 cm H 2O, p lateau p ressu re = 10 cm H 2O. The
resulting Rinsp is (20 10) 1 = 10 cm H 2O / L/ sec.
a. Total inspiratory resistance is normally 10 15 cm H 2O/
L/ sec.
b. The m inim al flow resistance in large-bore end otra-
cheal tubes is 3 7 cm H 2O/ L/ sec (11), so nonp u lm o-
nary resistive elem ents can accou nt for a consid erable
p ortion of the total insp iratory resistance. This is a m a-
jor shortcom ing of the inspiratory resistance m easu re-
m ent.

REFERENCES
1. Pinsky MR. Card iovascu lar issu es in respiratory care. Chest
2005; 128:592S597S.
2. Ornato JP, Ship ley JB, Racht EM, et al. Mu lticenter stu d y of a
p ortable, hand -size, colorim etric end -tid al carbon d ioxid e d etec-
tion d evice. Ann Em erg Med 1992; 21:518523.
3. Mizu tani AR, Ozake G, Benu m off JL, et al. Au scu ltation cannot
d istingu ish esop hageal from tracheal p assage of tu be. J Clin
Monit 1991; 7:232236.
4. Good m an LR, Pu tm an CE. Critical Care Im aging. 3rd ed , Phila-
d elp hia: WB Saund ers, 1992:3556.
5. Dreyfu ss D, Saum on G. Ventilator-ind u ced lu ng inju ry. Am J
Respir Crit Care Med 1998; 157:294323.
6. Fan E, N eed ham DM, Stew art TE. Ventilator m anagem ent of
acu te lu ng inju ry and acu te resp iratory d istress synd rom e.
JAMA 2005; 294:28892896.
7. The Acute Respiratory Distress Synd rom e N etw ork. Ventilation
w ith low er tid al volu m es as com p ared w ith trad itional tid al vol-
u m es for acute lu ng inju ry and the acute resp iratory d istress syn-
d rom e. N Engl J Med 2000; 342:13011308.
8. Tobin MJ. Respiratory m onitoring. JAMA 1990; 264:244251.
Basics of Mechanical Ventilation 297

9. Marini JJ. Lung m echanics d eterm inations at the bed sid e: instru -
m entation and clinical ap plication. Resp ir Care 1990; 35:669696.
10. Katz JA, Zinn SE, Ozanne GM, Fairley BB. Pulm onary, chest w all,
and lu ng-thorax elastances in acute resp iratory failu re. Chest
1981; 80:304311.
11. Marini JJ. Strategies to m inim ize breathing effort d uring m echan-
ical ventilation. Crit Care Clin 1990; 6:635662.
Chapter 19
MODES OF
POSITIVE-PRESSURE
BREATHING
Positive airw ay pressu re can be u sed to inflate the lu ngs,
p revent the lu ngs from d eflating, p rovid e fu ll ventilatory
supp ort, or su p port sp ontaneou s breathing. This chap ter
p resents these d ifferent forms of p ositive-p ressu re breathing.

I. THEVENTILATOR BREATH
The cornerstone of p ositive-p ressu re breathing is the p osi-
tive-pressu re lu ng inflation (i.e., the ventilator breath) like the
one show n in Figu re 19.1. These lu ng inflations can be vol-
u m e-cycled (w here inflation continu es to a p reset volu m e),
pressu re-cycled (w here inflation continu es to a p reset p res-
sure), or tim e-cycled (w here inflation continu es for a p reset
period of tim e). The d escription that follow s is for volu m e-
cycled ventilation, w hich is the m ost com m on m ethod of
positive-pressure breathing.

A. Basic Features
The com p onents of a ventilator breath are d escribed below
u sing the corresp ond ing nu m bers in Figure 19.1.

1. Initiating the Breath


The initial p ortion of the tracing has a negative p ressu re
d eflection, w hich rep resents a sp ontaneou s insp iratory
effort by the p atient. If the negative pressu re reaches a

299
300 Mechanical Ventilation

3
e
r
u
s
s
e
r
P
(+) 2 4
y
a
I E
w
r
i
A
l
a
m
xi
0 5
o
r
P
1 I:E =1:2
()

FIGURE19.1 Changes in airway pressure during a ventilator breath. The


components of the ventilator breath are marked by the circled numbers
(see text for explanation).

threshold level (w hich is u su ally set 2 cm H 2O below the


baseline p ressu re), a p ressu re-activated valve in the ven-
tilator is opened , and the ventilator d elivers the breath.
Patients w ho are able to initiate or trigger ventilator
breaths w ill be ventilated at their ow n intrinsic rate.

2. Lung Inflation
The lu ngs are u su ally inflated at a constant flow rate,
w hich p rod u ces a stead y rise in airw ay p ressu re and
lu ng volu m e. Insp iratory flow rates are u su ally set at 60
L/ min (1 L/ sec), w hich ensu res rap id lu ng inflation (i.e.,
a typ ical inflation volu m e of 500 m L w ill be d elivered in
less than one second ) and allow s enou gh tim e for the
lu ngs to em pty.

3. Peak Airway Pressure


The p eak p ressu re at the end of the lu ng inflation is d e-
term ined by three factors: the inflation volu m e, the resist-
Modes of Positive-Pressure Breathing 301

ance to flow in the airw ays and ventilator tubing, and the
com pliance (d istensibility) of the lu ngs and chest w all.
This p ressu re can be u sed to evalu ate the m echanical
p roperties of the lu ngs, as d escribed in Chap ter 18.

4. Exhalation
Exhalation is a passive process (at least d u ring quiet
breathing), and is d riven by the elastic recoil p ressu re of
the lu ngs. Exhalation is faster in p atients w ith noncom -
p liant lu ngs (e.g., ARDS), and slow er in p atients w ith
obstru ctive airw ay d isease (e.g., asthm a). The tim e al-
low ed for exhalation should be at least tw ice the tim e of
lu ng inflation: this is exp ressed as an I:E ratio of 1:2, as
show n.

5. End-Expiratory Pressure
Und er norm al circu mstances, the lu ngs em pty the tid al
volu m e before the next breath begins, and the p ressure in
the airw ays and d istal airsp aces retu rns to zero (atm os-
p heric) p ressu re at the end of exp iration. Positive p res-
su re can be ap p lied to the airw ays at the end of exp ira-
tion as d escribed later in the chap ter.

II. COMMON PATTERNS OFVENTILATION


This section d escribes tw o com m on m ethod s of d elivering
ventilator breaths: assist-control ventilation and intermittent
mandatory ventilation.

A. Assist-Control Ventilation
Assist-control ventilation is the trad itional m ethod of d eliv-
ering positive-pressu re lu ng inflations. As the nam e im p lies,
this m ethod allow s p atients to initiate ventilator breaths
(assisted ventilation), bu t can also p rovid e ventilator breaths
for patients u nable to interact w ith the ventilator (controlled
ventilation).
302 Mechanical Ventilation

1. Ventilatory Pattern
The upper panel of Figure 19.2 show s tw o ventilator
breaths d elivered d u ring assist-control ventilation (ACV).
The first is a p atient-initiated or triggered breath sim i-
lar to the one in Figu re 19.1. The second breath is not p re-
ced ed by an insp iratory effort, and is not initiated by the
p atient. The first breath is an exam ple of assisted ventila-
tion, and the second breath is an exam p le of controlled
ventilation.

2. Rate of Ventilation
Du ring assisted (triggered ) ventilation, the p atients in-
trinsic breathing rate d eterm ines the nu m ber of ventila-
tor breaths d elivered each m inu te. Du ring controlled
(nontriggered ) ventilation, the nu m ber of ventilator
breaths d elivered each minu te is selected on the ventilator
control panel. This rate is usually set at 10 to 12 breaths/
minute.

3. Rapid Breathing
A ventilator breath is d elivered for each insp iratory effort
d u ring assisted ventilation, and this can create p roblems
for patients w ho are breathing rap id ly; i.e., the shorter
tim e to exhale d u ring rap id breathing can ham p er the
ability to fu lly exhale the tid al volu m e. Incom p lete em p-
tying of the lu ngs lead s to air trap p ing and p rogressive
hyperinflation, and can cu lm inate in alveolar ru p tu re
w ith p neu m othorax and p neu mom ed iastinu m . The fol-
low ing m easu res w ill red u ce the risk of air trapping:
a. Use low tid al volu mes (6 m L/ kg) instead of trad ition-
al tid al volu m es (12 m L/ kg).
b. Increase the inspiratory flow rate: this prolongs expira-
tion and allow s m ore tim e to exhale the tid al volum e.
c. Sed ation is ad vised bu t m ay not be effective for slow -
ing resp irations. Neuromuscular paralysis may be need-
ed for patients in respiratory distress, but this should
only be used as a short-term measure.
Modes of Positive-Pressure Breathing 303

d . Change to a m od e of ventilation that allow s sponta-


neou s breathing (e.g., IMV, CPAP). This help s because
rap id breathing is u su ally accom p anied by red u ced
tid al volum es (excep t in anxiety states), w hich com -
p ensates for the shorter exhalation tim es.

B. Intermittent Mandatory Ventilation


Interm ittent m and atory ventilation (IMV) allow s p atients to
breathe sp ontaneou sly in the interval betw een ventilator
breaths. This d esign is m ore su itable than assisted (trig-
gered ) ventilation for rapid ly breathing patients because
only a fraction of the p atients insp iratory efforts w ill trigger
a ventilator breath.

1. Ventilatory Pattern
The p attern of breathing d u ring IMV is show n in the
low er p anel of Figure 19.2. The first breath (d otted line)

FIGURE19.2 Ventilatory patterns during assist-control ventilation (ACV)


and synchronized intermittent mandatory ventilation (SIMV). The
dotted line in the SIMV panel represents a spontaneous breath.
304 Mechanical Ventilation

is a spontaneou s breath, and the second breath is a p osi-


tive-p ressu re lu ng inflation that is synchronized to the
patients own breathing pattern (hence the term synchro-
nized IMV). IMV thus com bines spontaneou s breathing
w ith p eriod s of assist-control ventilation.

2. IMV Rate
The nu m ber of p ositive-p ressu re lu ng inflations d u ring
IMV is selected on the control panel of the ventilator. This
rate is usu ally set at 10 to 12 bp m initially, and can be
ad ju sted u p w ard or d ow nw ard as d ictated by the p a-
tients sp ontaneou s breathing (few er breaths are requ ired
as the p atients sp ontaneou s breathing ap p roaches nor-
mal or prem orbid levels).

3. Spontaneous Breathing
The w ork of breathing is increased d u ring the p eriod of
sp ontaneou s breathing (becau se of the high resistance
im posed by tracheal tu bes and ventilator tu bing), and
this is often a sou rce of p atient d istress d u ring IMV. Ad d -
ing pressure-su pport ventilation (d escribed later in the
chapter) at 10 cm H 2O d ecreases the w ork of sp ontaneou s
breathing (1), and improves p atient tolerance of IMV.

4. Cardiac Performance
IMV has an ad verse effect on card iac ou tp u t in p atients
w ith left-ventricular d ysfu nction (2). This effect is the
resu lt of the negative intrathoracic p ressu res generated
d u ring the sp ontaneou s breathing p eriod . (N egative
p ressu re in the thorax hold s the ventricles op en d u ring
systole, w hich im p ed es ventricu lar em p tying).

5. When to Use IMV


The p rincip al role of IMV is for p atients w ho are breath-
ing rap id ly and are at risk for air trap ping d u ring ACV.
IMV shou ld N OT be u sed to w ean p atients from m echan-
ical ventilation, as exp lained in Chap ter 21.
Modes of Positive-Pressure Breathing 305

III. PRESSURE-MODULATED VENTILATION

A. Pressure-Controlled Ventilation

1. Pressu re-controlled ventilation (PCV) u ses a constant,


p reselected pressu re to inflate the lungs.

2. The ventilatory p attern d u ring PCV is show n in the top


p anel in Figure 19.3 N ote the absence of an insp iratory
effort (i.e., a negative pressu re d eflection) at the begin-
ning of the ventilator breaths. This highlights the fact that
ventilation d u ring PCV is com p letely controlled by the
ventilator, w ith no p atient interaction (sim ilar to con-
trolled ventilation in ACV).

3. The proposed advantage of PCV over ACV is a decreased


risk of ventilator-induced lung injury (described in Chapter
16) because of the lower airway pressures. H ow ever, this is
u np roven.

4. There is one m ajor d isad vantage w ith PCV; i.e., the infla-
tion volume varies with changes in the mechanical properties
of the lungs. This is d em onstrated in Figu re 18.1. N ote that
w hen the inflation p ressu re is constant (p = k), the infla-
tion volum e d ecreases w hen there is an increase in air-
w ay resistance or a d ecrease in lu ng com p liance (d isten-
sibility). This behavior is a major concern in p atients w ith
acu te resp iratory failu re becau se the m echanical p roper-
ties of the lungs are likely to change frequ ently in these
p atients.

B. Inverse Ratio Ventilation


1. When PCV is com bined w ith a p rolonged inflation tim e,
the resu lt is inverse ratio ventilation (IRV) (3).
306 Mechanical Ventilation

2. The ventilatory p attern d u ring IRV is show n in the m id -


d le p anel of Figure 19.3. A d ecrease in insp iratory flow
rate is u sed to prolong the tim e for lu ng inflation, and the
u su al I:E ratio of 1:2 is reversed to a ratio of 2:1.

3. The p rolonged inflation tim e d u ring IRV p revents alveo-


lar collap se and im p roves gas exchange. H ow ever, pro-
longed inflation tim es also ham per exhalation and favor
p rogressive hyperinflation and alveolar ru p tu re.

4. The only ind ication for IRV at p resent is for p atients w ith
ARDS w ho have refractory hypoxemia or hyp ercap nia
d uring ACV (4).

FIGURE 19.3 Ventilatory patterns during pressure-controlled ventilation


(PCV ), inverse ratio ventilation (IRV ), and pressure-support ventilation
(PSV ).
Modes of Positive-Pressure Breathing 307

C. Pressure-Support Ventilation
1. Pressure-support ventilation (PSV) is a method of augment-
ing the tidal volume during spontaneous breathing (5).

2. The ventilatory p attern d u ring PSV is show n in the low er


p anel of Figu re 19.3. N ote that the inhaled gas is d eliv-
ered at a constant p ressu re (u su ally 5 to 10 cm H 2O),
w hich is accom p lished by ad ju sting the insp iratory flow
rate as need ed . The inflation p eriod is term inated w hen
the insp iratory flow rate falls below 25% of the p eak
inspiratory flow.

3. PSV is u sed m ost often d u ring w eaning from m echanical


ventilation. The goal of PSV in this setting is not to aug-
m ent the tid al volu m e, bu t to p rovid e enou gh p ressu re
(5 10 cm H 2O) to overcom e the resistance to flow in the
tracheal tu bes and ventilator tu bing.

IV. POSITIVE END-EXPIRATORY PRESSURE

A. Basic Features
1. In cond itions w here the lu ngs are stiff or noncom p liant
(e.g., ARDS), there is a tend ency for d istal airsp aces to
collap se at the end of exp iration, p articu larly d u ring low -
volu m e ventilation. To cou nteract this tend ency, the p res-
su re in the d istal airsp aces is not allow ed to retu rn to zero
(atm osp heric) p ressu re at the end of exp iration. The re-
su lting positive end-expiratory pressure (PEEP) acts like a
stent to keep d istal airsp aces op en at end -exp iration.

2. PEEP is created by p lacing a p ressu re-relief valve in the


expiratory lim b of the ventilator circu it. Exhalation p ro-
ceed s u ntil the airw ays p ressu re reaches the p ressu re
308 Mechanical Ventilation

level of the valve. Airflow ceases at this p oint, and the


airw ays p ressu re rem ains constant (at the valve p ressu re)
u ntil the onset of the next lu ng inflation.

FIGURE 19.4 Upper panel shows positive-pressure lung inflations with


positive end-expiratory pressure (PEEP), and lower panel shows spon-
taneous breathing with continuous positive airway pressure (CPAP).

3. The airw ay pressu re p attern p rod u ced by PEEP is show n


in the u pp er panel of Figu re 19.4. N ote that the entire
p ressu re w aveform is d isp laced u p w ard . The im plica-
tions of this d isp lacem ent are as follow s:
a. The increase in p eak airw ay p ressu re increases the risk
of barotrau m a (e.g., p neu m othorax).
b. The increase in m ean airw ay (intrathoracic) p ressu re
can retard venou s retu rn to the right sid e of the heart.
c. When airw ay pressures are used to evaluate lung mech-
anics (see Figure 18.4), the amount of PEEP should be
subtracted from the pressures.
Modes of Positive-Pressure Breathing 309

P EEP = 0 cm H2 O P EEP = 19 cm H2 O

FIGURE 19.5 CT images from a patient with ARDS showing aeration of


lung regions with atelectasis (recruitment) in response to PEEP. Images
from Reference 6.

B. Lung Recruitment
1. The m ajor benefit of PEEP is to keep the d istal airsp aces
open. This is show n in Figu re 19.5 (6). The increase in
aerated lu ng is lung recruitment, and it imp roves pu lmo-
nary gas exchange.

2. The beneficial effect of PEEP on lu ng recru itm ent occu rs


only in areas of atelectasis that contain p ockets of air
(called recru itable lu ng). When the lungs contain areas
of atelectasis that are airless (nonrecru itable lu ng),
PEEP is d istribu ted p rim arily to norm al lung regions,
resu lting in overd istension and ru p tu re of alveoli (7). CT
im ages of the lu ngs can id entify recruitable and non-
recru itable areas of lu ng (7).

3. The PaO 2/ FIO 2 ratio (a m easu re of alveolar-cap illary oxy-


gen exchange) can be used to monitor the effects of PEEP
on lu ng recruitment. ARDS is characterized by a PaO 2/
FIO 2 ratio that is below 200 (see Table 16.2). An increase
310 Mechanical Ventilation

in the PaO 2/ FIO 2 ratio after the ap p lication of PEEP (like


the response show n in Figu re 19.6) ind icates a favorable
effect on lu ng recruitm ent.

B. Cardiac Performance

1. PEEP can d ecrease card iac ou tp u t by several m echa-


nism s, inclu d ing red u ced venou s retu rn, red u ced ven-
tricu lar d istensibility, and increased right ventricu lar ou t-
flow im p ed ance (8,9).

2. The tend ency for PEEP to red u ce card iac ou tp u t is an


im portant consid eration because the beneficial effects of
PEEP on gas exchange can be erased by a concu rrent
d ecrease in card iac ou tpu t. This is d em onstrated by the
equ ation for system ic oxygen d elivery (DO 2):

DO2 = Q x 1.3 x Hb x S aO2 (19.1)

Thus, PEEP can im p rove arterial oxygenation (SaO 2), bu t


if there is a p rop ortional d ecrease in card iac ou tp u t (Q),
system ic oxygen d elivery (DO 2) w ill rem ain u nchanged .

3. An exam p le of how PEEP can im p rove gas exchange bu t


sim u ltaneou sly red u ce card iac ou tp u t is illu strated in
Figu re 19.6 (10). In this stu d y of p atients w ith ARDS, in-
cremental PEEP w as accom panied by a stead y increase in
the PaO 2/ FIO 2 ratio and a stead y d ecline in card iac ou t-
put. This d em onstrates how the effects of PEEP on gas
exchange can be m islead ing if the card iac ou tput is not
monitored .

C. Clinical Uses
The use of PEEP should be reserved for the following situations:

1. In p atients w ith ARDS w ho requ ire toxic levels of inhaled


oxygen (i.e., FIO 2 60%) to m aintain ad equ ate arterial ox-
Modes of Positive-Pressure Breathing 311

175 5.0
Ca rdia c
Index
150

C
a
125

r
d
i
4.5

a
c
2
I
n
O
100

d
I
F
e
x

2
(
O
Pa O 2 F IO 2

m
75
a
L
P

m
4.0

i
n
50


m
2
)
25

0 3.5

0 5 10 15

P EEP Leve l (cm H2 O)

FIGURE 19.6 Opposing effects of positive end-expiratory pressure


(PEEP) on pulmonary gas exchange (PaO 2/ FIO 2) and cardiac output in
patients with ARDS. From Reference 10.

ygenation (i.e., SaO 2 88 90%), PEEP-ind u ced lu ng re-


cru itment w ill increase the PaO 2/ FIO 2 ratio and allow a
d ecrease in the FIO 2 to less toxic or non-toxic levels.

2. Du ring low -volu me ventilation (see Tables 16.3 and 18.1),


low -level PEEP (5 7 cm H 2O) is u sed rou tinely to prevent
repeated closing and opening of d istal airw ays, w hich is
consid ered a source of lung injury (11).

V. CONTINUOUS POSITIVE AIRWAY


PRESSURE

A. Basic Features
1. Sp ontaneou s breathing from a p re-selected p ositive base-
312 Mechanical Ventilation

line p ressu re is called continuous positive airway pressure


(CPAP).

2. The airw ay p ressure p attern d u ring CPAP is show n in


Figu re 19.4. N ote that the negative p ressu re d eflection
from the inspiratory effort d oes not fall below zero (at-
mospheric) p ressu re. This eliminates the extra w ork in-
volved in generating a negative airw ay p ressu re to re-
ceive the inhaled gas.

B. Clinical Uses
The m ajor u ses of CPAP are in nonintu bated p atients, w here
CPAP is d elivered throu gh specialized face m asks or nasal
masks equip ped w ith pressu rized valves.

1. CPAP has been u sed as a m ethod of noninvasive ventila-


tion in p atients w ith acu te resp iratory failu re from a vari-
ety of d isord ers, inclu d ing ARDS, card iogenic p u lm o-
nary ed em a, and acu te exacerbations of COPD (1214).

2. In p atients w ith card iogenic pu lm onary ed em a, CPAP


m ay be p articu larly ad vantageou s becau se of the actions
of p ositive intrathoracic p ressu re to enhance ventricu lar
em ptying. (The card iac effects of p ositive intrathoracic
p ressu re are d escribed in Chapter 18).

3. In p atients w ith obstru ctive sleep ap nea, CPAP is u sed


to p revent collap se of the orop harynx d u ring negative-
p ressu re breathing efforts (15).

REFERENCES
1. Leu ng P, Ju bran A, Tobin MJ. Com p arison of assisted ventilator
m od es on triggering, p atients effort, and d ysp nea. Am J Resp ir
Crit Care Med 1997; 155:19401948.
2. Mathru M, Rao TL, El-Etr AA, Pifarre R. H em od ynam ic resp ons-
es to changes in ventilatory p atterns in p atients w ith nor-
Modes of Positive-Pressure Breathing 313

tory p atterns in patients w ith norm al and poor left ventricu lar
reserve. Crit Care Med 1982; 10:423426.
3. Malarkkan N , Snook N J, Lu m b AB. N ew aspects of ventilation in
acu te lu ng injury. Anesthesia 2003; 58:647667.
4. Wang SH , Wei TS. The ou tcom e of early p ressu re-controlled in-
verse ratio ventilation on p atients w ith severe acu te resp iratory
d istress synd rom e in su rgical intensive care unit. Am J Su rg 2002;
183:151155.
5. H ess DR. Ventilator w aveform s and the physiology of p ressu re
su pp ort ventilation. Resp ir Care 2005; 50:166186.
6. Barbas CSV, Lung recru itm ent m aneu vers in acute respiratory
d istress synd rom e and facilitating resolution, Crit Care Med
2003; 31(Su ppl):S265S271.
7. Gattinoni L, Cairon M, Cressoni M, et al. Lung recru itm ent in
p atients w ith the acute respiratory d istress synd rom e. N Engl J
Med 2006; 354:17751786.
8. Schm itt J-M, Viellard -Baron A, Au gard e R, et al. Positive end -
exp iratory pressure titration in acu te resp iratory d istress syn-
d rom e p atients: Im p act on right ventricu lar ou tflow im p ed ance
evalu ated by p ulm onary artery Dop pler flow velocity m easu re-
m ents. Crit Care Med 2001; 29:11541158.
9. Takata M, Robotham JL. Ventricu lar external constraint by the
lu ng and p ericard iu m d u ring p ositive end -exp iratory p ressu re.
Am Rev Resp ir Dis 1991; 43:872875.
10. Gainnier M, Michelet P, Thirion X, et al. Prone p osition and p os-
itive end -exp iratory p ressu re in acu te resp iratory d istress syn-
d rom e. Crit Care Med 2003; 31:27192726.
11. Musced ere JG, Mullen JBM, Gan K, et al. Tid al ventilation at low
airw ay pressures can au gm ent lu ng inju ry. Am J Resp ir Crit Care
Med 1994; 149:13271334.
12. Majid A, H ill N S. N oninvasive ventilation for acute resp iratory
failu re. Curr Op in Crit Care 2005; 11(1):7781.
13. Masip J, Roque M, Sanchez B, et al. N oninvasive ventilation in
acu te card iogenic ed em a. JAMA 2005; 294:31243130.
14. d e Lu cas P, Tarancon C, Pu ente L, et al. N asal continuou s p osi-
tive airw ay pressure in p atients w ith COPD in acu te resp iratory
failu re. Chest 1993; 104:16941697.
15. Pack AI. Ad vances in sleep -d isord ered breathing. Am J Resp ir
Crit Care Med 2006; 173(1):715.
Chapter 20
THEVENTILATOR-
DEPENDENT PATIENT
This chap ter d escribes the com m on p ractices and concerns in
p atients w ho requ ire m ore than a few d ays of m echanical
ventilation. The focu s is on issu es d irectly related to m echan-
ical ventilation. Less specific issues in ventilator-d ependent
patients, such as nutritional support, are described elsewhere.

I. INDWELLING ENDOTRACHEALTUBES
The follow ing are som e com m on concerns w ith ind w elling
end otracheal tubes.

A. Migration
1. Endotracheal tubes tend to migrate (in either direction) with
time. Proximal migration can lead to vocal cord injury from
the inflated balloon (cuff) at the distal end of the tube, and
distal migration can lead to intubation of the right main-
stem bronchus (which runs a straight course down from the
main carina).

2. The p osition of end otracheal tu bes shou ld be m onitored


rad iograp hically to p revent com p lications from migra-
tion. When the head is in a neu tral p osition, the tip of the
end otracheal tu be shou ld be 3 to 5 cm above the carina,
or m id w ay betw een the carina and vocal cord s. (The cari-
na is the point w here the trachea bifurcates to form the
right and left m ainstem bronchi).
a. If not visible, the carina is usu ally located over the in-

315
316 Mechanical Ventilation

tersp ace betw een the fou rth and fifth thoracic verte-
brae (T4T5), and the vocal cord s are situated over the
interspace betw een the fourh and fifth cervical verte-
brae (C4C5) (1).

B. Paranasal Sinusitis
1. N asotracheal (and nasogastric) tu bes can obstruct the os-
tia that d rain the p aranasal sinu ses, and this pred isposes
to a pu rulent sinusitis (2). This complication has also been
reported with orotracheal intubation (3) for unclear reasons.

2. The m axillary sinu s is alm ost alw ays involved (2).

3. Op acification or air-flu id levels in the m axillary or eth-


moid sinuses su ggests the d iagnosis of nosocom ial sinu s-
itis, but confirm ation requ ires asp iration of infected m a-
terial from the involved sinu s (2).

4. Paranasal sinusitis is not a common cause of fever in the


ICU, but it should be consid ered in intubated patients w ho
have no other apparent cause of fever (see Chapter 32).

C. Laryngeal Damage
1. Inju ry of the larynx and vocal cord s is a m ajor concern
w ith ind w elling end otracheal tu bes, and is one of the
major reasons for the transition from end otracheal (trans-
laryngeal) intubation to tracheostomy.

2. Som e type of laryngeal d am age (e.g., u lceration, ed em a)


is u su ally evid ent after 72 hours of translaryngeal intuba-
tion (4).

3. Fortu nately, m ost cases of laryngeal injury resolve w ith-


in w eeks after extu bation (5).
The Ventilator-Dependent Patient 317

II. TRACHEOSTOMY

A.Transition to Tracheostomy
1. Tracheostomy offers several ad vantages over endotracheal
intubation, including greater patient comfort, more effec-
tive clearing of secretions, red uced resistance for breath-
ing, and the ability to vocalize and ingest food orally.

2. There is no consensu s abou t the op timal tim e to sw itch


from end otracheal intu bation to tracheostom y. H ow ever,
the follow ing recom m end ation is reasonable (6):
a. A fter 5 to 7 days of endotracheal intubation, assess the like-
lihood of extubation in the following week: if the likelihood
is low, proceed to tracheostomy.

B.Techniques
1. Tracheostomy is trad itionally performed as an open surgi-
cal proced ure, but less invasive percutaneous techniques
are gaining in popularity.

2. Percu taneou s tracheostomy is very sim ilar to the Seld in-


ger technique for cannulating blood vessels (see Figure
5.2). A need le is u sed to p u nctu re the trachea (in a sp ace
betw een the tracheal rings), and a gu id ew ire is p assed
throu gh the need le and into the trachea. The tracheosto-
my tube is then ad vanced over the guid ew ire (after a se-
ries of d ilator tu bes are u sed to increase the size of the
tracheal stom a).

3. Em ergency tracheostomy is u su ally p erform ed throu gh


an op ening in the cricothyroid m em brane, ju st below the
larynx. This techniqu e, know n as cricothyroidotomy, has a
high incid ence of laryngeal inju ry and subglottic steno-
sis, and p atients w ho su rvive follow ing a cricothyroid o-
318 Mechanical Ventilation

tom y shou ld have a regu lar tracheostom y (su rgical or


p ercutaneou s) as soon as they are stable (6).

C. Complications
1. Com bining surgical and p ercu taneou s tracheostom y, the
m ortality rate is less than 1%, and m ajor ad verse events
occu r in 5 to 10% of cases (6). The acu te com p lications of
m ost concern are bleed ing and infection.

2. The p ooled resu lts of several stu d ies com p aring su rgical
and p ercutaneou s tracheostom y show less bleed ing and
few er infections w ith the p ercu taneou s techniqu e (7).
H ow ever, the resu lts of ind ivid u al stu d ies are conflicting.

3. Tracheal stenosis is a late com p lication that ap p ears in


the first 6 m onths after the tracheostom y tu be is re-
m oved . Most cases of tracheal stenosis occu r at the tra-
cheotom y site and are cau sed by tracheal narrow ing af-
ter the stom a closes. The incid ence of tracheal stenosis
ranges from zero to 15% (6), bu t m ost cases are asymp to-
m atic.

III. CLEARING SECRETIONS

A. Respiratory Secretions
1. The m u cosa of the resp iratory tract is norm ally covered
by a p rotective blanket of secretions. This blanket has a
hyd rop hilic (w ater-solu ble) layer, and a hyd rophobic
(w ater-in solu ble) layer. The h yd rop hilic layer faces
inw ard and keep s the m u cosal su rface m oist. The hyd ro-
p hobic layer, w hich faces tow ard the lu m en of the air-
w ays, is com p osed of a m eshw ork of m u cop rotein
strand s (called m u cu s thread s) held together by d isu lfid e
The Ventilator-Dependent Patient 319

brid ges. This m eshw ork trap s p articles and d ebris in the
airw ays, and is responsible for the viscoelastic p rop erties
of sp u tu m .

2. Und er norm al circu m stances, the resp iratory secretions


are m oved ou t of the lu ngs by the continu ou s action of
cilia on the lu m inal surface of m u cosal cells in the air-
w ays. This p rocess is called mucociliary clearance, and it
helps to clear d u st and d ebris from the airw ays.

3. An abu nd ance of p articu late m atter w ill increase the vis-


cosity of respiratory secretions and hind er mu cociliary
clearance. When this occu rs, cou ghing p rovid es an ad d i-
tional m eans of clearing secretions.

4. These norm al m echanism s of clearing resp iratory secre-


tions are d efective in critically ill (e.g., ventilator-d epend -
ent) p atients. Therefore, other measu res su ch as tracheal
su ctioning are u sed to help clear secretions.

B.Tracheal Injections of Saline


Isotonic saline is rou tinely injected into the airw ays ju st p rior
to tracheal suctioning, p resu m ably to facilitate the clearance
of respiratory secretions. This practice is ill-ad vised for the
follow ing reasons.

1. The hyd rop hobic ou ter layer of resp iratory secretions is


resp onsible for their viscoelastic p roperties. This layer is
not w ater solu ble, w hich m eans that saline cannot liquefy
or reduce the viscosity of respiratory secretions. Ad d ing sa-
line to thick, resp iratory secretions is like p ou ring w ater
over grease.

2. The injection of saline throu gh tracheal tu bes can p red is-


p ose to pu lm onary infections. Bacterial biofilms have
been d em onstrated on the inner su rface of end otracheal
tu bes and tracheostom y tu bes (8), and saline injections
can d islod ge these bacterial biofilm s. Clinical stud ies
320 Mechanical Ventilation

have show n that the injection of 5 m L of saline can d is-


lod ge u p to 300,000 colonies of viable bacteria from the
inner su rface of end otracheal tu bes (9). The d islod ged
bacteria can becom e a nid u s of infection if they reach the
low er airw ays.

TABLE 20.1 Mucolytic Therapy with N-Acetylcysteine (NAC)


Aerosol Therapy: Use 10% NAC solution.
Mix 2.5 mL NAC with 2.5 mL saline and
place mixture (5 mL) in a small-volume
nebulizer for aerosol delivery.
Warning: Can provoke bronchospasm, and
is not recommended in asthmatics.
Tracheal Injection: Use 20% NAC solution.
Mix 2 mL NAC with 2 mL saline and
inject 2 mL aliquots into the trachea.
Warning: Can promote bronchorrhea with
repeated use.

C. Mucolytic Therapy
1. N -Acetylcysteine (Mu com yst) acts on the hyd rop hobic
region of resp iratory secretions to break the d isu lfid e
brid ges betw een m ucop rotein strand s. By d isru pting the
elem ents responsible for the viscoelastic properties of
respiratory secretions, N -acetylcysteine (N AC) acts as a
mucolytic agent to liqu efy secretions (10).

2. N AC can be u sed to relieve airw ays obstruction cau sed


by tenaciou s secretions. The d ru g is available in a liqu id
p reparation (10 or 20% solu tion) that can be given as an
aerosol sp ray, or injected d irectly into the airw ays (Table
20.1). Direct injection into the airw ays is p referred be-
cau se aerosolized N AC is irritating and can p rovoke
coughing and bronchosp asm (particu larly in asthm atics).
The Ventilator-Dependent Patient 321

3. If intratracheal injection of N AC d oes not relieve an ob-


stru ction, bronchoscop y is p erform ed , and the N AC is
ap plied d irectly to the m u cou s plu g. Follow ing relief of
the obstruction, N AC can be instilled tw o or three tim es
a d ay for the next few d ays. Rep eated use of N AC is not
ad vised becau se the d rug solu tion is hyp ertonic (even
w ith the saline ad d itive) and can p rovoke bronchorrhea.

IV. ALVEOLAR DISRUPTION


Overd istension and ru p tu re of alveoli is a com m on occu r-
rence d u ring m echanical ventilation and is clinically ap p ar-
ent in as m any as 25% of ventilator-d epend ent p atients (11).

A. Clinical Manifestations
Air that escapes from d isrupted alveoli can prod u ce a vari-
ety of clinical m anifestations.

1. The air can d issect along tissu e p lanes in the lungs and
p rod u ce pulmonary interstitial emphysema, and air can
m ove into the m ed iastinu m to p rod u ce pneumomedi-
astinum.

2. Air that reaches the m ed iastinu m can m ove into the neck
to prod u ce subcutaneous emphysema, or can p ass below
the d iaphragm to prod uce pneumoperitoneum.

3. If the alveolar d isru ption is close to the su rface of the


lung, air can enter the p leu ral sp ace to p rod u ce a pneu-
mothorax.

4. Each of these entities can occu r alone or in com bination


w ith the others (11,12).

B. Pneumothorax
Rad iograp hic evid ence of p neu mothorax is reported in 5 to
322 Mechanical Ventilation

15% of ventilator-d epend ent p atients (11,12). Pred isp osing


factors inclu d e high inflation pressu res and inflation vol-
um es, intrinsic PEEP (d escribed later in the chap ter), and d if-
fu se lu ng inju ry. Pneu m othorax is p articu larly p revalent in
patients w ith severe Pneumocystis jirovecii p neu m onia.

1. Clinical Presentation
Pneumothoraces are often clinically silent, at least initially.
a. The m ost reliable clinical sign is subcutaneous emphyse-
ma, first app arent in the u p per thorax and base of the
neck.
b. Pneu m othorax may not be accom panied by d im in-
ished breath sou nd s in ventilator-d ep end ent p atients
becau se sou nd s transm itted from the ventilator tubing
can be m istaken as breath sou nd s.
c. Continu ed accu m u lation of air in the p leu ral sp ace
w ill eventu ally p rod uce a tension pneumothorax, w hich
is characterized by a shift in the m ed iastinu m tow ard
the u ninvolved hem ithorax w ith hem od ynam ic insta-
bility.

2. Radiographic Detection
The rad iograp hic ap p earance of p neu m othorax is atyp i-
cal in ICU patients because the patients are u su ally su -
p ine and pleural air does not collect at the lung apex in the
supine position (12,13).
a. Pleural air can collect anterior to the lu ng in the su p ine
p osition, and this m ay not be evid ent on p ortable chest
film s. This is d em onstrated in Figu re 20.1. In this case
(a trau m atic pneu m othorax), the chest x-ray is u nre-
vealing, but the CT im age show s an anterior p neu mo-
thorax in the left hem ithorax.
b. Basilar and subpulmonic collections of air are also com-
mon features of pneumothorax in the supine position (13).

3. Pleural Evacuation
The d etection of a pneu m othorax in a ventilator-d ep end -
The Ventilator-Dependent Patient 323

FIGURE 20.1 A portable chest x-ray and CT image of the thorax in a


young male with blunt trauma to the chest. An anterior pneumothorax
is evident on the CT image (indicated by the asterisk) but is not appar-
ent on the chest x-ray.

ent patient shou ld alw ays prom pt im m ed iate insertion of


a chest tu be to evacu ate the pleu ral air. Delays in p leu ral
evacu ation can lead to a tension p neu m othorax.
a. Once the chest tu be is inserted , the p leu ral d rainage
system d escribed next is used for continued rem oval
of air from the p leu ral sp ace.

C. Pleural Drainage System


A triple-cham ber system like the one show n in Figu re 20.2 is
u sed to d rain both air and flu id from the p leu ral sp ace (14).
This is the sam e system u sed by the p op u lar Pleu r-Evac
324 Mechanical Ventilation

Chest Drainage Systems (Teleflex Med ical). The follow ing is


a brief d escrip tion of how the system w orks.

1. The first cham ber in the system (the collection bottle) col-
lects fluid from the pleu ral space and allow s air to pass
throu gh to the next bottle in the series. Becau se the inlet
of this cham ber is not in d irect contact w ith the flu id ,
p leu ral flu id can accu m u late in the bottle w ithou t im p os-
ing a back pressu re on the pleural space.

2. The second cham ber (the w ater-seal bottle) acts like a


one-w ay valve that allow s air to p ass throu gh to the next
bottle (aw ay from the p leu ral sp ace) bu t prevents air
from m oving in the op p osite d irection (tow ard the p leu -
ral sp ace). This one-w ay valve is created by su bm erging
the inlet tu be u nd er w ater. This creates a "w ater-seal" that
p revents air from entering the p leu ral sp ace.
a. Air that is evacu ated from the p leu ral sp ace w ill pass
throu gh the w ater in the second cham ber, creating
bu bbles. Therefore, the presence of bu bbles in the w a-
ter-seal cham ber is evid ence of continu ed air leakage
from the pleural space.

3. The third cham ber in the system (the su ction-control bot-


tle) is attached to a negative-p ressu re sou rce (su ction),
and the cham ber is d esigned to set a m axim u m lim it on
the negative pressu re im p osed on the p leural sp ace. This
m axim u m p ressu re is d eterm ined by the height of the
w ater colu m n in the air-inlet tu be. N egative p ressu re
(from w all su ction) d raw s the w ater d ow n the air-inlet
tu be, and w hen the negative p ressu re exceed s the height
of the w ater colu m n, air is entrained from the atm os-
p here. Therefore, the p ressu re in the bottle can never be-
com e m ore negative than the height of the w ater colum n
in the air-inlet tube.
a. Water is ad d ed to the su ction-control cham ber to a-
chieve a w ater level of 20 cm . The w all su ction is then
activated and slow ly increased until bu bbles ap p ear in
The Ventilator-Dependent Patient 325

the w ater. This bu bbling ind icates that atm osp heric air
is being entrained , and thus the m aximu m allow able
negative p ressu re has been achieved .

4. Why Use Suction?


The p ractice of u sing negative p ressu re to evacu ate pleu -
ral air is u nnecessary and p otentially harm fu l.
a. N egative p ressu re is u sed to help re-inflate the lu ngs,
bu t this is not necessary because the lungs w ill re-
inflate w hen p leu ral air is evacu ated and the intra-
p leu ral pressure d rop s to atm osp heric (zero) p ressu re.
b. Creating a negative pressure in the pleural space is
cou nterp rod u ctive in the p resence of an air leak in the
lungs becau se negative intrap leu ral p ressu re increases
the transp ulm onary pressure (the pressure d ifference
betw een alveoli and the pleural space) that d rives air
out of the lu ngs and into the p leu ral sp ace. Thu s,
applying negative pressure to the pleural space promotes air
leakage through a bronchopleural fistula. Ap plying su c-
tion to the p leu ral space is not ad vised if there is a per-
sistent air leak.

FIGURE 20.2 A triple-chamber drainage system for evacuating air and


fluid from the pleural space.
326 Mechanical Ventilation

V. INTRINSIC PEEP
As m entioned in Chapter 19, p ositive end -expiratory p res-
su re (PEEP) is ap p lied to the airw ays in certain cond itions to
prevent the d istal airspaces from collap sing at the end of
expiration. In ad d ition to this ap p lied or extrinsic PEEP, there
is an internally generated or intrinsic PEEP that is prod u ced
by incom plete emp tying of the lu ngs d u ring exp iration. The
follow ing is a d escrip tion of the intrinsic form of PEEP and
how it can be m easu red .

A. Pathogenesis
1. When the tid al volu m e is exhaled com p letely and there is
no airflow at the end of exp iration, the end -exp iratory

Occult
P EEP
P P ROX PALV
I E I E


P = Vx R


P P ROX V PALV
R

If: V 0,
The n: P 0
And: PALV > P P ROX

FIGURE 20.3 The features of intrinsic PEEP. The lower portion of the fig-
ure indicates that, when exhalation is incomplete and flow persists at
end-expiration (V 0), alveolar pressure will be positive relative to prox-
imal airway pressure (PALV > Pprox). This is depicted in the graphs in the
upper portion of the figure. The positive alveolar pressure at end-expi-
ration is intrinsic PEEP.
The Ventilator-Dependent Patient 327

p ressu re returns to zero (atm osp heric p ressure) in both


the alveoli and p roxim al airw ays.

2. When the tid al volu m e is not exhaled com p letely and


there is p ersistent airflow at the end of expiration, the
end -exp iratory pressure in the alveoli w ill be positive
w hile the end -exp iratory p ressu re in the p roxim al air-
w ays retu rns to zero (see the grap hs in the u p p er p ortion
of Figu re 20.3). This p ositive end -exp iratory p ressu re
(PEEP) in the alveoli is called intrinsic PEEP.

3. Becau se intrinsic PEEP is not ap p arent w hen m onitoring


p roxim al airw ays pressu res, it is also called occult PEEP
(15).

4. Intrinsic PEEP is the physiologic expression of hyperinfla-


tion from air trapping.

B. Predisposing Factors
Any cond ition that favors incom plete exhalation w ill pred is-
p ose to the d evelopm ent of hyp erinflation and intrinsic
PEEP. These pred isp osing cond itions can be sep arated into
ventilator-related and d isease-related cond itions.

1. The ventilator-related cond itions have been d escribed in


Chap ter 19 and includ e volu m e-cycled ventilation w ith
relatively large tid al volu m es (10 to 12 mL/ kg), and the
u se of assist-control ventilation for p atients w ho are
breathing rapid ly.

2. The d isease-related cond itions inclu d e rap id breathing


and obstructive airw ays d isease; i.e., asthm a and chronic
obstru ctive p ulm onary d isease (COPD).

3. Most or all p red isp osing cond itions can be p resent at the
sam e tim e. In p atients w ith asthm a and COPD, intrinsic
PEEP m ay be u niversal d u ring conventional (large tid al
volu m e) m echanical ventilation (1618).
328 Mechanical Ventilation

C. Consequences
The consequ ences of extrinsic PEEP d escribed in Chapter 19
also app ly to intrinsic PEEP. The follow ing consequ ences
d eserve m ention because of their possible im pact on clinical
ou tcom es.

1. Reduced Cardiac Output


Intrinsic PEEP has been im p licated as a cau se of failed
attem p ts at card iop u lm onary resu scitation (18). As d e-
scribed in Chapter 13, m anu al ventilation d u ring CPR is
often excessive (both in rate and inflation volu m e), w hich
means that intrinsic PEEP m ay be com m onplace d u ring
CPR, and the ability of PEEP to red u ce venou s retu rn w ill
im pair the ability of chest com pressions to prom ote car-
d iac outp u t. The incid ence and m agnitud e of intrinsic
PEEP d u ring CPR d eserves fu rther stud y.

2. Increased Work of Breathing


Intrinsic PEEP can increase the w ork of breathing by
increasing the pressu re that m u st be generated to trigger
a ventilator breath; e.g., if the ventilator breath is trig-
gered at a negative p ressu re of 2 cm H 2O and there is 5
cm H 2O of intrinsic PEEP, the total p ressure that m u st be
generated by the p atient to trigger the ventilator breath is
7 cm H 2O. This increased w ork of breathing can im p ed e
the ability to w ean from m echanical ventilation.

D. Monitoring Intrinsic PEEP


The m ost accu rate m ethod of m easu ring intrinsic PEEP is to
measure intraesophageal (pleu ral) p ressu re at end -expira-
tion, but this m easu rem ent is d ifficu lt to perform and not
read ily available. The follow ing m ethod s can be u sed to
d etect intrinsic PEEP, but none of them p rovid es an accu rate
qu antitative m easurem ent of the intrinsic PEEP level.
The Ventilator-Dependent Patient 329

1. End-Expiratory Air Flow


Expiratory flow tracings (available on m any of the new er
ventilator m od els) can be u sed to id entify p ersistent flow
at end -expiration. This confirm s the presence of intrinsic
PEEP, bu t p rovid es no qu antitative inform ation.

2. End-Expiratory Occlusion
During controlled ventilation (i.e., w hen the p atient is
com p letely p assive), intrinsic PEEP can be d etected by
occlu d ing the exp iratory tu bing at the end of exp iration
(16). This m aneu ver blocks airflow and allow s the p res-
su re in the p roxim al airw ays to equ ilibrate w ith alveolar
p ressu re.
a. A su d d en rise in p roxim al airw ays p ressu re in re-
sponse to end -expiratory occlu sion is evid ence of in-
trinsic PEEP (see the u p p er left panel in Fig. 20.3).
b. This method d oes not provid e accurate measurements
of intrinsic PEEP becau se the occlusion cannot be timed
to coincid e w ith the very end of expiration.

3. Response to Extrinsic PEEP


The application of extrinsic PEEP normally causes an equiv-
alent increase in the peak inspiratory pressure. H ow ever,
in the presence of intrinsic PEEP, the p eak insp iratory
p ressu re m ay be u naffected by extrinsic PEEP (this is
explained below ).
a. Failure of extrinsic PEEP to produce an equivalent rise in
peak airway pressure is evidence of intrinsic PEEP (19).
b. The level of extrinsic PEEP that first prod uces a rise in
p eak airw ay pressu res can be used as the m easure of
intrinsic PEEP (19).

E. Management
Maneuvers d esigned to p rom ote exhalation (e.g., low -vol-
u m e ventilation) can red u ce the severity of intrinsic PEEP.
330 Mechanical Ventilation

Ad d ing extrinsic PEEP can also red u ce intrinsic PEEP, as


d escribed below.

1. Extrinsic PEEP
When intrinsic PEEP is d u e to collap se of sm all airw ays
at end -exp iration (e.g., in asthm a and COPD), extrinsic
PEEP can help to keep the small airw ays open, and this
w ill facilitate exhalation and red u ce intrinsic PEEP. The
am ou nt of extrinsic PEEP shou ld be enou gh to cou nter-
balance the p ressu re cau sing sm all airw ays collap se (the
critical closing pressure) but shou ld not exceed the level of
intrinsic PEEP (so exp iratory flow is not imp aired ) (20).
To accom plish this, the amount of extrinsic PEEP should
match the level of intrinsic PEEP. Unfortu nately, this is d if-
ficult to accom plish because of the d ifficulty in obtaining
an accu rate m easu re of intrinsic PEEP.

REFERENCES
1. Good m an LR. Pu lm onary su pp ort and m onitoring app aratu s. In:
Good m an LR, Pu tm an CE, ed s. Critical care im aging. 3rd ed .
Philad elp hia: WB Saund ers, 1992;3559.
2. Rouby J-J, Lau rent P, Gosnach M, et al. Risk factors and clinical
relevance of nosocom ial m axillary sinusitis in the critically ill.
Am J Resp ir Crit Care Med 1994; 150:776783.
3. van Zanten AR, Dixon JM, N ip shagen MD, et al. H osp ital-ac-
qu ired sinu sitis is a com m on cau se of fever of u nknow n origin in
orotracheally intu bated critically ill p atients. Crit Care 2005;
9:R583R590.
4. Gallagher TJ. Endotracheal intubation. Crit Care Clin 1992; 8:665676.
5. Colice GL. Resolu tion of laryngeal injury follow ing translaryn-
geal intu bation. Am Rev Resp ir Dis 1992; 145:361364.
6. Tracheotom y: ap plication and tim ing. Clin Chest Med 2003;
24:389398.
7. Freem an BD, Isabella K, Lin N , Buchm an TG. A m eta-analysis of
p rosp ective trials com paring percu taneous and su rgical tra-
cheostom y in critically ill patients. Chest 2000; 118:14121418.
The Ventilator-Dependent Patient 331

8. Ad air CG, Gorm an SP, Feron BM, et al. Im p lications of end otra-
cheal tu be biofilm for ventilator-associated pneum onia. Inten-
sive Care Med 1999; 25:10721076.
9. H agler DA, Traver GA. End otracheal saline and su ction cath-
eters: sources of low er airw ays contam ination. Am J Crit Care
1994; 3:444447.
10. H old iness MR. Clinical p harm acokinetics of N -acetylcysteine.
Clin Pharm acokinet 1991; 20:123134.
11. Gam m on RB, Shin MS, Bu chalter SE. Pu lm onary barotrau m a in
m echanical ventilation. Chest 1992; 102:568572.
12. Marcy TW. Barotraum a: d etection, recognition, and management.
Chest 1993; 104:578584.
13. Tocino IM, Miller MH , Fairfax WR. Distribution of pneum otho-
rax in the su pine and sem irecu m bent critically ill ad ult. Am J
Rad iol 1985; 144:901905.
14. Kam AC, OBrien M, Kam PCA. Pleu ral d rainage system s. An-
esthesia 1993; 48:154161.
15. Pepe P, Marini JJ. Occu lt p ositive end -expiratory p ressu re in
m echanically ventilated patients w ith airflow obstru ction. Am
Rev Respir Dis 1982; 126:166170.
16. Blanch L, Bernabe F, Lucangelo U. Measu rem ent of air trap p ing,
intrinsic positive end -exp iratory p ressu re, and d ynam ic hyp erin-
flation in m echanically ventilated patients. Resp ir Care 2005;
50:110123.
17. Mughal MM, Cu lver DA, Minai OA, Arroliga AC. Au to-p ositive
end -expiratory pressu re: m echanism s and treatm ent. Cleve Clin
J Med 2005; 72:801809.
18 Rogers PL, Schlichtig R, Miro A, Pinsky M. Auto-PEEP d u ring
CPR. An occu lt cause of electrom echanical d issociation. Chest
1991; 99:492493.
19. Slu tsky AS. Mechanical ventilation. Chest 1993; 104:18331859.
20. Tobin MJ, Lod ato RF. PEEP, au to-PEEP, and w aterfalls. Chest
1989; 96:449451.
Chapter 21
DISCONTINUING
MECHANICAL
VENTILATION
This chap ter d escribes the transition from ventilatory su p -
p ort to u naid ed breathing. This p rocess is u neventfu l in m ost
p atients, bu t it can consu m e over half the tim e on a ventila-
tor in problem patients.

I. IDENTIFYING CANDIDATES

A. Readiness Criteria
1. When ventilator-d epend ent patients show evid ence of sig-
nificant and continued clinical improvement, the checklist
in Table 21.1 can be used to identify candidates for a trial
of spontaneous (unaid ed ) breathing off the ventilator.

2. Patients w ho satisfy the criteria in Table 21.1 shou ld be


rem oved from the ventilator briefly to obtain the m eas-
u rem ents in Table 21.2 These m easu rem ents have been
u sed to pred ict the likelihood that a p atient w ill tolerate
a trial of sp ontaneou s breathing.
a. N o single m easu rem ent in Table 21.1 can pred ict w ith
certainty w hich p atients are read y to resum e sponta-
neou s breathing (1,2). H ow ever, w hen taken together,
these m easu rem ents p rovid e an im p ression of how
d ifficult it w ill be for the patient to resu m e sponta-
neou s breathing. Tw o of the m ore p red ictive m easure-
ments are d escribed next.
333
334 Mechanical Ventilation

TABLE 21.1 Checklist to Identify Candidates for a Trial of


Spontaneous Breathing
Respiratory Criteria:
PaO2 60 mm Hg on FIO2 < 40 50% and PEEP 58 cm H2O
PaO2 normal or baseline
Patient is able to initiate an inspiratory effort
Cardiovascular Criteria:
No evidence of myocardial ischemia
Heart rate 140 beats/min
Blood pressure normal without vasopressors or with minimum
vasopressor support (e.g., dopamine < 5 g/kg/min)
Adequate Mental Status:
Patient is arousable, or Glasgow Coma Score 13
Absence of Correctable Comorbid Conditions:
Patient is afebrile
There are no significant electrolyte abnormalities.

From Reference 1.

A. Rapid-Shallow Breathing Index


1. Rap id , shallow breathing is com m on in p atients w ho d o
not tolerate spontaneou s breathing (6). The tend ency for
rap id shallow breathing is evalu ated by the ratio of res-
p iratory rate to tid al volu m e (RR/ VT), w hich is called the
rapid-shallow breathing index (RSBI). For a healthy ad ult
w ith a tid al volu m e of 500 m L (0.5 L) and a resp iratory
rate of 10 bp m , the RSBI is: 10/ 0.5 = 20/ L

2. The p red ictive valu e of the RSBI from a land m ark stu d y
(2) show ed the follow ing:
a. When the RSBI w as above 105/ L, 95% of the attem p ts
to w ean (d iscontinue) m echanical ventilation failed .
Discontinuing Mechanical Ventilation 335

b. When the RSBI w as below 105/ L, 80% of the w ean at-


tem p ts w ere su ccessfu l.
c. The results of this stu d y have been used to establish a
threshold RSBI of 100/L for predicting success or failure to
resume spontaneous breathing (i.e., an RSBI below 100/ L
p red icts success, and an RSBI above 100/ L p red icts
failu re).

TABLE 21.2 Identifying Patients Who Will Tolerate a


Spontaneous Breathing Trial (SBT)
Reference Range Threshold for
Measurement in Adults Successful SBT
Tidal Volume (VT) 57 mL/kg 46 mL/kg
Respiratory Rate (RR) 1018 bpm 3038 bpm
Total Ventilation (VE) 56 L/min 1015 L/min
RR/VT Ratio 2040/L 100/L
Maximum Inspiratory -90 to -120 cm H2O -15 to -30 cm H2O
Pressure (PImax)
All meas urements s hould be obtained during s pontaneous breathing.
From Reference 1.

B. Maximum Inspiratory Pressure


1. The strength of the resp iratory mu scles can be evalu ated
by having a patient exhale to resid u al lu ng volu m e and
then inhale as forcefu lly as p ossible against a closed
valve (8). The airw ay p ressu re generated by this maneu -
ver is called the maximum inspiratory pressure (P Im ax).

2. H ealthy ad u lts can generate a negative P Im ax of 90 to


120 cm H 2O (see Table 21.2), w ith m en generating higher
pressu res than w om en.
336 Mechanical Ventilation

a. When the P Im ax is less than -20 cm H 2O, there is little


or no chance of w eaning from m echanical ventilation
(2). H ow ever, a P Im ax greater than -20 cm H 2O d oes
not ensu re a successfu l attem p t at w eaning.

High Flow Ra te

Pa tie nt

Humidifie d Oxyge n S ource

FIGURE 21.1 Diagram of the T-shaped circuit used for spontaneous


breathing trials.

II. SPONTANEOUS BREATHING TRIALS


The spontaneous breathing trial (SBT) can be cond ucted w hile
the patient is still connected to the ventilator circuit, or the
patient can be removed completely from the ventilator and
allow ed to breathe from an independent source of oxygen.
The ad vantages and d isad vantages of each m ethod are
d escribed next. There is no evid ence that either m ethod is
su perior to the other (1).

A. Breathing Through the Ventilator


1. Sp ontaneou s breathing trials are u su ally cond u cted
w hile the p atient is attached to the ventilator. The ad van-
Discontinuing Mechanical Ventilation 337

tage of this m ethod is the ability to m onitor the tid al vol-


u m e and resp iratory rate d u ring the trial. The d raw back
is the extra w ork of breathing im posed by the flow resist-
ance of the ventilator tu bing.

2. Pressu re-su p port ventilation (d escribed in Chap ter 20) is


u sed cou nteract the increased w ork of breathing through
the ventilator circu it. A p ositive p ressu re of 5 7 cm H 2O
w ill accom p lish this goal w ithou t au gm enting the p a-
tient's sp ontaneou s tid al volu m e.

B. Breathing Through a T-Piece


1. Spontaneous breathing trials can be conducted w ith the pa-
tient disconnected from the ventilator using a T-shaped
breathing circuit like the one in Figure 21.1. Oxygen-en-
riched gas is d elivered at high flow rates throu gh the hor-
izontal arm of the T-shaped circu it. The rapid flow cre-
ates a su ction that d raw s exhaled gas ou t of the lu ngs.
This red u ces the w ork of breathing and p revents re-
breathing of exhaled gas.

2. Becau se of the T-shap ed breathing circu it, sp ontaneou s


breathing trials w ith the p atient d isconnected from the
ventilator are often called T-piece trials.

3. The ad vantage of T-p iece trials is the red u ced w ork of


breathing. The d isad vantage of T-p iece trials is the inabil-
ity to m onitor the patients tid al volu m e and respiratory
rate.

C. Protocol
1. The initial trial of sp ontaneou s breathing shou ld last be-
tw een 30 and 120 m inu tes (1). Abou t 80% of p atients w ho
tolerate this am ou nt of tim e w ithou t ventilatory su p p ort
can be p erm anently rem oved from the ventilator (1).
338 Mechanical Ventilation

2. For cases of short-term ventilatory sup p ort (e.g., card iac


su rgery), a su ccessfu l one-hou r p eriod of sp ontaneou s
breathing is enou gh to d iscontinu e ventilatory su p p ort.

3. For p rolonged m echanical ventilation ( > 72 hrs), longer


p eriod s of spontaneou s breathing are need ed before d is-
continu ing m echanical ventilation. Patients shou ld toler-
ate at least 8 hou rs (and som etimes u p to 24 hou rs) of
sp ontaneou s breathing before rem oving the ventilator
from the room .

D.Troubleshooting
Rapid breathing is comm on d u ring spontaneou s breathing
trials, and can be a sign of failu re to su stain u naid ed breath-
ing. H ow ever, rap id breathing can also be a m anifestation of
anxiety, w hich is com m on w hen patients are rem oved from
ventilatory su p port (3).

1. The Tidal Volume


The flow d iagram in Figu re 21.2 show s a sim ple ap-
p roach to the p atient w ith rap id breathing based on the
p atients tid al volu m e. Anxiety cau ses hyp erventilation,
w hich is associated w ith an increase in tid al volu m e,
w hereas failu re to su stain sp ontaneou s breathing w hen
rap id breathing d evelop s is associated w ith a d ecrease in
tid al volu m e (rapid , shallow breathing).

2. The Arterial PCO2


In cases w here anxiety is expected , the arterial PCO 2
(PaCO 2) can be a u sefu l m easu rem ent.
a. A d ecrease in PaCO 2 is evid ence of ad equ ate ventila-
tion, and su ggests an u nd erlying anxiety, w hereas a
normal or increasing PaCO 2 is evid ence of resp iratory
failu re. (Remember that a normal PaCO 2 in the face of a
high minute ventilation is a sign of ventilatory failure).
Discontinuing Mechanical Ventilation 339

III. FAILURE TO WEAN

A. Persistence
1. Failu re to w ean from m echanical ventilation is alm ost
never an irreversible or p erm anent cond ition, and p a-
tients w ho fail initial w ean attem p ts shou ld continu e to
have d aily trials of spontaneou s breathing. The p u rp ose
of this is not to acclim ate the p atient to life off the venti-
lator, but sim ply to provid e m ultiple opp ortu nities to
d etect w hen the p atient no longer need s ventilatory as-
sistance (4).

RAPID BREATHING

TIDAL
VOLUME

(De cre a s e d) (Not De cre a s e d)

Re s ume Ve ntila tory


S upport ARTERIAL PCO2

(De cre a s e d) (Not De cre a s e d)

S e da te Re s ume Ve ntila tory


S upport

FIGURE 21.2 Flow diagram for the evaluation of rapid breathing during
a spontaneous breathing trial.
340 Mechanical Ventilation

2. Failu re to w ean shou ld also p romp t a search for cond i-


tions that m ight be resp onsible for the continu ed ventila-
tor d ep end ence. This search shou ld inclu d e the cond i-
tions that follow.

B. Low Cardiac Output


1. The transition from p ositive-p ressu re ventilation to neg-
ative-p ressu re sp ontaneou s breathing can p rom p t a d e-
crease in card iac stroke ou tp u t (5). (The negative intra-
thoracic p ressu re hold s the ventricles op en and op p oses
ventricu lar em p tying).

2. One of the consequences of a low card iac ou tp u t is resp i-


ratory m u scle w eakness (6). The d iap hragm m axim ally
extracts oxygen from the blood (just like the heart),
w hich m eans that oxygen u p take (VO 2) in the d iap hragm
is flow -d ep end ent. A d ecrease in card iac ou tpu t w ill
jeop ard ize tissu e oxygenation in the d iap hragm and re-
d u ce the strength of d iap hragm atic contractions (6).

3. Becau se of the relationship betw een card iac outpu t and


respiratory muscle strength, attention should be d irected
to the card iac output w henever a patient w ith know n car-
d iac d ysfunction is unable to w ean from the ventilator.

C. Overfeeding
1. An increase in the d aily intake of calories w ill increase
metabolic CO 2 prod u ction, as d emonstrated in Figure 21.3
(7). If the d aily intake of calories exceed s the d aily caloric
requirem ents, the excess CO 2 that is prod u ced w ill stim u-
late ventilation and increase the w ork of breathing, and
this can jeopard ize a sp ontaneou s breathing trial (7,8).

2. In patients w ith lung d isease and abnormal gas exchange,


excess metabolic CO 2 production can lead to an increase in
the arterial PCO 2 and acute respiratory acid osis.
Discontinuing Mechanical Ventilation 341

3. To avoid this problem, the d aily intake of calories should


not exceed the d aily requirement. (See Chapter 36 to learn
how the d aily caloric requ irem ent is d eterm ined ).

D. Neuromuscular Weakness
1. Ventilator-d ep end ent p atients can d evelop a sp ecific typ e
of neu rom u scu lar w eakness that is fou nd only in ICU p a-
tients. There are 2 d isord ers that are resp onsible for most
cases of ICU-acqu ired neu rom u scu lar w eakness, and
they are know n collectively as critical illness polyneuropa-
thy and myopathy (9). These d isord ers are d escribed in
Chap ter 41.

2. Resp iratory m u scle strength can be im p aired by d ep le-


tion of m agnesium and p hosp horus (8,10). The clinical
significance of this is unclear, bu t correcting the p roblem
w ill op tim ize the cond itions for w eaning.

250

Exce s s CO 2
P roduction from
Ove rfe e ding
200
VCO 2
(mL min m 2 )

150

Fa s ting REE 1.5 x REE 2 x REE


Da ily Inta ke of Ca lorie s

FIGURE 21.3 The influence of daily caloric intake on metabolic CO 2 pro-


duction (VCO2) in mechanically ventilated patients. REE is the resting
energy expenditure (in kcal/ 24 hours), which is a measure of daily
caloric requirements. Each data point represents a mean value. (From
Reference 7).
342 Mechanical Ventilation

IV.TRACHEAL DECANNULATION
When u naid ed breathing is no longer a concern, the next step
is to consid er rem oving the end otracheal tu be or tracheosto-
my tu be. At this p oint, there are 2 qu estions that m u st be an-
sw ered :

1) Is the p atient able to p rotect the airw ay and clear secre-


tions?
2) Is there any evid ence of laryngeal inju ry that w ou ld com -
p rom ise breathing after the tu be is rem oved ?

A. Protecting the Airway


All of the cond itions m entioned below are need ed for opti-
mal airw ay protection.

1. The p atient shou ld be aw ake or easily arou sed and able


to follow com m and s.

2. The volu m e of resp iratory secretions shou ld be m inim al.

3. The gag and cou gh reflexes shou ld be p resent, and cou gh


strength shou ld be ad equ ate. The strength of cou ghing
can be evaluated by placing a file card or piece of paper
1-2 cm from the end of the tracheal tu be and asking the
p atient to cou gh. If w etness ap p ears on the card , the
cough strength is consid ered ad equ ate (11).

4. The absence of a cou gh or gag reflex shou ld d elay tra-


cheal d ecannu lation if these reflexes are likely to return.
If these p rotective m echanism s are p erm anently lost, the
d ecision to d ecannu late the trachea is a com plex one that
is beyond the scop e of this little book.

B. Laryngeal Edema
1. Translaryngeal Intubation
Inju ry to the larynx is a com m on consequ ence of end otra-
Discontinuing Mechanical Ventilation 343

cheal (translaryngeal) intu bation, and is often the resu lt


of a trau m atic or p rolonged intu bation. The laryngeal
ed em a that d evelops can obstruct the larynx after the
end otracheal tu be is rem oved .
a. Severe laryngeal ed em a is rep orted in as m any as 40%
of cases of p rolonged translaryngeal intu bation (12),
and 5% of p atients exp erience severe u p p er airw ay ob-
stru ction follow ing extu bation (13).

2. The Cuff-Leak Test


The cu ff-leak test is u sed to id entify p atients w ith severe
laryngeal ed em a prior to extu bation. The test is p er-
form ed w hile the p atient is receiving volum e-cycled ven-
tilation.
a. The volu m e of exhaled gas is m easu red w ith the cu ff
inflated and again after the cuff is d eflated . If there is
no obstru ction at the level of the larynx, cu ff d eflation
w ill result in the escape of exhaled gas arou nd the
end otracheal tu be, and the volu m e of gas exhaled
throu gh the end otracheal tu be w ill d ecrease.
b. Unfortu nately, there is a lack of agreem ent abou t the
m agnitu d e of the volu m e change that is significant.
Volu m e changes of 110 m L, 140 m L, and 25% have
been proposed as the threshold volum e for id entifying
a p atent larynx (1214).
c. Desp ite this lack of agreem ent, the absence of a vol-
u m e change after cu ff d eflation can be used as evi-
d ence of laryngeal obstru ction.

3. Tracheostomy
Laryngeal ed em a also occu rs w ith tracheostom y, and
laryngeal obstru ction can be a problem after rem oval of
tracheostomy tu bes (15). The laryngeal d am age associat-
ed w ith tracheostom y tu bes can be the resu lt of an end o-
tracheal intu bation that p reced ed the tracheostom y, or
can be the resu lt of ischem ic injury to the larynx d u ring
the tracheostom y p roced u re.
344 Mechanical Ventilation

4. Fenestrated Tube
Breathing through a fenestrated (w ind ow ed ) tracheosto-
my tu be like the one in Figu re 21.4 can be u sefu l in d e-
tecting laryngeal obstru ction. When the inner cannu la is
removed , the fenestration allow s the p atients breathing
efforts to m ove air throu gh the larynx. If the opening of
the tube is capped and the cuff is deflated, the patient must
breathe entirely through the larynx. Difficu lty breathing in
this situ ation raises su sp icion for a laryngeal obstru ction,
w hich can be confirm ed u sing d irect laryngoscop y.

5. Steroids (for Anything That Swells)


a. The antiinflam m atory actions of steroid s ju stifies their
u se to treat laryngeal ed em a associated w ith anaphy-
laxis, becau se this ed em a is p rod u ced by inflam m a-
tion.
b. Steroids are also used to treat the laryngeal ed ema asso-
ciated with tracheal intubation, but this does not seem
justified because this edema is produced by trauma.
There are 2 stu d ies evalu ating the u se of steroid s for

Fe ne s tra te d Tra che os tomy Tube

Oute r
cannula

Inne r ca nnula
Cuff

FIGURE21.4A fenestrated tracheostomy tube. When the inner cannula is


removed, the fenestration (window) allows breathing efforts to move air
through the larynx.
Discontinuing Mechanical Ventilation 345

this typ e of (trau m atic) laryngeal ed em a, and the re-


su lts are conflicting (16,17).
c. The u se of steroid s for trau m atic laryngeal ed em a is an
exam p le of steroids for anything that swells (18).

V.THE POST-EXTUBATION PERIOD

A. A Paradox
1. The cross-sectional area of the glottis (the narrow est p or-
tion of the u p p er airw ay) is 66 m m 3 in the average-sized
ad ult, w hereas the cross-sectional area of an average-
sized ad u lt tracheal tu be (8 m m internal d iam eter) is 50
mm 3 (19). The larger cross-sectional area of the glottis cre-
ates less resistance for airflow, so the w ork of breathing
shou ld be red u ced after extu bation.

2. H ow ever, there is a p arad oxical increase in the w ork of


breathing follow ing extu bation (20). This is a consistent
observation, and is u nexp lained .

B. Post-Extubation Stridor
1. Laryngeal obstru ction follow ing extu bation can p rod u ce
a sonorou s sou nd know n as stridor. Becau se the obstru c-
tion is extrathoracic, the strid or occu rs d u ring insp iration
(i.e., the negative intrathoracic pressu re is transm itted to
the larynx and cau ses insp iratory narrow ing).

2. Post-extu bation strid or is not alw ays an ind ication for


im m ed iate reintu bation. If the p atient is not exhibiting
signs of respiratory d istress, inhalation of aerosolized
epinephrine (2.5 m L of 1% ep inep hrine) is a pop u lar (bu t
u np roven) treatm ent op tion. A racem ic m ixtu re of epi-
nephrine (w hich has equal am ounts of the l-isom er and
346 Mechanical Ventilation

d-isom er) has been p op u lar in this situ ation, but has no
p roven su periority over the stand ard (l-isom er) p rep ara-
tion (21).

REFERENCES
1. MacIntyre N R, Cook DJ, Ely EW Jr, et al. Evid ence-based guid e-
lines for w eaning and d iscontinu ing ventilatory su p p ort: A col-
lective task force facilitated by the Am erican College of Chest
Physicians, the Am erican Association for Resp iratory Care, and
the Am erican College of Critical Care Med icine. Chest 2001;
120(Suppl):375S395S.
2. Yang K, Tobin MJ. A p rospective stu d y of ind exes pred icting the
outcom e of trials of w eaning from m echanical ventilation. N
Engl J Med 1991; 324:14451450.
3. Bouley GH , From an R, Shah H . The experience of d yspnea d u r-
ing w eaning. H eart Lung 1992; 21:471476.
4. Fru tos-Vivar F, Esteban A. When to w ean from a ventilator: an
evid ence-based strategy. Cleve Clin J Med 2003; 70:389-397.
5. Pinsky MR. Card iovascu lar issu es in resp iratory care. Chest 2005;
128:592S597S.
6. Nishimura Y, Maeda H, Tanaka K, et al. Respiratory muscle strength
and hemodynamics in heart failure. Chest 1994; 105:355359.
7. Talpers SS, Rom berger DJ, Bu nce SB, Pingleton SK. N u tritionally
associated increased carbon d ioxid e p rod uction. Chest 1992; 102:
551555.
8. Benotti PN , Bistrian B. Metabolic and nutritional aspects of w ean-
ing from m echanical ventilation. Crit Care Med 1989; 17:181185.
9. H u d son LD, Lee CM. N eu rom uscu lar sequ elae of critical illness.
N Engl J Med 2003; 348:745747.
10. Malloy DW, Dhingra S, Solren F, et al. H yp om agnesem ia and res-
p iratory m u scle p ow er. Am Rev Resp ir Dis 1984; 129:427431.
11. Kham iees M, Raju P, DeGirolam o A, et al. Pred ictors of extu ba-
tion ou tcom e in patients w ho have su ccessfu lly com pleted a
spontaneou s breathing trial. Chest 2001; 120:12621270.
12. Chung Y-H, Chao T-Y, Chiu C-T, Lin M-C. The cuff-leak test is a
simple tool to verify severe laryngeal edema in patients undergoing
long-term mechanical ventilation. Crit Care Med 2006; 34:409414.
Discontinuing Mechanical Ventilation 347

13. Kriner EJ, Shafazand S, Colice GL. The end otracheal tu be cu ff


leak test as a pred ictor for p ostextu bation strid or. Resp ir Care
2005; 50:16321638.
14. Prinianakis G, Alexopou lou C, Mam id akis E, et al. Determ inants
of the cuff-leak test: a p hysiological stud y. Crit Care 2005; 9:
R24R31.
15. Colice C, Stu kel T, Dain B. Laryngeal com p lications of p rolonged
intu bation. Chest 1989; 96:877884.
16. Cheng K-C, H ou C-C, H u ang H -C, et al. Intravenous injection of
m ethylp red nisolone red u ces the incid ence of p ostextu bation stri-
d or in intensive care u nit p atients. Crit Care Med 2006; 34:
13451350.
17. Gau ssorgu es P, Boyer F, Pip erno D, et al. Do corticosteroid s p re-
vent postintubation laryngeal ed em a? A p rospective stu d y of 276
ad u lts. Crit Care Med 1988; 16:649652.
18. Shem ie, S. Steroid s for anything that sw ells: Dexam ethasone and
p ostextu bation airw ay obstru ction. Crit Care Med : 1996; 24:
16131614.
19. Kaplan JD, Schu ster DP. Physiologic consequ ences of tracheal
intu bation. Clin Chest Med 1991; 12:425432.
20. Mehta S, N elson DL, Klinger JR, et al. Pred iction of p ost-extu ba-
tion w ork of breathing. Crit Care Med 2000; 28:13411346.
21. N u tm an J, Brooks LJ, Deakins K, et al. Racem ic versu s l-epinep h-
rine aerosol in the treatm ent of postextu bation laryngeal ed em a:
resu lts from a prospective, rand om ized , d ouble-blind stu d y. Crit
Care Med 1994; 22:15911594.
Chapter 22
ACID-BASE
INTERPRETATIONS
This chap ter review s som e basic featu res of acid -base p hysi-
ology, and then u ses these featu res to p resent an organized
ap proach to the id entification of acid -base d isord ers.

I. BASIC CONCEPTS

A. Hydrogen Ion Concentration


1. The hyd rogen ion concentration [H +] in extracellu lar flu -
id is d eterm ined by the balance betw een the PCO 2 and
the bicarbonate concentration [H CO 3] (1,2). The relation-
ship betw een these variables is d efined in Equ ation 22.1.
[H+] = 24 x PCO2 / [HCO3 ] (22.1)

The norm al [H +] in arterial blood is show n below u sing a


PCO 2 of 40 m m H g and a [H CO 3] of 24 m Eq/ L.
[H+] = 24 x (40/24) = 40 nEq /L (22.2)

2. N ote that [H +] is exp ressed in nanoequ ivalents p er liter


(nEq/ L), w hile [H CO 3] is exp ressed in m illiequ ivalents
per liter (m Eq/ L). This means that the H + concentration
in extracellular fluid is one-millionth the H CO 3 concentra-
tion (i.e., one nanoequ ivalent is 10-6 m illiequ ivalents).

3. Becau se the [H +] is so m u ch low er (by 6 ord ers of m agni-


tu d e) than the concentration of H CO 3 and other electro-
lytes, it is exp ressed in logarithm ic terms as the p H :
pH = -lo g [H+] (22.3)
349
350 Acid-Base Disorders

The p H varies inversely w ith the [H +], so an increase in


the [H +] red u ces the p H , and a d ecrease in [H +] raises the
p H . The [H +] and corresp ond ing p H valu es in arterial
blood are show n in Table 22.1. The norm al [H +] of 40
nEq/ L corresp ond s to a p H of 7.40. N ote that over the
p hysiologic pH range, the [H +] varies by only 18 nEq/ L.
This is a testam ent to the acid -base control system .

TABLE 22.1 Relationship Between pHand [H+] in Arterial Blood


pH [H+] (nEq/L)
7.7 20
7.6 26
7.5 32 Physiologic
7.4 Normal 40 Range
7.3 50 (18 nEq/L)
7.2 63
7.1 80
7.0 100

B.Types of Acid-Base Disorders


Acid -base d isord ers are characterized by a change in the
PCO 2 or H CO 3 concentration in extracellu lar flu id (p lasm a).

1. A change in the PCO 2 represents a respiratory acid -base


d isord er: an increase in PCO 2 is a respiratory acidosis, and
a d ecrease in PCO 2 is a respiratory alkalosis.

2. A change in H CO 3 is a metabolic acid -base d isord er: a


d ecrease in H CO 3 is a metabolic acidosis, and an increase in
H CO 3 is a metabolic alkalosis.

3. Every acid -base d isord er elicits a compensatory response


that limits the im pact of the d isord er on the p H .
Acid-Base Interpretations 351

a. Com p ensatory resp onses op erate by controlling the


PCO 2/ H CO 3 ratio. For exam p le, if there is an increase
in arterial PCO 2 (respiratory acid osis), the comp ensa-
tory resp onse w ill involve an increase in the p lasm a
H CO 3 concentration, and this w ill keep the PCO 2/
H CO 3 ratio (and the p H ) relatively constant. Table 22.2
show s the com pensatory ad ju stm ents for each of the
p rim ary acid -base d isord ers.
b. Com pensatory responses d o not correct the prim ary
acid -base d isord er; i.e., they lim it, bu t d o not p revent,
the change in pH .

TABLE 22.2 Primary Acid-Base Disorders and Associated


Compensatory Changes
[H+] = 24 x PCO2 / HCO3
Compensatory
Primary Disorder Primary Change Change*
Respiratory acidosis Increased PCO2 Increased HCO3
Respiratory alkalosis Decreased PCO2 Decreased HCO3
Metabolic acidosis Decreased HCO3 Decreased PCO2
Metabolic alkalosis Increased HCO3 Increased PCO2
*Compensatory changes are designed to keep the PCO2 / HCO3 ratio constant.

II. PREDICTIVE EQUATIONS


The d iagnosis of acid -base d isord ers requ ires that you not
only id entify the prim ary d isord er, bu t also evalu ate com -
p ensatory resp onses (to id entify ad d itional or second ary
acid -base d isord ers). This latter task requ ires the equ ations
includ ed in this section, w hich d efine the exp ected com pen-
sation for p rim ary acid -base d isord ers. These equ ations
(w hich are also show n in Figu re 22.1) w ill be incorp orated
into a d iagnostic schem e that is p resented in the next section.
352 Acid-Base Disorders

A. Metabolic Acid-Base Disorders


The com p ensatory resp onse to m etabolic acid -base d erange-
ments is an im m ed iate change in m inute ventilation that
changes the arterial PCO 2 (PaCO 2) in the sam e d irection as
the prim ary change in H CO 3 (see Table 22.2).

P RIMARY DIS ORDER


EXP ECTED RES ULTS
Me tabo lic Ac ido s is
Expe c te d PaCO2 = (1.5 x HCO 3 ) + (8 2)

Me tabo lic Alkalo s is


Expe c te d PaCO2 = (0.7 x HCO 3 ) + (21 2)

Ac ute Re s pirato ry
Ac ido s is
pH = 0.008 x Pa CO 2
Expe c te d pH = 7.40 [0.008 x (Pa CO 2 40) ]

Ac ute Re s pirato ry
Alkalo s is
pH = 0.008 x Pa CO 2
Expe c te d pH = 7.40 + [0.008 x (40 Pa CO 2 ) ]

Chro nic Re s pirato ry


Ac ido s is
pH = 0.003 x Pa CO 2
Expe c te d pH = 7.40 [0.003 x (Pa CO 2 40) ]

Chro nic Re s pirato ry


Alkalo s is
pH = 0.003 x Pa CO 2
Expe c te d pH = 7.40 + [0.003 x (40 Pa CO 2 ) ]

FIGURE 22.1 Useful formulas for acid-base interpretations.


Acid-Base Interpretations 353

1. Metabolic Acidosis
Metabolic acid osis is characterized by a p rim ary d ecrease
in the plasma H CO 3 concentration, and the com p ensa-
tory resp onse is an increase in m inu te ventilation, w hich
d ecreases the arterial PCO 2 (PaCO 2) to a level that is p re-
d icted by Equ ation 22.4 (3). (The H CO 3 in Equ ations 22.4
and 22.5 is the m easu red concentration in p lasm a, in
mEq/ L).
a. COMPENSATION FOR METABOLIC ACIDOSIS:

Expe c te d PaCO2 = (1.5 x HCO3 ) + (8 2) (22.4)

2. Metabolic Alkalosis
Metabolic alkalosis is characterized by a p rim ary in-
crease in the p lasm a H CO 3 concentration. The com p ensa-
tory resp onse is a d ecrease in m inu te ventilation, w hich
increases the PaCO 2 to a level p red icted by Equation 22.5
(4).
a. COMPENSATION FOR METABOLIC ALKALOSIS:

Expe c te d PaCO2 = (0.7 x HCO3 ) + (21 2) (22.5)

B. Respiratory Acid-Base Disorders


The com p ensatory resp onse to resp iratory acid -base d isor-
d ers takes place in the kid neys and involves an ad justm ent
in H CO 3 reabsorption in the p roxim al tu bu les. This response
is not im med iate, but begins to ap p ear in 6 to 12 hou rs, and
is fu lly d evelop ed after a few d ays. Because of this d elay, res-
piratory acid -base d isord ers are classified as acu te (u ncom -
pensated ) and chronic (fu lly com p ensated ).

1. Acute Respiratory Disorders


Prior to the onset of renal com p ensation, a change in
PaCO 2 of 1 m m H g w ill p rod u ce a change in p H of 0.008
pH u nits (1,5).
pH = 0.008 x PaCO2 (22.6)
354 Acid-Base Disorders

This relationship is incorp orated into Equ ations 22.7 and


22.8 using 7.40 for the norm al p H and 40 m m H g for the
norm al PaCO 2.
a. ACUTE RESPIRATORYACIDOSIS:

Expe c te d pH = 7.40 [0.008 x (PaCO2 40)] (22.7)

b. ACUTE RESPIRATORYALKALOSIS:

Expe c te d pH = 7.40 + [0.008 x (40 PaCO2 )] (22.8)

2. Chronic Respiratory Disorders


When renal com pensation is fully d evelop ed , a change in
PaCO 2 of 1 m m H g w ill p rod u ce a change in pH of 0.003
pH u nits (5).

pH = 0.003 x PaCO2 (22.9)

This relationship is incorp orated into Equ ations 22.10 and


22.11 using 7.40 as a normal arterial pH and 40 mm H g as
a normal PaCO 2.
a. CHRONIC RESPIRATORYACIDOSIS:

Expe c te d pH = 7.40 [0.003 x (PaCO2 40)] (22.10)

b. CHRONIC RESPIRATORYALKALOSIS:

Expe c te d pH = 7.40 + [0.003 x (40 PaCO2 )] (22.11)

II. SCHEMEFORACID-BASEINTERPRETATIONS
The follow ing is a stru ctu red ap p roach to the d iagnosis of
acid -base d isord ers that p roceed s in three stages. The first
tw o stages are d esigned to id entify p rim ary and second ary
acid -base d isord ers u sing only three variables: arterial p H ,
PaCO 2, and plasm a H CO 3 concentration. The last stage in-
volves the evalu ation of m etabolic acid osis. The d etection of
Acid-Base Interpretations 355

acid -base d isord ers requ ires the norm al ranges for acid -base
p aram eters, w hich are listed below.
Arterial pH = 7.36 7.44
Arterial PCO 2 = 36 44 m m H g
Plasm a H CO 3 = 22 26 m Eq/ L

A. Identify the Primary Acid-Base Disorder


This stage requ ires only the p H and PaCO 2. If either of these
measurements is ou tsid e the norm al range, there is an acid -
base d isord er, and you shou ld p roceed as follow s:

1. If the p H and PaCO 2 are both abnorm al, com p are the d i-
rectional change.
a. If both change in the sam e d irection, the p rim ary acid -
base d isord er is m etabolic.
b. If both change in opposite d irections, the primary acid -
base d isord er is respiratory.
c. EXAMPLE: Consid er a p atient w ith a p H of 7.23 and a
PaCO 2 of 23 m m H g. The p H and PaCO 2 are both re-
d u ced (ind icating a prim ary m etabolic d isord er), and
the p H is low (ind icating an acid osis), so this cond ition
rep resents a primary metabolic acidosis.

2. If either the p H or PaCO 2 is norm al, there is a mixed m et-


abolic and respiratory acid -base d isord er (one is an aci-
d osis and the other is an alkalosis). There is no p rim ary
acid -base d isord er in this instance becau se com p ensatory
responses to p rim ary acid -base d isord ers never fully cor-
rect the p roblem (i.e., never norm alize the pH and
PaCO 2).
a. If the pH is norm al, the d irection of change in PaCO 2
id entifies the respiratory d isord er.
b. If the PaCO 2 is norm al, the d irection of change in the
p H id entifies the m etabolic d isord er.
c. EXAMPLE: Consid er a p atient w ith an arterial p H of
356 Acid-Base Disorders

7.37 and a PaCO 2 of 55 m m H g. The p H is norm al, so


there is a m ixed m etabolic and resp iratory acid -base
d isord er. The PaCO 2 is elevated . so the respiratory d is-
ord er is an acid osis, and thus the m etabolic d isord er
m u st be an alkalosis. Therefore, the acid -base d isord er
in this case is a mixed respiratory acidosis and metabolic
alkalosis.

B. Evaluate Compensatory Responses


If there is a p rim ary acid -base d isord er, proceed as d irected
below. If there is a m ixed acid -base d isord er, skip this stage
and go to the third stage (if ap p licable).

1. If there is a p rim ary metabolic acid osis or alkalosis, use


Equ ations 22.4 or 22.5 to calcu late the expected PaCO 2.
a. If the m easu red PaCO 2 is higher than p red icted , there
is an ad d itional (second ary) resp iratory acid osis.
b. If the m easu red PaCO 2 is low er than p red icted , there is
an ad d itional (second ary) resp iratory alkalosis.

2. If there is a resp iratory acid osis or alkalosis, u se the


PaCO 2 to calculate the expected pH using Equations
22.7 22.11. Com p are the m easu red p H to the exp ected
pH to d eterm ine if the cond ition is acu te, p artially com -
pensated , or fully com p ensated .
a. If the m easu red p H is betw een the exp ected p H for the
acu te (u ncom p ensated ) and chronic (com p ensated )
cond ition, the d isord er is called a partially compensated
resp iratory acid osis or alkalosis.
b. For respiratory acid osis, if the p H is low er than exp ect-
ed for the acu te cond ition, there is a second ary m eta-
bolic acid osis, and if the p H is higher than exp ected for
the chronic (com p ensated ) cond ition, there is a sec-
ond ary m etabolic alkalosis.
c. For respiratory alkalosis, if the p H is higher than ex-
pected for the acu te cond ition, there is a second ary
Acid-Base Interpretations 357

metabolic alkalosis, and if the p H is low er than expect-


ed for the chronic (com p ensated ) cond ition, there is a
su p erim p osed m etabolic acid osis.
d . EXAMPLE: Consid er a p atient w ith a PaCO 2 of 23 m m
H g and a p H of 7.57, w hich rep resents a p rim ary res-
p iratory alkalosis. The exp ected p H for an acu te resp i-
ratory alkalosis is d escribed in Equ ation 22.8, and is
7.40+ [0.008 x (40 23)] = 7.54. The m easu red p H is high-
er than expected , so this cond ition represents an acute
respiratory alkalosis with a secondary metabolic alkalosis.

C. Evaluate Metabolic Acidosis


The final stage of this ap p roach is for p atients w ith a m eta-
bolic acid osis, and it involves tw o d eterm inations know n as
gaps.

1. The first is the anion gap, w hich is an estim ate of u nm ea-


sured anions in the extracellular flu id that help s to id en-
tify the cau se of a m etabolic acid osis.

2. The second gap is a com parison of the change in the


anion gap and the change in the seru m H CO 3 concentra-
tion. The d ifference or gap betw een these tw o m eas-
u rem ents (also know n as the gap-gap) can u ncover m ixed
m etabolic d isord ers (e.g., a m etabolic acid osis and alka-
losis) that w ould otherw ise go u nd etected .

3. These tw o measurements are d escribed in the next section.

III. THE GAPS

A. Anion Gap
The anion gap is u sed to d eterm ine if a m etabolic acid osis is
d u e to an accum u lation of nonvolatile acid s (e.g., lactic acid )
or a net loss of bicarbonate (e.g., d iarrhea) (68).
358 Acid-Base Disorders

1. What is the Anion Gap?


To achieve electrochem ical balance, the concentration of
negatively charged anions m ust equal the concentration
of p ositively charged cations. All ions p articip ate in this
balance, inclu d ing rou tinely m easu red ions like sod ium
(N a), chlorid e (CL), and bicarbonate (H CO 3), as w ell as
unm easu red cations (UC) and unm easu red anions (UA).
The electrochemical balance equation can thus be written as:

Na + UC = CL + HCO3 + UA (22.12)

Rearranging the term s yield s the follow ing relationship s:

Na (CL + HCO3 ) = UA UC (22.13)

The d ifference (UA UC) is a m easu re of the relative


abu nd ance of u nm easu red anions and is called the anion
gap (AG). The anion gap is m easured as the d ifference
betw een the p lasm a sod iu m concentration and the su m
of the p lasm a chlorid e and bicarbonate concentrations.

2. Reference Range
The norm al valu e of the AG w as originally record ed at
12 4 m Eq/ L (range = 8 to 16 m Eq/ L) (7). With the ad op -
tion of new er au tom ated system s that m ore accu rately
measure serum electrolytes, the normal value of the A G has
decreased to 7 4 mEq/L (range = 3 to 11 m Eq/ L) (9). This
new er reference range has not been u niversally ad op ted ,
and this is a sou rce of error in the interpretation of the AG.

3. Interpreting the Anion Gap


Metabolic acid oses are characterized as having an elevat-
ed AG or a norm al AG..
a. Elevated AG m etabolic acid oses are cau sed by the ad -
d ition of a fixed (nonvolatile) acid to the extracellu lar
flu id (e.g., lactic acid , ketoacid s).
b. N orm al AG m etabolic acid oses are characterized by a
net loss of H CO 3 and a com pensatory increase in chlo-
Acid-Base Interpretations 359

rid e concentration. (In the high AG m etabolic acid os-


es, the loss of H CO 3 is not accom panied by increased
chlorid e becau se the anions from the d issociated acid s
balance the loss of H CO 3). This cond ition is also called
hyperchloremic metabolic acidosis.
c. The clinical cond itions responsible for elevated AG and
normal AG metabolic acid oses are listed in Table 22.3.

TABLE 22.3 Interpretations of the Anion Gap


High AG Acidoses Normal AG Acidoses
Lactic acidosis Diarrhea
Ketoacidosis Isotonic saline infusion
End-stage renal failure Early renal insufficiency
Methanol ingestion Renal tubular acidosis
Ethylene glycol ingestion Acetazolamide
Salicylate toxicity Ureterenterostomy

4. Reliability
The AG can be u nreliable, as d em onstrated by the nu -
merous rep orts of lactic acid osis w ith a normal AG (10,
11). This d iscrep ancy m ay be d u e to a d isregard for the
influence of plasm a album in on the AG (explained next).

5. Influence of Albumin
As ind icated in Table 22.4, albumin is the major unmeasured
anion in plasma. This m eans that a d ecrease in seru m albu -
min w ill d ecrease the AG, and this can lead to errors in
the interp retation of the AG (e.g., a high AG metabolic
acid osis can p resent w ith a norm al AG in the p resence of
hypoalbu m inem ia).
a. The sp uriou s influ ence of hyp oalbu m inem ia on the
anion gap can be elim inated by calcu lating the AG as
show n below u sing the album in (g/ d L) and phos-
360 Acid-Base Disorders

p hate (m g/ d L) concentrations (12,13) (this is p ossible


becau se albu m in and p hosp hate are resp onsible for
the m ajority of the norm al anion gap ).

AG = [2 x albumin ] + [0.5 x PO4 ] (22.14)

The albu m in-d erived AG is then com p ared to the tra-


d itional AG [N a (CL = H CO 3)]. If the trad itional AG
is greater than the albu m in-d erived AG, the d ifference
is a tru e m easu re of nonvolatile acid s.

TABLE 22.4 Determinants of the Anion Gap


Unmeasured Anions Unmeasured Cations
Albumin (15 mEq/L)* Calcium (5 mEq/L)
Organic Acids (5 mEq/L) Potassium (4.5 mEq/L)
Phosphate (2 mEq/L) Magnesium (1.5 mEq/L)
Sulfate (1 mEq/L)
__________________________ __________________________

Total UA: (23 mEq/L) Total UC: (11 mEq/L)


Anion Gap = UA UC = 12 mEq/L
*If albumin is reduced by 50% , anion gap = 4 mEq/L.

B.The Gap-Gap
1. What is the Gap-Gap?
In the p resence of a high AG m etabolic acid osis, it is p os-
sible to d etect another m etabolic acid -base d isord er (a
norm al AG m etabolic acid osis or a m etabolic alkalosis)
by com p aring the AG excess (the d ifference betw een the
measured and norm al AG) to the H CO 3 d eficit (the d iffer-
ence betw een the m easu red and norm al H CO 3 concentra-
tion in p lasm a). The AG excess/ H CO 3 d eficit ratio is
show n below (12 m Eq/ L is the norm al AG and 24 m Eq/ L
is the norm al p lasm a H CO 3 concentration).
Acid-Base Interpretations 361

AG Exc e s s /HCO3 De fic it = (AG 12) /(24 HCO3 )


(22.15)

This ratio is som etim es called the gap-gap becau se it is a


measure of the d ifference (gap) betw een another gap (the
anion gap ) and the changes in H CO 3 concentration.

2. Mixed Metabolic Acidoses


When a fixed acid accu m u lates in extracellu lar flu id (i.e.,
high AG m etabolic acid osis), the d ecrease in seru m H CO 3
is equ ivalent to the increase in AG, and the AG excess/
H CO 3 d eficit ratio is u nity (=1). H ow ever, w hen a hyp er-
chloremic acid osis appears, the d ecrease in H CO 3 is
greater than the increase in the AG, and the ratio (AG
excess/ H CO 3 d eficit) falls below u nity (<1).
a. Thu s, in the presence of a high AG m etabolic acid osis,
a gap -gap (AG excess/ H CO 3 d eficit) <1 ind icates the
coexistence of a norm al AG m etabolic acid osis (5,14).

3. Metabolic Acidosis and Alkalosis


When alkali is ad d ed in the p resence of a high AG acid o-
sis, the d ecrease in seru m bicarbonate is less than the
increase in AG, and the gap -gap (AG excess/ H CO 3 d ef-
icit) is greater than u nity (>1).
a. Thu s, in the p resence of a high AG m etabolic acid osis,
a gap -gap (AG excess/ H CO 3 d eficit) >1 ind icates the
coexistence of a m etabolic alkalosis (5,14).

REFERENCES
1. N arins RG, Em m ett M. Sim ple and m ixed acid -base d isord ers: a
p ractical ap proach. Med icine 1980; 59:161187.
2. Whittier WL, Ru tecki GW. Prim er on clinical acid -base p roblem
solving. Dis Mon 2004; 50:117162.
3. Albert M, Dell R, Winters R. Qu antitative d isp lacem ent of acid -
base equ ilibrium in m etabolic acid osis. Ann Intern Med 1967;
66:312315.
362 Acid-Base Disorders

4. Javaheri S, Kazem i H . Metabolic alkalosis and hyp oventilation in


hum ans. Am Rev Respir Dis 1987; 136:10111016.
5. Morganroth ML. An analytical ap p roach to d iagnosing acid -base
d isord ers. J Crit Illness 1990; 5:138150.
6. Casaletto JJ. Differential d iagnosis of m etabolic acid osis. Em erg
Med Clin N Am 2005; 23:771787.
7. Em m et M, N arins RG. Clinical use of the anion gap . Med icine
1977; 56:3854.
8. Ju d ge BS. Metabolic acid osis: d ifferentiating the causes in the
p oisoned p atient. Med Clin N Am 2005; 89:11071124.
9. Winter SD, Pearson JR, Gabow PA, et al. The fall of the seru m
anion gap . Arch Intern Med 1990; 150:311313.
10. Iberti TS, Liebow itz AB, Papad akos PJ, et al. Low sensitivity of
the anion gap as a screen to d etect hyperlactatem ia in critically ill
p atients. Crit Care Med 1990; 18:275277.
11. Schw artz-Gold stein B, Malik AR, Sarw ar A, Brand tsetter RD.
Lactic acid osis associated w ith a norm al anion gap . H eart Lu ng
1996; 25:7980.
12. Kellu m JA. Determ inants of p lasm a acid -base balance. Crit Care
Clin 2005; 21:329346.
13. Kellu m JA, Kram er DJ, Pinsky MJ. Closing the gap: a sim ple
m ethod of im p roving the accu racy of the anion gap. Chest 1996;
110:185.
14. H aber RJ. A practical app roach to acid -base d isord ers. West J
Med 1991; 155:146151.
Chapter 23
ORGANIC ACIDOSES
This chap ter d escribes the clinical d isord ers associated w ith
the p rod u ction of organic (carbon-based ) acid s, inclu d ing
lactic acid , ketoacid s, oxalic acid (from ethylene glycol inges-
tion), and form ic acid (from m ethanol ingestion) (1,2).

I. LACTIC ACIDOSIS

A. Clinical Presentation
1. Lactic acidosis typically presents as a high anion gap meta-
bolic acid osis in association with one of the conditions pre-
sented in the next section. H ow ever, a norm al anion gap
has also been rep orted in cases of lactic acid osis (3), and
thu s the anion gap should not be used as a screening test for
lactic acidosis. (See Chap ter 22 for inform ation on the an-
ion gap .)

2. The d iagnosis of lactic acid osis requ ires a blood lactate


concentration. The blood samp le shou ld be p laced on ice
to retard lactate p rod u ction by red blood cells. A lactate
level above 2 m Eq/ L is consid ered abnorm al.

B. Etiologies
1. Circulatory Shock
In p atients w ith a low card iac ou tp u t d u e to hyp ovol-
em ia or heart failu re, an increase in blood lactate levels is
taken as evid ence of im p aired tissu e oxygenation. This
cond ition is generally know n as circulatory shock. The d e-
gree of elevation in blood lactate levels is d irectly corre-
363
364 Acid-Base Disorders

lated w ith the m ortality rate in circulatory shock, as


show n in Figu re 23.1 (4).
1.0
l
a
v
vi
r
u
S
f
0.5
o
y
t
i
l
i
b
a
b
o
r
P
0
.7 1.0 1.5 2.5 4.5 7.0 12.0 20 30
La cta te (mmol/L)

FIGURE 23.1 The relationship between blood lactate levels and survival
in patients with circulatory shock. From Reference 4.

2. Sepsis
a. Some patients w ith sepsis have mild elevations of blood
lactate (2 to 5 mEq/ L) with a normal lactate :pyruvate
ratio and a normal blood p H . These patients have stress
hyperlactatemia, w hich is consid ered a resu lt of hyper-
metabolism w ithout im paired cellular oxygen utiliza-
tion (5).
b. Patients w ith severe sep sis can have m arked eleva-
tions in blood lactate w ith increased lactate :p yru vate
ratios and a red u ced blood p H . These p atients have a
d efect in cellular oxygen utilization that has been called
cytopathic hypoxia (6).
c. In severe sepsis, a blood lactate level above 4 mEq/ L is
associated w ith a poor prognosis (7).

3. Thiamine Deficiency
Lactic acid osis is one of the m anifestations of thiamine
d eficiency (8). Thiam ine is a cofactor for p yru vate d ehy-
d rogenase (the enzym e that catalyses the conversion of
Organic Acidoses 365

pyruvate to acetyl coenzyme A), and thiamine d eficiency


d iverts glucose m etabolism to the production of lactate.
See Chapter 36 for m ore on thiam ine d eficiency.

4. Drugs
A variety of d ru gs can prod u ce lactic acid osis, inclu d ing
(in alphabetical ord er) acetam inop hen, ep inep hrine, line-
zolid , m etform in, p rop ofol, nitropru ssid e, and nu cleo-
sid e reverse transcrip tase inhibitors (912).

5. Propylene Glycol
Prop ylene glycol is a solvent that enhances the solubility
of intravenou s m ed ications, inclu d ing lorazep am , d iaze-
p am , esm olol, nitroglycerin, and p henytoin. The metabo-
lism of propylene glycol takes place primarily in the liver,
and the principal metabolites are lactate and pyruvate (13).
a. Prop ylene glycol toxicity has been reported in 19% to
66% of ICU patients receiving high-d ose lorazep am or
d iazep am for m ore than 2 d ays (13,14). Signs of toxici-
ty inclu d e agitation, com a, seizu res, tachycard ia, hy-
p otension, and hyp erlactatem ia.

6. Other Causes
Other p ossible cau ses of hyp erlactatem ia in ICU p atients
includ e seizures (from increased lactate prod u ction), hep-
atic insufficiency (from red u ced lactate clearance), and
acute asthma (p ossibly from enhanced lactate p rod u ction
by the respiratory m u scles) (1517).

C. D-Lactic Acidosis
1. The lactate p rod u ced by m am m alian tissu es is a levo-iso-
mer (bend s light to the left). A d extro-isom er of lactate
(bend s light to the right) is prod u ced by certain strains of
bacteria that can pop u late the bow el.

2. D-lactate generated by bacterial ferm entation in the bow -


el can enter the system ic circulation and p rod u ce a m eta-
366 Acid-Base Disorders

bolic acid osis, often com bined w ith a m etabolic enceph-


alopathy (18). Most cases of d -lactic acid osis have been
rep orted after extensive sm all bow el resection or after
jeju noileal bypass for m orbid obesity (18,19).

3. D-lactic acid osis can p rod u ce an elevated anion gap , bu t


the stand ard laboratory assay for lactate m easu res only
l-lactate. If d -lactic acid osis is susp ected , you m u st re-
qu est a specific d -lactate assay.

D. Alkali Therapy
1.The p rim ary goal of therap y in lactic acid osis is to correct
the und erlying cau se of the acid osis. A lkali therapy to cor-
rect the acidosis has no proven value (20) and is not recom -
m end ed for the rou tine treatm ent of lactic acid osis.

2. For p atients w ith severe acid osis (pH < 7.1) w ho are he-
m od ynamically u nstable, a trial infu sion of sod iu m bi-
carbonate (7.5% N aH CO 3, 0.9 m Eq H CO 3 p er liter) can be
attem pted by ad ministering one-half of the estim ated
bicarbonate d eficit (21).

HCO3 de fic it (mEq) = 0.6 x wt (kg ) x (15 plas ma HCO3 ) (23.1)

(w here 15 m Eq/ L is the target p lasm a H CO 3). If card io-


vascu lar im provem ent occu rs, bicarbonate therap y can
be continued to m aintain the p lasm a H CO 3 at 15 m Eq/ L.
If there is no im p rovem ent, fu rther bicarbonate ad m inis-
tration is not w arranted .

II. DIABETIC KETOACIDOSIS

A. Pathogenesis
1. In cond itions of red u ced nu trient intake (or red u ced glu -
cose entry into cells), ad ip ose tissu e releases free fatty
Organic Acidoses 367

acid s, w hich are taken u p in the liver and m etabolized


to acetoacetate and -hyd roxybutyrate. These ketones
are released from the liver and can be u sed as oxid ative
fu els by vital organs su ch as the heart and central nerv-
ou s system .

2. Acetoacetate and -hyd roxybu tyrate are strong acid s,


and their accu m u lation in blood can p rod u ce a m etabol-
ic acid osis (i.e., ketoacidosis). In d iabetic ketoacid osis, the
p rincip al ketone in blood is -hyd roxybu tyrate (see Fig-
u re 23.2).

B. Clinical Features
1. Diabetic ketoacid osis (DKA) is u su ally seen in insu lin-
d epend ent d iabetics, bu t in 20% of cases, there is no pre-
viou s history of d iabetes m ellitu s.

12
AKA

10 DKA
)
L
8
/
q
E
m
Thre s hold
(
for De te ction
s
6
l
e
v
of Ke tone s
e
L
d
4
o
DKA
o
l
B
AKA
2

0
Ace toa ce ta te -Hydroxybutyra te

FIGURE 23.2 The concentrations of acetoacetate and -hydroxybutyrate


in the blood in diabetic ketoacidosis (DKA) and alcoholic ketoacidosis
(AKA). The horizontal dashed line represents the minimum concentra-
tion of acetoacetate that will produce a positive nitroprusside reaction.
368 Acid-Base Disorders

2. DKA is m ost often the resu lt of inap p rop riate insu lin
d osing, bu t som e p atients have a concu rrent illness, m ost
com monly an infection.

3. The hallm ark of DKA is the com bination of hyp ergly-


cem ia, a seru m bicarbonate below 20 m Eq/ L, and an ele-
vated anion gap . The blood glu cose is u su ally above 250
mg/ d L, but it m ay be low er or even norm al in abou t 20%
of cases (22).

4. The increase in ketoacid s shou ld p rod u ce an elevated


anion gap ; how ever, this is variable, and the anion gap
can be norm al in DKA (23). The renal excretion of ketones
is accom p anied by an increase in chlorid e reabsorption in
the renal tubules, and the resu lting hyp erchloremia lim -
its the increase in the anion gap.

C. Diagnosis
1. The d iagnosis of DKA requ ires confirm ation of elevated
ketoacid s in blood and urine. The assay used m ost of-
ten is the nitroprussid e reaction, w hich is a colorim etric
method for the d etection of acetoacetate. A p ositive reac-
tion requ ires a m inim u m acetoacetate concentration of
3 m Eq/ L.

2. The nitrop ru ssid e reaction does not detect -hydroxybutyr-


ate (22), w hich is the p red om inant ketoacid in DKA (30).
As such, this reaction is insensitive for monitoring the se-
verity of ketoacid osis. This is d em onstrated in Figu re 23.2.
N ote that the reaction is barely p ositive in DKA d espite a
total ketoacid concentration of 13 14 m Eq/ L in blood .

D. Management
The m anagem ent of DKA is su m m arized in Table 23.1.
Organic Acidoses 369

TABLE 23.1 Management of Diabetic Ketoacidosis


Insulin: 0.1U/kg IVpush, then 0.1 U/kg/hr by continuous infusion.
Decrease dose rate 50% when serum HCO3 rises above
16 mEq.
Fluids: Start 0.9% saline, 1 L/hr for the first 2 hrs.
Follow with 0.45% saline at 250500 mL/hr.
Total fluid deficit is usually 50100 mL/kg.
Potassium: If serum K = ___ mEq/L, give ___ mEq over next hour.
<3 40
34 30
45 20
56 10
<6 0
Phosphate: If serum PO4 is <1.0 mg/dL, give 7.7 mg/kg over 4 hrs.

1. Insulin Therapy
a. Insu lin is given intravenou sly, starting w ith a bolus
d ose of 0.1 units per kilogram bod y w eight (some feel
this is unnecessary) and follow ed w ith a continuous
infusion of 0.1 u nits per kilogram p er hou r. Becau se
insulin adsorbs to intravenous tubing, the initial 50 m L of
infusate should be run throu gh the IV setu p before the
insu lin d rip is started .
b. The blood glucose levels should be measured every 1
to 2 hours d uring intravenous insulin therapy. The goal
is to d ecrease the blood glucose by 50 to 75 m g/ d L per
hou r (24). If this goal is not achieved , the insu lin infu -
sion rate shou ld be d ou bled (24). Fingerstick glucose
d eterm inations can be p erform ed if the blood glu cose
is below 500 m g/ d L.
370 Acid-Base Disorders

2. Fluids
a. Volu m e d eficits average 50 to 100 m L/ kg (or 4 to 8 L
for a 175 lb ad u lt) in DKA.
b. Flu id therap y usu ally begins w ith 0.9% (isotonic) sa-
line infused at a rate of one liter p er hou r for the first 2
hou rs. This is follow ed by infu sion of 0.45% saline at
250 to 500 m L/ hour.
c. When the blood glu cose falls to 250 mg/ d L, d extrose
can be ad d ed to the intravenous fluid s, and the infu-
sion rate should then be slow ed to 100 to 250 mL/ hou r.
d . If there is evid ence of hyp ovolemic shock (i.e., hypo-
tension), colloid flu id s may be preferred u ntil the blood
pressu re normalizes. The p referred colloid in this situ-
ation is 5% albumin because 6% hetastarch prod u ces an
increase in seru m am ylase levels, and this can lead to
confusion because low -grad e pancreatitis may be com-
mon in DKA (22).

3. Potassium
Potassiu m d epletion is alm ost u niversal in DKA, and the
average d eficit is 3 to 5 m Eq/ kg. H ow ever, the seru m
p otassium is usually norm al (74% of p atients) or even
elevated (22% of p atients) at p resentation. The seru m po-
tassiu m falls d u ring insu lin therap y (transcellu lar shift),
and this fall can be d ram atic. Therefore, p otassiu m re-
p lacem ent shou ld be started as soon as p ossible (see
Table 23.1), and the seru m p otassiu m shou ld be m oni-
tored hou rly for the first 4 to 6 hou rs of therap y.

4. Phosphate
a. Phosp hate d epletion is com m on in DKA, and averages
1 to 1.5 m m ol/ kg. H ow ever, p hosp hate rep lacem ent
has little im p act on the ou tcom e in DKA, and is not
recom m end ed as a rou tine m easu re (22).
b. The serum phosphate level should be measured 4 hours
after the start of therapy. If the level is severely d e-
pressed (less than 1 mg/ d L), phosphate replacement is
Organic Acidoses 371

ad vised (see Table 23.1 for the recommend ed replace-


ment d ose).

5. Alkali Therapy
Alkali therapy with sodium bicarbonate d oes not improve
the outcome in DKA and is not recommended, regardless
of the severity of the acidemia (22).

E. Monitoring Acid-Base Status


1. The seru m bicarbonate m ay not be a reliable p arameter
for follow ing the acid -base changes in DKA. Aggressive
fluid replacement often prod uces a hyperchloremic acid o-
sis by promoting ketoacid excretion in the urine, w hich
increases chlorid e reabsorp tion in the renal tu bules. This
p revents the bicarbonate from rising d esp ite a resolving
ketoacid osis. In this situ ation, the pattern of the acid osis
is changing (i.e., changing from a high anion gap to a low
anion gap acid osis).

2. The m ost ap p rop riate p aram eter to m onitor d u ring the


therap y of DKA is the gap -gap : i.e., the anion gap ex-
cess :bicarbonate d eficit ratio (this param eter is d escribed
in Chap ter 22). This ratio is 1.0 in p u re ketoacid osis, and
d ecreases tow ard zero as the ketoacid osis resolves and is
replaced by the hyp erchlorem ic acid osis. When the ke-
tones have been cleared from the blood stream , the ratio
ap proaches zero.

III. ALCOHOLIC KETOACIDOSIS

A. Pathogenesis
Alcoholic ketoacidosis (AKA) is a complex disorder with sever-
al sources of ketosis, including reduced nutrient intake, hepatic
oxidation of ethanol (which generates NADH and enhances
372 Acid-Base Disorders

-hydroxybutyrate formation), and dehydration (which impairs


ketone excretion in the urine).

B. Clinical Features
1. AKA is usually seen in chronic alcoholics, and typically
appears 1 to 3 days after a period of heavy binge drinking (25).

2. The p resentation u su ally inclu d es nau sea, vomiting, and


abd om inal p ain. Electrolyte abnorm alities are com m on,
p articularly the hypos (e.g., hyp onatrem ia, hyp okalem ia,
hyp ophosp hatem ia, hyp om agnesem ia, hyp oglycem ia).

3. Mixed acid -base d isord ers are com m on in AKA. More


than half the p atients can have lactic acid osis (cau sed by
other cond itions) (25), and m etabolic alkalosis occu rs in
p atients w ith p rotracted vom iting.

C. Diagnosis
1. The d iagnosis of AKA is su ggested by the ap p earance of
a high anion gap m etabolic acid osis in the ap prop riate
clinical setting (i.e., after a p eriod of binge d rinking), and
the d iagnosis is confirm ed by the p resence of ketones in
the blood and u rine.

2. The ratio of -hyd roxybu tyrate to acetoacetate in blood


can be as high as 8:1 in AKA, and the plasma levels of
acetoacetate m ay not be high enou gh to be d etected by
the nitrop ru ssid e reaction (see Figu re 23.2). Therefore, the
nitroprusside reaction for detecting ketones can be negative in
A KA . When this occu rs, the d iagnosis of AKA requ ires
elimination of the other cond itions (e.g., lactic acid osis)
that can p rod u ce a high anion gap m etabolic acid osis.

D. Management
1. AKA is corrected sim p ly by infu sing d extrose-containing
Organic Acidoses 373

saline solutions. The glu cose helps retard hep atic ketone
p rod u ction, w hile the infu sed volum e prom otes the renal
clearance of ketones. The ketoacid osis u su ally resolves
w ithin 24 hou rs.

2. Alkali therap y is not necessary in AKA (25).

IV. TOXIC ALCOHOLS


Tw o alcohols are noted for their ability to generate organic
acid s: ethylene glycol and m ethanol.

A. Ethylene Glycol Intoxication


1. Pathophysiology
Ethylene glycol is a solvent u sed prim arily in antifreeze
and d eicing solu tions. When ingested , ethylene glycol is
rap id ly absorbed from the GI tract, and 80% of the ingest-
ed d ose is metabolized in the liver.
a. Metabolism by alcohol d ehyd rogenase in the liver p ro-
d u ces glycolic acid , as show n in Figu re 23.3. This is the
m ajor m etabolite of ethylene glycol, and it p rod u ces a
m etabolic acid osis w ith an elevated anion gap (26).
b. The form ation of glycolic acid involves the conversion
of N AD to N ADH , and this p rom otes the conversion
of p yru vate to lactate. As a resu lt, seru m lactate levels
are also elevated in ethylene glycol p oisoning (26,27).
c. The final m etabolite of ethylene glycol is oxalic acid ,
w hich can com bine w ith calciu m to form calcium ox-
alate crystals in the renal tu bu les. These crystals (w hich
are recognizable on m icroscopic exam ination of the
u rine) can d amage the renal tu bu les and prod u ce
acu te renal failu re.

2. Clinical Presentation
a. Early signs of ethylene glycol intoxication inclu d e nau-
374 Acid-Base Disorders

sea, vomiting, and apparent inebriation. Because ethyl-


ene glycol is od orless, there is no od or of alcohol on
the breath.
b. Severe cases are accom p anied by com a, generalized
seizu res, renal failu re, p u lm onary ed em a, and card io-
vascu lar collap se (26).
c. Laboratory stud ies show a metabolic acid osis w ith an
elevated anion gap.
d . Serum lactate levels can be elevated (usually 5 6 mEq
/ L). Hypocalcemia can be present, and calcium oxalate
crystals are visualized in the urine in about 50% of cases (28).
e. A p lasm a assay for ethylene glycol is available, and a
level > 25 m g/ d L is consid ered toxic (26,29). H ow ever,
p lasm a levels can be negligible (d u e to m etabolism of
the p arent com p ou nd ) in p atients w ho p resent late af-
ter ingestion.

3. Treatment
The results of the ethylene glycol assay are often not avail-
able immed iately, and therapy is started based on a high
clinical suspicion of ethylene glycol intoxication. Treat-
ment involves inhibition of alcohol d ehyd rogenase, and
hem od ialysis if necessary.
a. The trad itional use of ethanol to inhibit alcohol d ehy-
d rogenase has been rep laced by the d ru g fomepizole,
w hich inhibits alcohol d ehyd rogenase (see Figu re 23.3)
w ithout the sid e effects that accom p any ethanol. The
best resu lts are obtained w hen therapy begins w ithin 4
hou rs after ingestion. The recom m end ed d osage is 15
m g/ kg IV as an initial d ose, then 10 m g/ kg every 12
hou rs for 48 hou rs, then 15 m g/ kg every 12 hou rs until
the p lasm a ethylene glycol level is 25 m Eq/ L or low er
(26,30).
b. H em od ialysis increases the clearance of ethylene gly-
col and its m etabolites. The ind ications for imm ed iate
hem od ialysis inclu d e severe acid em ia (pH < 7.1), and
evid ence of end -organ d amage (e.g., com a, seizures,
Organic Acidoses 375

and renal failu re) (26,30). Mu ltip le cou rses of hem o-


d ialysis may be necessary. Fom ep izole shou ld be given
every 4 hours if hem od ialysis is continued .
c. ADJUNCTS. Thiamine (100 m g IV d aily) and pyridox-
ine (100 mg IV d aily) can d ivert glyoxylic acid to non-
toxic m etabolites (see Figu re 23.3).

B. Methanol Intoxication
Methanol is a com m on ingred ient in shellac, varnish, w ind -
shield w asher flu id and solid cooking fu el (Sterno) (26,31).

1. Pathophysiology
a. Like ethylene glycol, methanol is rapid ly absorbed from
the GI tract and is metabolized by alcohol d ehyd roge-
nase in the liver (see Figure 23.3).
b. The m etabolite, form ic acid , is a m itochond rial toxin
that acts by inhibiting cytochrom e oxid ase. Tissu es

ETHYLENE GLYCOL METHANOL

P yruva te P yruva te
NADH NADP H
AD FMP AD
NAD NADP
La cta te La cta te
Glycolic Acid Formic Acid

Thia mine Non-Toxic


Glyoxylic Acid
P yridoxine Me ta bolite s

Oxa lic Acid

FIGURE 23.3 The metabolism of ethylene glycol and methanol. AD =


alcohol dehydrogenase. FMP = fomepizole.
376 Acid-Base Disorders

that are p articu larly su scep tible to d am age are the reti-
na, op tic nerve, and basal ganglia (31).
c. Seru m lactate levels can be elevated for the sam e rea-
son as exp lained for ethylene glycol, but the ad d ed
mitochond rial toxicity of form ic acid can result in
higher seru m lactate levels.
2. Clinical Presentation
a. Early signs (w ithin 6 hou rs of ingestion) inclu d e
ap p arent inebriation w ithou t the od or of ethanol (as in
ethylene glycol intoxication).
b. Later signs (6 to 24 hou rs after ingestion) inclu d e visu -
al d istu rbances (e.g., scotom a, blu rred vision, com -
p lete blind ness), d ep ressed consciou sness, com a, and
generalized seizu res. Pancreatitis has also been d e-
scribed (26).
c. Exam ination of the retina can reveal papilled em a and
generalized retinal ed em a.
d . Laboratory stud ies show the sam e acid -base abnor-
malities as d escribed for ethylene glycol intoxication
(althou gh lactate levels m ay be higher).
e. Pancreatic enzym es can be also be elevated , and elevat-
ed CPK levels in blood (from rhabd om yolysis) has
been rep orted (26).
f. A plasma assay for methanol is available, and a level
above 25 mg/ d L is consid ered toxic. As exp lained w ith
ethylene glycol intoxication, p lasm a levels can be m is-
lead ing late after ingestion becau se the parent com -
p ou nd m ay be com p letely d egrad ed .
3. Treatment
Treatm ent is the sam e as d escribed for ethylene glycol
intoxication, excep t:
a. Visu al im pairm ent is an ind ication for d ialysis.
b. Ad junctive therapy w ith thiam ine and pyrid oxine is
not ind icated .
Organic Acidoses 377

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1. Gau thier PM, Szerlip H M. Metabolic acid osis in the intensive
care u nit. Crit Care Clin 2002; 18:289308.
2. Ju d ge BS. Metabolic acid osis: d ifferentiating the causes in the
p oisoned p atient. Med Clin N Am 2005; 89:11071124.
3. Iberti TS, Liebow itz AB, Papad akos PJ, et al. Low sensitivity of
the anion gap as a screen to d etect hyperlactatem ia in critically ill
p atients. Crit Care Med 1990; 18:275277.
4. Weil MH , Afifi AA. Exp erim ental and clinical stu d ies on lactate
and pyruvate as ind icators of the severity of acute circu latory
failu re (shock). Circu lation 1970; 16:9891001.
5. Mizock BA. Metabolic d erangem ents in sepsis and sep tic shock.
Crit Care Clin 2000; 16:319336.
6. Fink MP. Cytop athic hyp oxia. Crit Care Clin 2001; 17:219238.
7. Ad u en J, Bernstein WK, Khastgir T, et al. The u se and clinical
im p ortance of a su bstrate-sp ecific electrod e for rap id d eterm ina-
tion of blood lactate concentrations. JAMA 1994; 272:16781685.
8. Cam pbell CH . The severe lactic acid osis of thiam ine d eficiency:
acu te, p erniciou s or fu lm inating beriberi. Lancet 1984; 1:446449.
9. Ju d ge BS. Metabolic acid osis: d ifferentiating the causes in the
p oisoned p atient. Med Clin N orth Am 2005; 89:11071124.
10. Ogedegbe AO, Thomas DL, Diehl AM. Hyperlactatemia syndromes
associated with HIV therapy. Lancet Infect Dis 2003; 3:329337.
11. Apod aca AA, Rakita RM. Linezolid ind u ced lactic acid osis. N
Engl J Med 2003; 348:8687.
12. Yann-Erick C, Cariou A, Monchi M, et al. Detecting life-threaten-
ing lactic acid osis related to nu cleosid e-analog treatm ent of
hu m an im m u nod eficiency viru s-infected p atients and treatm ent
w ith L-carnitine. Crit Care Med 2003; 31:10421047.
13. Wilson KC, Reard on C, Theod ore AC, Farber H W. Prop ylene gly-
col toxicity: a severe iatrogenic illness in ICU p atients receiving
IV benzod iazep ines. Chest 2005; 128:16741681.
14. Arroglia A, Shehab N, McCarthy K, Gonzales JP. Relationship of
continuous infusion lorazepam to serum propylene glycol concen-
tration in critically ill ad ults. Crit Care Med 2004; 32:17091714.
15. Kruse JA, Zaid i SAJ, Carlson RW. Significance of blood lactate
levels in critically ill p atients w ith liver d isease. Am J Med 1987;
83:7782.
378 Acid-Base Disorders

16. Brivet F, Bernad in M, Cherin P, et al. H yperchlorem ic acid osis


d u ring grand m al seizu re acid osis. Intensive Care Med 1994;
20:2731.
17. Mou ntain RD, H effner JE, Brackett N C, Sahn SA. Acid -base d is-
tu rbances in acu te asthm a. Chest 1990; 98:651655.
18. Thu rn JR, Pierpoint GL, Lu d vigsen CW, Eckfeld t JH . D-lactate
encephalopathy. Am J Med 1985; 79:717720.
19. Bu stos D, Ponse S, Pernas JC et al. Fecal lactate and the short
bow el synd rom e. Dig Dis Sci 1994; 39:23152319.
20. Forsythe SM, Schm id t GA. Sod ium bicarbonate for the treatm ent
of lactic acid osis. Chest 2000; 117:260267.
21. Rose BD. Clinical p hysiology of acid -base and electrolyte d isor-
d ers. 4th ed . N ew York: McGraw -H ill, 1994:590.
22. Charfen MA, Fernand ez-Frackelton M. Diabetic ketoacid osis.
Em erg Med Clin N Am 2005; 23:609628.
23. Gam blin GT, Ashburn RW, Kem p DG, Beu ttel SC. Diabetic keto-
acid osis presenting w ith a norm al anion gap. Am J Med 1986;
80:758760.
24. Kitabachi AE, Um pierrez GE, Mu rp hy MB, et al. Am erican
Diabetes Association. H yp erglycem ic crisis in d iabetes. Diabetes
Care 2004; 27(Sup pl):S94S102.
25. Wrenn KD, Slovis CM, Minion GE, Rutkow sli R. The synd rom e
of alcoholic ketoacid osis. Am J Med 1991; 91:119128.
26. Weiner SW. Toxic alcohols. In: Gold frank LR, Flom enbau m N E,
H offm an RS, et al., ed s. Gold franks toxicologic em ergencies. 7th
ed . N ew York, McGraw -H ill, 2002:14471459.
27. Gabow PA, Clay K, Su llivan JB, Lep off R. Organic acid s in ethyl-
ene glycol intoxication. Ann Intern Med 1986; 105:1620.
28. Borkan SC. Extracorporeal therapies for acu te intoxications. Crit
Care Clin 2002; 18:393420.
29. Caravati EM, Erd m an AR, Christianson G, et al. Ethylene glycol
exposu re: an evid ence-based consensu s gu id eline for out-of-hos-
p ital m anagem ent. Clin Toxicol 2005; 43:327345.
30. Brent J, McMartin K, Phillips S, et al. Fom ep izole for the treatment
of ethylene glycol poisoning. N Engl J Med 1999; 340:832838.
31. Barceloux DG, Bond GR, Krenzelok EP, et al. Am erican Acad em y
of Clinical Toxicology practice guid elines on the treatm ent of
m ethanol p oisoning. J Toxicol Clin Toxicol 2002; 40:415446.
Chapter 24
METABOLIC
ALKALOSIS
Although metabolic acidosis seems to get the most attention,
one of every three acid -base disord ers in hospitalized patients
is a metabolic alkalosis (1). This chapter d escribes the causes,
consequences, and correction of metabolic alkalosis (13).

I. ORIGINS OF METABOLIC ALKALOSIS


Metabolic alkalosis is characterized by an increase in extra-
cellu lar bicarbonate (H CO 3) concentration, and is u su ally the
resu lt of one (or m ore) of the follow ing cond itions.

A. Loss of Gastric Secretions


1. Gastric secretions are rich in hyd rogen and chlorid e ions
(concentration of each is 50 to 100 m Eq/ L), and loss of
these secretions from vom iting or nasogastric (N G) su c-
tion can prod u ce a p rofou nd m etabolic alkalosis.

2. Desp ite the loss of gastric acid , chlorid e d ep letion is the


major factor responsible for the m etabolic alkalosis from
vom iting and N G suctioning. Chlorid e d ep letion stimu -
lates H CO 3 reabsorp tion in the kid neys, and the resu lting
increase in extracellular H CO 3 creates a m etabolic alkalo-
sis. (The H CO 3 that is ad d ed to the extracellu lar flu id bal-
ances the chlorid e loss to m aintain electrical neu trality).

3. Other factors that contribu te to the alkalosis from loss of


gastric secretions are hyp ovolem ia and hyp okalem ia.

379
380 Acid-Base Disorders

B. Diuretics
Thiazid e d iu retics and loop d iu retics like fu rosem id e p ro-
mote m etabolic alkalosis by increasing the urinary loss of
sod iu m , chlorid e, p otassiu m , and m agnesiu m .

1. The p rincip al action of these d iu retics is to increase sod i-


u m and chlorid e loss in the u rine. The chlorid e loss is
accomp anied by increased H CO 3 reabsorption in the kid -
neys (to m aintain electrical neu trality), and the resu lting
increase in extracellu lar flu id H CO 3 concentration p ro-
d u ces a m etabolic alkalosis. Sod iu m loss p rom otes extra-
cellu lar flu id loss, and this p romotes metabolic alkalosis
by mechanism s exp lained in the next section.

2. Diu retics increase u rinary p otassiu m excretion by the fol-


low ing m echanism s:
a. Sod iu m d elivery to the d istal tubules is increased , and
this p rom otes p otassiu m secretion via the sod iu m
potassiu m exchange p u m p in the d istal tu bu le.
b. Magnesiu m reabsorp tion in the kid neys u su ally mir-
rors sod iu m reabsorp tion, so these d iu retics also pro-
mote m agnesiu m loss in the u rine. Magnesiu m d eple-
tion p lays an im p ortant role in d iu retic-ind u ced p otas-
siu m d ep letion, as d escribed in Chap ter 28.
Potassiu m d epletion prom otes m etabolic alkalosis by m ech-
anism s exp lained later in this section.

C.Volume Depletion
1. Volu m e d ep letion p rom otes m etabolic alkalosis in tw o
w ays.
a. There is a d irect link betw een the reabsorp tion of sod i-
u m and H CO 3 in the renal tu bu les, so the increased
sod iu m reabsorption in resp onse to volu m e d ep letion
is accom panied by an increase in H CO 3 reabsorp tion.
Metabolic Alkalosis 381

b. Volu me d epletion also stimulates renin release, and the


subsequent increase in ald osterone prod uction serves
to promote H + secretion in the d istal tu bules.

2. The imp ortance of volu m e d ep letion as a cau se of m eta-


bolic alkalosis is being qu estioned becau se volu m e
rep lacem ent d oes not correct m etabolic alkalosis w ithou t
chlorid e rep letion (2). Since volu m e rep lacem ent is usu -
ally accom p anied by chlorid e rep lacement (i.e., in saline
solu tions), this d istinction m ay not be clinically relevant.

D. Hypokalemia
1. Hypokalemia promotes metabolic alkalosis via tw o mech-
anisms:
a. Transcellu lar shift of H + into cells.
b. Increased H + secretion in the d istal renal tu bu les.

2. The enhanced secretion of H + in the d istal renal tubu les


involves a N a + H + transporter that requires ad equate
d elivery of sod iu m to the d istal tu bu les. In the setting of
hypovolem ia, m ost of the filtered sod iu m is reabsorbed
in the p roxim al tu bu les, and the effects of hyp okalem ia
on H + secretion are m inim al.

E. Chronic CO2 Retention


The com p ensatory resp onse to CO 2 retention is an increase in
H CO 3 reabsorption in the p roximal tu bu les of the kid neys. If
chronic hypercapnia is corrected su d d enly (e.g., by overven-
tilation w hen mechanical ventilation is initiated ), the com -
p ensatory m etabolic alkalosis w ill becom e a prim ary acid -
base d isord er.

F. Administration of Organic Anions


The ad m inistration of organic anions su ch as lactate (in lac-
382 Acid-Base Disorders

tated Ringer s solu tion), acetate (in p arenteral nu trition solu-


tions), and citrate (in banked blood ) cou ld p rod u ce a m eta-
bolic alkalosis. H ow ever, only citrate ad m inistration in
blood transfu sions is cap able of causing a m etabolic alkalo-
sis (4), and a m inim u m of 8 u nits of blood m u st be trans-
fu sed before the p lasm a H CO 3 begins to rise (5).

II. CLINICAL CONSEQUENCES


Despite the p otential for harm , m etabolic alkalosis has no
ap parent d eleteriou s effects in m ost p atients. The follow ing
ad verse effects are the ones m ost often m entioned .

A. Neurologic Manifestations
The neu rologic m anifestations attribu ted to alkalosis inclu d e
d epressed consciou sness, generalized seizu res, and carp op e-
d al sp asm s. H ow ever, these m anifestations are alm ost al-
w ays associated w ith resp iratory alkalosis, not m etabolic
alkalosis. This is exp lained by the greater tend ency for resp i-
ratory alkalosis to influ ence the acid -base statu s of the cen-
tral nervou s system .

B. Hypoventilation
1. The resp iratory com p ensation for m etabolic alkalosis is
d escribed by the equation show n below (w here PaCO 2 is
the arterial PCO 2 and H CO 3 is the plasm a H CO 3 in
mEq/ L) (6).

Expe c te d PaCO2 = (0.7 x HCO3 ) + (21 2) (24.1)

This equ ation is u sed to p lot the relationship betw een


H CO 3 and arterial PCO 2 show n in Figu re 24.1. N ote that
the threshold for hyp ercap nia (PaCO 2 of 46 m m H g ) is
Metabolic Alkalosis 383

not reached u ntil the H CO 3 rises above the range of 34


39 m Eq/ L.

2. Figure 24.1 d em onstrates that respiratory depression occurs


only in severe cases of metabolic alkalosis.

55

Pa CO 2 = 0.7 x HCO 3 + (21 2)

50

Hype rca pnia


Pa CO 2
45 Thre s hold
(mm Hg)

40

25 30 35 40 45

S e rum HCO 3 (mEq L)

FIGURE 24.1 The relationship between plasma bicarbonate (HCO 3) and


arterial PCO 2 (PaCO 2) based on the equation shown at the top of the
graph. Note that the serum HCO 3 must rise above the range of 3439
mEq/ L to produce hypercapnia.

C. Systemic Oxygenation
Alkalosis has a nu m ber of effects that can threaten tissue
oxygen availability (see Figu re 24.2).

1. Alkalosis red u ces m yocard ial contractility and p romotes


p erip heral vasoconstriction (by d ecreasing ionized or
free p lasm a calciu m ): both effects can lead to a d ecrease
in card iac outpu t.

2. Alkalosis shifts the oxyhemoglobin d issociation cu rve to


384 Acid-Base Disorders

the left (Bohr effect), w hich im p airs the ability of hem o-


globin to release oxygen to the tissu es.

3. Intracellu lar alkalosis can increase cellu lar O 2 consu mp -


tion by stim u lating the activity of enzym es in the gly-
colytic p athw ay. H ow ever, this effect is p red om inantly
seen w ith resp iratory alkalosis (7).
The clinical significance of these effects is unclear, bu t they
m ay be im p ortant in p atients w ith circu latory failure or cir-
cu latory shock.

Glucos e
3 O2
S a O2
CO 2 + H2 O
2
O2
Pa O 2

1 Q HbO 2
Ca pilla ry

EFFECTS OF METABOLIC ALKALOS IS


1 De cre a s e s Ca rdia c Output
2 S hifts HbO 2 Curve to the Le ft
3 Incre a s e s Tis s ue O 2 Cons umption

FIGURE 24.2 Effects of alkalosis on the determinants of systemic oxy-


genation.

III.THE EVALUATION
Metabolic alkaloses are trad itionally classified as chlorid e-
responsive or chlorid e-resistant, based on the u rinary chlo-
rid e concentration (see Table 24.1).
Metabolic Alkalosis 385

TABLE 24.1 Classification of Metabolic Alkalosis


Chloride-Responsive Chloride-Resistant
Urinary chloride <15 mEq/L: Urinary chloride > 25 mEq/L:
1. Loss of gastric acid 1. Mineralocorticoid excess
2. Diuretics 2. Potassium depletion
3. Volume depletion
4. Posthypercapnia

A. Chloride-Responsive Alkalosis
1. A chloride-responsive m etabolic alkalosis is characterized
by a low u rinary chlorid e concentration; i.e., less than 15
m Eq/ L.

2. This typ e of m etabolic alkalosis is the resu lt of gastric


acid loss, d iu retic therap y, volu m e d epletion, or renal
com pensation for hypercap nia.

3. The m ajority of m etabolic alkaloses in hosp italized


p atients are chlorid e-resp onsive.

B. Chloride-Resistant Alkalosis
1. A chloride-resistant m etabolic alkalosis is characterized by
an elevated u rinary chlorid e concentration; i.e., above 25
m Eq/ L.

2. Most cases of chlorid e-resistant alkalosis are caused by


primary m ineralocorticoid excess (e.g., hyperad renal con-
d itions) or severe potassiu m d epletion (these tw o cond i-
tions often co-exist).

3. This type of metabolic alkalosis is u su ally associated w ith


volu m e expansion rather than volu m e d epletion.
386 Acid-Base Disorders

IV. MANAGEMENT
Most m etabolic alkaloses in hosp italized p atients are chlo-
rid e-resp onsive, so chlorid e rep lacem ent is the m ainstay of
therapy for m etabolic alkalosis. The chlorid e can be rep laced
as sod ium chlorid e, potassiu m chlorid e, or hyd rochloric acid
(H CL).

A. Saline Infusion
1. Because volu me d epletion is common in chlorid e-respon-
sive metabolic alkalosis, infu sion of isotonic saline (0.9%
sod ium chlorid e) is the most common method of chlorid e
replacement.

2. The volu m e of isotonic saline need ed can be d eterm ined


by estim ating the chlorid e (CL) d eficit in m Eq/ L, as
show n below :

CL de fic it = 0.2 x wt (kg ) x (no rmal c urre nt P CL) (24.2)

w here P CL is p lasm a chlorid e in m Eq/ L. The factor 0.2


represents the volu m e of d istribution for chlorid e as a
fraction of bod y w eight.

3. The volu m e of isotonic saline need ed to correct the chlo-


rid e d eficit is then d eterm ined as follow s:

Vo lume o f 0.9% NaCl (L) = CL de fic it /154 (24.3)

w here 154 is the chlorid e concentration (in m Eq/ L) in


isotonic saline.
EXAMPLE. A patient w ho w eighs 70 kg has a m etabolic
alkalosis from rep eated vom iting. The p lasm a chlorid e
is 80 m Eq/ L. Using a norm al seru m chlorid e of 100
m Eq/ L, the chlorid e d eficit is 0.2 x 70 x (100 80) = 280
m Eq. The volu m e of isotonic saline need ed to correct
this d eficit is 280/ 154 = 1.8 liters.
Metabolic Alkalosis 387

B. Potassium Chloride
1. Potassium chlorid e ad ministration is ind icated only w hen
metabolic alkalosis is accompanied by hypokalemia.

2. It is im p ortant to em p hasize that the ad m inistration of


potassium chloride will not replenish potassium stores if there
is concurrent magnesium depletion (8). (See Chap ter 28 for
more inform ation on this top ic.)

C. Hydrochloric Acid Infusion


Infu sions of d ilu te solu tions of hyd rochloric acid (H CL ) p ro-
d u ce the m ost rap id correction of m etabolic alkalosis (1).
H ow ever, becau se of the risks involved (see later), H CL infu -
sions are reserved only for the m ost severe and refractory
cases of m etabolic alkalosis.

1. The d ose of H CL is determined by estimating the hydro-


gen ion (H +) d eficit in m Eq/ L using the equation below.

H+ de fic it = 0.5 x wt (kg ) x (c urre nt de s ire d P HCO3 )


(24.4)

w here P H CO 3 is plasm a H CO 3 in mEq/ L. The factor 0.5 rep -


resents the volume of d istribution for H + as a fraction of
bod y w eight. The d esired H CO 3 shou ld be above the nor-
m al range (the goal is not to correct the alkalosis, but to
red uce the severity), and can be set halfw ay betw een the
actual and norm al H CO 3.

2. The H + d eficit is corrected w ith 0.1N H CL, w hich con-


tains 100 m Eq H + p er liter. The volum e of 0.1N H CL
need ed to correct the H + d eficit is d eterm ined as show n
below.

Vo lume o f 0.1N HCL (L) = H+ de fic it /100 (24.5)


388 Acid-Base Disorders

3. Becau se H CL solutions are sclerosing, they m u st be in-


fused throu gh a large, central vein (9), and the infu sion
rate shou ld not exceed 0.2 m Eq/ kg/ hr (3).

4. The corrosive effects of H CL solu tions are a m ajor con-


cern. In ad d ition to sclerosis, extravasation of H CL solu -
tions can p rod u ce severe tissu e necrosis (10). Becau se of
their toxic p otential, H CL infu sions shou ld be u sed very
jud iciou sly.

D. Chloride-Resistant Alkalosis
1. The m anagem ent of chlorid e-resistant m etabolic alkalo-
sis is aim ed at treating the u nd erlying cau se of the m in-
eralocorticoid excess (e.g., hyp erad renalism , heart fail-
u re) and correcting potassiu m d eficits.

2. The carbonic anhyd rase inhibitor, acetazolamide, blocks


H CO 3 reabsorption in the p roxim al tu bu le, and has been
u sed su ccessfu lly in treating cases of chlorid e-resistant
m etabolic alkalosis.
a. The recom m end ed d ose is 5 to 10 m g/ kg IV (or PO),
and the m aximu m effect occu rs after an average of 15
hou rs (11).
b. Acetazolamid e promotes both volume d epletion and
p otassium d epletion, and it should not be u sed in cases
of chlorid e-resistant metabolic alkalosis that are accom-
p anied by either of these cond itions.

REFERENCES
1. Khanna A, Ku rtzm an N A. Metabolic alkalosis. Resp ir Care 2001;
46:354365.
2. Galla JH . Metabolic alkalosis. J Am Soc N ephrol 2000; 11:360375.
3. And rogu e H J, Mad ias N . Managem ent of life-threatening acid -
base d isord ers. Part 2. N Engl J Med 1998; 338:107111.
Metabolic Alkalosis 389

4. Driscoll DF, Bistrian BR, Jenkins RL. Develop m ent of m etabolic


alkalosis after m assive transfusion d u ring orthotop ic liver trans-
p lantation. Crit Care Med 1987; 15:905908.
5. Rose BD, Post TW. Metabolic alkalosis. In: Clinical p hysiology of
acid -base and electrolyte d isord ers. 5th ed . N ew York: McGraw -
H ill, 2001:551577.
6. Javaheri S, Kazem i H . Metabolic alkalosis and hyp oventilation in
hum ans. Am Rev Resp ir Dis 1987; 136:10111016.
7. Rastegar H R, Wood s M, H arken AH . Respiratory alkalosis in-
creases tissue oxygen d em and . J Su rg Res 1979; 26:687692.
8. Whang R, Flink EB, Dyckner T, et al. Mg depletion as a cause of
refractory potassium d epletion. Arch Intern Med 1985; 145:1686
1689.
9. Brim iou lle S, Vincent JL, Du faye P, et al. H yd rochloric acid infu -
sion for treatm ent of m etabolic alkalosis: effects on acid -base bal-
ance and oxygenation. Crit Care Med 1985; 13:738742.
10. Jankau skas SJ, Gu rsel E, Antonenko DR. Chest w all necrosis sec-
ond ary to hyd rochloric acid use in the treatm ent of m etabolic
alkalosis. Crit Care Med 1989; 17:963964.
11. Marik PE, Ku ssm an BD, Lipm an J, Krau s P. Acetazolam id e in the
treatm ent of m etabolic alkalosis in critically ill p atients. H eart
Lu ng 1991; 20:455458.
Chapter 25
OLIGURIA AND
ACUTE RENAL
FAILURE
A d ecrease in u rine ou tp u t can be a norm al ad ap tation to hy-
p ovolem ia or a sign of acu te renal failu re. This chapter d e-
scribes how to d istingu ish betw een these tw o cond itions,
and also d escribes the cau ses and m anagem ent of acu te re-
nal failure.

I. OLIGURIA

A. Definition
1. Oligu ria is trad itionally d efined as a u rine ou tp u t of less
than 400 m L/ d ay (1), bu t no one w aits 24 hou rs to m ake
the d iagnosis, so this translates to an average u rine out-
p ut of less than 17 m L/ hr.

B. Categories
The cau ses of oligu ria are trad itionally sep arated into three
categories based on the anatom ic location of the p roblem .
The cond itions in each category are listed in Table 25.1 (2).

1. Prerenal Conditions
The p rerenal cond itions are located p roxim al to the kid -
neys and are characterized by a d ecrease in renovascular
flow. Prerenal d isord ers are resp onsible for abou t 30 to

391
392 Renal and Electrolyte Disorders

40% of cases of oligu ria in the ICU (1). This typ e of olig-
u ria u sually resolves w hen the und erlying d isord er (e.g.,
hypovolem ia) is treated .

TABLE 25.1 Usual Causes of Acute Oliguria in the ICU


Prerenal Renal Postrenal
Conditions Failure Obstruction
Hypovolemia Circulatory shock Papillary necrosis
Decompensated Myoglobinuria Retroperitoneal mass
heart failure
Drugs that impair Nephrotoxic drugs Urethral stricture
renal autoregulation*
Radiocontrast dye Prostatic hypertrophy
Severe sepsis with
multiorgan failure
Surgery
*Includes nons teroidal antiinflammatory agents (ketorolac), angiotens in-
converting enzyme inhibitors , and angiotens in receptor blockers .
Cardiac surgery and abdominal aortic aneurysm repair.

2. Renal Disorders
a. Acu te renal failu re is responsible for about 50% of
cases of acu te oligu ria. The renal d isord er m ost often
involved is a cond ition know n as acute tubular necrosis
(ATN ) (1).
b. The hallm ark of ATN is inju ry to the renal tubular
epithelial cells. The inju red cells are slou ghed into the
tu bu lar lu m en to create an obstru ction that increases
p roxim al p ressu re in the tu bu les. This d ecreases the
net filtration p ressu re across the glom eru lar capillaries
and red u ces the glom eru lar filtration rate (GFR).
c. The cau ses of ATN inclu d e severe sep sis, circu latory
shock, and toxic inju ry from d ru gs (e.g., am inoglyco-
sid es), rad iocontrast d ye, and m yoglobinu ria.
Oliguria and Acute Renal Failure 393

3. Postrenal Obstruction
Obstru ction d istal to the renal p arenchym a is resp onsible
for only about 10% of cases of oligu ria in the ICU (3). The
obstru ction can involve the m ost d istal p ortion of the
renal collecting d u cts (pap illary necrosis), the u reters (ex-
tralu m inal obstru ction from a retrop eritoneal m ass), or
the u reters (strictu res or extralu m inal obstru ction from
p rostatic enlargem ent). Ureteral obstru ction from stones
d oes not cause oliguria unless the patient has a solitary
kid ney.

TABLE 25.2 Prerenal Azotemia vs. Acute Renal Failure


Acute
Parameter Azotemia Renal Failure
Urine Sodium <10 mEq/L > 20 mEq/L
Fractional Excretion <1% > 2%
of Sodium
Urine Osmolality > 450 mosm/kg 290 10 mosm/kg
BUN/Creatinine 20/1 10/1
Ratio in Plasma

C. Evaluation
The follow ing stu d ies can help to d istingu ish p rerenal con-
d itions from intrinsic renal failure in cases of acu te oligu ria.
(see Table 25.2).

1. Urine Sodium
a. A d ecrease in renal p erfu sion is accom p anied by sod i-
u m conservation and a d ecrease in u rinary sod iu m
excretion. A urine sodium below 20 mEq/L usually indi-
cates a prerenal cause of oliguria (1).
b. Intrinsic renal d isease is u su ally accom p anied by ob-
394 Renal and Electrolyte Disorders

ligatory sod ium loss in the u rine and an increase in


u rinary sod ium excretion. Therefore, a urine sodium
above 40 mEq/L suggests an intrinsic renal disorder as a
cause of oliguria.
CAVEAT. Prerenal cond itions can be associated w ith a
high u rinary sod iu m (> 40 m Eq/ L) w hen they are su -
p erim p osed on chronic renal insu fficiency (w here
there is obligatory sod iu m loss in the u rine), or w hen
there is ongoing d iuretic therap y.

2. Fractional Excretion of Sodium


The fractional excretion of sodium (FEN a ) elim inates the in-
fluence of sod iu m intake on u rinary sod ium . The FEN a is
the fraction of filtered sodium that is excreted in the urine,
and is equivalent to the sod ium clearance divided by the
creatinine clearance (see Table 25.3) (4).
a. The FEN a is norm ally less than 1%; i.e., less than 1% of
the filtered sod iu m is excreted in the u rine.
b. In the setting of oliguria, an FEN a <1% suggests a prerenal
condition, and an FEN a >2% suggests intrinsic renal disease.
c. One excep tion to the above criteria is ATN d u e to myo-
globinu ria, w here the FEN a can be less than 1% (1).

3. Urine Osmolality
a. The norm al resp onse to hyp ovolem ia involves an in-
crease in free w ater reabsorption in the kid neys (m ed i-
ated , in p art, by antid iu retic horm one.) This resu lts in
a relatively concentrated u rine and an increase in u rine
osm olality.
b. Urinary concentrating ability is im paired in renal fail-
u re, and the u rine osm olality tend s to m irror the osm o-
lality of plasm a. This condition is known as isosthenuria.
c. In the setting of oligu ria, a urine osmolality >450 mosm
/kg is evidence of a prerenal condition, and a urine osmolal-
ity of 280 300 mosm/kg is evidence of an intrinsic renal
disorder (5).
Oliguria and Acute Renal Failure 395

CAVEAT. Prerenal cond itions may not cause the expect-


ed rise in urine osmolality if there is underlying renal
d isease, ongoing use of d iuretics, or d iabetes insipid us.

4. Urine Microscopy
Microscop ic exam ination of the u rine sed im ent can p ro-
vid e the follow ing inform ation:
a. The p resence of abu nd ant tu bu lar ep ithelial cells w ith
ep ithelial cell casts establishes the d iagnosis of ATN .
b. The presence of w hite cell casts id entifies an interstitial
nep hritis (see later).
c. The presence of pigmented casts identifies myoglobinuria.

TABLE 25.3 Quantitative Assessment of Renal Function


Creatinine Clearance (Men):

CLCR (mL/min) = (140 age) x weight (kg)


72 x Serum creatinine (mg/dL)
Creatinine Clearance (Women):
CLCR (mL/min) = 0.85 x ClCR for men
Fractional Excretion of Sodium:
[ ] [ ]
FENA = Urine Na /Plasma Na x 100
Urine [Cr]/Plasma [Cr]

5. BUN/ Creatinine Ratio


a. In norm al su bjects and p atients w ith intrinsic renal
failu re, the ratio of blood u rea nitrogen (BUN ) to crea-
tinine in plasm a is abou t 10/ 1.
b. The reabsorption of urea in the proximal renal tubules is
linked to the reabsorption of sodium, so in cond itions
where sodium reabsorption is increased (e.g., hypo-
volemia), increased urea reabsorption leads to an increase
396 Renal and Electrolyte Disorders

in plasma BUN and an increase in the BUN/ creatinine


ratio (5).
c. A plasma BUN /creatinine ratio of 20 or higher suggests a
prerenal cause for oliguria. This cond ition is called prere-
nal azotemia.
CAVEAT. The BUN / creatinine ratio is also influ enced
by the rate of u rea p rod u ction. Therefore, cond itions
associated w ith an increase in u rea p rod u ction (e.g., GI
bleed ing) can also increase the BUN / creatinine ratio,
and cond itions associated w ith a d ecrease in u rea p ro-
d u ction (e.g., hep atic insu fficiency) can p revent the
normal rise in the BUN / creatinine ratio in prerenal
d isord ers.

6. Creatinine Clearance
Althou gh not often u sed in the evalu ation of oligu ria, the
creatinine clearance can be estimated using the equations
in Table 25.3. The creatinine clearance is u sed as a rough
estim ate of the glom eru lar filtration rate (GFR), w hich is
a m easu re of the fu nctional renal m ass. (The creatinine
clearance overestim ates GFR because creatinine is secret-
ed by the renal tu bu les.
a. In acute oliguric renal failure, the creatinine clearance is
less than 25% of normal. (The creatinine clearance varies
w ith age, body size, and gender, but the normal range
should be about 70 100 mL/ min for most patients.)
b. In prerenal cond itions, the creatinine clearance can
d ecrease (if the cond ition is severe enou gh to cau se a
d ecrease in GFR), bu t the m agnitud e of change w ill be
m u ch less than in renal failu re.

7. Renal Ultrasound
a. There are no laboratory tests that w ill id entify p ostre-
nal obstru ction as a cause of oligu ria (acu te obstru c-
tion has u rinary ind ices similar to prerenal cond itions,
and chronic obstru ction has u rinary ind ices sim ilar to
intrinsic renal failu re).
Oliguria and Acute Renal Failure 397

b. If postrenal obstruction is a possibility, u ltrasou nd im-


ages of the kid neys can p rovid e valuable information.
Signs of obstruction includ e an increase in the size of
the kid neys and enlargement of the renal calyces.

II. IMMEDIATE CONCERNS


The m ost im m ed iate concerns in the oligu ric p atient are to
id entify and correct volum e d eficits and d iscontinu e nephro-
toxic d ru gs (if p ossible).

A. Correct Volume Deficits


1. Prom p t correction of volu m e d eficits is im p ortant be-
cau se severe and prolonged hypovolem ia can p rom ote
renal inju ry.

2. As m entioned in Chap ter 10 (see Section I-B), oligu ria


d u e to hypovolem ia u su ally involves a volum e d eficit of
2030 m L/ kg (id eal bod y w eight).

3. Either colloid or crystalloid flu id s can be u sed for volu m e


replacem ent, bu t the volu m e of crystalloid flu id s shou ld
be three to fou r tim es the estim ated volu m e d eficit (see
Chap ter 10, Section IV-B).

4. If the volu m e statu s of the p atient is not clear, a fluid


challenge is a reasonable m easu re (the risks of p rolonged
oligu ria ou tw eigh the risks of any retained volu m e). Flu -
id challenges shou ld em p loy 500 m l to 1,000 m L for crys-
talloid flu id s, or 300 mL to 500 m L for colloid flu id s, in-
fu sed over 30 m inu tes (6).

B. Dopamine & Furosemide


1. Low -d ose d opam ine (2 g/ kg/ m in), can p rom ote renal
vasod ilation, bu t there is no associated im p rovement in
398 Renal and Electrolyte Disorders

GFR in the setting of acu te renal failu re (7,8). As a resu lt,


low -d ose d opam ine is N OT recom m end ed for the m an-
agem ent of acu te oligu ric renal failure (8).

2. Furosem id e has been u sed in oliguric renal failu re in an


attem p t to p rom ote u rine ou tpu t and lim it volu m e reten-
tion. H ow ever, this effect is u nlikely becau se less than
10% of the fu rosem id e d ose reaches the site of action in
the renal tu bu les in p atients w ith renal failu re (9).

III. SPECIFIC RENAL DISORDERS

A. Inflammatory Renal Injury


1. Acute, oligu ric renal failure occurs in 25% of patients w ith
severe sepsis and 50% of patients w ith septic shock (10).
The renal impairment in these d isord ers is just one part of
a more w id espread cond ition of mu ltiorgan failu re (11).

2. The cu lp rit in this typ e of renal failu re is the inflam m ato-


ry response. The term malignant intravascular inflamma-
tion has been u sed to d escribe inflam m ation that resu lts
in m u ltiorgan d am age (12).

3. The m anagem ent of inflam m atory organ inju ry is su p -


p ortive, and is d escribed in Chapter 33.

B. Contrast-Induced Renal Failure


1. General Features
a. Injection of iod inated rad iocontrast d yes is the third
lead ing cau se of acu te renal failu re in hospitalized
p atients (13). The m echanism of inju ry is believed to
involve hyperosm olar d am age in the end otheliu m of
sm all blood vessels and oxid ative inju ry in renal tu bu -
lar epithelial cells.
Oliguria and Acute Renal Failure 399

b. Predisposing cond itions includ e diabetes, hyperten-


sion, pre-existing renal d isease, congestive heart failure,
and the osmolality and volume of the contrast agent.
c. The renal inju ry is u su ally ap p arent w ithin 72 hou rs
after d ye ad ministration. Oligu ria is u ncom m on, but
can occur in patients w ith pre-existing renal d isease.
Most cases resolve w ithin 2 w eeks, and few requ ire
hem od ialysis (13).

2. Preventive Measures
The follow ing regim en of intravenou s hyd ration and N -
acetylcysteine (an antioxid ant) has p roven su ccessfu l in
lim iting the incid ence and severity of contrast-ind uced
nep hrop athy in high-risk p atients (13,14):

Volume infusion:Isotonic saline at 100 to 150 m L/ hr start-


ed at 3 to 12 hou rs before the p roced u re. For emer-
gent p roced u res, at least 300 to 500 m L isotonic
saline should be infu sed ju st p rior to the p rocedure.
Urine output should be maintained at 150 mL/ hr
for at least 6 hou rs after the p roced u re (13).

N -acetylcysteine:600 m g by m ou th tw ice d aily from 24


hou rs before to 24 hou rs after the proced u re (13).
For em ergent proced u res (su ch as coronary angio-
p lasty), give 600 m g IV ju st before the p roced ure,
and follow w ith an oral d ose of 600 m g tw ice d aily
for 48 hours after the p roced u re (15).

C. Acute Interstitial Nephritis (AIN)


1. AIN is an inflam m atory cond ition that involves the renal
interstitiu m and can progress to acu te renal failu re, u su-
ally w ithou t oliguria (16). Most cases are the resu lt of a
hypersensitivity d ru g reaction, bu t infections (u su ally
viral or atypical p athogens) can also be involved .

2. The d ru gs m ost often im p licated in AIN are listed in Ta-


400 Renal and Electrolyte Disorders

ble 25.4. Antibiotics are the m ost frequent offend ers (par-
ticu larly the p enicillins).

TABLE 25.4 Drugs That Can Cause Interstitial Nephritis


Antibiotics CNS Drugs Diuretics
Aminoglycosides Carbamazepine Acetazolamide
Amphotericin Phenobarbital Furosemide
Cephalosporins Phenytoin Thiazides
Fluoroquinolones NSAIDs Others
Penicillins Aspirin Acetaminophen
Sulfonamides Ibuprofen ACE Inhibitors
Vancomycin Ketorolac Iodinated dyes
Naproxen Ranitidine
NSAIDs = non-s teroidal antiiinflammatory drugs ; ACE = angiotens in-con-
verting enzyme. From Reference 16.

3. The d iagnosis of AIN can be d ifficu lt. In cases of d ru g-


ind uced AIN , the characteristic signs of a hyp ersensitivi-
ty reaction (e.g., fever, rash, eosinop hilia) can be absent,
and the onset of renal failu re can be d elayed for m onths
after treatm ent w ith the offend ing d ru g is started (17).
The p resence of eosinop hils and leu kocyte casts on u rine
microscopy are the m ost characteristic find ings. A renal
biopsy can secu re the d iagnosis.

4. In cases of d rug-ind u ced AIN , im m ed iate d iscontinu a-


tion of all p ossible offend ing d rugs is m and atory. Oral
p red nisone at a d ose of 0.5 to 1 m g/ kg d aily for one to
four w eeks m ay help to sp eed recovery (16,17). Com plete
resolu tion can take m onths.

D. Myoglobinuric Renal Failure


1. General Features
Acute renal failure develops in about one-third of patients
Oliguria and Acute Renal Failure 401

with diffuse muscle injury (rhabdomyolysis) (18,19). The


culprit is myoglobin released by injured muscle cells, which
is capable of damaging the renal tubular epithethial cells
after it is filtered through the glomerulus. Predisposing fac-
tors for myoglobinuric renal failure include the extent of
skeletal muscle injury and the added presence of hypov-
olemia, acidosis, or hypophosphatemia.
2. Diagnosis
Myoglobin can be d etected in u rine u sing the orthotolu i-
d ine d ipstick reaction (H em astix) that is u sed to d etect
blood in u rine. If the test is p ositive, the u rine shou ld be
centrifu ged (to separate erythrocytes) and the superna-
tant shou ld be p assed throu gh a m icrop ore filter (to re-
move hem oglobin). A p ersistently p ositive test after these
measures is evid ence of m yoglobin in urine.
3. Management
a. Avoid ing and correcting hyp ovolem ia is the m ost ef-
fective m ethod for lim iting the incid ence and severity
of m yoglobinu ric renal failu re.
b. Alkalinizing the urine (with sodium bicarbonate infu-
sions) has been effective in limiting the renal injury from
myoglobin in animal studies, but this is difficult to ac-
complish and usually not necessary.
c. Abou t 30% of patients w ho d evelop myoglobinuric re-
nal failu re w ill requ ire d ialysis (19), but the renal fail-
ure is rarely permanent.

IV. RENAL REPLACEMENTTHERAPY

A. General Considerations
1. Renal replacement therapy (RRT) involves the u se of sem i-
p erm eable m em branes to rem ove flu id and toxic su b-
stances from the blood stream . The basic m ethod s of RRT
are hemodialysis and hemofiltration.
402 Renal and Electrolyte Disorders

2. Abou t 70% of p atients w ith acu te renal failu re w ill re-


qu ire RRT. The ind ications for RRT in acu te renal failu re
are u rem ic encep halop athy, volu m e overload , and life-
threatening hyperkalem ia or m etabolic acid osis.

B. Hemodialysis

1. Method
The basis of flu id and solu te rem oval by hem od ialysis is
illustrated in Figure 25.1.
a. H emodialysis removes solutes by diffusion across a semi-
permeable d ialysis membrane. Water (fluid) removal is
passive, and follows solute removal.
b. The removal of solutes by d iffusion is d riven by the con-
centration grad ient of solutes across a semipermeable
membrane. N ormally, as solutes move from one com-
partment to another, the concentration gradient for the
solute d ecreases, and this slow s the rate of solute clear-
ance. In hemodialysis, the concentration gradient for
solute clearance is maintained by m oving the blood and
d ialysis fluid in opposite d irections (a technique known
as countercurrent exchange) (20). The blood is moved (by
a pump) at a rate of 200 to 300 mL/ min (roughly 23
times faster than the normal GFR), and the d ialysate
moves even faster, at 500 to 800 mL/ m in (20).

2. Vascular Access
a. Short-term hem od ialysis is performed through special-
ized large-bore, d ou ble-lum en catheters like the one
show n in Figure 4.2 (Chapter 4).
b. These catheters are placed in the internal ju gular or
fem oral veins. The su bclavian vein cannulation is not
ad vised becau se of a high incid ence of vascu lar steno-
sis, w hich m akes the ip silateral arm veins u nsu itable
for chronic d ialysis access (21).
Oliguria and Acute Renal Failure 403

c. During d ialysis, blood is w ithd raw n from one lu m en


of the catheter, p um p ed throu gh the d ialysis cham ber,
and then retu rned to the p atient throu gh the other lu -
men. The large d iam eter of each lu m en allow s the rap-
id flow rates (200 300 m l/ m in) need ed for effective
d ialysis.

He mo dialys is

Blood Dia lys a te

S olute cle a ra nce drive n by a conce ntra tion gra die nt

He mo filtratio n

Hydros ta tic
pre s s ure

Blood Ultra filtra te

S olute cle a ra nce drive n by a pre s s ure gra die nt

FIGURE 25.1. Schematic representation of solute and fluid removal by


hemodialysis and hemofiltration. The smaller circles represent small
solutes (e.g., urea) that are readily cleared from the bloodstream, and the
larger circles represent larger molecules such as inflammatory cytokines
that are partly cleared by hemofiltration but not by dialysis.
404 Renal and Electrolyte Disorders

3. Advantages & Disadvantages


The rap id flow rates u sed d u ring d ialysis can be an ad -
vantage or a d isad vantage.
a. The ad vantage is the ability to achieve a d ays w orth of
solu te clearance in ju st a few hou rs.
b. The d isad vantage is the p otential for hem od ynam ic
com prom ise. H yp otension d evelop s d u ring or shortly
after one-third of hem od ialysis treatm ents (20), and d i-
alysis is often not p ossible (or not effective) in p atients
w ith circulatory shock.

B. Hemofiltration

1. Method
The m echanism of solu te and flu id rem oval by hem ofil-
tration is illu strated in Figu re 25.1.
a. H em ofiltration u ses a hyd rostatic p ressure grad ient to
d rive flu id through a sem iperm eable m em brane. Sm all
solutes pass through the m em brane by m oving along
w ith the bu lk flow of flu id . This method of solu te clear-
ance is know n as solvent drag (20).
b. H emofiltration can remove large volumes of fluid (up
to 3 liters per hour), bu t the rate of solute clearance is
m uch slow er than d uring hemod ialysis. As a resu lt, he-
m ofiltration mu st be performed continuously to p ro-
vid e effective solu te clearance.
c. Becau se sm all solu tes are cleared w ith w ater, the con-
centration of sm all solu tes (e.g., u rea) in blood d oes
not d ecrease d u ring hem ofiltration u nless a solu te-free
flu id is infu sed to rep lace som e of the u ltrafiltrate that
is lost (this is often necessary becau se of the large vol-
u m es lost d uring hem ofiltration).

2. Vascular Access
a. H em ofiltration w as originally p erform ed by cannu lat-
Oliguria and Acute Renal Failure 405

ing an artery (rad ial, brachial, or fem oral) and a large


vein (internal ju gu lar or femoral). This m ethod of arte-
riovenous hemofiltration u ses the m ean arterial pressure
as the filtration p ressu re (i.e., the p ressu re d riving flu-
id across the hem ofiltration m em brane).
b. The more popular method at present is venovenous he-
mofiltration, where venous blood is withdrawn and re-
placed through a double-lumen catheter similar to the
one used for hemodialysis. This method requires a pump
to create an effective filtration pressure.

3. Advantages & Disadvantages


There are 2 m ajor ad vantages w ith hem ofiltration:
a. H emofiltration allow s more grad ual fluid removal than
hemod ialysis, and thus is less likely to prod uce hemo-
d ynamic compromise.
b. H em ofiltration rem oves larger m olecu les than hem o-
d ialysis d ialysis, and clinical trials have show n that he-
m ofiltration can rem ove harm fu l cytokines from the
blood stream in patients w ith severe sepsis and m u lti-
organ failu re (22).
The major d isad vantages of hemofiltration are as follow s:
c. H em ofiltration m ust be used continuou sly to p rovid e
effective d ialysis, and this is tim e-consu ming and of-
ten not possible (becau se of m echanical p roblem s). A
m ethod know n as hemodiafiltration (w hich com bines
the featu res of d ialysis and hem ofiltration) is m ore
suitable for patients w ith renal failure.
d . H em ofiltration requ ires anticoagu lation to m aintain
p atency in the circu it. Despite attem pts to restrict anti-
coagu lation to the hem ofiltration circu it, system ic anti-
coagu lation can occu r, w hich increases the risk of hem -
orrhage.
e. Becau se hem ofiltration requ ires a hyd rostatic pressu re
grad ient for solu te clearance, it is not w ell-su ited for
hyp otensive p atients.
406 Renal and Electrolyte Disorders

REFERENCES
1. Klahr S, Miller SB. Acute oliguria. N Engl J Med 1998; 338:671675.
2. Bellom o R. Defining, qu antifying, and classifying acu te renal
failure. Crit Care Clin 2005; 21:223237.
3. Abernathy VE, Lieberthal W. Acu te renal failu re in the critically
ill patient. Crit Care Clin 2002; 18:203222.
4. Steiner RW. Interpreting the fractional excretion of sod iu m . Am J
Med 1984; 77:699702.
5. Rose BD, Post TW. Clinical p hysiology of acid -base and elec-
trolyte d isord ers. 5th ed . N ew York: McGraw -H ill, 2001:426-428.
6. Vincent J-L, Gerlach H . Fluid resu scitation in severe sepsis and
sep tic shock: an evid ence-based review. Crit Care Med 2004;
32(Sup pl):S451S454.
7. Kellu m JA, Decker JM. Use of d op am ine in acu te renal failu re: a
m eta-analysis. Crit Care Med 2001; 29:15261531.
8. H olm es CL, Walley KR. Bad m ed icine: Low -d ose d opam ine in
the ICU. Chest 2003; 123:12661275.
9. Brater DC, And erson SA, Brow n-Cartw right D. Resp onse to
fu rosem id e in chronic renal insu fficiency: rationale for lim ited
d oses. Clin Pharm acol Ther 1986; 40:134139.
10. Schrier RW, Wang W. Acu te renal failure and sepsis. N Engl J
Med 2004; 351:159169.
11. Balk RA. Pathogenesis and m anagem ent of m u ltip le organ d ys-
fu nction or failure in severe sep sis and septic shock. Crit Care
Clin 2000; 16:337352, 2000.
12. Pinsky MR, Vincent J-L, Deviere J, et al. Seru m cytokine levels in
hu m an sep tic shock: Relation to m u ltip le-system organ failu re
and m ortality. Chest 1993; 103:565575.
13. McCu llou gh PA, Som an S. Contrast-ind u ced nep hropathy. Crit
Care Clin 2005; 21:261280.
14. Liu R, N air D, Ix J, et al. N -acetylcysteine for the p revention of
contrast-ind u ced nephrop athy. A system atic review and m eta-
analysis. J Gen Intern Med 2005; 20:193200.
15. Marenzi G, Assanelli E, Marana I, et al. N -acetylcysteine and con-
trast-ind u ced nep hrop athy in p rim ary angiop lasty. N Engl J Med
2006; 354:27722782.
16. Taber SS, Mueller BA. Dru g-associated renal d ysfu nction. Crit
Care Clin 2006; 22:357374.
Oliguria and Acute Renal Failure 407

17. Ten RM, Torres VE, Millner DS, et al. Acute interstitial nep hritis.
Mayo Clin Proc 1988; 3:921930.
18. Beetham R. Biochem ical investigation of su sp ected rhabd om yol-
ysis. Ann Clin Biochem 2000; 37:581587.
19. Sharp LS, Rozycki GS, Feliciano DV. Rhabd om yolysis and sec-
ond ary renal failure in critically ill su rgical p atients. Am J Su rg
2004; 188:801806.
20. OReilly P, Tolw ani A. Renal replacem ent therap y III. IH D, CRRT,
SLED. Crit Care Clin 2005; 21:367-378.
21. H ernand ez D, Diaz F, Ru fino M, et al. Su bclavian vascu lar access
stenosis in d ialysis patients: natu ral history and risk factors. J
Am Soc N ephrol 1998; 9:15071511.
22. Morgera S, Haase M, Kuss T, et al. Pilot stud y on the effects of high
cutoff hemofiltration on the need for norepinephrine in septic
patients with acute renal failure. Crit Care Med 2006; 34:20992104.
Chapter 26
HYPERTONIC
AND HYPOTONIC
CONDITIONS
This chap ter d escribes cond itions that alter the osm otic
p rop erties of extracellu lar flu id . In most of these cond itions,
the p rim ary p roblem is an im balance betw een sod iu m and
w ater in the extracellu lar flu id , and the p resenting feature is
an abnorm al sod iu m concentration in p lasm a (i.e., hyp erna-
trem ia or hyp onatrem ia). The chap ter begins w ith a qu ick
review of the factors that d eterm ine the osm otic activity of
extracellular fluid .

I. OSMOTIC ACTIVITY
The d istribu tion of w ater in the intracellu lar and extracellu -
lar flu id s is governed by the osm otic activity of the extracel-
lu lar flu id , w hich is d eterm ined p rim arily by the sod iu m
concentration in extracellu lar fluid (plasm a).

A. Definitions
1. The concentration of solutes in a solution can be expressed
in terms of osmotic activity, which is a reflection of the
number of solute particles in a solution. The unit of meas-
urement is the osmole (osm), which is 6 x 1023 particles
(Avogadros number) for a nondissociable substance (1).

2. Osmotic activity can be expressed in relation to the volume


of water in a solution, or the total volume of the solution.

409
410 Renal and Electrolyte Disorders

a. Osmotic activity per volume of solution is called osmolar-


ity, and is expressed as milliosmoles per liter (mosm/ L).
b. Osm otic activity per volu me of w ater is called osmolal-
ity, and is exp ressed as m illiosm oles p er kilogram of
H 2O (m osm/ kg H 2O).

3. The im p ortance of osm otic activity in biological system s


is the ability to influence w ater m ovem ent betw een fluid
com partm ents. Therefore, osm olality (i.e., osm otic activi-
ty p er volu m e of w ater) is the ap p rop riate m easu re of os-
motic activity in the biological w orld .

4. Extracellular flu id is mostly w ater (e.g., p lasm a is 93%


w ater), so there is little d ifference betw een osm olality
and osm olarity in extracellu lar flu id (plasma) ,and the
tw o term s are often u sed interchangeably (2).

B. Osmotic Activity of Plasma


1. The osm otic activity of p lasm a is d eterm ined by the fac-
tors in the equ ation show n below
[Gluc o s e ] [BUN]
Po s m = 2 x Plas ma [Na +] + +
18 2.8
(26.1)

w here Posm is the osm olarity of p lasm a in m osm / L, [N a +]


is the p lasm a sod iu m concentration in m Eq/ L, [glucose]
and [BUN ] are the p lasm a concentrations of glu cose and
u rea in mg/ d L, and the factors 18 and 2.8 are conversion
factors that exp ress glu cose and u rea concentrations in
m illiosm oles p er liter (mosm / L). N ote the follow ing:
a. The plasma sod ium concentration is d oubled to includ e
the osmotic activity of chloride.
b. The plasm a concentrations in this equ ation are m eas-
u red in relation to the total p lasm a volum e, so the cal-
cu lated Posm is expressed as osm olarity instead of os-
m olality. (The osm otic activity measu red in the clinical
laboratory is the osm olality.)
Hypertonic and Hypotonic Conditions 411

2. If the norm al p lasm a concentrations of sod iu m (140


m Eq/ L), glu cose (90 m g/ d L), and BUN (14 m g/ d L) are
u sed in Equ ation 26.1, the p lasm a osm olarity is (2 x 140)
+90/ 18 + 14/ 2.8 = 290 m osm / L.

C. Effective Osmotic Activity


1. The d riving force for w ater m ovem ent betw een tw o flu id
com partments is the difference in osm otic activity in the
tw o com p artm ents. This d ifference is called effective os-
motic activity.

2. The osm otic relationship betw een tw o flu id s is d escribed


by the term tonicity the flu id w ith the higher osm otic
activity is d escribed as hypertonic, the flu id w ith the
low er osm otic activity is d escribed as hypotonic, and flu -
id s w ith the sam e osm otic activity are d escribed as isoton-
ic.

3. The effective osm otic activity of p lasm a d oes not inclu d e


the osm otic activity of urea becau se urea passes read ily
across cell m em branes. This is reflected in Equ ation 26.2.
[Gluc o s e ]
Effe c tive P o s m = 2 x Plas ma [Na +] +
18
(26.2)

The osm olar concentration of urea is only 14/ 1.8 = 7.7


mosm / L, w hich is less than 3% of the total p lasm a osm o-
larity (290 m osm / L), so there is little d ifference betw een
total and effective p lasm a osm olarity.

4. Equ ation 26.2 d em onstrates that sod iu m is the p rincip al


factor that d eterm ines the effective osmolarity of plasm a
(extracellu lar flu id ). The effective osm olality of extracel-
lular fluid governs the m ovem ent of w ater betw een in-
tracellu lar and extracellu lar flu id s, w hich m eans that the
sodium concentration in plasma is the principal factor that
governs the distribution of water in the intracellular and extra-
cellular fluids.
412 Renal and Electrolyte Disorders

II. HYPERNATREMIA
Hypernatremia (i.e., plasma sodium concentration > 145 mEq/ L)
is a condition of sodium excess relative to water in the extracellu-
lar fluid (3).

TABLE 26.1 Changes in Total Body Sodium and Water


in Hypernatremia and Hyponatremia
Total Body
Extracellular
Condition Volume Sodium Free Water
Hypernatremia Decreased
Normal
Increased
Hyponatremia Decreased
Normal
Increased

A. Causes of Hypernatremia
H ypernatrem ia can be the resu lt of any of the follow ing con-
d itions:

1. Loss of hyp otonic flu id s; i.e., flu id s that have a low er so-
d ium concentration than extracellu lar flu id .

2. N et loss of free w ater; i.e., w hen sod iu m lost in hyp oton-


ic flu id s is rep laced , leaving a free w ater d eficit.

3. Gain of hyp ertonic flu id s; i.e., flu id s w ith a higher sod i-


u m concentration than extracellu lar flu id .
Each of these cond itions is associated w ith a specific extra-
cellu lar volu m e (i.e., low, norm al, or high), as show n in Table
26.1. Therefore, evalu ating the extracellular volu m e can be
Hypertonic and Hypotonic Conditions 413

u sed to id entify the sou rce of hyp ernatrem ia in ind ivid u al


p atients.

HYPERNATREMIA

AS S ES S
EXTRACELLULAR VOLUME

S o dium De ple te d S o dium Ove rlo ade d

(Low) (Norma l) (High)

Re s tore Va s cula r Diure s e a nd Re pla ce


Volume Quickly with Hypotonic Fluid

Re pla ce
Wa te r De ficit
ove r 48 Hours

FIGURE 26.1 Management of hypernatremia based on the extracellular


volume.

B. Extracellular Volume
The cond ition of the extracellu lar volu m e (ECV) p rovid es
the follow ing d iagnostic and therapeu tic inform ation. (see
Figu re 26.1).

1. Low ECV indicates loss of hypotonic fluids. Common caus-


es are excessive diuresis, vomiting, and diarrhea. The man-
agement strategy is to replace the sodium deficit quickly (to
maintain plasma volume) and to replace the free water
deficit slowly (to prevent intracellular overhydration).
414 Renal and Electrolyte Disorders

2. N ormal ECV ind icates a net loss of free w ater. This can
be seen in d iabetes insip id u s, or w hen loss of hyp otonic
flu id s (e.g., d iu resis) is treated by rep lacem ent w ith iso-
tonic saline in a 1:1 volu m e-to-volu m e ratio. The m an-
agem ent strategy is to rep lace the free w ater d eficit slow -
ly (to prevent intracellu lar overhyd ration).

3. High ECV ind icates a gain of hyp ertonic flu id s. This is


seen w ith aggressive u se of hyp ertonic saline or sod iu m
bicarbonate solu tions. The m anagem ent strategy is to in-
d u ce sod ium loss in the urine w ith d iuresis and to re-
p lace the u rine volu m e loss w ith flu id s that are hypoton-
ic to the urine.

TABLE 26.2 Sodium Concentration in Lost Body Fluids


Sodium Concentration
Body Fluid (mEq/L)
Sweat (normal) 20 80
Urine (normal) < 10
Urine (furosemide diuresis) 70 80
Gastrointestinal Fluids:
Gastric secretions 70 80
Pancreatic secretions 140 145
Small bowel secretions 60 70
Stool (diarrhea) 30 40
Urinary s odium s ecretion varies with s odium intake.

III. HYPOVOLEMIC HYPERNATREMIA


The m ost com m on cau se of hyp ernatrem ia is exaggerated
loss of one or m ore of the flu id s listed in Table 26.2.
Hypertonic and Hypotonic Conditions 415

A. Consequences of Hypotonic Fluid Loss


1. Hypovolemia
All bod y fluid s that are lost contain sod iu m , as show n in
Table 26.1, so hypotonic flu id loss w ill eventu ally lead to
sod iu m d epletion if the lost sod iu m is not rep laced . The
major consequ ence of sod ium d epletion is hypovolemia.

2. Hypertonicity
Hypernatremia from hypotonic fluid loss increases the ef-
fective osmolality of the extracellular fluid, and this draws
water out of cells and promotes cellular dehydration.
a. The principal manifestation of cellular d ehyd ration is
hypernatremic encephalopathy, w hich can be accompanied
by coma, seizures, and focal neurologic d eficits (4).
b. Dehydrated cells regain volume after several hours by
somehow generating an ad ditional osmotic force, and
this osmotic adaptation can create problems d uring free
w ater replacement (see later).

B.Volume Replacement
1. Volume (sodium) replacement is an immediate priority be-
cause hypovolemia can impair organ perfusion.

2. Crystalloid flu id s are p referred for sod iu m rep lacement


in hem od ynam ically stable patients becau se these fluid s
w ill rep lenish sod iu m u niform ly throu ghou t the extra-
cellu lar fluid . Isotonic saline is preferred because m ore
d ilu te solu tions can p rom ote cell sw elling and cerebral
ed em a (see later).

C. Free Water Replacement


When p lasm a volu me is restored , the next step is to d eter-
mine the free w ater d eficit and correct the d eficit over a peri-
od of 3 to 4 d ays.
416 Renal and Electrolyte Disorders

1. The Free Water Deficit


The calculation of free w ater d eficit is based on the recip-
rocal relationship betw een the total body w ater (TBW) and
the plasma sod ium concentration (P[Na +]); i.e., w hen one
parameter changes, the other changes in the opposite di-
rection. The product of these tw o variables (TBW x P[N a +])
remains constant, regard less of cond itions in the extracel-
lular fluid . This allow s the follow ing relationships.

Curre nt (TBW x P [Na+]) = No rmal (TBW x P [Na+])


(26.3)

Using 140 m Eq/ L for a norm al P[N a +] and rearranging


term s yield s the follow ing relationship:

Curre nt TBW = No rmal TBW x (140 /Curre nt P [Na+])


(26.4)

The norm al TBW (in liters) is 60% of lean bod y w eight (in
kg) in m en and 50% of lean bod y w eight in w om en. Once
the cu rrent TBW is d eterm ined , the free w ater d eficit is
sim p ly the d ifference betw een the norm al and cu rrent
TBW .

Wate r de fic it (L) = No rmal TBW Curre nt TBW (26.5)

EXAMPLE. For an ad ult m ale w ith a lean bod y w eight of


70 kg and a plasm a [N a +] of 160 m Eq/ L, the norm al TBW
is 0.6 x 70 = 42 liters, the cu rrent TBW is 42 x 140/ 160 =
36.8 liters, and the free w ater d eficit is 42 36.8 = 5.2
liters.

2. Replacing the Free Water Deficit


H ypotonic saline solu tions (u sually half-norm al saline)
are u sed to rep lace w ater d eficits, and the volu m e need -
ed to accom plish this is id entified using the equation
show n below. (5).

Re plac e me nt vo lume (L) = Wate r de fic it x (1/1 X) (26.6)


Hypertonic and Hypotonic Conditions 417

w here X is the ratio of the sod iu m concentration in the


resu scitation flu id to the sod iu m concentration in isoton-
ic saline (154 m Eq/ L).
EXAMPLE. If the replacem ent flu id is half-norm al saline
(N a = 75 m Eq/ L), and the w ater d eficit is 5.2 liters, as cal-
cu lated p reviou sly, the rep lacem ent volu m e w ill be
5.2 x (1/ 0.5) = 10.4 liters.

3. Risk of Cerebral Edema


a. Acu te hyp ernatrem ia d raw s flu id ou t of brain cells
and p rom otes cellu lar d ehyd ration. This effect is only
transient, and after several hou rs, there is an increase
in brain cell osm olality that d raw s flu id back into the
cells (3).
b. The osm otic ad aptation in brain cells can be p roblem -
atic d u ring free w ater rep lacem ent becau se hyp otonic
fluid s can accum ulate in brain cells and prod u ce cellu -
lar overhyd ration and cerebral ed em a. To lim it this
risk, free w ater d eficits shou ld be replaced slow ly; i.e.,
the decrease in plasma sodium should not exceed 0.5 mEq/L
per hour (3,4).

IV. OTHER HYPERTONIC CONDITIONS

A. Diabetes Insipidus
1. General Features
Diabetes insip id u s (DI) is a cond ition of im p aired w ater
conservation that results in hyp ernatrem ia w ithou t ap-
p arent volum e d eficits. (6,7) The u nd erlying abnorm ali-
ty in DI is loss of the actions of antid iu retic horm one
(ADH ) in the kid neys, w hich resu lts in a marked increase
in free w ater excretion in the urine. There are tw o typ es
of DI based on the cau se of the lost ADH activity.
418 Renal and Electrolyte Disorders

a. CENTRAL DI is characterized by the absence of ADH re-


lease from the posterior p itu itary. This cond ition is
most often the resu lt of trau m atic brain inju ry, anoxic
encep halop athy, and brain d eath. The onset is herald -
ed by polyu ria that u su ally is evid ent w ithin 24 hours
of the inciting event.
b. NEPHROGENIC DI is characterized by d efective end -or-
gan resp onsiveness to ADH . This cond ition can be
cau sed by d ru gs (i.e., am p hotericin, am inoglycosid es,
d op am ine, and lithiu m ), rad iocontrast d yes, hyp okal-
em ia, and the polyuric p hase of ATN (7,8).

2. Diagnosis
The hallm ark of DI is a d ilu te u rine in the face of hyp er-
tonic p lasm a.
a. In central DI, the u rine osm olarity is often below 200
m osm / L, w hereas in nep hrogenic DI, the u rine osm o-
larity is u su ally betw een 200 and 500 m osm / L (9).
b. The d iagnosis of DI is confirm ed by noting the u rinary
resp onse to flu id restriction. Failu re of the urine osm o-
larity to increase m ore than 30 m osm / L in the first few
hou rs of com p lete flu id restriction is d iagnostic of DI.
c. Once the d iagnosis of DI is confirm ed , the resp onse to
vasop ressin (5 u nits intravenou sly) w ill d ifferentiate
central from nep hrogenic DI. In central DI, the u rine
osm olality prom p tly increases by at least 50% after
vasop ressin ad m inistration, w hereas in nep hrogenic
DI, the u rine osm olality rem ains u nchanged .

3. Management
a. The fluid loss in DI is almost pure w ater, so the the goal
of management is to replace free w ater d eficits only. The
free w ater d eficit is calculated as d escribed earlier.
b. In central DI, vasopressin ad m inistration is requ ired
to prevent ongoing free w ater losses. The u su al d ose is
2 to 5 u nits of aqu eou s vasopressin by subcu taneou s
injection every 4 to 6 hou rs (7).
Hypertonic and Hypotonic Conditions 419

B. Nonketotic Hyperglycemia
1. General Features
N onketotic hyperglycem ia (N KH ) is a cond ition of pro-
gressive hyp erglycem ia w ithou t ketoacid osis. Because
glucose contribu tes to the effective osm olality of extracel-
lu lar flu id (see Equ ation 26.2), the p rogressive hyp er-
glycem ia in N KH prom otes hypertonic cell d ehyd ration
in the brain and prod u ces a hypertonic encephalopathy
sim ilar to the one d escribed for hyp ernatrem ia (4). This
cond ition is usu ally seen in p atients w ho have enough
end ogenou s insu lin to p revent ketosis. There m ay be no
p rior history of d iabetes (10).

2. Clinical Presentation
a. Depressed consciousness is very common at presenta-
tion, and a rise in plasma osmolality above 330 mosm/ kg
H 2O can precipitate coma and generalized seizures (10).
b. Hypovolemia may be evident, and can be profound (from
the glycosuria-induced osmotic diuresis).
c. The hyp erglycem ia in N KH is typ ically very severe,
w ith p lasma glu cose levels of 1000 m g/ d L or higher.

3. Fluid Management
The flu id m anagem ent of N KH is sim ilar to that d e-
scribed for hypovolem ic hyp ernatrem ia. Volu m e d eficits
are m ore p rofou nd in N KH (becau se of the osmotic d i-
u resis).

4. The Free Water Deficit


The p lasm a sod iu m concentration is not an accu rate re-
flection of free w ater d eficits in N KH becau se the hyp er-
glycem ia d raw s w ater from the intracellu lar sp ace, and
this creates a d ilu tional effect on the p lasm a sod iu m con-
centration. The m agnitud e of this effect d ep end s on the
severity of the hyp erglycem ia.
a. For every 100 mg/dL increment in the plasma glucose, the
420 Renal and Electrolyte Disorders

plasma sodium will decrease 1.6 to 2.4 mEq/L (the lower


number is more accurate w hen the blood glucose is be-
low 400 mg/ d L, and the higher number is more accurate
when the blood glucose is above 400 mg/ dL) (10,11).
b. To calcu late the free w ater d eficit in N KH (or any pa-
tient w ith hyperglycem ia), the p lasm a sod ium concen-
tration m u st be ad ju sted u sing the d ilu tional factors
just m entioned . For exam p le, if the blood glu cose is
800 m g/ d L, the sod iu m concentration shou ld be ad -
justed up w ard by 7 x 2.4 = 16.8 mEq/ L.

5. Insulin Therapy
a. The insu lin requ irem ents in N KH and d iabetic keto-
acid osis (DKA) are rou ghly the sam e (10), so the insu -
lin regim en for DKA d escribed in Chapter 23 (see Sec-
tion II-D) is also ap p rop riate for N KH .
b. Insulin therapy drives w ater into cells along with glu-
cose, and this effect can aggravate hypovolemia. There-
fore in patients w ith severe volume deficits (w hich is
common in N KH ), volume replacement should be start-
ed before insulin is given.

V. HYPONATREMIA
H yponatrem ia (seru m sod iu m concentration < 135 mEq/ L)
is the resu lt of excess w ater relative to sod ium in the extra-
cellu lar fluid (12).

A. Pseudohyponatremia
1. Plasm a is 93% w ater, and the remaining 7% is m ad e u p
of circu lating lipid s and p roteins. Sod iu m is confined to
the aqu eou s portion of p lasm a, bu t the stand ard m ethod
of m easu ring sod iu m concentration u ses total p lasm a
volum e (aqu eou s and nonaqueou s p ortions). The m eas-
Hypertonic and Hypotonic Conditions 421

u red sod ium concentration w ill therefore u nd erestimate


the actu al (aqu eou s p hase) sod iu m concentration, bu t the
d ifference is norm ally sm all becau se w ater m akes u p
over 90% of plasm a..

2. In cond itions w here there is an abu nd ance of circu lating


lip id s and p lasm a p roteins (e.g., severe hyp erlip id em ias
or hyp erp roteinem ias), the nonaqu eous p ortion of p las-
ma w ill increase in volu m e, and can grow to 30% of the
p lasm a volu m e. In this situ ation, the m easu red p lasm a
sod iu m can be consid erably low er than the actu al sod i-
u m concentration. This cond ition is called pseudohypona-
tremia (13), bu t it is really a laboratory artifact.

3. The hallm ark of p seu d ohyp onatremia is the com bination


of hyp onatrem ia and a norm al plasm a osm olality. The
d iagnosis is confirm ed if the plasm a sod ium concentra-
tion is m easu red w ith an ion-sp ecific electrod e (w hich
measures the aqueous p hase sod iu m ), and the hypona-
trem ia d isap p ears.

B. Diagnostic Approach
As is the case w ith hyp ernatrem ia, the extracellu lar volu m e
(ECV) can be high, norm al, or low in hyponatrem ia (see
Table 26.1), and the statu s of the ECV can be u sed to organ-
ize the d iagnostic ap proach to hyp onatrem ia, as show n in
Figu re 26.2.

1. Hypovolemic Hyponatremia
Volume d epletion pred isposes to hyponatrem ia by stimu-
lating the release of antidiuretic hormone (ADH), w hich
promotes water retention. The conditions associated w ith
hypovolemic hyponatremia can be grouped accord ing to
the urinary sod ium concentration, as show n below (see al-
so Figure 26.2).
422 Renal and Electrolyte Disorders

Urine [Na +] Site of Na + Loss Conditions


> 20 mEq/L Renal Diuresis
Adrenal Insufficiency
Cerebral Salt Wasting
< 20 mEq/L Extrarenal Vomiting
Diarrhea

2. Isovolemic Hyponatremia
When hyp onatrem ia is associated w ith an ap p arently
normal ECV, the p rincipal d isord ers to consid er inclu d e
inappropriate secretion of antid iu retic hormone (ADH ),
w ater intoxication (also know n as p sychogenic p olyd ip -
sia), and hyp othyroid ism (rare). The urine sod iu m and
u rine osm olality can help to d istingu ish w ater intoxica-
tion from inap prop riate ADH release, as show n below.
Clinical Disorder Urine Sodium Urine Osmolality
Inappropriate ADH > 20 mEq/L > 100 mOsm/kg H2O
Water Intoxication < 10 mEq/L < 100 mOsm/kg H2O

INAPPROPRIATEADH RELEASE. The inappropriate (nonosmot-


ic) release of ADH is characterized by an inappropriately con-
centrated urine (urine osmolality above 100 mOsm/ kg H 2O)
in the face of a hypotonic plasma (< 290 mosm/ kg H 2O). This
condition is a common cause of hyponatremia in hospital-
ized patients, and is considered the result of stress-induced
release of ADH. This condition differs from the syndrome of
inappropriate ADH (SIADH), which is associated with a vari-
ety of neoplasms, infections, and drugs (see Reference 14 for
a recent review of SIADH).

3. Hypervolemic Hyponatremia
H ypervolem ic hyponatrem ia is usu ally the result of salt
and w ater retention in p atients w ith heart failu re, renal
failu re, or hep atic failu re.

C. Symptoms
1. H yp onatrem ia p rom otes cerebral ed em a, and the resu lt-
Hypertonic and Hypotonic Conditions 423

ing encep halopathy p rod uces the sym ptom s of hypona-


trem ia. Sym p tom s range from lethargy and somnolence
to seizu res, com a, and brain d eath.

2. Acu te hyp onatrem ia (< 48 hrs) is m ore likely to p rod u ce


sym ptom s, probably becau se the severity of the cerebral
ed em a and cell sw elling d im inish w ith tim e (osm otic ad -
ap tation).

3. H yponatrem ic encep halop athy carries a p oor prognosis,


p articularly for w om en. One-third of patients w ho d evel-
op hyp onatrem ic encep halop athy d o not su rvive, and
80% of d eaths involve w om en (15).

HYPONATREMIA

AS S ES S
EXTRACELLULAR VOLUME

(Low) (Norma l) (High)

URINE URINE URINE


S ODIUM OS MOLALITY S ODIUM

> 20 < 20 > 100 < 100 > 20 < 20


mEq /L mEq /L mOs m /L mOs m /L mEq /L mEq /L

Diure s is Dia rrhe a S IADH P s ychoge nic Re na l He a rt Fa ilure


Adre na l Polydips ia Fa ilure Cirrhos is
Ins uffice ncy

FIGURE 26.2 Diagnostic approach to hyponatremia. SIADH = syndrome


of inappropriate antidiuretic hormone.
424 Renal and Electrolyte Disorders

D. Management

1. Extracellular Volume
The m anagem ent of hyp onatrem ia is gu id ed by the sta-
tu s of the ECV (i.e., low, norm al, or high), and the p res-
ence or absence of sym ptom s related to hyp onatrem ia.

LOW ECV: Infu se hyp ertonic saline (3% N aCl) in sym p to-
matic p atients, and isotonic saline in asym p tom atic p a-
tients.
NORMAL ECV: Com bine fu rosem id e d iuresis w ith infu-
sion of hypertonic saline in sym p tom atic p atients, or iso-
tonic saline in asym p tom atic p atients.
HIGH ECV: Use furosem id e-ind u ced d iuresis in asym p to-
matic p atients. In sym p tom atic p atients, com bine fu ro-
sem id e d iu resis w ith ju d iciou s u se of hyp ertonic saline.

2. Rate of Correction
Rapid correction of hyponatrem ia has been reported to
cau se a d em yelinating d isord er know n as central pontine
myelinolysis (16). The follow ing recom m end ations are d e-
signed to p revent osm otic d em yelination by lim iting the
rate of rise of the p lasma
a. For asym p tom atic hyp onatrem ia, the increase in plas-
m a sod iu m shou ld not exceed 0.5 m Eq/ L p er hou r (12
m Eq/ L in 24 hou rs) (17).
b. For sym p tom atic hyp onatrem ia, p articu larly w hen the
sym p tom s su ggest severe cerebral im p airm ent (e.g.,
obtund ation, com a, seizu res), hyp ertonic saline shou ld
be u sed to raise the plasm a sod iu m concentration by
1.5 to 2 m Eq/ L per hou r for 3 to 4 hou rs (17). Su bse-
qu ent rep lacem ent shou ld be ad ju sted so that the total
rise in sod iu m d oes not exceed 12 mEq/ L in the first 24
hou rs. (Rap id correction of p lasm a sod iu m can be
guid ed by the calcu lated sod iu m d eficit, w hich is d e-
scribed next).
Hypertonic and Hypotonic Conditions 425

3. Sodium Deficit
When hyp ertonic saline is u sed for rap id correction of
sym ptom atic hyp onatrem ia, the volu m e of flu id that is
requ ired can be d eterm ined by estim ating the sod iu m
d eficit in m Eq (17).

Na + de fic it = No rmal TBW x (De s ire d P[Na+] Curre nt P[Na+])


(26.7)

The d esired P[N a +] is obtained by ad d ing the exp ected


increment in plasma sod iu m (e.g., 2 m Eq/ L p er hou r x 4
hou rs = 8 m Eq/ L) to the cu rrent P[N a +].
a. The sod iu m d eficit is d ivid ed by 513 (the concentra-
tion of sod iu m in 3% N aCl) to d eterm ine the volu m e
of hyp ertonic saline (in liters) need ed to p rod u ce the
d esired increm ent in p lasm a sod iu m.

REFERENCES
1. Rose BD, Post TW. The total bod y w ater and the plasma sod ium
concentration. In: Clinical physiology of acid -base and electrolyte
d isord ers. 5th ed . N ew York: McGraw -H ill, 2001:241257.
2. Erstad BL. Osm olality and osm olarity: narrow ing the term inolo-
gy gap. Pharm acotherapy 2003; 23:10851086.
3. Ad rogu e H J, Mad ias N E. H ypernatrem ia. N Engl J Med 2000;
342:14931499.
4. Arieff AI, Ayus JC. Strategies for d iagnosing and m anaging hy-
p ernatrem ic encephalopathy. J Crit Illness 1996; 11:720727.
5. Marino PL, Krasner J, OMoore P. Flu id and electrolyte exp ert,
Philad elphia: WB Saund ers, 1987.
6. Makaryus AN , McFarlane SI. Diabetes insip id u s: d iagnosis and
treatm ent of a com plex d isease. Cleve Clin J Med 2006; 73:6571.
7. Blevins LS Jr, Wand GS. Diabetes insip id us. Crit Care Med 1992;
20:6979.
8. Garofeanu CG, Weir M, Rosas-Arellano MP, et al. Cau ses of re-
versible nephrogenic d iabetes insipid u s: a system atic review. Am
J Kid ney Dis 2005; 45:626637.
426 Renal and Electrolyte Disorders

9. Geheb MA. Clinical app roach to the hyperosm olar p atient. Crit
Care Clin 1987; 3:797815.
10. Rose BD, Post TW. H yperosm olal states: hyperglycem ia. In:
Clinical physiology of acid -base and electrolyte d isord ers. 5th ed .
N ew York: McGraw -H ill, 2001:794821.
11. H illier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the
correction factor for hyperglycemia. Am J Med 1999; 106:399403.
12. Ad rogu e H J, Mad ias N E. H yp onatrem ia. N Engl J Med 2000;
342:15811589.
13. Weisberg LS. Pseud ohyponatremia: A reappraisal. Am J Med 1989;
86:315318.
14. Ellison DH , Berl T. The synd rom e of inap prop riate antid iu resis.
N Engl J Med 2007; 356:2064-2072.
15. Arieff A. Influ ence of hyp oxia and sex on hyp onatrem ic enceph-
alop athy. Am J Med 2006; 119:559564.
16. Bru nner JE, Red m ond JM, H aggar AM, et al. Central p ontine
m yelinolysis and p ontine lesions after rap id correction of hyp o-
natrem ia: a prospective m agnetic resonance im aging stu d y. Ann
N eu rol 1990; 27:6166.
17. Rose BD, Post TW. Hypoosmolal states hyponatremia. In: Clinical
physiology of acid-base and electrolyte disorders. 5th ed. New York:
McGraw-Hill, 2001:696745.
Chapter 27
POTASSIUM
Monitoring the p otassiu m (K+) level in p lasm a as an ind ex of
total bod y p otassiu m is sim ilar to evalu ating an iceberg by
its tip, becau se less than 1% of the total am ou nt of K+ in the
bod y is located in plasm a. With this shortcom ing in mind ,
this chap ter d escribes the cau ses and consequ ences of hyp o-
kalem ia and hyp erkalem ia.

I. POTASSIUM DISTRIBUTION

A.Total Body vs. Serum K +

1. The total bod y K+ in healthy ad u lts is abou t 50 m Eq/ kg


(1,2), so a 70 kg ad u lt w ill have 3,500 m Eq of total bod y
K+. H ow ever, only 70 m Eq (2% of the total am ou nt) is
located in extracellu lar flu id .

2. The p lasm a accounts for ap proxim ately 20% of the extra-


cellu lar flu id , so the K+ content of p lasm a (seru m ) w ill be
0.2 x 70 = 14 m Eq, w hich is abou t 0.4% of the total am ount
of K+ in the bod y.

B. Changes in Serum K +

1. The relationship betw een changes in total bod y and se-


ru m K+ is cu rvilinear, as show n in Figu re 27.1 (3,4). The
slop e of the curve d ecreases on the d eficit sid e of the
graph, ind icating that the change in serum K+ is m u ch
sm aller w hen K+ is d ep leted than w hen it accum u lates.

2. In an average-sized ad u lt w ith a norm al seru m K+ (i.e.,


427
428 Renal and Electrolyte Disorders

3.5 to 5.5 m Eq/ L), a total bod y K+ d eficit of 200 to 400


m Eq is requ ired to p rod u ce a 1 m Eq/ L d ecrease in seru m
K+, w hereas a total bod y excess of 100 to 200 m Eq is
requ ired to p rod u ce a 1 m Eq/ L rise in seru m K+ (4).

3. Thus, K+ d epletion must be tw ice as great as K+ accu mu -


lation to prod uce a significant (1 mEq/ L) change in se-
ru m K+. This d ifference is d ue to the large pool of intracel-
lular K+, w hich can replenish extracellu lar stores w hen K+
is lost.

(70 kg Adult)

S e rum K+ ACIDOS IS

ALKALOS IS

FIGURE 27.1 The relationship between changes in serum and total body
potassium. (Redrawn from Reference 3.)

II. HYPOKALEMIA
H ypokalem ia (d efined as a seru m K+ below 3.5 m Eq/ L) can
be the resu lt of an intracellu lar shift of K+ (transcellu lar shift)
or total bod y K+ d ep letion.

A.Transcellular Shift
The follow ing cond itions can resu lt in hyp okalem ia from K+
movem ent into cells:
Potassium 429

1. Inhaled -agonist bronchod ilators can cau se a m ild d e-


crease in seru m K+ (0.5 m Eq/ L or less) in the usu al ther-
ap eu tic d oses (5). The m echanism of action is stim u lation
of -recep tors on the cell m em branes of skeletal m u scle
cells. The hyp okalem ic effect of inhaled -agonists is
magnified w hen they are given w ith glu cose and insulin
(5) or d iuretics (6).

2. Alkalosis (respiratory or m etabolic) can p rom ote the ex-


change of K+ for intracellu lar H + via a m em brane H +K+
exchange p u m p. H ow ever, alkalosis has a variable and
u np red ictable effect on seru m K+ (7).

3. H ypotherm ia (accid ental or ind uced ) cau ses a transient


d rop in serum K+ that u su ally resolves d u ring rew arm ing
(8). Lethal cases of hyp othermia can be accom p anied by
hyperkalem ia becau se of w id esp read cell d eath (9).

4. Insulin d rives K+ into cells via the glucose transporter, and


the effect lasts 1 2 hours.

B. K Depletion
+

Potassiu m d epletion can be the resu lt of either renal or extra-


renal K+ losses. The site of K+ loss can often be id entified by
u sing a com bination of urinary K+ and chlorid e concentra-
tions, as show n in Figure 27.2.

1. Renal Loss
a. The lead ing cau se of renal K+ loss is d iu retic therapy.
Other cau ses inclu d e nasogastric d rainage, alkalosis,
and m agnesiu m d ep letion.
b. The u rinary chlorid e is low (less than 15 m Eq/ L) w hen
nasogastric d rainage or alkalosis is involved , and it is
high (greater than 25 m Eq/ L) w hen m agnesiu m d e-
pletion or d iu retics are resp onsible.
c. Magnesium d epletion impairs potassium reabsorption
across the renal tu bules and may play a very im portant
430 Renal and Electrolyte Disorders

role in promoting and sustaining potassium d epletion,


particu larly in patients receiving d iu retics (10).

2. Extrarenal Loss
The major cause of extrarenal K+ loss is diarrhea. The K+
concentration in stool is 75 m Eq/ L, and in d iarrheal states,
the d aily volume of stool can rise from < 200 mL/ d ay to
> 10 L/ d ay, so severe or prolonged diarrhea can result in
profound K+ losses.

HYPOKALEMIA

R /O Tra ns ce llula r S hift

URINE
POTAS S IUM

(< 30 mEq /L) (> 30 mEq /L)

Dia rrhe a
URINE
CHLORIDE

(< 15 mEq /L) (> 25 mEq /L)

NG Dra ina ge Diure tic


Alka los is Mg De ple tion

FIGURE 27.2 Diagnostic approach to hypokalemia.

C. Clinical Manifestations
Severe hypokalemia (serum K+ below 2.5 mEq/ L) can be ac-
companied by d iffuse muscle w eakness (2). Mild er d egrees of
hypokalemia (serum K+ 2.5 to 3.5 m Eq/ L) are often asympto-
matic.
Potassium 431

1. ECG Abnormalities
a. Abnormalities in the ECG, including prominent U waves
(more than 1 mm in height), flattening and inversion of
T waves, and prolongation of the QT interval, can be
present in more than 50% of cases of hypokalemia (11).
b. N one of the ECG changes is specific for hyp okalem ia.
The T w ave changes and U w aves can be seen w ith
d igitalis or left ventricu lar hyp ertrop hy, and QT pro-
longation can be seen w ith hypocalcem ia and hypo-
magnesem ia.

2. Arrhythmias
There is a m isconcep tion abou t the ability of hyp okal-
em ia to prom ote card iac arrhythm ias. Hypokalemia alone
does not produce serious ventricular arrhythmias (2,11). H y-
p okalem ia is often com bined w ith other cond itions that
can p rom ote arrhythm ias (e.g., m agnesium d ep letion, d i-
gitalis, m yocard ial ischem ia), and the hyp okalem ia m ay
enhance the proarrhythm ic effects of these other cond i-
tions; e.g., hyp okalem ia is w ell know n for the ability to
p rom ote d igitalis-ind u ced arrhythm ias.

D. Management
The first concern in hyp okalem ia is to elim inate or treat any
cond ition that prom otes transcellular shift of K+ (2). If the hy-
pokalem ia is d u e to K+ d epletion, p roceed as d escribed next.

1. Estimating Deficits
A d eficit of 10% of the total bod y K+ is exp ected for every
1 m Eq/ L d ecrease in the seru m K+ (12). The correlation
betw een K+ d eficits and the severity of hyp okalem ia is
show n in Table 27.1.

2. Replacement Fluids
a. The u su al rep lacem ent flu id is p otassiu m chlorid e
(KCL), w hich is available w ith K+ concentrations of
432 Renal and Electrolyte Disorders

1 and 2 m Eq/ m L, and com es in am p u les containing


10, 20, 30, and 40 m Eq of KCL. These solu tions are
extrem ely hyperosm otic (the 2 m Eq/ L solu tion has an
osm olality of 4000 m osm / L) and m u st be d ilu ted (13).
b. A p otassium p hosphate solu tion is also available (con-
tains 4.5 m Eq K+ and 3 m m ol p hosp hate p er m L) and
is p referred by some for K+ rep lacem ent in d iabetic
ketoacid osis (becau se of the phosp hate d ep letion that
accom p anies ketoacid osis).

TABLE 27.1 Potassium Deficits in Hypokalemia*


Potassium Deficit
Serum K+ (mEq/L) mEq % Total Body K+
3.0 175 5
2.5 350 10
2.0 470 15
1.5 700 20
1.0 875 25
*Estimated deficits for a 70 kg adult with a total body K+ of 50 mEq/kg.

3. Infusion Rate
a. The stand ard m ethod of intravenou s K+ rep lacem ent
is to ad d 20 m Eq of K+ to 100 m L of isotonic saline and
infu se this m ixtu re over 1 hou r (14).
b. The m axim u m rate of intravenou s K+ replacem ent is
u su ally set at 20 mEq/ hou r (14), bu t d ose rates u p to
40 m Eq/ hou r occasionally m ay be necessary (e.g.,
w ith seru m K+ below 1.5 m Eq/ L or seriou s arrhyth-
mias), and d ose rates as high as 100 m Eq/ hou r have
been u sed safely (15).
c. A large central vein should be u sed for infusion be-
cau se of the irritating prop erties of the hyp erosm otic
Potassium 433

K+ solu tions. H ow ever, if the d esired rep lacem ent rate


is greater than 20 m Eq/ hou r, the infu sion shou ld not
be given throu gh a central vein becau se of the risk of
local hyperkalem ia in the right heart cham bers, w hich
can p red isp ose to card iac stand still. In this situ ation,
the p otassiu m d ose can be sp lit and ad m inistered via
tw o p erip heral veins.

4. Response
a. The serum potassiu m m ay be slow to rise at first, be-
cau se of the position on the flat part of the cu rve in
Figu re 27.1. Fu ll rep lacem ent u su ally takes a few d ays,
p articu larly if p otassiu m losses are ongoing.
b. If the hypokalemia is refractory to K+ replacement, check
for magnesium depletion because magnesium depletion
promotes urinary K+ losses and can cause refractory hypo-
kalemia (16). The evaluation for magnesium depletion is
described in Chapter 28.

III. HYPERKALEMIA
While hypokalemia is often well tolerated, hyperkalemia (se-
rum K+ > 5.5 mEq/ L) can be a life-threatening condition (17).

A. Pseudohyperkalemia
Local release of K+ can lead to sp u riou s elevations of the se-
ru m K+ in the follow ing situations:

1. Traum atic hem olysis d u ring the venip u nctu re has been
rep orted as a cau se of the elevated seru m K+ in 20% of
blood sam p les show ing hyp erkalem ia (18).

2. In cases of severe leu kocytosis (> 50,000/ m m 3) or throm -


bocytosis (p latelet cou nt >106/ m m 3), K+ release from
cells d u ring clot form ation in the sp ecim en tu be can p ro-
434 Renal and Electrolyte Disorders

d u ce sp u rious hyp erkalem ia. When this cond ition is su s-


p ected , the serum K+ should be m easu red in an u nclotted
blood sam p le.

3. Muscle contraction distal to a tourniquet (during fist clench-


ing) can lead to K+ release from muscle cells (19).

TABLE 27.2 Drugs That Can Cause Hyperkalemia


ACE Inhibitors NSAIDs
Angiotensin Receptor Blockers Pentamidine
-Blockers Penicillin
Cyclosporine Tacrolimus
Digitalis TMPSMX
Diuretics (K+-sparing) Succinylcholine
Heparin
ACE = Angiotens in-converting enzyme; NSAIDs = nons teroidal anti-
inflammatory drugs ; TMPSMX= trimethoprims ulfamethoxazole.
Es pecially when combined with K+ -s paring diuretics .

B. Enhanced Cellular Release


The follow ing cond itions can resu lt in hyp erkalem ia from
enhanced K+ release from cells.

1. Acid osis is often listed as a cau se of hyp erkalemia be-


cau se of the tend ency for acid osis to enhance K+ release
from cells and red uce renal K+ excretion. H ow ever, hy-
p erkalemia d oes not alw ays accom pany respiratory aci-
d osis (7), and there is no clear evid ence that organic aci-
d oses (i.e., lactic acid osis and ketoacid osis) p rod u ce hy-
p erkalemia (7).

2. Rhabd om yolysis can release large am ou nts of K+ into the


extracellu lar flu id , bu t if renal fu nction is norm al, the ex-
tra K+ is prom ptly cleared by the kid neys.
Potassium 435

3. Certain d ru gs can p rom ote hyp erkalem ia via transcellu -


lar K+ shifts, su ch as -recep tor antagonists and d igitalis
(Table 27.2). Digitalis toxicity can cau se severe hyp erkal-
em ia (i.e., seru m K+ > 7 m Eq/ L).

4. Massive blood transfusions (i.e., when the transfusion vol-


ume exceeds the normal blood volume) can promote hyper-
kalemia, but only in patients with circulatory shock (20).
Potassium leaks from erythrocytes in stored blood, but the
amounts are small (see Table 30.2) (21).

C. Impaired Renal Excretion


Impaired renal excretion of K+ is the most common cause of hy-
perkalemia, and is characterized by a urinary K+ < 30 mEq/ L
in the face of hyperkalemia.

1. Renal insu fficiency can prod uce hyp erkalemia w hen the
glom erular filtration rate (GFR) falls below 10 mL/ min-
ute (22). H yp erkalemia is seen relatively early w hen renal
insu fficiency is d u e to interstitial nephritis, or is associat-
ed w ith hyporeninem ic hyp oald osteronism (22). The lat-
ter cond ition is seen in eld erly d iabetic patients w ho have
d efective renin release in resp onse to red uced renal blood
flow.

2. Ad renal insu fficiency is a w ell-know n cau se of hyp er-


kalem ia from im paired renal K+ excretion, bu t is not a
com mon cau se of hyp erkalem ia in the ICU.

3. Dru gs that imp air renal K+ excretion are am ong the lead -
ing cau ses of hyp erkalem ia (2,23). A list of p ossible of-
fend ers is show n in Table 27.2.
a. The d ru gs m ost often im plicated are angiotensin-con-
verting enzym e inhibitors, angiotensin recep tor block-
ers, K+-sp aring d iu retics, and nonsteroid al antiinflam -
m atory d ru gs (23,24). The p otential for hyp erkalem ia
436 Renal and Electrolyte Disorders

is m agnified w hen these d rugs are given along w ith


p otassiu m sup plem ents.

16

V-fib

12

Comple te He a rt Block

mEq L 8 Firs t-de gre e He a rt Block

Pe a ke d T Wave

4 Norma l

FIGURE 27.3 The ECG manifestations of progressive hyperkalemia.


(Adapted from Burch GE, Winsor T. A primer of electrocardiography.
Philadelphia: Lea & Febiger, 1966:143.)

D. ECG Abnormalities
1. The m ost seriou s consequ ence of hyp erkalemia is the
slow ing of electrical cond u ction in the heart.

2. The ECG can begin to change w hen the seru m K+ reach-


es 6.0 m Eq/ L, and it is alw ays abnormal w hen the seru m
Potassium 437

K+ reaches 8.0 m Eq/ L (22). Figu re 27.3 show s the ECG


changes associated w ith progressive hyperkalem ia.

3. The earliest change in the ECG is a tall, tap ering (tented )


T w ave that is m ost evid ent in p record ial lead s V2 and V3.
As the hyperkalem ia p rogresses, the P w ave am p litu d e
d ecreases and the PR interval lengthens. The P w aves
eventu ally d isappear and the QRS d u ration becom es
prolonged . The final event is ventricu lar asystole or ven-
tricu lar fibrillation.

E. Acute Management
The acu te m anagem ent of hyp erkalem ia is gu id ed by the
seru m K+ level and the ECG (2,17). The therapeu tic m aneu -
vers are outlined in Table 27.3.

1. Membrane Antagonism
Calcium d irectly antagonizes the m em brane actions of
p otassium .
a. When hyp erkalem ia is severe (i.e., above 7 m Eq/ L) or
accomp anied by ad vanced ECG changes (i.e., loss of P
w aves and p rolonged QRS d u ration), calciu m glu -
conate is given in the d ose show n in Table 27.3. A sec-
ond d ose can be given if there is no resp onse w ithin a
few m inu tes.
b. When hyperkalemia is accompanied by circulatory com-
promise, calcium chloride is preferred to calcium gluco-
nate because 10% calcium chloride contains three times
more elemental calcium (per mL) than 10% calcium glu-
conate, and the extra calcium could help to promote car-
d iac contraction and maintain peripheral vascular tone.
c. Calciu m m u st be given cau tiou sly to p atients on d igi-
talis becau se hypercalcem ia can potentiate d igitalis
card iotoxicity. For p atients receiving d igitalis, the cal-
ciu m glu conate shou ld be ad d ed to 100 m L of isotonic
438 Renal and Electrolyte Disorders

saline and infu sed over 20 to 30 m inu tes. If the hyp er-
kalem ia is a m anifestation of d igitalis toxicity, calciu m
is contraind icated .
d . The resp onse to calciu m lasts only 20 or 30 m inu tes, so
other therap ies shou ld be initiated to enhance p otassi-
u m clearance.

TABLE 27.3 Acute Management of Hyperkalemia


Condition Treatment Comments
ECG changes or Calcium gluconate Response lasts only
serum K+ >7 mEq/L (10%): 10 mL IV 2030 min.
over 3 min; can Do not give bicarbon-
repeat in 5 min. ate after calcium.
ECG changes Calcium chloride Calcium chloride
and circulatory (10%): 10 mL IV contains 3 times
compromise over 3 min. more calcium than
calcium gluconate.
AVblock refractory 1. 10 U regular Insulin-dextrose treat-
to calcium treatment insulin in 500 mL ment should drop the
of 20% dextrose: serum K by 1 mEq/L
infuse over 1 hr. for 1 2 hrs.
2. Transvenous
pacemaker
Digitalis cardiotoxicity 1. Magnesium Do not use calcium
sulfate: 2 g as for the hyperkalemia
IVbolus. of digitalis toxicity.
2. Digitalis-specific
antibodies if
necessary.
After acute phase Kayexalate: oral dose Oral dosing is
or when no ECG of 30 g in 50 mL of preferred.
changes 20% sorbitol, or Enemas poorly
50 g in 200 mL tolerated by patients
20% sorbitol as and nurses.
a retention enema.
Potassium 439

2. Transcellular Shift
Com bined therapy w ith insulin and d extrose w ill d rive
p otassiu m into m u scle cells and d ecrease the seru m po-
tassiu m by an average of 1 m Eq/ L, bu t this effect is tem -
p orary (lasts 1 2 hours), and shou ld be com bined w ith
measures d esigned to enhance p otassiu m excretion.

3. Enhanced Clearance
Measu res aim ed at enhancing the rem oval of K+ from the
bod y can be u sed alone (in m ild cases of hyp erkalemia
w ithou t ad vanced ECG changes) or as a follow -up to cal-
cium and insu lin-d extrose therapy.
a. Sod iu m p olystyrene su lfonate (Kayexalate) is a cation-
exchange resin that prom otes K+ clearance across the
gastrointestinal m u cosa. It can be given orally or by
retention enem a, and it is m ixed w ith 20% sorbitol to
prevent concretion. For each m Eq of K+ rem oved , 2 to
3 m Eq of sod iu m is ad d ed . If there is concern abou t the
ad d ed sod iu m , one or tw o d oses of fu rosem id e can be
u sed to enhance natriuresis (excep t in the presence of
renal failure).
b. The loop d iu retics (e.g., fu rosem id e) enhance u rinary
p otassiu m excretion, bu t are ineffective if renal failu re
is the cau se of hyp erkalem ia.
c. H em od ialysis is the m ost effective m ethod of rem ov-
ing K+ in p atients w ith renal failure.

REFERENCES
1. Rose BD, Post TW. Potassiu m hom eostasis. In: Clinical p hysiolo-
gy of acid -base and electrolyte d isord ers. 5th ed . N ew York:
McGraw -H ill, 2001:372402.
2. Schaefer TJ, Wolford RW. Disord ers of p otassium . Em erg Med
Clin N orth Am 2005; 23:723747.
3. Brow n RS. Extrarenal p otassiu m hom eostasis. Kid ney Int 1986;
30:116127.
440 Renal and Electrolyte Disorders

4. Sterns RH, Cox M, Feig PU, et al. Internal potassium balance and
the control of the plasma potassium concentration. Med icine 1981;
60:339354.
5. Allon M, Copkney C. Albuterol and insulin for treatment of hy-
perkalemia in hemodialysis patients. Kidney Int 1990; 38:869872.
6. Lipw orth BJ, McDevitt DG, Stru thers AD. Prior treatm ent w ith
d iu retic au gm ents the hyp okalem ic and electrocard iograp hic
effects of inhaled albuterol. Am J Med 1989; 86:653657.
7. Ad rogu e H J, Mad ias N E. Changes in plasm a p otassiu m concen-
tration d u ring acu te acid -base d istu rbances. Am J Med 1981;
71:456467.
8. Bernard SA, Buist M. Ind u ced hyp otherm ia in critical care m ed -
icine: a review. Crit Care Med 2003 ;31:20412051.
9. Schaller MD, Fischer AP, Perret CH. Hyperkalemia: A prognostic
factor during acute severe hypothermia. JAMA 1990; 264:18421845.
10. Salem M, Mu noz R, Chernow B. H yp om agnesem ia in critical ill-
ness. A com m on and clinically im p ortant p roblem . Crit Care Clin
1991; 7:225252.
11. Flakeb G, Villarread D, Chap m an D. Is hyp okalem ia a cau se of
ventricular arrhythm ias? J Crit Illness 1986; 1:6674.
12. Stanaszek WF, Rom ankiew icz JA. Cu rrent ap p roaches to m an-
agem ent of p otassium d eficiency. Dru g Intell Clin Pharm 1985;
19:176184.
13. Trissel LA. Hand book on Injectable Drugs. 13th ed. Bethesda, MD:
American Society of Health System Pharmacists, 2005:1230.
14. Kruse JA, Carlson RW. Rapid correction of hyp okalem ia u sing
concentrated intravenou s p otassiu m chlorid e infu sions. Arch
Intern Med 1990; 150:613617.
15. Kim GH , H an JS. Therapeu tic ap proach to hyp okalem ia. N ep h-
ron 2002; 92(Su pp l 1):2832.
16. Whang R, Flink EB, Dyckner T, et al. Magnesium d epletion as a
cau se of refractory potassiu m rep letion. Arch Intern Med 1985;
145:16861689.
17. Evans KJ, Greenberg A. H yperkalem ia: a review. J Intensive Care
Med 2005; 20:272290.
18. Rim m er JM, H orn JF, Gennari FJ. H yp erkalem ia as a com p lica-
tion of d rug therapy. Arch Intern Med 1987; 147:867869.
19. Don BR, Sebastian A, Cheitlin M, et al. Pseu d ohyp erkalem ia
cau sed by fist clenching d u ring phlebotom y. N Engl J Med 1990;
322:12901292.
Potassium 441

20. Leveen HH, Pasternack HS, Lustrin I, et al. Hemorrhage and trans-
fusion as the major cause of cardiac arrest. JAMA 1960; 173:770777.
21. Michael JM, Dorner I, Bru ns D, et al. Potassiu m load in CPD-pre-
served w hole blood and tw o types of packed red blood cells.
Transfusion 1975; 15:144149.
22. William s ME, Rosa RM. H yp erkalem ia: d isord ers of internal and
external potassiu m balance. J Intensive Care Med 1988; 3:52-64.
23. Perazella MA. Drug-ind uced hyperkalem ia: old culprits and new
offend ers. Am J Med 2000; 109:307314.
24. Palm er BF. Managing hyp erkalem ia cau sed by inhibitors of the
renin-angiotensin -ald osterone system . N Engl J Med 2004;
351:585592.
Chapter 28
MAGNESIUM
Magnesium is the second most abund ant intracellular cation,
and it serves as a cofactor for all reactions involving ATPase
enzym es (inclu d ing the m em brane p um p that generates the
electrical grad ient across cell m em branes). Unfortu nately, the
tip of the iceberg analogy used for p otassiu m also applies
to magnesium; i.e., only a minor fraction (0.3%) of total bod y
magnesium is located in plasma (13), so monitoring the
plasma magnesiu m p rovid es little information abou t total
bod y magnesium.

I. MAGNESIUM BALANCE

A. Serum Magnesium
1. The norm al range for seru m m agnesiu m d ep end s on the
d aily m agnesiu m intake, w hich varies accord ing to geo-
graphic region. The norm al range for healthy ad u lts re-
sid ing in the United States is show n in Table 28.1 (4).

2. Only 67% of the magnesium in plasma is in the ionized


(active) form, and the remaining 33% is either bound to
plasma proteins (19% of the total) or chelated with divalent
anions such as phosphate and sulfate (14% of the total) (5).

3. The stand ard assay for m agnesiu m m easu res the total
concentration in plasma. Therefore, w hen the total m ag-
nesiu m is abnorm ally low, it is not p ossible to d etermine
if the problem is a d ecrease in the ionized (active) frac-
tion or a d ecrease in the bou nd fractions (e.g., hypop ro-
teinemia).

443
444 Renal and Electrolyte Disorders

4. The level of ionized m agnesiu m can be m easu red w ith an


ion-sp ecific electrod e. H ow ever, since the total am ou nt of
m agnesiu m in plasm a is sm all, the d ifference betw een
the ionized and bou nd m agnesiu m content m ay not be
large enough to be clinically relevant.

TABLE 28.1 Reference Ranges for Magnesium*


Traditional
Parameter Units SI Units
Serum magnesium:
Total 1.42.0 mEq/L 0.71.0 mmol/L
Ionized 0.8 1.1 mEq/L 0.40.6 mmol/L
Urinary magnesium 515 mEq/24 hr 2.57.5 mmol/24 hr
*Pertains to healthy adults res iding in the United States . From
Reference 4.
Convers ions : mmol x 2 = mEq or mEq x 0.5 = mmol

B. Urinary Magnesium
1. The normal range for u rinary m agnesiu m excretion is
show n in Table 28.1. Und er norm al circum stances, only
sm all qu antities of m agnesiu m are excreted in the urine.

2. When m agnesiu m intake is d eficient, the kid neys con-


serve m agnesium , and u rinary m agnesiu m excretion
falls to negligible levels. This is show n in Figu re 28.1.
N ote that, after the start of a m agnesium -d eficient d iet,
the u rinary magnesiu m excretion p rom p tly falls to negli-
gible levels, w hile the seru m magnesiu m rem ains in the
norm al range. This illu strates the relative valu e of u ri-
nary m agnesiu m over seru m m agnesium levels in the
d etection of m agnesiu m d eficiency.
Magnesium 445

12 2.0

P la s ma Mg
)
8
g
r
M
g
h
)
L
M
4
/
a
2
q
e
m
1.0
/
E
n
q
s
i
m
E
r
a
U
(
m
l
4
P
Urine Mg
(
0 0.0
0 1 2 3 4 5 6 7
Days of Mg-Fre e Die t

FIGURE 28.1 Urinary and plasma magnesium levels in a healthy volun-


teer placed on a magnesium-free diet. Solid bars on the vertical axes
indicate the normal range for urine and plasma magnesium. (Adapted
from Shils ME. Experimental human magnesium deficiency. Medicine
1969; 48:6182).

II. MAGNESIUM DEFICIENCY

A. Incidence
H yp om agnesem ia is reported in as m any as 60 to 70% of ICU
p atients (1,6), bu t this u nd erestim ates the tru e incid ence of
magnesium d eficiency becau se the seru m m agnesium con-
centration can be norm al in patients w ith m agnesium d efi-
ciency (2,3).

B. Predisposing Conditions
Because serum magnesium levels have a limited ability to
detect magnesium d epletion, recognizing the cond itions that
predispose to magnesium depletion may be the only clue to an
und erlying magnesium imbalance. The cond itions that most
often promote magnesium depletion are listed in Table 28.2.
446 Renal and Electrolyte Disorders

TABLE 28.2 Markers of Possible Magnesium Depletion


Predisposing Conditions Clinical Findings
Drug therapy:* Electrolyte abnormalities:*
Furosemide (50%) Hypokalemia (40%)
Aminoglycosides (30%) Hypophosphatemia (30%)
Amphotericin, pentamidine Hyponatremia (27%)
Digitalis (20%) Hypocalcemia (22%)
Cisplatin, cyclosporine
Cardiac manifestations:
Diarrhea (secretory) Torsades de pointes
Digitalis toxicity
Alcohol abuse (chronic)
Diabetes mellitus Hyperactive CNS Syndrome
*Numbers in parenthes es indicate incidence of as s ociated hypo-
magnes emia.

1. Diuretic Therapy
a. Diuretics are the leading cause of magnesium deficiency.
Diuretic-induced inhibition of sodium reabsorption also
interferes with magnesium reabsorption, and the urinary
magnesium losses can parallel urinary sodium losses.
b. The d iuretic effect is m ost p ronou nced w ith loop d i-
u retics like furosem id e, and magnesium deficiency has
been reported in 50% of patients receiving chronic therapy
with furosemide (7).
c. The thiazid e d iuretics also prom ote m agnesiu m d eple-
tion, bu t p rim arily in eld erly p atients (8).
d . Magnesiu m d ep letion is not a com plication of therapy
w ith potassium -sp aring d iu retics (9).

2. Antibiotic Therapy
The antibiotics that p rom ote m agnesiu m d ep letion are
the am inoglycosid es, am photericin and pentam id ine (10,
11). The am inoglycosid es block m agnesiu m reabsorp tion
Magnesium 447

in the ascend ing loop of H enle, and hyp om agnesemia


has been rep orted in 30% of patients receiving am inogly-
cosid e therapy (11).

3. Other Drugs
A variety of other d ru gs have been associated w ith m ag-
nesium d epletion, inclu d ing d igitalis, and the chem other-
apeutic agents cisplatin and cyclosporine (10,12). Digitalis
shifts magnesium into cells, and the chemotherapeutic
agents promote renal magnesium excretion.

4. Alcohol-Related Illness
H yp om agnesem ia is rep orted in 30% of hosp ital ad m is-
sions for alcohol abu se, and in 85% of ad m issions for
d eliriu m trem ens (13,14). Malnu trition and chronic d iar-
rhea m ay p lay a role in the m agnesiu m d ep letion in these
cond itions.

5. Secretory Diarrhea
Secretions from the low er GI tract have a high m agne-
siu m concentration (10 to 14 m Eq/ L) (15), so a secretory
d iarrhea can be accom panied by profou nd m agnesiu m
d epletion.

6. Diabetes Mellitus
Magnesiu m d ep letion is com m on in insu lin-d ep end ent
d iabetics, probably as a resu lt of glycosu ria-ind u ced u ri-
nary m agnesiu m loss (16). H yp omagnesem ia is rep orted
in only 7% of ad m issions for d iabetic ketoacid osis, bu t
the incid ence increases to 50% over the first 12 hours
after ad m ission (17), p robably as a resu lt of insu lin-in-
d u ced m ovem ent of m agnesiu m into cells.

C. Clinical Manifestations
There are no sp ecific clinical m anifestations of m agnesiu m
d eficiency, bu t the follow ing clinical find ings shou ld raise
su sp icion of an u nd erlying m agnesiu m d eficiency.
448 Renal and Electrolyte Disorders

1. Electrolyte Abnormalities
Magnesiu m d ep letion is often accom p anied by abnormal
levels of other electrolytes in blood (See Table 28.2) (18).
a. Magnesium d epletion enhances renal potassiu m excre-
tion, and hypokalem ia is reported in alm ost half of p a-
tients w ith m agnesiu m d ep letion (18). The hyp okal-
emia that accompanies magnesium d epletion can be re-
fractory to potassium replacem ent therap y, and m ag-
nesium repletion is often necessary before potassium
repletion is possible (19).
b. Hypocalcemia is common in magnesium depletion and
is due to a combination of impaired parathormone re-
lease (20) and impaired end-organ response to parathor-
mone (21). As is the case with hypokalemia, the hypocal-
cemia that accompanies magnesium deficiency is diffi-
cult to correct unless magnesium deficits are corrected.
c. H ypophosphatemia can be associated w ith magnesium
d epletion, but is a cause (rather than an effect) of mag-
nesium d epletion. The mechanism is enhanced renal ex-
cretion of magnesium (22).

2. Arrhythmias
a. Magnesiu m d ep letion p rolongs the QT interval on the
ECG and can provoke a polym orp hous ventricular
tachycard ia know n as torsades de pointes (see Chap ter
15, Section VI).
b. Because both d igitalis and magnesiu m d eficiency act
to inhibit the sod iu m -p otassiu m p u m p on cell m em -
branes, m agnesiu m d eficiency p rom otes d igitalis car-
d iotoxicity. Intravenous m agnesium can abolish d igi-
talis-toxic arrhythm ias, even w hen seru m m agnesiu m
levels are norm al (23,24).

3. Neurologic Findings
a. The neu rologic m anifestations of m agnesiu m d eficien-
cy can inclu d e altered m entation, generalized seizu res,
trem ors, and hyperreflexia.
Magnesium 449

b. A neu rologic synd rom e d escribed recently that can


abate w ith m agnesium therap y d eserves m ention. The
clinical presentation is characterized by ataxia, slu rred
sp eech, m etabolic acid osis, excessive salivation, d if-
fu se m u scle sp asm s, generalized seizu res, and pro-
gressive obtu nd ation (25). The clinical featu res are of-
ten triggered by lou d noises or bod ily contact, hence
the term reactive central nervous system magnesium defi-
ciency has been u sed to d escribe this d isord er.

TABLE 28.3 Magnesium Retention Test


Indications
1. For suspected Mg++ deficiency when the serum Mg++ concentra-
tion is normal.
2. For identifying the end-point of Mg++ replacement therapy.
Contraindications
1. Renal failure or ongoing renal magnesium wasting.
Method
1. Add 24 mmol (48 mEq) of Mg++ (6 g of MgSO4) to 250 mL of
isotonic saline and infuse over 1 hour.
2. Collect urine for 24 hrs. after the Mg++ infusion is started.
Results
1. Urinary Mg++ excretion < 12 mmol (24 mEq) in 24 hrs
(< 50% of the infused Mg++) is evidence of Mg++ depletion.
2. Urinary Mg++ excretion >19 mmol (38 mEq) in 24 hrs
( > 80% of the infused Mg++) is evidence against Mg++ depletion.
From Reference 26.

D. Diagnosis
As m entioned several tim es, the seru m m agnesiu m level is
an insensitive m arker of m agnesiu m d ep letion. The m ost
sensitive ind ex of total bod y m agnesiu m stores is a sp ecial-
ized test d escribed next.
450 Renal and Electrolyte Disorders

1. Magnesium Retention Test


Magnesiu m reabsorp tion in the renal tu bu les is close to
the m axim u m tu bu lar reabsorp tion rate (Tm ax), so m ost of
an infu sed m agnesiu m load w ill be excreted in the u rine
w hen total bod y m agnesiu m stores are normal. H ow -
ever w hen m agnesiu m stores are d eficient, magnesiu m is
reabsorbed in the renal tu bu les, and a smaller fraction of
an infu sed m agnesiu m load is excreted in the u rine.
a. The m agnesiu m retention test, w hich is ou tlined in Ta-
ble 28.3, m easu res the fraction of an intravenou s m ag-
nesiu m load that is excreted in the urine (26,27).
b. When less than 50% of the infused magnesium is re-
covered in the urine, magnesium d eficiency is likely,
and w hen more than 80% of the infused magnesium is
excreted in the urine, magnesium d eficiency is unlikely.
c. This test is reliable only w hen renal fu nction is not im-
p aired and w hen there is no ongoing renal magnesiu m
w asting.

E. Magnesium Preparations
1. The m agnesiu m p rep arations available for oral and p ar-
enteral u se are listed in Table 28.4. The oral p rep arations
can be u sed for d aily m aintenance therap y (5 m g/ kg in
norm al su bjects). Intravenou s m agnesiu m is p referred
for replacing d eficits becau se intestinal absorption of
magnesiu m can be erratic.

2. The stand ard intravenou s p rep aration is m agnesiu m su l-


fate (MgSO 4). Each gram of MgSO 4 has 8 m Eq (4 m m ol)
of elem ental m agnesiu m .

3. The 50% MgSO 4 solu tion (500 mg/ m L) has an osm olari-
ty of 4000 m osm/ L, so it m ust be d ilu ted to a 10% (100
mg/ mL) or 20% (200 m g/ m L) solu tion for intravenous
use (28). Saline solu tions shou ld be u sed as the d ilu ent.
Ringer s solu tions are not ad vised becau se the calcium in
Magnesium 451

Ringer s solutions w ill cou nteract the actions of the in-


fu sed m agnesiu m .

TABLE 28.4 Oral and Parenteral Magnesium Preparations


Preparations Elemental Mg++
Oral preparations:
Magnesium chloride enteric-coated 64 mg (5.3 mEq)
tablets
Magnesium oxide tablets (400 mg) 241 mg (19.8 mEq)
Magnesium oxide tablets (140 mg) 85 mg (6.9 mEq)
Magnesium gluconate tablets (500 mg) 27 mg (2.9 mEq)
Parenteral solutions:
Magnesium sulfate (50%)* 500 mg/mL (4 mEq/mL)
Magnesium sulfate (12.5%) 120 mg/mL (1 mEq/mL)
*Should be diluted to a 20% s olution for intravenous injection.

F. Replacement Protocols
The follow ing m agnesiu m rep lacem ent p rotocols are recom -
mend ed for p atients w ith norm al renal fu nction (29).

1. Mild, Asymptomatic Hypomagnesemia


a. Assu m e a total m agnesiu m d eficit of 1 to 2 m Eq/ kg.
b. Because 50% of the infu sed m agnesiu m can be lost in
the u rine, assum e that the total m agnesiu m requ ire-
ment is tw ice the m agnesiu m d eficit.
c. Replace 1 mEq/ kg for the first 24 hours, and 0.5 mEq/ kg
daily for the next 3 to 5 days.

2. Moderate Hypomagnesemia
The follow ing therap y is intend ed for p atients w ith a
seru m m agnesiu m level less than 1 m Eq/ L or w hen hy-
p om agnesem ia is accom p anied by other electrolyte ab-
normalities:
452 Renal and Electrolyte Disorders

a. Ad d 6 g MgSO 4 (48 m Eq Mg) to 250 or 500 m L isoton-


ic saline and infuse over 3 hou rs.
b. Follow w ith 5 g MgSO 4 (40 m Eq Mg) in 250 or 500 m L
isotonic saline infu sed over the next 6 hou rs.
c. Continue w ith 5 g MgSO 4 every 12 hou rs (by continu -
ou s infu sion) for the next 5 d ays.

3. Life-Threatening Hypomagnesemia
The follow ing p rotocol is recom m end ed w hen hyp om ag-
nesem ia is accom panied by serious card iac arrhythm ias
(e.g., torsad es d e pointes) or generalized seizu res.
a. Infu se 2 g MgSO 4 (16 m Eq Mg) intravenou sly over 2 5
m inu tes.
b. Follow w ith 5 g MgSO 4 (40 m Eq Mg) in 250 or 500 mL
isotonic saline infu sed over the next 6 hou rs.
c. Continue w ith 5 g MgSO 4 every 12 hou rs (by continu -
ou s infu sion) for the next 5 d ays.
Serum m agnesiu m levels w ill rise after the initial m agne-
siu m bolu s but w ill begin to fall after 15 m inutes. There-
fore, it is im p ortant to follow the bolu s d ose w ith a con-
tinu ou s m agnesiu m infusion. Seru m m agnesiu m levels
m ay norm alize after 1 to 2 d ays, but it w ill take several
d ays to rep lenish the total bod y m agnesiu m stores.

4. Renal Insufficiency
When magnesium is replaced in the setting of renal insuf-
ficiency, no more than 50% of the magnesium in the stan-
d ard replacement protocols should be ad ministered (29),
and the serum magnesium should be monitored carefully.

III. HYPERMAGNESEMIA
H yperm agnesem ia (i.e., seru m Mg ++ > 2 m Eq/ L) is rep orted
in 5% of hospitalized patients (30) and is fou nd almost ex-
clusively in patients w ith renal insufficiency.
Magnesium 453

A. Etiologies
1. Hemolysis
The magnesium concentration in erythrocytes is approxi-
mately three times greater than that in serum (31). Trau-
matic d isruption of erythrocytes can prod uce a spurious
hyp erm agnesem ia. In hem olytic anem ia, the seru m m ag-
nesiu m is expected to rise by 0.1 m Eq/ L for every 250 m L
of erythrocytes that lyse completely (31), so hypermagne-
semia is expected only w ith massive hemolysis.

2. Renal Insufficiency
The renal excretion of magnesium becomes impaired when
the creatinine clearance falls below 30 mL/ minute (32).
However, hypermagnesemia is not a prominent feature of
renal insufficiency unless magnesium intake is increased.

3. Other Conditions
Other cond itions that can be associated w ith hyp erm ag-
nesem ia includ e d iabetic ketoacid osis (transient), ad renal
insu fficiency, hyp erp arathyroid ism , and lithiu m intoxi-
cation (32). The hyp erm agnesem ia in these cond itions is
u su ally m ild .

B. Clinical Manifestations
1. The clinical consequ ences of p rogressive hyp ermagne-
sem ia are listed below (32).

Manifestation Serum Mg++


Hyporeflexia >4 mEq/L
1st AVBlock >5 mEq/L
Complete Heart Block > 10 mEq/L
Cardiac Arrest > 13 mEq/L

2. The seriou s consequ ences of hyp erm agnesem ia are d u e


to calciu m antagonism in the card iovascu lar system . The
454 Renal and Electrolyte Disorders

p red om inant effect is d elayed card iac cond u ction (con-


tractility and vascu lar tone are relatively u naffected ).

C. Management
1. H em od ialysis is the treatm ent of choice for severe hyp er-
m agnesem ia.

2. Intravenous calcium gluconate (1 g IV over 2 to 3 minutes)


can be used to antagonize the cardiovascular effects of hy-
permagnesemia, but the effects are transient and should
not delay hemodialysis (33).

REFERENCES
1. Noronha JL, Matuschak GM. Magnesium in critical illness: metabo-
lism, assessment, and treatment. Intensive Care Med 2002; 28:667679.
2. Elin RJ. Assessment of magnesium status. Clin Chem 1987; 33:19651970.
3. Reinhart RA. Magnesium m etabolism . A review w ith sp ecial ref-
erence to the relationship betw een intracellular content and se-
ru m levels. Arch Intern Med 1988; 148:24152420.
4. Low enstein FW, Stanton MF. Seru m m agnesiu m levels in the
United States, 19711974. J Am Coll N u tr 1986; 5:399414.
5. Altura BT, Altu ra BM. A m ethod for d istinguishing ionized , com -
p lexed and protein-bou nd Mg in norm al and d iseased su bjects.
Scand J Clin Lab Invest 1994; 217:8387.
6. Tong GM, Ru d e RK. Magnesiu m d eficiency in critical illness. J
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Chapter 29
CALCIUM AND
PHOSPHORUS
Calcium and p hosphorus are responsible for mu ch of the
stru ctu ral integrity of the bony skeleton. Althou gh neither is
found in abu nd ance in the soft tissu es, both p lay an im por-
tant role in vital cell functions. Phosp horu s p articipates in
aerobic energy p rod u ction, w hile calcium has a vital role in
several d iverse p rocesses, inclu d ing blood coagu lation, neu-
rom uscu lar transm ission, and card iovascu lar p erform ance.

I. CALCIUM IN PLASMA

A. Plasma Fractions
1. The calciu m in p lasm a is p resent in three form s, as d e-
p icted in Figu re 29.1.

2. Abou t half of the calciu m is ionized and biologically ac-


tive, w hile the other half is bou nd to other molecu les and
is biologically inactive (1,2). Most (80%) of the bound cal-
cium is bou nd to album in, and the rem aind er is com -
p lexed to sm all anions like su lfates and p hosp hates.

B.Total vs. Ionized Calcium


1. The concentration of total and ionized calciu m in p lasm a
is show n in Table 29.1.

2. Althou gh only the ionized calciu m is biologically im p or-


tant, m ost clinical laboratories measu re the total p lasm a
calciu m, and this can be m islead ing.
457
458 Renal and Electrolyte Disorders

10
Ca
8
)
Ca A Ca
L
P rote in-Bound
d
Ca Ca
/
Ca
Fra ction
g
m
Ca A Ca
6 Ca A Ca
(
Ca
m
Ca
Che la te s
u
HCO 3 -Ca -HCO 3 HCO 3 -Ca -HCO 3
i
c
4
l
a
Ca ++ Ca ++ Ca ++ Ca ++
C
Ca ++ Ionize d Ca ++
l
a
t
2 Fra ction
o
Ca ++ Ca ++ Ca ++ Ca ++
T
Ca ++ Ca ++

0
Norma l Hypoa lbumine mia

FIGURE29.1 The three fractions of calcium in plasma and their contribu-


tion to the total plasma calcium concentration. The column on the right
shows how a decrease in plasma albumin can reduce the total plasma
calcium without affecting the ionized