Академический Документы
Профессиональный Документы
Культура Документы
Short Course on
Intensive Care Medicine
1997 Handbook
The Australian
Short Course on
Intensive Care Medicine
1997 Handbook
Editor
L.I.G. Worthley
Published in 1997 by
The Australasian Academy of Critical Care Medicine
Department of Critical Care Medicine
Flinders Medical Centre, Bedford Park
South Australia 5042
ISSN 1327-4759
1997 The Australasian Academy of Critical Care Medicine
Requests to reproduce original material should be addressed to
the publisher.
Printed by Gillingham Printers Pty Ltd
153 Holbrooks Road
Underdale
South Australia 5032
CONTENTS
page
1
11
17
27
39
53
61
75
81
Scoring systems and the prediction of outcome in the intensive care unit
D. Bihari
91
Pulmonary embolism
L. Worthley
97
107
115
Trainee Presentations
121
Index
155
iii
iv
1st
FMC
Travel to
2nd
RAH
3rd
QEH
Travel to
4th
FMC
Travel to
Lecture
Head injury
management
QEH
Interactive
Biochemistry in
the ICU
FMC
Lecture
Acute renal failure
0815
FMC
Lecture
Introduction:
- ICU clinical methods
- The ICU exam
L.W
Lecture
Principles of
mechanical ventilation
J.M
Clinical cases
P.P
Clinical cases
A.H.
Interactive
Path forms
A.B
Clinical cases
Lecture
Trauma
1245
Lunch
B.G
Lunch
Lecture
Myocardial
infarction
update
J.H
Travel to WCH
1400
Interactive
0900
1015
1130
ECGs
1515
1630
1745
L.W
Lecture
Understanding fluid
and electrolyte
disorders
L.W
Interactive
Lecture
Severity scoring
systems: principles and
practice
D.B
Clinical cases
Path forms
L.W
Travel To RAH
D.B
Travel to RAH
X-Rays
L.W
Lunch
Lecture
Common paediatric
ICU problems
Lecture
Management of acute
asthma
S.K
Short questions
J.C
Interactive
Lecture
Nutrition in the
critically ill
A.V
Interactive
S.K.
A.S
Travel to RAH
Presentations
L.W.
Interactive
Clinical
vignettes
L.W.
Code
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
REGISTRANTS
Institution
Intensive Care Unit, John Hunter Hospital, New South Wales
Intensive Care Unit, Royal Brisbane Hospital, Queensland
Intensive Care Unit, Queen Elizabeth Hospital, Hong Kong
Intensive Care Unit, Royal Childrens Hospital. Victoria
Intensive Care Unit, Royal Prince Alfred Hospital, New South Wales
Intensive Care Unit, Liverpool Hospital, New South Wales
Intensive Care Unit, Royal Perth Hospital, Western Australia
Intensive Care Unit, Alfred Hospital, Victoria
Intensive Care Unit, Liverpool Hospital, New South Wales
Intensive Care Unit, St George Hospital, New South Wales
Intensive Care Unit, Queen Elizabeth Hospital, South Australia
Intensive Care Unit, Prince of Wales Hospital, Hong Kong
Intensive Care Unit, Illawarra Regional Hospital, New South Wales
Intensive Care Unit, Princess Alexandra Hospital, Queensland
Intensive Care Unit, Monash Medical Centre, Victoria
Intensive Care Unit, Princess Alexandra Hospital, Queensland
Intensive Care Unit, St Vincents Hospital, Victoria
Intensive Care Unit, The St. George Hospital, New South Wales
Intensive Care Unit, Westmead Hospital, New South Wales
Intensive Care Unit, Prince of Wales Hospital, Hong Kong
Intensive Care Unit, Griffith Base Hospital, New South Wales
Intensive Care Unit, Starship Childrens Hospital, New Zealand
Intensive Care Unit, Royal Perth Hospital, Western Australia
Intensive Care Unit, Liverpool Hospital, New South Wales
Intensive Care Unit, John Hunter Hospital, New South Wales
Intensive Care Unit, Austin and Repatriation Hospital, Victoria
Intensive Care Unit, Monash Medical Centre, Victoria
Intensive Care Unit, Tuen Mun Hospital, Hong Kong
Intensive Care Unit, Royal Childrens Hospital, Victoria
Intensive Care Unit, Waikato Hospital, New Zealand
Intensive Care Unit, Auckland Hospital, New Zealand
Intensive Care Unit, Royal Childrens Hospital, Victoria
Intensive Care Unit, The Geelong Hospital, Victoria
Intensive Care Unit, Royal Adelaide Hospital, South Australia
Intensive Care Unit, Royal Brisbane Hospital, Queensland
Intensive Care Unit, St Vincents Hospital, New South Wales
Intensive Care Unit, Liverpool Hospital, New South Wales
FACULTY
QEH
RAH
WCH
Dr. M.OFathartaigh (M.OF) Dr. J. Myburgh (J.M) Dr. N. Matthews (NM)
Dr. J. Moran
(J.M)
Dr. P. Thomas (P.T) Dr. S. Keeley (S.K)
Dr. S. Peake
(S.P)
Dr. B. Griggs
(B.G) Dr. A. Slater
(A.S)
Dr. J. Horowitz
(J.H)
Dr. R. Young
(R.Y)
Dr. P. Pannall
(P.P)
Dr. D. Clayton (D.C)
Name
Dr. C. Bhringer
Dr. B. Venkatesh
Dr. P. W. Cheung
Dr. D. Stephens
Dr. D. Green
Dr. C. Woolfe
Dr. C. Edibam
Dr. M. Pinder
Dr. C. Nolan
Dr. M. Parmar
Dr. C. Motherway
Dr. C. A. Cheng
Dr. P Nair
Dr. J. Evans
Dr. V. Pellegrino
Dr. D. Chu
Dr. B. Dixon
Dr. H. L. Chee
Dr. J. Awad
Dr. R. Calcroft
Dr. D. Corbett
Dr. J. Liang
Dr. F. Colreavy
Dr. N. Kavanagh
Dr. P. Frost
Dr. H Opdam
Dr. E. Wheatley
Dr. P. Lam
Dr. C. Hill
Dr. K. OConnor
Dr. T. Williams
Dr. T. Duke
Dr. P. Seal
Dr. N. Widdicombe
Dr. D. Mullany
Dr. M Gopalakrishnan
Dr. A. Purdon
FMC
Dr. L. Worthley
Dr. A. Vedig
Dr. A. Bersten
Dr. A. Holt
Dr. E. Everest
GUESTS
Dr. D. Bihari
(L.W)
(A.V)
(A.B)
(A.H)
(E.E)
(J.C)
vi
PREFACE
The Australian Short Course on Intensive Care Medicine is a teaching programme with lectures
and interactive sessions. This handbook includes many of the course lectures and the one page
summaries of the 5 minute talks given by the registrants and is designed to be a working text.
During the sessions, you may find it useful to mark and note the text to facilitate your recall and
review of the course at a later date. I hope that you find this book useful.
Dr. L.I.G. Worthley
Adelaide, April 1997
vii
viii
1. Sympathomimetic amines
Exogenous catecholamines, synthetic amines and related agents are amongst the most
commonly used drugs in intensive care practice. In general their use can be classified as:
perfusion pressure;
cardiac output, and hence systemic oxygen delivery (DO2); or
manipulation of regional vascular resistance.
Certainly, an inadequate perfusion pressure can contribute to cerebral, left ventricular (LV),
right ventricular (RV), renal or diaphragmatic ischaemia and dysfunction in various disease
states. Recent studies question the endpoint of targeting supranormal DO2; however, at the
lower end of the spectrum an inadequate cardiac output may also result in hypotension or a
lactic acidosis. Finally, while the aim of specifically manipulating regional vascular resistance
(for example renal vasodilation with low-dose dopamine) remains attractive, few data suggest
this is ever achieved in clinical usage.
Drugs and receptors
While changes in - and -adrenoceptor number and function have been described in sepsis
and heart failure, the general approach of examining receptor based effects remains a useful
introduction to these drugs.
1: intracellular Ca2+ via G-protein mediated activation of phospholipase C and then the
phosphoinositol pathway and diacylglycerol. Direct vascular smooth muscle vasoconstriction,
myocardial contractility without an in heart rate.
2: adenyl cyclase activity via an inhibitory G-protein. Prejunctional action inhibits
neurotransmitter release, but also found at postjunctional sites where they mediate contraction.
1 : force and rate of cardiac contraction, renin secretion, relax coronary arteries and
gastrointestinal smooth muscle. 1+2-adrenoceptors linked to adenyl cyclase (c-AMP) via a
stimulatory G-protein. Presynaptic 1-adrenoceptors facilitate neurotransmitter release.
2 : smooth relaxation at bronchi, most blood vessels, uterus; force and rate of cardiac
contraction (comprise 15% of myocardial -receptors); prejunctional 2 -receptors act to
facilitate release of neruotransmitters.
3 : lipolysis in white adipose tissue, thermogenesis in brown adipose tissue, insulin
secretion, glycogen synthesis in skeletal muscle, inhibition of gastrointestinal and smooth
muscle contraction, myocardial contractility,1 bronchial smooth muscle relaxation and
vasodilatation of skin and fat. Not downregulated in chronic heart failure, and some suggestion
that it is coupled to an inhibitory G-protein that is upregulated in heart failure.
DA-1: vasodilatation of regional vascular beds including renal, splanchnic, and cerebral, found
both on the brush border and the basolateral membranes in renal proximal tubule with agonistinduced natriuresis (Fig 1).
1
Basolateral membrane
L-dopa
L-AADC
DA
DA
Dopamine (DA)
PIP2
Na+
DA-1
c-AMP
DA-1
PLC
IP3
DAG
Na+
PKC
Na+
K+
H+
Na+ reabsorption
Natriuresis
1
++
++
2
++
++
++
+
-
1
++
++
++
++
++
++
+
++
+
+
+
+
++
++
3
+
+
++
?
?
?
?
?
DA-1
DA-2
++
++
++
Legend: DA, dopamine; +, agonist activity; -, antagonist activity; (-) and (+), isomers; (),
racemic mixture; ?, uncertain.
Given their receptor affinity it is possible to broadly predict the circulatory effects of
individual drugs. However, numerous factors contribute to their final effect. In addition to the
3
reactive hyperaemia
Flow
subautoregulatry
slope
autoregulated zone
autoregulatory threshold
Blood pressure
As BP falls progressive vasodilatation maintains a relatively constant flow down to the
autoregulatory threshold. At this point the vasodilator reserve has been exhausted and flow
becomes linearly dependent upon PP (the subautoregulatory slope). Consequently, the
4
2. Other Drugs
1. Milrinone: of the FIII selective phosphodiesterase inhibitors milrinone is the most
commonly used in critically ill patients. Since phosphodiesterase inhibits the conversion of
c-AMP to AMP these drugs increase c-AMP levels independent of the -receptor complex.
There are broadly five classes of phosphodiesterase; theophylline a non-selective
phosphodiesterase inhibitor acts at the heart, peripheral circulation, bronchial smooth
muscle, kidney (differential effects on the intrarenal distribution of blood flow) and brain.
The FIII selective phosphodiesterase inhibitors predominantly act on the heart and
peripheral circulation with lesser effects elsewhere. Although the long term use of this class
of agents appears to increase mortality in congestive heart failure,15 the combination of
6
10
Definition
Lactic acidosis has been variously defined as a blood lactate concentration of greater than 2
mmol/L or more commonly of greater than 5 mmol/L, in combination with acidemia - also
being variously defined as an arterial pH of either < 7.35 or of < 7.25.1 One problem with all
definitions is that although acidemia may be present it may be partially or completely
compensated by preexisting metabolic or respiratory alkalemia.
Formation of lactic acid
Formation and metabolism of lactate in cells is catalysed by lactate dehydrogenase
Pyruvate + NADH + H+
LDH
<-->
Lactate + NAD+
Whole body lactate production during health is about 0.8 mmol/kg/hr which results in blood
lactate concentrations of < 1 mmol/L and basal lactate concentrations about 10 x basal pyruvate
concentrations. Lactate formation is in part dependent upon pyruvate concentrations with
pyruvate being sourced from lactate (via LDH), from proteolysis (about 15 %) and from
glycolysis (about 85%). Glucose is obtained from absorption, from glycogen, and from
gluconeogenesis, and its glycolysis is controlled by 3 unidirectional enzymes. The activity of
one of these enzymes is increased by increasing intracellular pH. Alkalosis therefore increases,
and acidosis decreases both pyruvate and lactate formation from glycolysis. During oxygen
excess, pyruvate is oxidised (in cells with mitochondria) and lactate does not accumulate. The
onset of anaerobic metabolism is associated with lactate accumulation and an increase in the
lactate/pyruvate ratio. Measurement of the lactate/pyruvate ratio (reflecting the cellular
cytoplasmic redox state) however, is considered to be a poor indicator of the mitochondrial
redox potential, and therefore of little clinical use.
Classification (Types A and B)
Although most causes of lactic acidosis are acquired, some are congenital and are associated
with defects in gluconeogenesis, in pyruvate dehydrogenase, in the TCA cycle or in the
respiratory chain. Cohen and Woods 1976 classification of lactic acidosis has been widely
recognised.2 In this classification, Type A lactic acidosis includes patients with clinical
evidence of tissue hypoxia and is by far the most common in critically ill patients. In these
patients, lactic acidosis is primarily due to increased generation of lactate due to tissue hypoxia.
Causes include: shock, regional hypoperfusion, severe hypoxaemia, severe anaemia, carbon
monoxide poisoning and severe asthma.
Type B lactic acidosis is much less common, and includes patients with no clinical evidence
of tissue hypoxia. The type B subgroups are: B1 (presence of an underlying disease state)
including diabetes, liver disease, malignancy, sepsis, pheochromocytoma, thiamine deficiency;
B2 (drug or toxin induced) including biguanides, ethanol, methanol, ethylene glycol, fructose,
11
Lactic Acidosis
sorbitol, xylitol, salicylates, paracetamol, adrenaline, salbutamol, cyanide, nitroprusside,
isoniazid, propylene glycol; and B3 (inborn errors of metabolism including glucose-6
phosphatase deficiency, fructose 1,6 di-phosphatase deficiency, pyruvate carboxylase
deficiency and oxidative phosphorylation defects. Some patients with type B lactic acidosis
have increased lactate generation (for example some malignancies and toxins which impair
cellular oxygen utilisation), and others have decreased lactate clearance (liver disease being
probably the most common).
Combined (Types A and B) abnormalities
Many patients have combined abnormalities and both increased lactate generation from
tissue hypoxia and decreased lactate clearance may be present simultaneously. For example, in
patients with cancer, there may be a high anaerobic glycolysis rate and hepatic lactate
metabolism may also be impaired by tumour replacement. In non insulin dependent diabetes
there may be a mild defect in pyruvate oxidation and in diabetic ketoacidosis there may be an
inhibitory effect of ketones on hepatic lactate uptake. Thiamine and biotin are essential
cofactors for pyruvate dehydrogenase activity and for conversion of pyruvate to oxaloacetate so
chronic malnutrition may be associated with cofactor deficiency causing lactic acidosis, by
increasing pyruvate availability and thereby increasing lactate generation. Ethanol oxidation
encourages the conversion of pyruvate to lactate and inhibits other pathways of pyruvate
metabolism. Phenformin increases glycolysis to lactate in peripheral tissues, inhibits pyruvate
oxidation, increases splanchnic lactate production, and decreases hepatic lactate clearance.
Interestingly, although phenformin was considered a classic inducer of type B lactic acidosis
and was used in frequently cited animal models used to study lactic acidosis, it was later
realised to be a potent cardiac depressant which induced type A lactic acidosis concurrently.
Catecholamines induce hepatic vasoconstriction and impair hepatic lactate clearance, and
adrenaline also increases hepatic glycogenolysis (to lactate).3
Lactic acidosis in critically ill patients
Critically ill patients do not usually have solely type A or B lactic acidosis. For example in
patients with sepsis there may be decreased myocardial preload and myocardial depression,
both of which reduce cardiac function and may therefore reduce oxygen delivery to tissues.
Also in sepsis, hypotension may reduce critical perfusion pressures to vital organs. However, at
the same time there are excess catecholamines which may impair hepatic lactate extraction (by
reducing regional hepatic blood flow), increasing lactate production via increased
glycogenolysis. At the same time and in addition, pyruvate dehydrogenase activity is reduced in
both skeletal muscle and liver. There may also be defects in mitochondrial pyruvate oxidation
during sepsis which might increase pyruvate availability further. A second example of critically
ill patients with mixed type A and B lactic acidosis may be observed in patients with shock
superimposed on a background of alcoholic cirrhosis. These patients have increased lactate
production from tissue hypoxia together with decreased lactate clearance due to liver disease
and commonly have much greater blood lactate concentrations than patients with healthy livers
who have undergone a similar shock insult. Determining the severity of a shock insult from a
single blood lactate concentration may therefore be quite misleading.
In critically ill patients with shock, type A lactic acidosis occurs when tissue perfusion is
inadequate to sustain aerobic metabolism. Thus, an increasing blood lactate concentration in
patients with shock is a good indicator of ongoing impaired tissue perfusion and is correlated
with increased risk of a fatal outcome.4 More recent data reported from the placebo patients in a
multicentre clinical trial confirms the relationship between increased blood lactate
concentrations (mean 10.4 mmol/L) and a fatal outcome (83% mortality).5 In these patients a
12
Lactic Acidosis
blood lactate concentration of 5 mmol/L indicated a mortality approaching 80%. Survival was
better in those whose hyperlactemia resolved, and in those without shock. The clinical
relevance of these observations is that it is extremely important to monitor acid-base status and
blood lactate concentrations repeatedly in patients presenting acutely with shock and lactic
acidosis. Failure of improvement in acidemia or in blood lactate concentrations during the first
few hours of resuscitation suggests that either the initial therapies have been inadequate, or that
there is an additional lactic acid clearance problem. Similarly, if resuscitation measures
(excluding buffer agents like bicarbonate) and appropriate surgery are associated with
decreasing acidosis and decreased blood lactate concentrations, then survival is more likely.
Hyperlactemia may also occur without tissue hypoperfusion - due to impaired lactate
clearance, in hypermetabolic states where accelerated aerobic glycolysis may contribute (sepsis,
trauma, burns), in conditions with increased muscle activity (extreme exercise and seizures) or
during exogenous lactate administration (intravenous haemofiltration fluid). In some of these
patients (for example patients with seizures) very high blood lactate concentrations have
minimal prognostic value because the lactic acidosis is usually cleared very rapidly and few
significant physiologic effects have been described. Furthermore, there is recent evidence using
NMR spectroscopy, that the hyperlactemia of sepsis may occur without tissue hypoxia.6 Clearly
the genesis of hyperlactemia in sepsis is complex and requires further investigation.
Cardiac dysfunction in patients with lactic acidosis
Lactic acidosis may cause cardiac dysfunction, or instead lactic acidosis may be an
epiphenomenon - an end result of tissue hypoperfusion due to cardiac dysfunction from other
factors. Although this subject continues to be controversial, an extensive literature review7
concluded that in most critically ill patients with lactic acidosis cardiac dysfunction is present
but is due to a combination of other factors of which cytokines appear to be increasingly
important. Lactic acidosis in most patients is a consequence rather than a cause of cardiac
dysfunction and therapies intended to correct acidosis or clear lactate may miss the point and
leave a patient clinically deteriorating despite improving blood gases. A false sense of security
may be induced in clinicians during the often short therapeutic window which exists for
resuscitation to be successful. Bicarbonate and other buffers may suffer from this problem in
addition to adverse side effects of the agents themselves.
For many years it was believed that acidemia was a major cause of cardiac dysfunction in
patients, and for this reason, aggressive attempts to normalise arterial pH as rapidly as possible
with buffer therapies - usually bicarbonate, were often part of widespread clinical practice.8
This belief was based upon an extensive body of research in isolated muscle preparations,
isolated heart preparations, in animal models and upon a handful of clinical case reports.
Together these studies suggested that acidosis (respiratory, hydrochloric, ammonium chloride,
and others) decreased cardiac function, decreased the haemodynamic response to
catecholamines, increased arrhythmias, and shortened survival.
This literature is in large part however not generally applicable to critically ill patients who
have lactic acidosis. Respiratory and metabolic acidosis are now recognised to have different
cardiovascular effects.9 None of the animal models truly imitate human lactic acidosis; drugs
and anaesthetics themselves known to decrease myocardial contractility were often used, many
studies were uncontrolled, and interspecies differences are significant and difficult to interpret
making application from animal models to clinical practice hazardous. Furthermore, studies that
demonstrated significantly deceased cardiac function during metabolic acidosis often did so at
an arterial pH much below that which is seen clinically in critically ill patients - ie outside the
physiologically observed range in humans. (Arterial pH's of 6.6 - 6.9). By contrast, in a group
of critically ill patients with severe shock and a high mortality, taking part in a prospective
13
Lactic Acidosis
study of bicarbonate therapy in lactic acidosis a mean arterial pH of 7.22 was reported.10
Clearly many factors including respiratory compensation which may be therapeutically applied
by mechanical ventilation, combine to ensure that the arterial pH experienced by critically ill
patients with lactic acidosis is usually within a range of about 7.1 - 7.30. Finally, many studies
in large animals made inferences about changes in myocardial contractility without measuring
myocardial contractility directly. Reliable load independent measurements of left ventricular
contractility which are applicable to large animal models and to human studies have only been
developed in recent years.
A generation or a clearance problem
In health, lactate is continually produced as a metabolic product, predominantly in skeletal
muscle, and at the same time is metabolised, primarily in the liver and kidneys. In health, owing
to constant turnover, blood lactate concentrations remain low. However, during shock when
compensatory mechanisms are insufficient to maintain tissue oxygen delivery and aerobic
metabolism, anaerobic metabolic processes commence and lactate production increases. Blood
lactate concentrations then increase depending upon the capacity of the metabolising organs to
accommodate the increased load. Shocked patients who have liver disease often develop greater
blood lactate concentrations than previously healthy subjects who have the same degree of
tissue hypoxia. Production of acid is closely related to tissue hypoxia because hydrogen ions
cannot easily be oxidised under anaerobic conditions. Production of lactate may also be directly
related to tissue hypoxia but may also relate instead more closely to acceleration of glycolysis
in situations unrelated to tissue hypoxia.
Conclusion
In critically ill patients therefore, lactic acidosis is both a problem of increased lactate
generation and decreased lactate clearance. In most patients it is primarily a generation
problem. However there are many clinical scenarios where increased lactic acid generation is
complicated by decreased clearance, and there are some patients in whom decreased clearance
is the primary problem. In all cases, therapies which decrease lactate generation or increase
clearance are likely to be more successful than those which solely increase pH. However all
therapies have been unsuccessful when the underlying process causing lactic acidosis is
irreversible.
REFERENCES
1. Hindman B. Sodium bicarbonate in the treatment of subtypes of acute lactic acidosis:
physiologic considerations. Anesthesiology 1990;72:1064-1076.
2. Cohen R and Woods H. Clinical and biochemical aspects of lactic acidosis. Boston:
Blackwell Scientific Publications, 1976.
3. Stacpoole P. Lactic acidosis. Endo Metab Clin North Am 1993;22:221-245.
4. Broder G, WeiL M. Excess lactate: an index of reversibilitv of shock in human patients.
Science 1964;143:1457-1459.
5. Stacpoole P, Wright E, Baumgauter T, et al. Natural history and course of acquired lactic
acidosis in adults. Am J Med 1994;97:47-54.
6. Hotchkiss R, Karl I. Revaluation of the role of cellular hypoxia and bioenergetic failure in
sepsis. JAMA 1992;267:1503-1510.
7. Cooper DJ.
Cardiac dysfunction and lactic acidosis during hyperdynamic and
hypovolemic shock. MD Thesis. University of Adelaide. 1996.
8. Narins R, Cohen J. Bicarbonate therapy for organic acidosis: the case for its continued
use. Ann Intern Med 1987;106:615-618.
14
Lactic Acidosis
9.
10.
11.
12.
13.
14.
15.
15
16
Introduction
Malnutrition is common in patients in hospital and for some time, the association between
malnutrition and increased morbidity and mortality during hospitalisation has been recognised.
Whilst it seems intuitively likely that well nourished patients respond better to treatment, such
intuitive thinking has been difficult to prove using the technique of randomised controlled
clinical trials.1 In the intensive care unit, where patients are often severely catabolic and
extraordinarily heterogeneous in the severity of their illness and their underlying comorbidities, it has been even more difficult to define precisely the role of nutritional support in
reducing morbidity and mortality from critical illness.2 That all patients can be given nutritional
support has been made possible by the development of two techniques: firstly, the intraluminal
administration of specific enteral diets using a feeding tube placed somewhere in the upper
gastrointestinal tract; and secondly, by the intravenous infusion of hypertonic nutrient solutions
which usually requires the presence of central venous catheter. A considerable problem has
surrounded the assessment of outcome in patients supported in these ways as most
investigations have centred upon biochemical and physical indices of host wasting rather than
examining hard endpoints of clinical outcome, for example 28 day / ICU / hospital mortality
rates or even length of ICU stay or duration of ventilatory support. Clearly starvation is not an
option for the critically ill patient since experience from the concentration camps of Nazi
Germany, the British prisons in Northern Island and famines in Africa all confirm that death is
inevitable in initially well nourished individuals after some 60 to 80 days of starvation (water
and electrolytes being provided in some form). The debate concerns the exact timing of
nutritional support in the critically ill, its route of administration and finally, the formulation of
the diet which now may be used to modulate the host response to critical illness.3
1.
The Stress Response to Surgery, Trauma and Infection - Catabolism and Septic
Autocannabolism
Not surprisingly, the metabolic stress applied to an individual patient effects the extent of
the risk that malnutrition creates in the setting of elective surgery in critical illness. Depending
upon the severity of the injury and the duration of the disease, weight loss associated with the
loss of body fat and skeletal muscle mass may vary from being relatively insignificant to being
life-threatening, primarily through the development of immunosuppression and a decrease or
delay in wound healing and tissue repair. Muscle weakness may be reflected in a patients
inability to weaned from a mechanical ventilator. Catabolic disease causes an increase in the
extracellular fluid compartment accompanied by sodium retention and initial weight gain.7
Adipose tissue and the body cell mass actually shrink resulting in loss of weight, body fat and
protein. The underlying rationale for providing nutritional support to such patients is that the
accelerated net break down of body protein (measured as the nitrogen excretion) can be slowed
by the administration of adequate quantities of energy, protein (amino acids) and other essential
nutrients. In fact, it is extraordinary difficulty to prevent weight loss and negative nitrogen
balance in severely catabolic patients and it is now generally accepted that aggressive
nutritional support does not prevent substantial body protein loss during severe catabolic
illness. It is the treatment of the underlying problem that eventually reverses the catabolic
phase of the illness and it is at that time that anabolism can be promoted by the provision of
nutrients.8
Infection and injury are followed by a series of well described neurohormonal events
together with the release of mediators of the acute inflammatory response. A complex network
of events characterises the host response to injury and infection and when for some reason this
host response is inappropriate - either exaggerated and prolonged or inappropriately subdued,
the consequence is widespread and severe tissue injury arising either as a result of the infection
itself or the host response itself.9 It is this acute inflammatory response which increases the
metabolic rate as a consequence of fever, the activation of the sympathetic nervous system and
the release of catecholamines, the direct effect of cytokines, the increased synthetic activity of
the liver in the production of acute phase proteins, the presence of a large wound and very often
increases in the work of breathing. In general, the increase in metabolic rate is less than 10% in
the majority of patients undergoing uncomplicated elective surgery. On the other hand, in
severely injured patients, the increase in metabolic rate may be as great as 20 to 50%
particularly in those patients who suffer a severe burn. In any event, the patients previous
18
Results
5.
22
Methods of placement
Nasoenteric
Nasogastric
Nasoduodenal / jejunal
Enterocutaneous
Percutaneous endoscopic
gastroscopy (PEG)
Percutaneous endoscopic
jejunoscopy(PEJ)
placement of feeding
tube as above beyond the pylorus.
Feeding gastroscopy
jejunostomy
More evidence surrounds the importance of supplementing TPN regimens with glutamine.26
Previously considered a non-essential amino acid, glutamine deficiency may occur in the setting
of acute catabolic illness with a rapid decline occurring in the concentration of free glutamine in the
intracellular amino acid pool of skeletal muscle. Glutamine is exported from skeletal muscle and
used by the visceral organs - as an ammonia donor in the kidney in its role in acid-base homeostasis
and as a primary oxidisable fuel source for enterocytes and colonocytes in the gastrointestinal tract.
It is also required (in combination with glycine and cyteine) for the formation of the tri-peptide,
glutathione, an important component of the cellular protection mechanisms against oxygen radical
injury. Glutamine supplementation (0.2 - 0.5 g per kilogram) may certainly improve nitrogen
balance and increase skeletal muscle concentrations of the amino acid. There are now 2 studies
demonstrating that the addition of glutamine can reduce the number of nosocomial infections and
length of hospital stay in patients undergoing bone marrow transplantation1 and a single study in
general ICU patients demonstrating much the same thing. The effect is more marked in patients
receiving TPN, not surprisingly since the standard amino acid solutions contain none whereas all
enteral feeds contain some glutamine albeit in low concentrations.
Finally, a recent study in a relatively homogeneous group of patients requiring intensive care
suggested that supplementation of enteral feeds with three specific immunonutrients may have
beneficial effects.27 These ingredients - arginine, purine nucleotides (in the form of yeast RNA) and
omega-3 polyunsaturated fatty acids - were chosen because of their well established effects on in
vitro and in vivo markers of immune function - promotion of T cell blastogenesis, enhancement of
cellular immunity and increased levels of the trienoic eicosanoids respectively. These three have
been combined into a single, commercially available enteral feed ("IMPACT", Sandoz Nutrition Ltd.,
Switzerland) with the aim of appropriate immune modulation in those patients in whom sepsis is
considered likely. Whilst there are at least 8 studies demonstrating its benefits in elective surgery
patients further work is required to examine the potential benefits of such an immunonutrient feed
in the general population (ie. non-trauma) of critically ill patients.
23
6.
24
25
26
INTRODUCTION
There is good evidence that management of patients with severe trauma is improved if an
organized and systematic approach is used. The following guidelines and notes are consistent
with the approach to severe trauma recommended by the Royal Australasian College of
Surgeons through its Committee on Early Management of Severe Trauma (EMST).1 This
approach has now been adopted by the Royal Australasian College of Surgeons as Official
College Policy. It is a mandatory requirement for training in a number of specialities. All
medical personnel who may be involved in looking after acute trauma should ensure that they
are familiar with the EMST approach. In many larger hospitals a Trauma Team2 is used to
facilitate the rapid assessment and management of major trauma victims. These Teams are
called out for injured patients fulfilling standard callout criteria.
This chapter will contain a brief outline of the basic principles of the EMST system,
followed by a more detailed discussion of some airway, breathing and circulation issues.
Finally a brief mention is made of some of the various scoring systems used in trauma patients.
OUTLINE OF EMST
The EMST system is divided into four main phases. These are a) Primary Survey,
b) Resuscitation, c) Secondary Survey and d) Definitive Care. These are expected to proceed
sequentially, with the exception that the Primary Survey and Resuscitation usually proceed in
parallel with life threatening problems being managed as soon as they are found.
a) Primary Survey: This includes five points
Airway:
Airway maintenance with cervical spine control.
Breathing:
Oxygenation and ventilation.
Circulation:
Circulation with haemorrhage control.
Disability:
Rapid neurological status. Includes AVPU (Alert, responds to Voice,
responds to Pain, Unresponsive) scale and pupils.
Exposure:
Completely undress the patient.
b) Resuscitation: Matching this to the Primary Survey.
Airway:
Manoeuvres include removal of foreign debris, chin lift, jaw thrust,
oropharyngeal airway, nasopharyngeal airway, oro- or naso- tracheal
intubation and cricothyrotomy.
Maintain the cervical spine in a neutral position with manual
immobilization by a second person if necessary.
Breathing:
Always administer high concentrations of oxygen (minimum is 12
litres/minute via face mask.)
Alleviate tension pneumothorax.
Seal open pneumothorax.
Ventilate if ventilatory failure.
27
28
33
<750
<15
<100
Normal
<2 sec
14-20
>30
Normal
Crystalloid
750-1500
15-30
>100
Normal
>2 sec
20-30
20-30
Anxious
Colloid
1500-2000
30-40
>120
Decrease
>2 sec
30-40
5-15
Confused
Blood
4
>2000
>40
>140
Decrease
>2 sec
>35
0-5
Lethargic
Blood
Crystalloid:
Colloid:
Blood:
Comments
Shaft of femur
1000-1500 mls
Double if compound
500-750 mls
Double if compound
Shaft of humerus
500-750 mls
Double if compound
250-500 mls
Double if compound
Pelvis
1500 mls+
Intraabdominal
Any amount
Includes retroperitoneum
Intrathoracic
Any amount
If the class of haemorrhage is worse than the obvious injuries would predict then it is likely
that there is concealed blood loss. This can be either in the pelvis, abdomen (including
retroperitoneum) or chest. In an adult it is virtually never in the head. Hypotension in the
presence of a head injury should not be assumed to be due to the head injury. Thus a person
with an isolated shaft of femur fracture who has a class 4 haemorrhage is bleeding from
somewhere else. Inadequate response to resuscitation fluids also suggests ongoing and perhaps
concealed bleeding.
34
35
36
38
INTRODUCTION
Acute renal failure (ARF) with its adverse effects on body water balance, electrolyte
composition, drug elimination and immune, central nervous and gastro-intestinal function is
associated with a mortality in excess of 50%. However, the true impact of ARF is best seen in
the multi-system injury of the critically ill where the occurrence of ARF markedly worsens the
outcome of other system failure. For example, the mortality from adult respiratory distress
syndrome is more than trebled by ARF.1 While the mortality from ARF has not changed over
the last 20 years despite improvement in our understanding of the pathophysiology of ARF and
advances in medical and dialytic therapies, the outcome is primarily determined by the nature
and magnitude of the precipitating insult, which has changed over this period of time. For
example, the incidence of critically ill patients with ARF has increased and they are older with
greater comorbidity and multi-system injury which has resulted in the improvement in outcome
being difficult to measure.
The spectrum of ARF has changed with the emergence of increasing numbers of patients
with non-oliguric renal failure (over 50% of reported cases in some series). This trend probably
reflects an improvement in care, particularly in circulatory resuscitation leading to a reduction
in renal injury and renal dysfunction. This assertion is supported by laboratory studies showing
fluid replacement, shorter periods of ischaemia and smaller doses of nephrotoxins result in nonoliguric ARF in otherwise oliguric models.2 The benefits of non-oliguric ARF include fewer
complications, requirement of less frequent dialysis and lower mortality rate.
PATHOPHYSIOLOGY
Ischaemic Renal Injury
The apparent sensitivity of the kidney to ischaemia is not explained by total organ blood
flow. This seemingly luxurious blood flow does not subserve renal metabolic demands but is
driven by glomerular filtration and the excretion of flow dependent waste.
Distribution of renal blood flow and oxygen consumption within the kidney
The kidney has a unique arrangement of blood vessels. The glomerular afferent arterioles
give rise to the glomerular capillaries, which then coalesce to form the efferent arterioles,
which in turn give rise to the peritubular capillary network. In the juxtamedullary region only,
these branches contribute to the vasa recta. The majority of renal blood flow is therefore
supplied to the renal cortex with little flow to the renal medulla. The vasa recta, along with
tubules of the medulla, form a hairpin loop descending down into the medulla enabling a
countercurrent exchange of solutes and the development of a mechanism that allows the
efficient concentration of urine. The countercurrent exchange of solutes is also associated with
oxygen diffusion from descending to the ascending branches of the vasa recta leading to a
reduced delivery of oxygen to the medulla. Limited medullary blood flow is also important in
39
43
A
B
B l ood pressure
Figure 1. A represents the normal kidney with intact autoregulation demonstrating a constant
glomerular filtration rate as blood pressure is lowered. Below the autoregulatory threshold
glomerular filtration rate becomes linearly dependent on pressure. B represents the acutely
injured kidney with its linear pressure-function relationship over the entire pressure range. No
autoregulatory threshold is identified and the line is depressed representing the vasoconstricted
state of the acutely injured kidney
Cardiac output:
While the pressure dependency of the kidney in the critically ill appears more important,
cardiac output cannot be ignored. This is particularly so in patients with low output states and
vasoconstriction and intact blood pressure. In patients with congestive cardiac failure there is a
linear reduction in renal blood flow with decreased cardiac output, with no relationship
between renal blood flow and blood pressure.30 In these patients the restoration of cardiac
output to more normal levels and correction of mixed venous desaturation with inotropes and
vasodilators improves renal function.
Haematocrit:
The optimal haematocrit for the kidney oxygen delivery is 40.31 This is much greater than
that usually aimed for in critically ill patients, and from a purely kidney perspective transfusion
thresholds should be higher.
Intra-abdominal pressure:
When clinically relevant intra-abdominal pressure should be measured by instilling 50-100
ml of sterile fluid into the empty bladder and measuring the pressure through a manometer side
port to the urinary catheter. Threshold pressure for decompression is 30 cm water. The timing
of decompression may be dictated by other factors, for example correction of coagulopathy in
post operative haemoperitoneum. However, sustained pressures of this magnitude will result in
progressive oliguria and declining renal function.
44
46
49
51
52
Introduction
The number of pregnant patients admitted to Critical Care units remains small. Some are
due to complications of an existing condition exacerbated by the pregnancy (eg. congenital
heart disease), while others are specifically related to the pregnancy. This review will
concentrate on conditions caused by pregnancy, or attempts to achieve pregnancy. A state of
the art review addressing all aspects of Critical Care in the pregnant patient appeared in the
American Journal of Respiratory and Critical Care Medicine in 1995.1
Pre-eclampsia
Severe pre-eclampsia or eclampsia is the most common pregnancy related complication
leading to admission to Critical Care units. The cause of this unique abnormality in the
maternal vascular endothelium, unlike that seen in any other type of hypertension is not clear.
Numerous terms have been used to describe the disorder. The Australian Society for the
study of Hypertension of Pregnancy recent released a consensus statement on the classification
and management of hypertension in pregnancy.2 They have elected to use the term Preeclampsia so that clinicians do not limit their thoughts to an abnormality of blood pressure in
pregnancy, but rather to a complex multi-system disorder that leads to or from an impaired
placental function and can affect the maternal brain, kidneys, liver, coagulation and cardiac
systems.
Hypertension in pregnancy
The types of hypertension encountered in pregnancy can be
Pre-eclampsia: mild or severe
Chronic hypertension: essential or secondary
Pre-eclampsia superimposed on chronic hypertension
Patients are considered to have hypertension if they have either of the following
1. Systolic blood pressure140 mmHg and /or diastolic blood pressure 90mmHg
(phase IV - muffling - Korotkoff sound)
or
2. Rise in the systolic pressure 25 mmHg and/or rise in the diastolic pressure
15 mmHg from preconception or first trimester readings (confirmed by two
readings six hours apart)
The rise in diastolic pressure is of greater significance, correlating with a sharp rise in perinatal
mortality.3
53
55
56
Grade four. Grade three features plus clinically apparent ascites with or without
pleural effusions or dyspnoea.
58
59
60
Analgesics are agents that reduce the sensation of pain without producing a loss of
consciousness. Hypnotics are agents that produce a condition of insensibility from which
arousal by physical stimulation may be achieved easily. Sedatives are agents that may relieve
the patients anxiety without making the patient excessively drowsy. Tranquillisers are agents
used to calm agitated and delirious patients without causing excessive drowsiness1.
These agents are used singly or in combination in intensive care patients to treat, pain,
delirium, acute confusional states, and to facilitate mechanical ventilation (i.e. to allow the
patient to tolerate an endotracheal tube and to facilitate patient synchronization with the
ventilator).
ANALGESICS
Opioids
There are specific sites on cell surfaces of the gastrointestinal tract, central nervous system,
peripheral sensory nerves and in the substantia gelatinosa of the spinal cord which interact in a
highly selective fashion with opioid drugs. These receptors mediate the major known
pharmacological actions of opioids and the functions of endogenous opioid-like substances,
and are known as opioid receptors. The mammalian brain contains peptides known as the
enkephalins and endorphins, which interact with opioid receptors and have pharmacological
properties similar to those of morphine2. In the substantia gelatinosa, enkephalin secreting
neurones terminate presynaptically on pain mediating primary afferent fibres, inhibiting the
release of the neurotransmitter, substance P, to the dorsal horn spinothalamic neurone. There
are also important links between the opioid pathways and noradrenaline and serotonergic
pathways, with selective alpha 2 agonists (e.g. clonidine), noradrenaline uptake inhibitors (e.g.
desimipramine) and serotonin uptake inhibitors and release facilitators (e.g. tramadol),
enhancing the effect of opioid analgesia3.
The major opioid receptor subtypes (mu, delta and kappa) are coupled to intracellular
processes via G proteins. Mu and delta receptors operate through the potassium channel,
whereas the kappa receptor operates through the calcium channel4. The previously described
sigma receptors are most likely due to N-methyl-D-aspartate receptor activity. The clinical
effects of opioid receptor stimulation, the opioid subtypes, and the receptor subtype agonists
and antagonists are listed in Table 15.
Opioid peptides
The opioid peptides (i.e. enkephalins, endorphins and dynorphins) originate from the three
prohormones of pro-enkephalin (producing methionine enkephalin, and leucine enkephalin),
pro-opiomelanocortin (producing beta-endorphin) and pro-dynorphin (producing dynorphin A
and dynorphin B). The enkephalins are found in the gastrointestinal tract (particularly the
61
Kappa
Delta
Clinical effects
Analgesia (supraspinal)
Respiratory depression
Depression temp regulation
Miosis
Euphoria
Physical dependence
Analgesia (spinal)
Sedation
Miosis
Little or no resp depression
Agonist
Antagonist
Met-enkephalin
Beta-endorphin
Morphine
Naloxone
Pentazocine
Nalorphine
Dynorphins
Naloxone
Butorphanol
Morphine
Nalorphine (partial)
Pentazocine
leu-enkephalin
Naloxone
Beta-endorphin
? Respiratory depression
Opioid analgesics
Action: Opioid analgesics (or narcotics) reproduce some of the effects of the endogenous
opioid peptides. Their clinical effects include the following.
1. CNS effects.
Analgesia: the sites of action for analgesic effects are located principally in the
brainstem and the spinal cord. The degree of pain relief is related to the dose of opioids,
intensity and type of pain, and patient's perception of pain. Opioids tend to preserve the
perception of pain, whilst the threshold of pain tolerance is increased (particularly for
visceral rather than musculoskeletal pain).
Dysphoria, drowsiness, sedation and coma: these effects are often dose dependent.
Nausea and vomiting: these effects are due to chemoreceptor trigger zone stimulation.
Miosis: this is due to direct stimulation of the Edinger-Westphal nucleus (as a rare
phenomenon, dilated pupils with morphine toxicity has been described6).
Excitatory effects: agitation and delirium may occur due to excessive N-methyl-Daspartate receptor stimulation (although rare, it is more commonly observed with
pethidine, pentazocine and fentanyl)
Physical and psychological dependence: these effects are common with recreational use
of opioids.
2. CVS effects. venous capacitance is often increased both directly and indirectly (e.g. due
to histamine release). Both morphine and pethidine release histamine causing pruritus, urticaria,
hypotension and a decrease in the systemic vascular resistance. The histamine-release effect is
not blocked by naloxone. Fentanyl does not release histamine or decrease blood pressure even
in large doses. While it is commonly believed that opioids have a direct vagal effect, this has
62
63
Natural
Morphine
Codeine
Semisynthetic
Pethidine
Synthetic
Phenoperidine
Fentanyl
Alfentanyl
Pentazocine
duration plasma
Dose/70 kg
of action protein
IM
IV infusion
(h)
binding (%) (mg/4h) (mg/h)
10
120
3-4
3-4
2-4
2-4
35
7
10
1-5
100
3-4
2-4
65
100
25 - 50
1
0.1
0.4
15
3-4
3-4
1-2
3-4
1-2
0.5 - 1
0.25 - 0.5
2-4
65
83
91
60
0.5 - 1
0.05 - 0.3
0.1 - 4
10
Opioid antagonists
Opioid antagonists bind to opioid receptors without activating the receptor. Partial opioid
agonists (i.e. opioid agonist/antagonists) have an intermediate effect.
Naloxone is a pure antagonist with no agonist activity, it reverses the analgesia, respiratory
depression, sedative and miosis associated with opioids. Its effect, if administered
intravenously (e.g. 0.1 - 0.4 mg), begins in minutes and lasts for 15 - 90 min. It has also been
reported to reverse the respiratory depression associated with diazepam14 and ethanol
toxicity15. Naloxone, in doses of 10 - 20 mg, has also been used with some success in septic
shock16. However, it may cause hypertension, pulmonary oedema, and ventricular fibrillation
when administered to antagonize the effect of prolonged opioid administration17
Opioid withdrawal
During opiate withdrawal, the first 8 - 16 h of abstinence is usually uneventful. Over the
next few hours there is excessive yawning, lacrimation, diaphoresis, rhinorrhoea, insomnia,
agitation, tremor, waves of 'goose flesh', hot and cold flushes, tachycardia, hypertension, joint
and muscle aches, abdominal pain, nausea, vomiting, diarrhoea and pyrexia. The symptoms
peak at 48 - 72 h then slowly subside over 5 - 10 days.
Paracetamol and non-steroidal anti-inflammatory drugs
Non-steroidal anti-inflammatory drugs (NSAIDs) are a large group of structurally diverse
organic acids which reversibly (the acetylation of cyclooxygenase by aspirin is an exception as
it is irreversible) inhibit prostaglandin synthesis and cause analgesic, antipyretic, antiplatelet
and anti-inflammatory therapeutic effects and gastric mucosal damage and renal dysfunction
side effects18. While paracetamol also inhibits cyclooxygenase and has analgesic and
antipyretic actions it has no antiplatelet and anti-inflammatory actions and does not cause
gastric mucosal damage.
Indications: Analgesia (particularly for dental pain, headache and musculoskeletal pain),
antipyretic effects, anti-inflammatory effects (for rheumatic and connective tissue diseases),
antiplatelet effects (for TIAs, post coronary artery bypass surgery, ischaemic heart disease),
prophylactic effects (pre eclampsia, colon carcinoma) and other rare disorders (e.g. closure of
patent ductus, Bartter's syndrome). Paracetamol (1 g, 4-hourly) is the antipyretic and
musculoskeletal analgesic agent of choice in the acutely ill patient. While aspirin and
64
duration plasma
Formulation
of action protein
(mg/tab)
(h)
binding (%)
Paracetamol
Aspirin
Diclofenac
Diflunisal
Ibuprofen
Indomethacin
2
0.25*
1.1
13
2.1
4.6
4-8
4 - 8**
4-8
12 - 24
4-8
6 - 12
20
70
99
99
99
90
Ketoprofen
Naproxen
Piroxicam
Sulindac
1.8
14
57
14
4-8
12 - 24
24
12 - 24
95
99
99
96
Dose/70 kg
Oral
(mg/24h)
500
2000 - 4000
100 -325
600 - 2600
25 - 50
75 - 150
250
500 - 1000
200 - 400
1200 - 1600
25
50 - 200
100 (suppository)
50 - 100
100 - 200
250 - 500
375 - 1000
10
10 - 20
100 - 200
200 - 400
65
Drug
therapeutic
equivalence
Diazepam
Flurazepam
Clonazepam
Nitrazepam
Lorazepam
Alprazolam
Temazepam
Oxazepam
Midazolam
Flumazenil
10
elimination
half-life (h)
plasma protein
binding (%)
20
5
20 - 40
20 - 40
20
20
15
15
10
6
2-5
96
1-5
40
0.1
2.5
98
Dosage
IV (mg/70 kg/h)
2 - 10
0.25 - 0.5
90
0.5-2
98
Benzodiazepine antagonists
Flumazenil has an elimination half-life of 1 h, and in large doses may have an intrinsic (i.e.
agonist or reverse agonist) activity. With intravenous administration of 0.5 - 1 mg, complete
reversal of the benzodiazepine effect is apparent after 5 min, and the duration of action varies
from 15 - 140 min depending on the dose. In the presence of long-acting benzodiazepines, a
continuous infusion of 0.1 - 0.4 mg/70 kg/h of flumazenil may be used to maintain a state of
alertness. It has been used to reverse benzodiazepine sedation associated with, weaning patients
from mechanical ventilation, reversing anaesthesia (e.g. endoscopy anaesthesia), and treating
overdosage. It has also been used to reverse hepatic encephalopathy and alcohol intoxication24.
The side-effects associated with flumazenil are usually mild and include agitation, nausea
and vomiting. However, malignant side effects have also been reported and include deaths
which were probably due to partial or ineffective reversal of respiratory depression25,
convulsions in patients in whom epilepsy had been controlled by benzodiazepines26 or when
used to treat a combined tricyclic and benzodiazepine overdosage27, and seizures with
ventricular tachycardia when used to treat combined tricyclic28 or chloral hydrate29, and
benzodiazepine overdosage.
Barbiturates
Thiopentone and phenobarbitone have been used as a sedative agent in the critically ill
patient, particularly when a reduction in the cerebral oxygen consumption and ICP may be
desirable (e.g. neurosurgical patients). A dosage of 15 - 20 mg/kg (i.e., 1000 - 1500 mg/70 kg)
will saturate the distribution space for thiopentone. Thus a continuous infusion of thiopentone
at 2 - 4 mg.kg-1.h-1 (i.e. 150-300 mg/70 kg/h) should keep a plasma level at 10-15 mg/l. As the
half-life of thiopentone is 5 - 12 h, to reduce the plasma level by 95% will take 1 - 2 days, and
with hepatic or cardiac failure this may increase up to 7 days.
67
Propofol
Propofol is a non water soluble agent formulated as an aqueous emulsion in a 1% Intralipid
solution. It may be used as an induction agent (e.g. 2 - 2.5 mg/kg or 150 - 175 mg/70 kg,
usually titrated at 40 mg every 10 s until the patient shows signs of anaesthesia), anaesthetic
agent (e.g. 6 - 12 mg.kg-1.h-1 or 400 - 800 mg/70 kg/h) or as a sedative agent (e.g., 1.5 - 6
mg.kg-1.h-1 or 100 - 400 mg/70 kg/h) in the intensive care patient. It has no anticonvulsant or
analgesic effects and may even provoke epilepsy in an epileptic patient30. Propofol is excreted
in the urine as 1-glucuronide, 4-glucuronide and 4-sulphate conjugates of 2,6-di-isopropyl-1,4quinol which may produce green urine with prolonged infusions31.
The major advantage of propofol is the rapid speed of recovery in comparison to other
agents. In a two-compartment model, the elimination half-life is 100 - 300 min; it is 98% bound
to plasma proteins.
Propofol produces a dose-dependent reduction in blood pressure, predominantly due to a
fall in systemic vascular resistance, which may present as a profound reduction in blood
pressure in the critically ill and elderly patient. While it appears to have no significant
adrenocortical function inhibition, and has the advantage of rapid reversal when discontinued,
propofol as a single sedative agent used for 3 or more days has been associated with metabolic
acidosis, bradycardia, progressive and unresponsive myocardial failure, lipaemic serum and
death, in five paediatric intensive care patients32.
The lipid base of propofol supports bacterial growth when contaminated, and infectious
complications have occurred due to bacterial contamination of propofol infusions, particularly
when 50-100 ml ampoules have been used as multidose vials33. It is recommended that the
unused portion of a propofol infusion should be discarded after 6 h after initial use (or within
12 h if administered directly from the vial for sedation in an intensive care unit)34.
Ketamine
Ketamine is a phencyclidine derivative with NMDA receptor antagonist and opioid receptor
agonist effects (as well as calcium channel, muscarinic receptor, and serotonin receptor
activities), providing analgesic as well as sedative effects35. An intravenous infusion of 3 -15
g/kg/min has been used in intensive care patients (particularly when severe bronchospasm or
shock exists)36.
TRANQUILIZERS
Phenothiazines
These are DA1 and DA2 dopamine receptor blockers, which may block muscarinic, alpha1-adrenergic and H1 histamine receptors as well. Their antipsychotic activity is due largely to
their DA2 dopamine receptor blocking effect in the limbic system.
Chlorpromazine is the standard phenothiazine tranquilliser. An initial oral or intramuscular
dose of 50 - 100 mg is commonly administered to manage an agitated patient and its effect is
usually assessed 1 h later. If required, further doses of 50 - 100 mg may be administered hourly.
While up to 1000 mg has been used in some severely disoriented patients, if 400 - 600 mg does
not produce the desired effect, then supplemental doses of a benzodiazepine (e.g. diazepam 2 10 mg) will act synergistically and produce profound sedation which often lasts for 24 - 48 h.
While an intravenous bolus dose of 2.5 - 10 mg of chlorpromazine often causes severe
hypotension, an intravenous infusion at 10-20 mg/h usually does not, and can be used safely.
The elimination half-life of chlorpromazine is 24 - 48 h.
68
Sedation-agitation scale*
Score
Description
Example
+3
Immediate threat to safety Pulling at endotracheal tube
or catheters, trying to climb over
bedrail, striking at staff.
+2
Dangerously agitated
+1
Agitated or restless
-1
Oversedated
-2
Very oversedated
-3
Unarousable
72
43. Hansen-Flaschen J, Cowen J, Raps EC. Neuromuscular blockade in the intensive care
unit. More than we bargained for. Am Rev Resp Dis 1993;147:234-236.
44. Segredo V, Caldwell JE, Matthay MA, Sharma ML, Gruenke DL, Miller RD. Persistent
paralysis in critically ill patients after long-term administration of vecuronium. N Engl J
Med 1992;327:524-528.
45. Bion JF, Bowden MI, Chow B, Honisberger L, Weatherley BC. Atracurium infusions in
patients with fulminant hepatic failure awaiting liver transplantation. Intens Care Med
1993;19:S94-S98.
46 . Meyer KC, Prielipp RC, Grossman JE, Coursin DB. Prolonged weakness after infusion of
atracurium in two intensive care unit patients. Anesth Analg 1994;78:772-774.
47. Parker CJ, Jones JE, Hunter JM. Disposition of infusions of atracurium and its metabolite,
laudenosine, in patients with renal and respiratory failure in an ITU. Br J Anaesth
1988;61:531-540.
48. Hunter JM. Atracurium and laudanosine pharmacokinetics in acute renal failure. Intens
Care Med 1993;19:S91-S93.
49. Watt I, Ledingham IM. Mortality amongst multiple trauma patients admitted to an
intensive therapy unit. Anaesthesia 1984;39:973-981.
50. Aitkenhead AR, Pepperman ML, Willatts SM, Coates PD, Park GR, Bodenham AR,
Collins CH, Smith MB, Ledingham IMcA, Wallace PGM. Comparison of propofol and
midazolam for sedation in critically ill patients. Lancet 1989;ii:704-709.
51. Sinclair ME, Sear JW, Summerfield RJ, Fisher A. Alfentanyl infusions in the intensive
care unit. Intens Care Med 1988;14:55-59.
73
74
Introduction
Intravenous therapy is indicated for replacement of fluid and electrolytes when enteric
feeding is contraindicated, when correction of acute fluid losses is required, and for
administration of intravenous drugs. An approach to decision-making in the paediatric patient
is:
- what volume should be given?;
- how quickly should it be given?; and
- what type of fluid is necessary?
There are several methods for calculating requirements for water, calories, and electrolytes
in paediatrics, and these are usually based on weight, body surface area, and caloric
requirements1. Therapy should be customised for individual variations in age, for growth rate,
metabolism and responses to trauma and illness. Repeated evaluation of clinical status and
therapeutic response is important in management. There are unique features in paediatric
patients which alter insensible water loss2. For example:
Increased insensible water loss may be due to:
- air currents;
- radiant heaters;
- low birth weight;
- motor activity;
- phototherapy;
- fever;
- increased minute ventilation;
- dry or cool inspired gases; and
- low ambient humidity.
Reduced insensible water loss may be due to:
- high ambient humidity;
- humidification of inspired gases;
- inactivity;
- hypothermia;
- inappropriate ADH secretion; and
- renal failure.
Technical Aspects
Venous cannulation in the paediatric patient is difficult when veins are small and difficult to
visualise. Optimal sites for percutaneous cannulation are the dorsum of the hand, the
antecubital fossa, the dorsum of the foot, the scalp and the long saphenous and external jugular
veins. Percutaneous central venous cannulation is routine with small bore, non-thrombogenic
catheters, but should not be persisted at the expense of resuscitation. Accidental infusion of
75
give 4mls/kg/hr
add 2mls/kg/hr
add 1ml/kg/hr
Adjustments for neonates allow a 10% to 15% weight loss in the first few days which
minimises morbidity4. Any calculated volume must incorporate fluid volumes flushed through
monitoring catheters, fluid given with drugs (eg antibiotics), and blood products. Low birth
weight neonates have relatively larger insensible water losses.
Continuous Haemofiltration
Haemofiltration is either arterio-venous (CAVH) with flow resulting from the arteriovenous pressure difference, or veno-venous (CVVH) requiring flow from an extrinsic pump.
Haemodiafiltration is where dialysate is perfused across the filter.
Indications for haemofiltration include renal failure, fluid overload, metabolic derangements
(electrolyte, acid base), and fluid volume limitations that restrict nutrition. Haemofiltration is
most useful for fluid removal in cardiovascularly unstable patients, but is less rapid and
effective than haemodialysis5. It removes middle weight vasoactive peptides that may lead to
capillary leakage. Problems of continuous haemofiltration in children are:
- additional arterial and/or venous lines are required;
- blood flow and ultrafiltrate flow are dependent on arterial blood pressure (which is
lower in children), pressure on the venous side of the filter, haematocrit, and position,
size and length of catheters;
- regional heparinisation may cause bleeding;
- platelets are trapped by the filter especially at low blood flows in paediatric patients;
- small blood aggregates are flushed into the venous circulation.
CAVH is simpler because the A-V pressure gradient drives blood through the filter. This
provides safety and haemodynamic stability. However because blood flow rates are low with
small paediatric cannulas and lower blood pressure, urea clearance is reduced. Blood flow can
be improved by increasing blood pressure, correcting hypovolaemia, and reducing blood flow
resistance by reducing cannula length, increasing cannula size, changing cannula position.
Continuous arterio-venous diafiltration improves urea clearance.
76
Calories/kg/day
120
90
75
60
30
Caloric intake should be increased for some disease processes where energy consumption is
high. Disease processes requiring increased caloric expenditure are:
- fever;
- surgery;
- sepsis;
- cardiac failure;
- respiratory failure;
- burns; and
- malnutrition.
Protein requirements are 2-3 gm/kg/day, while glucose requirements are 10-15 gm/kg/day,
although neonates may require up to 20 gm/kg/day. Fat administration prevents essential fatty
acid deficiency and when metabolised produces less CO2, which may be important in patients
77
78
79
80
Introduction
Through a review of the forces that are overcome during spontaneous breathing it is easier
to understand the forces and pressures generated during mechanical ventilation (MV).
Contraction of the respiratory muscles expands the thorax and lowers intrapleural pressure. The
resultant pressure gradient from airway to alveolus leads to inspiratory gas flow. With loss of
muscle contraction the alveolar to airway pressure gradient falls and gas flow ceases.
Expiration is normally passive with recruitment of expiratory muscles only occurring during
high minute ventilation and elevated respiratory work.
The pressures generated may be modelled using the equation of motion (essentially assumes
the respiratory system consists of a balloon and a tube):
P = Pel + Pres + Pinert
ie the total pressure is the sum of elastic pressure (Pel), resistive pressure (Pres) and inertive
pressure (Pinert). Inertive pressure (inertance x acceleration) is such a small component of the
total pressure during gas flow that it can be ignored. This allows simplification of the equation
to:
P = Pel + Pres
& .
P = EV + R V
When this is applied during MV:
&
Pao = ErsV + Rrs V
where Pao is the airway pressure, Ers is the dynamic respiratory system elastance and Rrs is the
dynamic respiratory system resistance. Of course the end-expiratory pressure may not be 0 so
the equation becomes:
& + Po
Pao = ErsV + Rrs V
where Po is an estimate of the alveolar pressure at end-expiration. This is equivalent to the total
PEEP and the intrinsic PEEP may be calculated as Po - Pmin, where Pmin is the minimum
recorded airway pressure referenced to atmosphere.
While more complex equations allow better modelling of the respiratory system,
particularly during disease states, most of the principals can be illustrated with this simple
model. It is important to note that respiratory work (W) can be calculated as:
W = PV
allowing easy development of the notion of elastic work and resistive work. Elastic work will
comprise lung and chest wall components, and viscolelastic properties of the lung and chest
wall; and flow resistive work will include airway and apparatus (depending upon the site of
measurement of Pao).
81
& O2. High levels of respiratory work commonly occur in acute respiratory
myocardial V
failure and demand massive increases in respiratory muscle blood flow to provide adequate
substrate. Laboratory studies demonstrate that despite a redistribution of regional blood
flow away from vital organs, respiratory muscle blood flow may become inadequate with
subsequent respiratory muscle fatigue and apnoea. In addition calculated oxygen
consumption by the respiratory muscles may become a large proportion of systemic oxygen
& O2). Consequently in shock states or acute hypoxaemic respiratory failure
consumption ( V
12
12
-5
normal
12 cmH2O PEEPi
-1
-1
-7
-15
-6
15
pre-inspn
inspiration
Legend: bar represents the upper airway; the circle is the representative alveolus; the
triangle is the pleural space; and DP is the change in pleural with initiation of inspiration. In
this example a large threshold load is imposed by PEEPi, and this is markedly reduced with
the application of CPAP.
6. Sedation and Paralysis: may result in hypotension and muscle weakness.
7. Other: agitation, sleep disturbance, renal dysfunction (predominantly due to cardiac
output), ICP due to impaired venous drainage with high levels of PEEP.
MODES OF VENTILATION
1. Controlled Mechanical Ventilation (CMV): the most basic form of MV supplying all
ventilation in the apnoeic patient; spontaneous breaths are not available. During pressure
controlled ventilation (PCV) each breath is delivered as a time preset pressure controlled
breath and VT varies; however, during CMV ventilators usually deliver time preset flow
controlled breaths, and the pressure profile will depend upon the inspiratory flow pattern,
Pel, Pres and PEEPtot.
The schematic diagram below represents these components during CMV with a constant
inspiratory flow pattern. In a relaxed patient if an inspiratory pause long enough to allow
equilibration were present, the airway pressure would decay bi-exponentially, due to
dissipation of flow-resistive and viscoelastic forces (usually a small component), to Pel.
While somewhat oversimplified this approach allows a reasonable understanding of the
forces the ventilator is overcoming during MV, rather than just noting that the patient is
84
& .
Rrs = (Ppk-Pplat)/ V
Ppk
Pres
Pel
Pressure
Pmean
}PEEP
tot
Time
2. Assist/control Ventilation (ACV): in addition to a preset background rate of CMV breaths,
patient inspiratory effort initiates a standard CMV breath. The ability to control respiratory
rate means that less sedation is required; however the respiratory muscles continue to
contract during these assisted breaths6 with only a small reduction in work compared to
unassisted spontaneous breaths7.
3. Intermittent Mandatory Ventilation (IMV): in concept IMV was introduced to allow
unimpeded spontaneous breaths while still ventilated with intermittent CMV breaths, to
minimize sedative use and reduce respiratory muscle discoordination allowing more rapid
weaning. In addition the reduction in intrathoracic pressure may ameliorate many of the
cardiovascular and respiratory complications of CMV.
Synchronized IMV (SIMV) is designed to avoid breath stacking by partitioning the
inspiratory time into patient initiated, or spontaneous, breaths. Neither IMV or SIMV has
been clearly shown to allow easier weaning than T-piece trials8, perhaps due to the
inspiratory workload imposed by the endotracheal tube, connector and ventilator demand
valve9,10. Since respiratory effort is strongly influenced by respiratory drive patient initiated
breaths do not effectively unload the respiratory muscles, with the workload decreased by
only 40% when over half the minute volume is supplied by SIMV breaths11.
4. Pressure Support Ventilation (PSV): during PSV spontaneous patient breaths are
supported to a preset pressure using additional gas flow. Inspiration is usually terminated
when the inspiratory gas flow falls to 25% of the initial flow rate or less than 5 L/min.
While PSV may assist in unloading the respiratory muscles12 and offset the apparatus work
85
& and VT, and is often 0.8-1.2 s. Longer inspiratory times elevate Pmean
determined by V
without increasing Ppk, and shorter times prolong expiration which may be desirable in
severe airflow obstruction as this will reduce gas trapping22. During inverse ratio ventilation
the inspiratory time is so prolonged that the I:E ratio is less than 1:1. The resultant
shortening of expiration often leads to gas trapping and PEEPi. This can be applied with
pressure controlled (PCIRV) or volume controlled (VCIRV) modes. While commonly used
in patients with ARDS there are no convincing studies that show benefit over conventional
ventilation when PEEPtot is matched23,24,25.
2. Inspiratory Flow Pattern: when the I:E ratio and VT are taken into account there is no
demonstrated difference between the available wave forms.
3. Inspiratory Pause: An end-inspiratory pause may improve oxygenation through
prolonging the inspiratory time; however, for a given mean airway pressure and inspiratory
time there is no advantage.
4. Sigh: the role of various recruitment manoeuvres (large VT, sigh or PEEP) remains
uncertain; however in their absence monotonous small -moderate VT ventilation results in
progressive atelectasis. A major factor contributing to this is lack of lung stretch leading to
release of surfactant26. This is particularly concerning as modern strategies of small VT
ventilation may promote stiff lungs; however regular suctioning preceded by hand
ventilation may well provide an appropriate stimulus.
PARTICULAR CLINICAL SETTINGS
1. ARDS
Increased permeability, increase in lung water, inflammatory infiltrate, proliferation of type
II cells, abnormal surfactant and fibrosing alveolitis results in dependent collapse, PO2,
physiologic dead space and respiratory work (Rrs due to lung volume and Crs due to
lung and chest wall effects). Ventilation with PEEP is a standard approach while the underlying
condition is diagnosed and treated. CT-based dependent collapse with ventilation of relatively
normal non-dependent lung has increased concerns that lung overdistension may occur unless
VT is reduced. However, inadequate PEEP will increase local shear forces (140 cmH2O
applied to atelectatic lung by surrounding normal lung at a transpulmonary pressure of 30
cmH2O27) due to repeated opening and closing of unstable alveoli. In states of abnormal
surfactant function this results in an acute lung injury. Ideally then tidal ventilation would occur
between the lower and upper inflection points of the lung volume-pressure relation,
representing the limits of recruitment of unstable alveoli with PEEP and pulmonary
overinflation. Amato and colleagues have titrated ventilation from static relations and
suggested this results in better outcome28, but some continuous measure such as volumedependent elastance servo controlled to ventilation is even more appealing.
87
Pressure
2. ASTHMA
Avoidance of MV remains an important goal in patients with acute severe asthma. While
the role of NIV, particularly CPAP, remains uncertain there are a number of potential
advantages. Many patients develop high levels of PEEPi with elevated threshold work making
a significant contribution to their work of breathing and ventilatory failure. Application of
CPAP below this level appears to help overcome this threshold and assists inspiration without
obviously worsening hyperinflation. This can be quite spectacular and allow effective
bronchodilator therapy time to act. However, skilled personal are essential in case intubation
becomes necessary.
In the intubated patients sedationparalysis is needed to allow an adequately long expiratory
time to be delivered so as to minimize dynamic hyperinflation and PEEPi in order to minimize
the risk of barotrauma or shock due to acute right heart failure and reduced venous return. This
will usually mean accepting low respiratory rates and markedly elevated PaCO2s until
improvement in the degree of airflow obstruction. PEEP should be reserved for improving
ventilator sensing during spontaneous or assisted breaths, and may exacerbate hyperinflation
during CMV.
3. WEANING
While it is often said that weaning, sometimes referred to as liberation, from the ventilator
should start once the patient is intubated, premature attempts can result in respiratory muscle
fatigue and atelectasis. Clearly the initial process should be resolving and it helps if the patient
is cooperative and demonstrates sufficient strength and good enough oxygenation to no longer
need ventilatory assistance. However this is not always possible and many of the predictive
indices such as oxygenation, the respiratory rate to tidal volume ratio (f/VT ratio), the
inspiratory occlusion pressure at 0.1 seconds (P0.1) and an index derived from compliance,
respiratory rate, oxygenation and pressure (CROP index) have wide confidence limits29, and do
88
89
90
Introduction
Intensive care is costly in both human and financial terms since technological advances
have made it possible to maintain the lives of patients in whom the prognosis is extremely
grave, if not hopeless. Together with the emphasis on evidence based medicine and given the
limited resources experienced by all health care systems in the developed world, unavoidable
questions arise regarding the appropriate application and benefit of intensive care. In this
regard, scoring systems have been developed and used for over the last decade for the
measurement of severity of illness and therapeutic intervention in an attempt to describe more
objectively the case mix of and outcome from intensive care. Currently, three severity of illness
scoring systems - APACHE II1 and III2, SAPS 23 and MPM I and II4,5 are in widespread use so
as to provide an estimated probability of hospital mortality for groups of patients. Their
refinement continues but there is a certain amount of confusion regarding their role in clinical
research, quality assurance and clinical decision making. These issues were addressed at the 2nd
European Consensus Conference in Intensive Care Medicine (Paris 1993)6 where five specific
questions relating to their use in predicting outcome in ICU patients were identified (table 1)
and some consensus obtained. Since that time little has changed although more emphasis has
been placed upon over time scoring systems as being more useful in the assessment of
individual patients5,7,8,9.
Table 1 - the five questions considered by the
Conference
1)
2)
3)
4)
5)
reliability -. the same score is obtained if measured in a stable patient at two different
times
criterion validity - the system should be measuring what it purports to be measuring
according to an independent standard
content validity - the system should be comprehensive, according to the intended purpose.
responsiveness - the system should detect change in patients who are changing over time.
discrimination - the system should discriminate between individuals with the same
condition, but with different degrees of severity
relative simplicity and ease of administration.
94
95
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Lemeshow S, Teres D, Klar J et al. Mortality prediction models (MPM II) based on an
international cohort of intensive care unit patients. JAMA 1993;270:2478-2486.
Lemeshow S, Lar J, Tere D et al. Mortality probability models for patients in the intensive
care unit for 48 and 72 hours - a propective multicentre study. Crit Care Med
1994;22:1351-1358.
Consensus Conference - Predicting outcome in ICU patients. Intensive Care Medicine
1994;20:390-397.
Chang RWS. Individual outcome prediction models for intensive care units. Lancet
1989;ii:143-146.
Atkinson S, Bihari D Smithies M et al. Identification of futility in Intensive Care. Lancet
1994;344:1203 - 120.
Silvester W, Bihari D. Overtime scoring systems. Curr Opinion Crit Care 1995;1:228 232.
Petros AJ, Marshall JC and van Saene HKF. Should morbidity replace mortality as an end
point for clinical trials in intensive care ? Lancet 1995;345:369-371.
Zimmerman JE, Wagner DP, Draper EA and Knaus WA. Improving intensive care unit
discharge decisions: supplementing physician judgement with predictions of next day risk
for life support. Crit Care Med 1994;22:1373-1384.
Cullen D, Civetta J, Briggs B, Ferrara L. Therapeutic intervention scoring system; a
method for quantitative comparison of patient care. Crit Care Med 1974;2:57-61.
Steingrub JS, Teres D. Comorbidities and organ failure assessment. Current Opinion in
Critical Care 1996;2:221-225.
Lemeshow S, Klar J and Teres D. Outcome prediction for individual intensive care
patients: useful, misused or abused ? Intensive Care Med 1995;21:770-776.
Boyd O, Grounds RM. Physiological scoring systems and audit. Lancet 1993;341:15731574.
Rowan K. The reliability of case mix measurement in intensive care. Current Opinion in
Critical Care 1996;2:209-213.
Sirio CA, Kimitaka T, Choichiro T et al. An initial comparison of intensive care in Japan
and the United States. Crit Care Med 1992;20:1207.
Malstam J, Lind L. Therapeutic intervention scoring system (TISS) - a method for
measureing workload and calculating costs in the ICU. Acta Anaesthesiol Scan
1992;36:758-763.
96
PULMONARY EMBOLISM
L.I.G. Worthley, FRACP, FANZCA, FFICANZCA
Consultant Intensivist,
Department of Critical Care Medicine,
Flinders Medical Centre, Bedford Park,
SOUTH AUSTRALIA 5042
INTRODUCTION
Pulmonary embolism is the partial or complete obstruction of pulmonary arterial blood flow
by an intravascular embolus. While any material may traverse the venous system to embolize in
the pulmonary vasculature, thrombus, air, fat or amniotic fluid are the only materials that
commonly cause clinical symptoms. Massive pulmonary embolus is defined as an embolus
which obstructs greater than 50% of the pulmonary vasculature.
THROMBOEMBOLISM
Cause. Pulmonary thromboembolism occurs in 1%-2% of hospital patients1, and originates
from the lower limbs (two thirds of which have no signs or symptoms) in 95% of cases. An
upper limb thrombus is almost never responsible for a pulmonary thromboembolism2.
Clinical features3. Virtually all patients who have a pulmonary embolism have dyspnoea
that is sudden in onset. The dyspnoea may be transient, although with severe embolism it is
usually persistent and also often out of proportion to the degree and extent of the objective
abnormal findings. The common clinical features of a minor pulmonary thromboembolism
include dyspnoea, pleuritic chest pain, tachycardia, pyrexia and tachypnoea. The common
clinical features of a massive pulmonary thromboembolism include diaphoresis, syncope,
pallor, abdominal pain and a sudden need to evacuate bowels (due to a sudden increase in
venous pressure with splanchnic engorgement), and signs of tachycardia, hypotension, right
ventricular heave, prominent right atrial a waves, and splitting of the second heart sound.
Haemoptysis is a late sign associated with pulmonary thromboembolism and only occurs if
pulmonary infarction has occurred4. As the lung has three sources of oxygen (pulmonary
circulation, bronchial circulation and airways) pulmonary infarction occurs in only 30% of
patients with pulmonary thromboembolism and more often in those patients who have cardiac
failure. The incidence of symptoms and signs associated with pulmonary thromboembolism are
listed in Table 1.
Investigations: The investigations include:
1. Plasma biochemistry: analysis reveals an increase in LDH in 60% of cases and an
increase in bilirubin in 30% of cases.
2. Plasma XDPs (D-dimer). These are increased in patients with pulmonary
thromboembolism. The sensitivity of this test is 97% (when measured by enzyme-linked
immunosorbent assay). However, the specificity of the test is low, so while venous thrombosis
and pulmonary embolism may be unlikely in a patient with normal plasma D-dimer
concentrations (i.e. it is useful in ruling out pulmonary embolism), a positive result requires
confirmation by more specific imaging techniques5.
97
Pulmonary Embolism
Table 26.1 The incidence of symptoms and signs of pulmonary thromboembolism
Symptoms
Incidence %
Dyspnoea
Chest pain
Pleuritic
Non pleuritic
Apprehension
Cough
Haemoptysis
Diaphoresis
Syncope
A need to evacuate
bowels
80
70
10
60
50
30
30
10
10
Signs
Incidence %
90
60
50
30
10
50
40
40
40
30
20
5
3. Arterial gas analysis: this reveals a low PaCO2 and PaO2 in 90% of cases of pulmonary
thromboembolism, due to hyperventilation and ventilation perfusion mismatch6. The end
expired CO2 is also reduced.
4. ECG: a transient rSR pattern in the anterior chest leads, S1, Q3-T3, clockwise rotation
and right axis deviation are the classical ECG findings of an acute pulmonary embolism,
although they are found in only 5-10% of cases. Commonly there is sinus tachycardia and T
wave inversion in the right precordial leads. Atrial flutter or fibrillation may also occur. While
the ECG may contribute very little to the diagnosis of pulmonary embolism, it often contributes
by excluding other disorders (e.g. myocardial infarction, pericarditis).
5. Chest X-ray: this may reveal oligaemic areas (reduced vascular markings) within the
lung fields, pulmonary artery hilar attenuation, and an elevated hemidiaphragm on the side of
the embolism. Atelectasis and pleural effusion are usually only seen with pulmonary infarction.
A normal chest X-ray, however, is the commonest finding in a patient with pulmonary
thromboembolism.
6. Echocardiography: an echocardiographic finding of a dilated right ventricle, mild to
moderate tricuspid regurgitation and a small (and often actively contracting) left ventricle, is
characteristic of pulmonary embolism, particularly when associated with shock. An
oesophageal echocardiograph may also demonstrate thrombus in the pulmonary artery.
7. Ventilation perfusion scan7. this may reveal a lung scan which is8,
- normal, which does not exclude the diagnosis of pulmonary emboli (i.e. there is a 9%
chance of pulmonary embolism)
- low probability (16% chance of pulmonary embolism)
- intermediate probability (33% chance of pulmonary embolism)
- high probability (greater than 88% chance of a pulmonary embolism)
8. Angiography: this has been used as the only precise method of diagnosing pulmonary
thromboembolism and should be performed in patients who have a high clinical probability for
pulmonary embolism associated with an intermediate, or low ventilation perfusion scan
probability9, and is mandatory if pulmonary embolectomy is to be performed. Pulmonary
angiography demonstrates pulmonary artery intravascular filling defects or 'cut-off' in patients
with pulmonary thromboembolism.
9. Swan-Ganz catheterization: special balloon catheters have been developed which enable
angiography to be performed at the bedside10. These may then be replaced by standard Swan98
Pulmonary Embolism
Ganz catheters which are used for fibrinolytic treatment and haemodynamic monitoring to
guide therapy. In one study of patients with a previously normal cardiovascular system, a mean
pulmonary arterial pressure of 22 mmHg correlated with a 30% pulmonary vascular
obstruction, and a mean pulmonary arterial pressure of 36 mmHg correlated with a 50%
pulmonary vascular obstruction11. The mean pulmonary arterial pressure rarely exceeded 40
mmHg, even with massive pulmonary thromboembolism (unless pulmonary hypertension
existed previously).
10. CT and MR Imaging: Spiral volumetric CT and pulmonary MR angiography are recent
techniques that have been used to detect pulmonary emboli in second to fourth division
pulmonary vessels with specificities and sensitivities approaching that of pulmonary
angiography12.
11. Ultrasound of iliac and femoral veins: As venous thromboembolism is one disorder
which may be asymptomatic or present with features of pulmonary embolism, with or without
deep vein thrombosis13, ultrasonography is often performed to assess the integrity of the lower
limb veins when the diagnosis of pulmonary thromboembolism is being considered.
Treatment. Pulmonary thromboembolism will either undergo natural fibrinolysis (and
resolve), or organisation. Resolution may be enhanced by administering heparin to allow
fibrinolysis to continue without thrombogenesis. Substantial angiographic resolution normally
occurs within the first 24 h, with further resolution being complete within 4-6 weeks.
Approximately 10% of patients with pulmonary thromboembolism undergo organization and
retain the pulmonary defect after 6 weeks14, and 1-2% of patients develop recurrent pulmonary
emboli with progressive pulmonary hypertension, hypoxaemia and right ventricular failure15.
Management of a patient with pulmonary embolism requires:
1.
2.
3.
99
Pulmonary Embolism
4.
5.
Fibrinolytic therapy: while thrombolytic therapy clears the pulmonary arteries of clot, and
improves the blood pressure and cardiac output more rapidly than heparin, the mortality of
groups of patients treated by either thrombolysis or heparin is the same after 1 month20.
However, as the improvement in right ventricular function is greater and the pulmonary
artery perfusion defect is less 24 h later21, and one year later22, in patients treated with
fibrinolytic therapy when compared to those treated with heparin, the long term morbidity
(e.g. pulmonary hypertension and right ventricular failure) may be less with fibrinolytic
therapy. Fibrinolytic therapy is usually reserved for patients in whom the haemodynamic
effects and the reduction in pulmonary artery cross-section area due to the
thromboembolism are severe, although some believe that it is the therapy of choice for
any patient who has a high clinical suspicion and a high probability lung scan, for
pulmonary embolism, and in whom there is no contraindications for thrombolytic
therapy23.
One of three agents may be used; streptokinase (250,000 IU over 30 min, followed by
100,000/h for 12-24 h, then continuous heparinization), urokinase (4,400 IU/kg in 15 min
followed by 4,400 IU/kg/h for 12-24 h, then continuous heparinization) or rt-PA (100 mg
over 2 h followed by continuous heparinization)24. The latter may be the treatment of
choice25, as rt-PA has a short half-life (i.e. the coagulation defect may be rapidly reversed
and an embolectomy may be performed without delay), it has a more rapid effect when
compared to urokinase26, it does not cause hypotension (c.f., streptokinase), and it may be
more effective in fibrinolysing older clots27.
Pulmonary embolectomy: as 66% of patients who have massive pulmonary
thromboembolism die within the first hour28 and 80% die within 2 h, the remaining
patients are often able to be managed with inotropic, fibrinolytic and anticoagulant agents
without the need for surgery. Embolectomy should be considered in patients who have
more than 50% occlusion of the pulmonary arteries (i.e. massive pulmonary embolism),
with continuing deterioration 1 h after the onset of thrombolytic treatment29.
AIR EMBOLISM
The introduction of air into the venous system and into the pulmonary artery, produces an
acute obstruction to pulmonary blood flow and an associated pulmonary vasoconstriction due
to platelet aggregation and release. Air may also enter the systemic circulation through
pulmonary arteriovenous anastomoses or through a patent foramen ovale when the right atrial
pressure rises to levels greater than left atrial pressure. In humans, an intravenous bolus of 100
ml of air (1.5 ml/Kg) has been reported to be fatal30, although in critically ill patients 20-50 ml
may be lethal.
Causes. Causes of air embolism include, cardiopulmonary bypass, central venous line
insertion or disconnection, cerebral venous or sagittal sinus trauma during head up anaesthesia
for neurosurgery, and barotrauma (e.g. decompression, positive pressure ventilation,
pneumothorax, diagnostic or therapeutic procedures requiring insufflation with an inert gas,
laparoscopy, diving accident and orogenital sexual activity)31.
Clinical features. The symptoms include, dyspnoea, altered state of consciousness, itching,
abdominal pain, chest pain, and paraesthesia. The signs include, mill-wheel murmur, cyanosis,
agitation, diaphoresis, dyspnoea, wheezing, hypotension, pulmonary oedema, hemiparesis,
paraplegia, and seizures.
Investigations. The arterial gas analysis reveals severe hypoxia and hypocapnia. The end
expired carbon dioxide is decreased, and echocardiography reveals air in the right ventricle.
Treatment. As soon as an air embolism is suspected, the patient is placed head down in the
left lateral decubitus position (so that air will float to the apex of the right ventricle, a
100
Pulmonary Embolism
manoeuvre which has been shown to improve survival30). The head-down position may also
reduce the incidence of cerebral embolism if gas appears in the arterial system because the
cerebral vessels arise from the upper part of the aortic arch32. Blood and air is aspirated through
a Swan-Ganz or central venous catheter, accompanied by closed-chest compression if the
patient is pulseless. Inhalation of 100% oxygen and hyperbaric oxygen33 (even if it is delayed
for 12 h) may be of benefit.
FAT EMBOLISM
Fat embolism may be defined as a blockage of blood vessels by intravascular fat globules
ranging from 3-40 in diameter34. Histological fat deposition in the pulmonary capillaries
occurs in all patients who have long bone and pelvic fractures, although only 1-2% of these
patients develop a clinical syndrome known as the fat embolism syndrome. Histological
evidence of fat embolism may also be found following external cardiac compression, hepatic
injury, gas gangrene, pancreatitis, burns, prolonged high-dose corticosteroid therapy, diabetes
mellitus, joint reconstruction, liposuction, and with lipid infusions. However, in these
conditions the finding is usually a post mortem histological finding of no clinical significance.
Intramedullary fat is the source of the fat embolism in patients who have fractures. The fat
enters torn venules which are kept patent in the Haversion canals and enter the circulation at the
site of injury35.
Clinical syndromes
Fulminant fat embolism syndrome
This is a massive pulmonary fat embolism which produces severe right heart failure, shock
and often death within the first 12-24 h of injury36. The disorder is due largely to an acute
cardiovascular pulmonary obstruction by fat, although platelet aggregation and release may
also contribute to the pulmonary hypertension and oedema. The average lethal dose of fat is 2050 ml. The volume of marrow fat from a femur is approximately 70-100 ml.
Fat embolism syndrome
Cause. Fat collects in the pulmonary or systemic capillary network and is acted upon by
lipoprotein lipases (activated by catecholamine release) liberating high concentrations of toxic
free fatty acids (FFAs) locally, causing platelet aggregation, a mild DIC and disruption of the
pulmonary and cerebral capillary wall. Pulmonary histology reveals intra-alveolar
haemorrhage, fat within pulmonary capillaries and oedema. Cerebral histology reveals diffuse
cerebral oedema with multiple haemorrhagic petechiae37. The capillary disruption causes a
subacute syndrome known as the fat embolism syndrome.
Clinical features. The fat embolism syndrome is characterised by an asymptomatic period
following bony injury of 12-72 h (commonly 36 h, although up to 6 days has been described)
after trauma or manipulation of the trauma site, followed by a symptomatic period with
petechiae, respiratory effects and cerebral effects. The symptoms include dyspnoea, chest
discomfort, wheeze and haemoptysis. The signs include tachypnoea, haemoptysis, tachycardia,
pyrexia, crepitations, rhonchi, petechiae, pallor, somnolence, restlessness, agitation,
disorientation, seizures, coma, decerebration, extensor plantar responses, expressive aphasia,
choreoathetoid movements, rigidity, hemiparesis, scotomas and failure to regain consciousness
following a general anaesthetic.
The petechial rash is the only feature pathognomonic of the fat embolism syndrome and
usually appears on the second or third day after injury, with crops of petechiae being visible for
1-2 days before they fade38. They appear bilaterally in the axilla, neck, front of the chest,
101
Pulmonary Embolism
mouth, palate and conjunctiva. Petechiae only rarely appear on the legs and they are never seen
on the face or the posterior aspect of the body. The latter may be due to the fact that fat
globules float and therefore distribute to branches of the aorta that arise from the top of the
arch, and to the side of the body that is uppermost39. While fat globules may be found in
sputum, urine or blood, they are nonspecific findings that may be observed in conditions
unrelated to fat embolism.
Investigations. The investigations include:
1. Plasma biochemistry and haematology: this may reveal hypocalcaemia (due to binding
of the FFA to calcium40), and an elevated serum lipase, anaemia, and thrombocytopenia (the
platelet count is < 150,000 in 50-80%).
2. Chest X-ray: this usually shows signs of generalized interstitial and alveolar
opacification with no pleural effusion.
3. Arterial gas analysis: the blood gas analysis often reveals hypoxia and hypocapnia. If an
arterial gas analysis is performed regularly in patients with long bone fractures, hypoxia is often
the first sign of the development of the fat embolism syndrome. Cyanosis is usually not
associated with hypoxia as the patient is often anaemic.
4. ECG: apart from sinus tachycardia, the ECG is usually normal. Although it may reveal
nonspecific T wave inversion (particularly in early precordial leads, indicating right ventricular
strain) or RBBB.
5. Cerebral CT scan: this may show generalized cerebral oedema in patients with severe
cerebral fat embolism41.
6. Cerebral magnetic resonance imaging: this may be useful in detecting cerebral lesions
in patients with neurological clinical features of fat embolism and a normal CT scan42.
Treatment. There is no specific therapy for the fat embolism syndrome. Heparin, aspirin,
alcohol, glucose, clofibrate, alpha-blockers, corticosteroids, albumin, dextran and aprotinin
(Trasylol) have not been shown to reduce its incidence or mortality when given either to reduce
the incidence (i.e. as prophylaxis) or as treatment for fat embolism syndrome43. The fat
embolism syndrome is a self-limiting condition, its mortality being related to the degree of
respiratory failure44. Therefore, treatment is aimed at maintaining satisfactory pulmonary gas
exchange throughout the course of the disease, and follows the same principles of management
of ARDS. To prevent continued embolization, all long bone fractures should be promptly
immobilized, because fracture mobility exacerbates liberation of fat into medullary venous
sinusoids45. Recovery from the fat embolism syndrome is usually complete within 2-4 weeks,
although some neurological signs may remain for 3 months46. While complete neurological
recovery from cerebral fat embolism often occurs (e.g. full recovery from decerebrate
posturing47), in some cases permanent neurological disorders may persist48.
AMNIOTIC FLUID EMBOLISM
As amniotic fluid embolism often appears in the pulmonary circulation of peripartum
women who are asymptomatic49, the aetiology of an amniotic fluid embolism syndrome is
probably multifactorial (e.g. due to amniotic fluid, placental tissue, meconium or an excessive
maternal reaction to these products).
The amniotic fluid embolism syndrome occurs characteristically during labour, although it
has been described during first trimester curettage abortion, uncomplicated second and third
trimester pregnancy, amniocentesis, abdominal trauma in pregnancy, vaginal or caesarean
section delivery, and postpartum period. The clinical features include an abrupt onset of a 'bad
taste' in the mouth, cough, dyspnoea, cyanosis, tachycardia and hypotension which is usually
102
Pulmonary Embolism
out of proportion to the blood loss. While acute right ventricular failure is the classical
haemodynamic defect, a global left ventricular dysfunction has also been described.50
Alteration in conscious state with agitation, seizures and coma may also occur. If the patient
survives, an ARDS and DIC often develop. The diagnosis of the amniotic fluid embolism
syndrome is a clinical one and based on the exclusion of other causes of ARDS. As amniotic
fluid embolism commonly occur during the peripartum period, the value of tests used to
demonstrate this (using a monoclonal antibody51 or zinc coproporphyrin52), in diagnosing the
amniotic fluid embolism syndrome, are yet to be determined. Treatment is aimed at maintaining
a satisfactory circulation and pulmonary gas exchange throughout the course of the disease, and
follows the same principles of management of shock and ARDS.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
Pulmonary Embolism
Pulmonary Embolism
105
106
Most patients with acute asthma respond to standard management in the Emergency
Department1. A small subset fail to respond despite therapy, deteriorate and require admission
to Intensive Care. Some of these patients will require intubation and mechanical ventilation2.
Others present after respiratory arrest, having been intubated outside hospital or in general
hospital wards3.
ASSESSMENT OF SEVERITY
Patients with severe asthma are typically breathless, anxious, sitting up in bed and focusing
on breathing. The general appearance of the patient is a good indicator of asthma severity and
must be carefully assessed. Important indicators are the use of accessory muscles, inability to
lie supine, diaphoresis, impaired sensorium and inability to speak. Of these, the last two may
signal patient exhaustion - a key reason for intubation and mechanical ventilation. Other
clinical signs of severe asthma include a respiratory rate of greater than 30 breaths per minute,
tachycardia greater than 120 breaths per minute, and a pulsus paradox of more than 12 mmHg
(normal being 4-10 mmHg)4. None of these latter signs, however, assist with deciding which
patient is coping well with their severe asthma and which is tiring. Wheezing may be a good
indicator of the presence of bronchospasm but is a poor indicator of severity. A quiet or silent
chest may indicate severe obstruction.
Direct measurement of the degree of airflow obstruction should be done using PEFR or
FEV1 unless the patient is so dyspnoeic or exhausted that the procedure might precipitate
respiratory arrest. Severe obstruction is indicated by a PEFR of less than 30-50% of predicted
or of the patients known personal best. This is usually a PEFR of less than 100-120 L/min.
PEFR measurements should not be performed in patients in extreme distress, because the result
is effort dependent and the attempt may precipitate respiratory arrest. When possible, repeated
measurements over time are of value as a failure to respond (or deterioration) after initial
therapy is one of the best ways to predict need for hospitalisation and intubation/mechanical
ventilation. Arterial blood gases have little role in patient assessment because hypoxemia is
rarely a problem, and hypercapnia is a late sign of impending respiratory arrest which should be
identifiable from the patients appearance. Decisions about hospitalisation and/or intubation
should be taken based on clinical assessment and the response to therapy.
STANDARD THERAPIES
1. Oxygen: Although hypoxemia is not usually a major problem in acute asthma, oxygen
should be given by face mask at a flow rate sufficient to maintain oxygen saturation above 9095% using a pulse oximeter. The 95% target is safer in patients at risk of rapid clinical
deterioration. When it occurs, hypoxemia is due to peripheral airway obstruction caused by
inflammation, mucus, and bronchoconstriction producing V/Q mismatch.
2. Inhaled Beta-adrenergic agonists: Inhaled beta-agonists are the mainstay of acute
therapy. The onset is rapid and they are usually well tolerated. Salbutamol is preferred, having
107
110
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Murphy DG, McDermott MF, Rydman RJ, Sloan EP, Zalenski RJ. Aminophyline in the
treatment of acute asthma when beta-2 adrenergics and steroids are provided. Arch
Intern Med 1993;153:1784-1788.
Coleridge J, Cameron P, Epstein J, Teichtahl H. Intravenous aminophylline confers no
benefit in acute asthma treated with intravenous steroids and inhaled bronchodilators.
Aust NZ J Med 1993;23:348-353.
Pierson WE, Bierman CW, Stamm SJ, VanArsdel PP. Double blind trial of
aminophyline in status asthmaticus. Pediatrics 1971;48:642-646.
Yung M, South M. Severe acute asthma in children: is it time to stop using
aminophylline? Anaesth Intens Care 1997 (in press).
Green SM, Rothrock Sg. Intravenous magnesium for acute asthma: failure to decrease
emergency treatment duration or need for hospitalisation. Ann Emerg Med 1992;21:260265.
Tiffany BR, Berk W, Todd IK, White S. magnesium bolus or infusion fails to improve
expiratory flow in acute asthma exaccerbations. Chest 1993;104:831-834.
Johnston RG, Noseworthy TW, Friesen EG, Yule HA, Pharm M, Shustack A. Isoflurane
therapy for status asthmaticus in children and adults. Chest 1990;97:698-701.
Bierman MI, Brown M, Muren O, Keenan RL, Glauser FL. Prolonged isoflurane
anesthesia in status asthmaticus. Crit Care Med 1986;14:832-833.
Gluck EH, Onorato DJ, Castriotta R. Helium-oxygen mixtures in intubated patients with
status asthmaticus and respiratory acidosis. Chest 1990;98:693-698.
Tuxen DV, Lane S. The effects of ventilatory pattern on hyperinflation, airway
pressures, and circulation in mechanical ventilation of patients with severe airflow
obstruction. Am Rev Respir Dis. 1987; 136:872-879.
Tuxen DV. Permissive hypercapnic ventilation. Am J Respir Crit Care Med. 1994; 150:
870-874.
Cooper DJ, Cailes JB, Scheinkestel CD, Tuxen DV. Does bicarbonate improve cardiac
or respiratory function during respiratory acidosis and acute severe asthma. Am Rev
Resp Dis 1993; 147(4):A614
Nates JL, Cooper DJ, Day B, Tuxen DV. Acute severe weakness syndromes in critically
ill patients - a review. Anaesth Intensive Care (submitted).
113
114
INTRODUCTION
Management of any acute postoperative cardiac surgical patient (i.e. coronary artery bypass
grafting, cardiac valve replacement, aneurysectomy, ventricular or atrial septal defect repair)
usually follows common principles which involve monitoring and correcting abnormalities
created by surgery, anaesthesia and cardiopulmonary bypass. Postoperative cardiac
performance will largely depend on the surgical result (e.g. effective revascularization or valve
repair) and the cardiopulmonary bypass time. If the cardiopulmonary bypass time is greater
than 150 min there is a greater risk of myocardial dysfunction (causing hypotension and
difficulty in weaning from cardiopulmonary bypass), clotting defects, air and cellular aggregate
microembolism, and ARDS from activation of inflammatory mediators. Postoperative
complications may also arise from surgical trauma which may cause atheromatous (cholesterol)
cerebral emboli, dissection of the aorta and damage to cardiac conducting pathways.
Postoperative management includes monitoring and treatment of haemodynamic instability
(i.e. hypotension and hypertension), cardiac arrhythmias, hypothermia, electrolyte and acidbase disturbances, respiratory insufficiency, bleeding disorders, renal impairment, and
neurological dysfunction, and (apart from specific surgical problems), is best performed using a
system oriented approach1.
MANAGEMENT
Postoperative transfer and ICU handover
As with any patient transfer from theatre to the ICU this period is hazardous. Before leaving
theatre, blood pressure, pulse, arterial saturation, oxygen supply, suction, mechanical
ventilation, and intravenous infusions (e.g. inotropes, vasodilators, blood) must be maintained
and adequately monitored.
On arrival to ICU a handover is performed and the patient's ventilation, wound drainage and
monitoring are reestablished and a chest X-ray, ECG, APTT, INR, complete blood picture and
a plasma biochemical screen are performed.
Circulation
Blood pressure, pulse and central venous pressure are monitored continuously. During the
first 30-60 min, if the peripheral perfusion is poor, femoral artery pressure measurement may be
required as there can be up to 30 mmHg difference between mean aortic and radial artery
pressure2. For long and complex procedures, or if the patient has a previously known poor
cardiac function, Swan-Ganz catheterization is performed to provide complex haemodynamic
monitoring. Temporary ventricular and atrial pacing wires may be inserted if cardiac surgery is
performed in and about the junctional tissue, to allow cardiac pacing if complete heart block
occurs. The blood pressure should be regulated between a MAP of 70 - 100 mmHg3, and blood
is usually administered if the haemoglobin value is 10 g/100 ml or less.
115
Surgical problems
Bleeding: Continuous bleeding may be due to poor surgical haemostasis, coagulation
abnormalities (e.g. partial heparin reversal, heparin rebound, warfarin therapy, hepatic failure,
DIC), or platelet abnormalities (aspirin or other NSAID therapy, uraemia). Heparin rebound
(i.e. heparin effect returns after 4 h due to release of stored heparin22) or partial heparin reversal
(APTT is usually greater than 40 s) is treated with 50 mg i.v. of protamine. While a large
excess of protamine can act as an anticoagulant a small amount of protamine excess has no
effect on bleeding23 and is often desirable to prevent heparin rebound. Fresh frozen blood and
platelet transfusions may also be used to correct coagulation abnormalities, and intravenous
desmopressin (0.3 g/kg over 30 min) are also effective in decreasing postoperative bleeding in
cardiac surgical patients, particularly those who have platelet dysfunction (e.g. uraemia,
preoperative NSAID therapy)24,25. Aprotinin has also been used to reduce postoperative
bleeding after cardiopulmonary bypass surgery26, although it may be associated with an
increased risk of graft occlusion and myocardial infarction27.
Reoperation may be necessary if bleeding continues at 200 ml/h or greater for three hours,
or is more than 400 ml in 1 h as it usually indicates poor surgical haemostasis.
Chest tubes: these are left in until drainage is less than 20 ml/h for three hours (usually 24-48
h postoperatively) and there is no air leak.
Prophylactic antibiotics: as the commonest postoperative infection is caused by
Staphylococcus aureus, prophylactic postoperative antibiotic therapy (cephalothin 1 g 6-hourly
for 48 h) for coronary artery bypass surgery or prosthetic valve surgery is often used to reduce
the incidence of infection. Administration of antibiotics for a longer than 2 days is of no added
benefit28.
Neurologic dysfunction
Postoperative cerebral dysfunction occurs in many cardiac surgery patients. The defects are
often subtle and usually transient varying from an acute confusional state (in up to 28% of
patients29, due to sleep deprivation, pain, alcohol or sedative withdrawal), to a hemiparesis due
to cerebral hypoperfusion, thrombosis or embolism (air, calcium or cholesterol particles).
Peripheral neuropathies may also occur due to interoperative injury to the brachial plexus
(more often with mammary artery grafting) or femoral or peroneal nerve.
REFERENCES
1.
2.
3.
4.
5.
6.
Worthley LIG. A system structured medical record for intensive care patient
documentation. Crit Care Med 1975;3:188-191.
Mohr R, Lavee J, Goor DA. Inaccuracy of radial artery pressure measurement after
cardiac operations. J Thorac Cardiovasc Surg 1987;94:286-290.
Editorial. Anaesthesia for patients with coronary disease. Br Med J 1980;281:341.
Scheidt S, Collins M, Goldstein J, Fisher J. Mechanical circulatory assistance with the
intraaortic balloon pump and other counterpulsation devices. Prog Cardiovasc Dis
1982;25:55-76.
Oliver MF, Opie LH. Effects of glucose and fatty acids on myocardial ischaemia and
arrhythmias. Lancet 1994;343:155-158.
Gradinak S, Coleman GM, Taegtmeyer H., Sweeney MS, Frazier OH. Improved cardiac
function with glucose-insulin-potassium after coronary bypass surgery. Ann Thorac Surg
1989;48:484-489.
118
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
Report of a Meeting at University of Texas Houston Health Science Center, Texas Heart
Institute, Houston. Metabolic support for the postischaemic heart. Lancet 1995;345:15521555.
Bennett-Guerrero E, Jiminez JL, White WD, et al. Cardiovascular effects of intravenous
triiodothyronine in patients undergoing coronary artery bypass graft surgery: a
randomized, double-blind, placebo-controlled trial JAMA 1996;275:687-692.
Tramr MR, Schneider J, Marti R-A, Rifat K. Role of magnesium sulfate in postoperative
analgesia. Anesthesiology 1996;84:340-347.
Raman J, Saldanha RF, Branch JM, Esmore DS, Spratt PM, Farnsworth AE, Harrison
GA, Chang VP, Shanahan MX. Open cardiac compression in the postoperative cardiac
intensive care unit. Anaesth Intens Care 1989;17:129-135.
Chong JL, Grebenik C, Sinclair M, Fisher A, Pillai R, Westaby S. The effect of a cardiac
surgical recovery area on the timing of extubation. J Cardiothorac Vasc Anesth 1993;7:15.
O'Donohue WJ Jr. Prevention and treatment of postoperative atelectasis. Chest
1985;87:1-2.
Markland ON, Moorthy SS, Mahomed Y, et al. Postoperative phrenic nerve palsy in
patients with open-heart surgery. Ann Thorac Surg 1985;39:68.
Marco JD, Hahn JW, Barner HB. Topical cardiac hypothermia and phrenic nerve injury.
Ann Thorac Surg 1977;23:235.
Grebenik CR, Allman C. Nausea and vomiting after cardiac surgery. Br J Anaesth
1996;77:356-359.
Palazzo MGA, Strunin L. Anaesthesia and emesis. I: aetiology. Can Anaesth Soc J
1984;31:178-187.
Grunberg SM., Hesketh PJ. Control of chemotherapy-induced emesis. N Engl J Med
1993;329:1790-1796.
Standards and guidelines for cardiopulmonary resuscitation (CPR) and emergency
cardiac care (ECC). JAMA 1992;268:2172-2288.
Woods KL, Fletcher S, Roffe C, Haider Y. Intravenous magnesium sulphate in suspected
acute myocardial infarction: results of the second Leicester Intravenous Magnesium
Intervention Trial (LIMIT-2). Lancet 1992;339:1553-1558.
Vyvyan HAL, Mayne PN, Cutfield GR. Magnesium flux and cardiac surgery. A study of
the relationship between magnesium exchange, serum magnesium levels and
postoperative arrhythmias. Anaesthesia 1994;49:245-249.
England MR, Gordon G, Salem M, Chernow B. Magnesium administration and
dysrhythmias after cardiac surgery. A placebo-controlled, double-blind randomised trial.
JAMA 1992;268:2395-2402.
Pifarre R, et al. Management of postoperative heparin rebound following cardiopulmonary
bypass. J Thorac Cardiovasc Surg 1981;81:378.
Ellison N, Ominsky AJ, Wollman H. Is protamine a clinically important anticoagulant? A
negative answer. Anesthesiology 1971;35:621.
Czer LSC, Bateman TM, Gray RJ, Raymond M, Stewart ME, Lee S, Goldfinger D, Chaux
A, Matloff JM. Treatment of severe platelet dysfunction and hemorrhage after
cardiopulmonary bypass: reduction in blood product usage with desmopressin. J Am Coll
Cardiol 1987;9:1139-1147.
Harker LA. Bleeding after cardiopulmonary bypass. N Engl J Med 1986;314:1446-1448.
119
26. Pocha E, Hidalgo F, Llorens R, Melero JM, Arroyo JL, Paramo JA. Randomised study of
aprotinin and DDAVP to reduce postoperative bleeding after cardiopulmonary bypass
surgery. Circulation 1994;90:921-927.
27. Van der Meer J, Hillege HL, Ascoop CAPL, Dunselman PHJM, Mulder BJM, van
Ommen GVA, Pfisterer M, van Gilst WH, Lie KI, for the CABADAS Research Group of
the Interuniversity Cardiology Institute of the Netherlands. Aprotonin in aortocoronary
bypass surgery: increased risk of vein-graft occlusion and myocardial infarction?
Supportive evidence from a retrospective study. Thromb Haemost 1996;75:1-3.
28. Goldmann DA, et al. Cephalothin prophylaxis in cardiac valve surgery. A prospective,
double blind comparison of two-day and six day regimens. J Thorac Cardiovasc Surg
1977;73:470.
29. Kornfield DS, Heller SS, Frand KA, et al. Delirium after coronary artery bypass surgery. J
Thorac Cardiovasc Surg 1978;76:93.
120
TRAINEE PRESENTATIONS
Each registrant has prepared a five minute talk and a one page summary (with one reference
only), on the topics listed below. The one page summaries that were received in time for
publication have been included (unedited).
List the;
1. actions, indications and complications of intravenous
verapamil.
2. indications and complications of intravenous NaHCO3.
3. actions, indications and complications of aspirin and
compare them with ticlopidine.
4. beneficial and adverse effects of permissive
hypercapnea and define permissive hypercapnea.
5. clinical features and management of a patient with
Burkholderia (pseudomonas) pseudomallei infection.
6. actions, indications and complications of intravenous
amiodarone.
7. indications and complications of intra-aortic balloon
counterpulsation.
8. actions, indications and complications of inhaled nitric
oxide.
9. actions, indications and complications of intravenous
ondensadron.
10. actions, indications and complications of intravenous
lignocaine.
11. indications and complications of intravenous calcium
chloride during a cardiac arrest.
12. clinical features and management of a patient with
hypophosphataemia.
13. clinical features and management of a patient with
Cryptococcus neoformans meningitis.
14. clinical features and management of a patient with
heparin induced thrombocytopenia.
15. differences between Haemaccel and 5% albumin
solutions.
16. complications associated with massive blood
transfusion.
17. clinical features and management of a patient who has
carcinoid syndrome.
18. differences in clinical features and investigations
between septic shock and toxic shock syndrome.
19. causes and management of a ventilated critically ill
patient who develops muscle weakness
20. actions, indications and complications of intravenous
milrinone.
21. causes and treatment of torsades de pointes.
22. actions, indications and complications of warfarin.
121
Dr. C. Bhringer.
page
123
Dr. B. Venkatesh.
Dr. P. W. Cheung.
124
125
Dr. D. Stephens.
127
Dr. D. Green.
128
Dr. C. Woolfe.
130
Dr. C. Edibam.
132
Dr. M. Pinder.
134
Dr. C. Nolan.
135
Dr. M. Parmar.
136
Dr. C. Motherway.
137
Dr. C. A. Cheng.
138
Dr. P Nair.
140
Dr. J. Evans.
142
Dr. V. Pellegrino.
144
Dr. D. Chu.
145
Dr. B. Dixon.
147
Dr. H. L. Chee.
148
Dr. J. Awad.
149
Dr. R. Calcroft.
151
Dr. D. Corbett.
Dr. J. Liang.
152
153
122
Dr. F. Colreavy.
Dr. N. Kavanagh.
Dr. P. Frost.
Dr. H Opdam.
Dr. E. Wheatley.
Dr. P. Lam.
Dr. C. Hill.
Dr. K. OConnor.
Dr. T. Williams.
Dr. T. Duke.
Dr. P. Seal.
Dr. N. Widdicombe.
Dr. D. Mullany.
Dr. M. Gopalakrishnan.
Dr. A. Purdon.
Circulation: -
123
124
Aspirin
Ticlopidine
Inhibition of
thromboxane
A2 generation
Non-selective inhibition
of cyclo-oxygenase
No
Yes (dose dependent)
Inhibition of ADP
action via 2methylo-thio-ADP
Unknown
No
No
Yes
Yes
No
Yes
No
Less
Active
No
Inactive
Yes
Yes
No
First line
Second line
Yes
Controversial
More effective
Equal in males
Yes
Higher dose (500 mg
/day) may be required
Yes
Yes
Yes
More effective
Yes
Yes
Yes
No
Yes
125
No
No
Complications
Major adverse effects
Costs
GI bleeding (25%-30%)
Reyes syndrome (< 12
year old)
Hypersensitivity
Provoke renal
impairment, papillary
necrosis or interstitial
nephritis
Thrombocytopenia
GI intolerance
Dizziness
Tinnitus
Deafness
Low
Neutropenia (2.4%)
severe if < 0.44 x
109/l (0.85%)
within first 3
months
Thrombocytopenia
Aplastic anaemia
Reversible
Diarrhoea (20%)
GI intolerance
GI pain
Increased total
cholesterol by 9%
High
Reference
Karsten Shror. Antiplatelet drugs: a comprehensive review. Drugs 1995;50:7-28.
126
127
Progression
Shock
Radiograph
Incubation
period
2 days
Acute
Infection at localised
site (only minority
present with
pneumonia). Symptoms
of localised abscess.
Septicaemic shock
(endemic areas only)
Rapid
Mortality
high
Frequent
Unilobar or
bilobar infiltrates
(mostly upper
lobes) and/or
nodular lesions
that coalesce
Subacute
Recrudescent disease
often involving lungs:
Chronic febrile wasting
condition resembles
reactivation TB
Mixed
Infrequent
Cavity formation
in upper lobes
resembling TB
Reports of
up to 26
years after
initial
infection
Chronic
Long-standing
suppurative abscesses
involving numerous
anatomic sites. Chronic
febrile wasting
condition with
occasional periods of
remission.
Slow
Rare
Cavity formation
in upper lobes
resembling TB
Weeks to
years after
initial
exposure
128
Subclinical
Characteristics
Progression
None or minimal
symptoms. Chronic
carrier state
None
Reactivation
if decreased
immunocompetence
occurs
Shock
Never
Radiograph
Incubation
period
Normal
Diagnosis
Clinical suspicion and history of travel in endemic area at any time
P pseudomallei grow on most laboratory media in 12 - 48 hours.
Bipolar safety pin pattern observed on Wayson or Wright stain.
Diagnosed presumptively using serological testing by indirect haemagglutination test
(IHA).
IHA titre > 1:40 generally regarded as evidence of melioidosis
Acute septicaemic form may have titres < 1:40)
IHA titres 1:40 to 1:160 in many subclinical carriers.
IHA > 1:640 highly suggestive of active melioidosis.
Fourfold rise in IHA titre is suggestive of active infection
Elevation in C-reactive protein (CRP) levels may be helpful in ascertaining active infection
in patients with low IgM antibody titres
Gram stain of infected tissue or pus may occasionally show no Gram-negative rods.
Prevention
No active immunisation available
Protective clothing in at-risk areas. Thorough cleansing of skin abrasions in endemic areas.
Infected persons or animals isolated and bodily fluids handled with biohazard precautions to
prevent spread.
Treatment
People with low-titre positive serological test responses but without other evidence of
infection do not require therapy.
Large abscesses should be surgically drained under antibiotic cover.
Acute melioidosis: Ceftazidime (120 mg/kg/day) plus Co-trimoxazole (20/100 mg/kg/day) or
doxycycline (40 mg/kg/day) or chloramphenicol (40 mg/kg/day) advocated.
Optimum duration of treatment undetermined. Recrudescence after apparent successful
antibiotic therapy reported.
Increase in CRP to more than 10 mg/dl suggests reactivation of infection
Regimen of choice: Combination i.v. chemotherapy followed by 6 - 12 months of oral
tetracycline or co-trimoxazole until further studies reveal a more efficacious
protocol
Reference
Sanford JP. Pseudomonas species (including melioidosis and glanders). In: Mandel GL,
Douglas RD, Bennet JE, eds. Principles and practice of infectious diseases 4th ed. New York
Churchill Livingstone, 1995;2003-2009.
129
RS:
Thyroid:
130
GIT:
131
133
134
135
136
Hypercalcaemia
Bradycardia/asystole
Sclerosis/tissue injury
Potentiation of digoxin toxicity
Increased extracellular calcium may lead to;
a) worse neurological outcome
b) increased stiffness of damaged and ischaemic myocardium with reduced contractility.
Reference
Standards and guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiac care
(ECC). JAMA 1992;268:2172-2288.
137
138
139
140
Differential diagnosis:
Tubercular meningitis, other opportunistic infections like toxoplasma, CMV and herpes
simplex. In HIV infection, CNS lymphoma, HIV encephalopathy and progressive multifocal
leukoencephalopathy should be considered.
Treatment:
a) Of acute infection
- Severe infection (altered sensorium, CSF WBC count < 20/cubic mm, Ag titre > 1:1024,
positive blood culture)
Amphotericin B 0.5 - 0.7 mg/kg/day i.v. + flucytosine 100-150 mg/kg/day i.v. or orally
for 2 weeks followed by fluconazole 400 mg/day for 8-10 weeks.
Alternatives to amphotericin B like high dose fluconazole and liposomal amphotericin B
have been tried
- Mild infection Fluconazole 800 mg loading dose, then 400 mg/day + flucytosine 100150 mg/kg/day orally. Clinical response is observed in 1-2 weeks, 50-60% relapse
within 6 months without maintenance therapy.
b) Of elevated ICP
Repeated lumbar punctures to drain CSF, acetazolamide or shunt surgery.
c) Prevention of relapse
Fluconazole 200 mg/day orally lifelong, especially with HIV infection. Found to be
more effective than weekly amphotericin B therapy. No evidence for use of
anticryptococcal prophylaxis in patients with low CD4 counts. May induce cryptococcal
and candida resistance.
Prognosis
Acute mortality rates are 10-30% usually in the first few weeks. Poor prognostic
indicators are age <35 years, CSF - raised opening pressures, low glucose, WBC <
20/cubic mm, Ag titre > 1:32, altered mental status, absence of headaches,
hyponatraemia, extraneural positive cultures, steroid therapy or chemotherapy for
haematological malignancy, abnormal CT scan.
Reference:
Jones GA, Nathwani D. Cryptococcal meningitis. Br J Hosp Med 1995;12:54 (9).
141
Cause
Proximal lower limb DVT.
Arterial embolism.
Oliguria/anuria/abdominal pain.
Abdominal pain-rigidity/ileus/melaena.
Mesenteric embolism/thrombosis.
Paraplegia/incontinence.
Management
Cease heparin and exclude other causes of thrombocytopenia
Re-evaluate need for anticoagulation.
TED stockings and sequential calf compression
142
Alternate anticoagulation:
Org 10172 (Danaparoid sodium): which inhibits Xa, can be used. Beginning with a 25
000 u bolus followed by an infusion of 400 u/hour for 4 hours then 300 u/hour for 4
hours then 200 u/hour.
Anacrod (defibrinating snake venom): 1 u/kg over 12 hours i.v. then titrated to
fibrinogen level 0.5 - 2 g/l
Warfarin:
Treat complications e.g. thrombolysis/PTCA/surgery
Continue monitoring platelet count
Reference
Warkentin TE, et al. Heparin-induced thrombocytopenia in patients treated with low molecular
weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330-1335.
143
5% ALBUMIN
Pooled volunteer donor
plasma. Cohn cold
fractionation and
chromatographic separation.
Viral removal and inactivation
procedures (limited against
non-enveloped viruses)
Composition:
m.w. 70 000
Negligible other proteins
Isotonic: Na/Cl/ Octanoate
Stable up to 1 year at room
temperature
Effects:
Redistribution half-life = 4 h
80% excreted in 48 h (renal)
Redistribution half-life = 16 h
Metabolic half-life = 20 days
(hepatic)
Not common
Nil
Rare
Rare
Not
Fibronectin
Yes
Nil
$17.50
Preparation:
Metabolism:
Side effects:
Allergy and anaphylactoid
Transmission infection
Compatibility with blood
products
Immune/Opsonisation
Cost:
Reference
Cone A. The use of colloids in clinical practice. Br J Hosp Med 1995;54.
144
145
Viral
HIV1, HIV2, HTLV1 & HTV2
HAV, HBV, HCV, HDV, NANBHV
CMV, EBV, Parovirus B19
Protozoal
Malaria, toxoplasmosis gondii
Parasitic
T cruzi, Microfilarisis
Non-infective
Iron overload
Metabolic alkalosis and hypokalaemia
Thrombophlebitis
Reference
Mollisin PL, Engelfriet CP, Contreras M. Transfusion in clinical medicine. 1993 Chapter 15 &
16: pp 677-784.
146
147
TSS
Clinical features
Temperature
Fever
Hypothermia
common
occasionally
> 38.9C
rare
Dermatologic
Rash
Desquamation
Mucous membranes
rare
rare
rare
Gastrointestinal
Ileus
Vomiting
Diarrhoea
common
uncommon
uncommon
rare
common
common
Musculoskeletal
Myalgia
rare
Multiorgan involvement
variable number
3 or more
Age/gender
all
menstruating females
Focus of infection
Systemic diseases
immunocompromised
diabetes
advanced malignancy,
trauma, burns
Investigations
Positive blood cultures
Common organisms cultured
40 - 45% of cases
not common
E coli
Klebsiella pneumoniae
Enterobacter spp.
Pseudomonas aeruginosa
Staphylococcus aureus
Reference:
Tolte RW, Williams DM. Clinical and laboratory manifestations of toxic shock syndrome. Ann
Intern Med 1982;96:843.
148
Encephalopathy
Myelopathy
Polyneuropathy
Myopathy
Neuromuscular
transmission defects
149
MANAGEMENT:
FBC, UEC, LFT, Ca, Mg, PO4, CK, glucose, thyroid function tests
Imaging - CXR, spine Xrays, CT/MRI head & spine as clinically indicated
Nerve conduction studies, electromyography
Lumbar puncture
Muscle and nerve biopsies
Treat underlying cause
Nutrition, vitamins, fluids and electrolytes
Physiotherapy, prevent bed sores and contractures
Tracheostomy where appropriate
Prophylaxis against venous thromboembolism
Supportive care
Reference
Bolton CF. Sepsis and the systemic inflammatory response syndrome: neuromuscular
manifestations. Crit Care Med 1996;24:1408-1416.
150
151
152
Reference:
Chernow B. The pharmacologic approach to the critically ill patient. 3rd edn, 194 Williams &
Willkins, p680.
153
154
INDEX
Abbreviated injury score, 37
Acute fatty liver of pregnancy, 56
treatment, 57
Acute phase proteins, 18
Acute renal failure, 39
adenosine antagonists, 46
atrial natriuretic peptide, 47
blood pressure augmentation, 45
calcium channel blockers, 46
dopamine, 47
endothelin antagonists, 47
frusemide, 45
intra-abdominal pressure and, 42, 44
mannitol, 47
mechanisms, 41
pathophysiology of, 39
prevention of, 42
prostaglandins, 46
solute loading, 45
theophylline, 46
treatment, 45
Acute respiratory distress syndrome
mechanical ventilation, 87
Adenosine, 41
Adenosine antagonists, 46
Adenyl cyclase, 1, 2
Adrenaline, 3, 108
Adrenergic receptors
alpha, 1
beta, 1
Air embolism, 100
causes, 100
clinical features, 100
investigations, 101
treatment, 101
Airway
acute management, 29
assessment, 29
devices, 29
Albumin, 144
Aminophyline, 109
Amiodarone, 130
Amniotic fluid embolism, 103
Angiotensin converting enzyme inhibitors,
7
Anticholinergics, 108
Corticosteroids
inhaled, 108
Cricothyroid insufflation, 30
Cricothyrotomy, 30
Critically ill
energy requirements of, 19
nitrogen requirements of, 19
Cryptococcus Neoformans, 140
dopamine and, 5
Glasgow coma score, 36
G-protein, 1, 2
Haemaccel, 144
Haemofiltration, 76
Haemorrhage
classification, 33
treatment, 35
Haemothorax
management of, 32
Haloperidol, 69
Heart failure, 2
Helium, 110
HELLP syndrome, 54
Heparin induced thrombocytopenia, 142
Hydrocortisone, 108
Hypertension in pregnancy, 53
Hypophosphataemia, 138
Hypovolaemia
management of, 33
Hypoxia
lactic acidosis and, 12
Delirium tremens, 69
Diacyl glycerol, 1, 2
Digoxin, 7
Dopamine, 2, 47
'low dose', 5
Dopaminergic receptors, 1
Dynorphins, 61
Early Management of Severe Trauma, 27
EMST. See Early management of severe
trauma
airway assessment, 30
definitive care, 28
primary survey, 27
resuscitation, 27
secondary survey, 28
Endorphins, 61
Endothelin, 42
Endotracheal intubation, 29
Enkephalins, 61
Enteral nutrition
immunonutrients and, 23
indications for, 20
paediatric, 78
Ethyl alcohol
withdrawal, 69
Infection
metabolic effects of, 18
Injury severity score, 37
Inositol triphosphate, 2
Inotropic agents
treatment with, 7
Intensive care patient
sedation, 69
Interleukin-10, 3
Intra-aortic balloon counterpulsation, 132
Intravenous therapy
paediatric, 75
Juxtamedullary glomeruli, 40
Ketamine, 68, 109
Kidney
autoregulation, 5
pressure-flow regulation, 5
Lactate/pyruvate ratio, 11
Lactic acid
metabolism of, 11
Lactic acidosis
buffer therapies and, 13
Gas trapping
assessment of, 111
Gastric mucosal blood flow, 5
dobutamine and, 5
156
Norpethidine, 63
NSAIDs. See Non-steroidal antiinflammatory drugs
dosage, 65
indications, 64
side-effects, 65
Nutrition
paediatric, 77
Nutritional assessment, 17
Nutritional support, 19
economic considerations, 24
glutamine in, 23
Ondansetron, 135
Opioid antagonists, 64
Opioid peptides, 61
Opioid receptors, 61
Opioid withdrawal, 64
Opioids, 61
clinical effects, 62
CNS effects, 62
cutaneous effects, 63
CVS effects, 62
GIT effects, 63
musculoskeletal effects, 63
respiratory effects, 63
side effects, 63
Ovarian hyperstimulation syndrome, 57
Paracetamol, 65
Parenteral Nutrition
bacterial translocation in, 21
gut atrophy in, 21
indications for, 19
paediatric, 78
PEEP. See Positive end-expiratory
pressure
Peritoneal dialysis, 77
Permissive hypercapnea, 127
Permissive hypercapnia, 112
Pethidine, 63
Phenobarbitone, 67
Phenothiazines, 68
phosphoinositol, 1
Phosphoinositol biphosphate, 2
Phospholipase C, 1
Plateau airway pressure, 111
Pneumothorax
management of, 31
Na+/K+-ATPase, 2
Naloxone, 64
Nephrotoxins, 41
Nitric oxide, 3, 134
Non-invasive ventilation, 86
Non-protein calories, 19
Non-steroidal anti-inflammatory drugs, 64
Noradrenaline, 3
157
tension
clinical features, 31
management of, 32
Positive end-expiratory pressure, 86
Post-operative cardiac surgery, 115
arrhythmias, 116
bleeding, 118
hypertension in, 116
hypotension in, 116
neurological dysfunction, 118
prophylactic antibiotics, 118
shivering, 117
Pre-eclampsia, 53
magnesium, 55
mild, 54
pathophysiology, 54
severe, 54
treatment, 55
Pro-opiomelanocortin, 61
Propofol, 68
Protein kinase C, 2
Pulmonary embolism, 97
Purine A2 receptor, 40
Pyruvate
formation of, 11
accuracy, 92
predictive power, 93
Sedation
scale, 70
Selective phosphodiesterase inhibitors, 6
Sepsis, 3
Septic inflammatory response syndrome, 5
Septic shock, 148
Sodium bicarbonate, 124
Splanchnic
perfusion pressure, 5
Surgery
metabolic effects of, 18
Sympathomimetic amines, 1
Systemic inflammatory response
syndrome, 21
Tertiary Survey, 28
Theophylline, 6
Thiopentone, 67
Thromboembolism
causes, 97
clinical features, 97
embolectomy, 100
investigations, 97
treatment, 99
Thrombolytic therapy, 100
Ticlopidine, 125
Torsades de pointes, 152
Torso injuries
treatment, 36
Toxic shock syndrome, 148
Transfusion
complications, 145
Trauma score, 36
Tubuloglomerular feedback, 40
Tumour necrosis factor, 3, 55
Receptors
down regulation of, 2
Renal dose dopamine, 47
Renal physiology
blood flow, 39
cortical blood flow, 40
outer medullary blood flow, 40
oxygen consumption, 39
vasoregulatory hormones, 40
Revised trauma score, 37
Right ventricular coronary perfusion
pressure, 6
Right ventricular failure, 6
Verapamil, 123
Volatile anaesthetics, 110
Salbutamol, 108
Scoring systems, 36, 91
Warfarin, 153
158