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A clinician, armed with the sepsis bundles, attacks the three heads of severe
sepsis: hypotension, hypoperfusion and organ dysfunction. Crit Care Med
2004; 320(Suppl):S595-S597
Grading of Recommendations
(Grading of Recommendations Assessment, Develop and Evaluation GRADE)
Systemic Inflammatory
Response Syndrome
Sepsis
Severe Sepsis
Septic Shock
Multi-Organ
Dysfunction/Failure
Syndrome
Systemic Inflammatory
Response Syndrome
Sepsis
Severe Sepsis
Septic Shock
Multi-Organ
Dysfunction/Failure
Syndrome
SIRS
Heart Rate > 90
Respiratory Rate > 20
WBC > 12K or < 4K
Temp > 38 C (100.4 F) or < 36 C (96.8 F)
Any two of the above
Very nonspecific
Sepsis
SIRS + signs of a suspected or known
infection
WBCs in normally sterile fluid
Infiltrate on chest x-ray
Bacteria in normally sterile fluid
Diagnostic
Criteria
for
Sepsis
Severe Sepsis
Sepsis + sepsis-induced tissue
hypoperfusion or organ dysfunction
Septic Shock
Severe Sepsis or sepsis-induced
hypoperfusion persistent despite:
Adequate/initial fluid challenge/resuscitation
Lactate > 4 mmol
Addition of pressors
MOFS
Altered organ function, involving two or
more organs, in an acutely ill patient
requiring medical intervention to achieve
homeostasis
Death
The permanent the cessation of all vital
functions in an individual who has
sustained either (1) irreversible cessation
of circulatory and respiratory functions, or
(2) irreversible cessation of all functions of
the entire brain, including the brain stem
Severe Sepsis/Septic Shock mortality =
~30-46%
Pathophysiology of Sepsis
Figure B, page 948, reproduced with permission from Dellinger RP. Cardiovascular
management of septic shock. Crit Care Med 2003;31:946-955.
1.
2.
3.
4.
5.
CVP of 8-12
unventilated/12-15
ventilated
MAP >65
Cardiac Output > 8 LPM
Hemoglobin > 10 gm/dL
ScvO2 > 70%
1.
2.
3.
4.
5.
CVP of 8-12
unventilated/12-15
ventilated
MAP >65
Cardiac Output > 8 LPM
Hemoglobin > 10 gm/dL
ScvO2 > 70%
Initial Resuscitation:
Goals of Early Goal Directed Therapy
CVP 8-12 cmH2O
12-15 cmH2O on the ventilator
MAP > 65 mmHg
May need to be higher in patients with HTN
UOP > 0.5 mL/Kg /hour
ScvO2 > 70%
Grade 1C
Crystalloid or Colloid
SAFE Study
Crystalloid (NS) = Colloid
(4% Albumin)
Less volume, more
PRBCs, higher CVP and
Albumin
No difference in mortality
(p = 0.87)
Trend for increased risk of
death in Trauma (0.06)
Trend for decreased risk
of death in Severe Sepsis
(0.09)
Grade 1B
SSC Recommendations
Crystalloids
Albumin
Grade 1B
Grade 2C
Fluid Volume
30 mL/Kg crystalloid
Grade 1C
Volume Responsiveness
CVP > 8 cmH2O
Grade 1C
Swan-Ganz Catheter
PCWP
Cardiac output
Non-invasive Monitors
PiCCO Catheter
FloTrac
Pulse Pressure Variation
CVP
Spontaneous Breathing > 8 cmH2O
Ventilatory Breathing > 12 cmH2O
Primarily based on expert opinion
Dellinger RP. Crit Care Med 2004; 32:858873
Rivers E. N Engl J Med 2001; 345:13681377
Practice parameters for hemodynamic support of
sepsis in adult patients with sepsis. Crit Care Med
1999; 27:639660
Non-invasive Monitoring
PPV
PPV
PPV
CVP
PCWP
Echocardiography
1. True
2. False
Grade 1D
ARDS
Sepsis
Alsous F. Chest 2000; 117:17491754
Rivers E. N Engl J Med 2001; 345:13681377
MAP
MAP
65 mm Hg
75 mm Hg
85 mm Hg
F/LT
Urinary
output (mL)
49 +18
56 +21
43 +13
.60/.71
6.0 +1.6
5.8 +11
5.3 +0.9
.59/.55
0.42 +0.06
0.44 +016
0.42 +0.06
.74/.97
41 +2
47 +2
46 +2
.11/.12
13 +3
17 +3
16 +3
.27/.40
Red Cell
Velocity (au)
Adapted from Table 4, page 2731, with permission from LeDoux, Astiz ME, Carpati CM,
Rackow ED. Effects of perfusion pressure on tissue perfusion in septic shock. Crit Care Med
2000; 28:2729-2732
Grade 1C
(Levophed)
3. Vasopressin
4. Phenylephrine
(Neosynephrine)
5. All the above
(Levophed)
3. Vasopressin
4. Phenylephrine
(Neosynephrine)
5. All the above
Vasopressors
Norepinephrine
Dopamine
Vasopressin
Epinephrine
Phenylephrine
Norepinephrine vs Dopamine
No significant difference in mortality (p = 0.10)
Trend for less death in the ICU (p = 0.07)
No difference at hospital discharge or 1 yr
Norepinephrine vs Dopamine,
Contd
Norepinephrine should be the first line
Grade 1B
vasopressor
Dopamine is an alternative to
Norepinephrine
Only in highly selected patients with low risk
of:
Tachyarrhythmias
Absolute or relative bradycardia
Grade 2C
Vasopressin
Adding Vasopressin to Norepinephrine
showed no mortality benefit compared to
Norepinephrine alone (p = 0.26)
Did lower Norepinephrine requirements
May have other potential physiologic benefits
Grade UG
Epinephrine
First line in pts poorly responsive to
Norepinephrine and Dopamine
No evidence of worse outcomes
Increased risk of:
Tachycardia
Elevated lactate
Decreased splanchnic circulation
Phenylephrine
Not recommended!!!
Except:
Norepinephrine induced arrhythmias
Cardiac output is high
Persistently low BP
Salvage therapy
Grade 1C
Hemodynamic Equations
DaO2 = CO x Hgb x SaO2
Oxygen delivery
O2 ER= VO2/DaO2
Oxygen extraction ratio
~ 0.2 to 0.3
Adapted from:
http://ht.edwards.com/resourcegallery/products/swanganz/pdfs/svo2edbook.pdf
ScvO2/SvO2 Goal
> 70%/65% respectively
Normal or shunt physiology
Ionotropic Therapy
Dobutamine:
Max dose 20 mcg/Kg/min
Titrate to NO pre-defined CO
Grade 1B
Target 7 to 9 g/dL
Consider earlier for myocardial
ischemia/ischemic coronary disease, severe
hypoxemia, acute hemorrhage, cyanotic heart
disease or lactic acidosis
No EPO
Grade 1B
Napolitano LM. Crit Care Med 2009; 37(12): 3124-3157
No high-dose Antithrombin
Studies had revealed that a subgroup with
severe sepsis and high risk of death = better
survival
Grade 1B
Selenium
Antioxidant
No use
Grade 2C
Diagnostic Testing
Lactate level
Within 3 hours
Cultures
Prior to antibiotic administration
Grade 1D
Imaging
If not too unstable
Grade 1C
Procalcitonin
Use low levels to assist with Abx D/C
Grade 2C
Antibiotic Therapy
IV route within the 1st hour
Septic Shock Grade 1B
Severe Sepsis Grade 1C
One or more drugs with activity against the likely
pathogens Grade 1B
Double cover if MDR pathogens Grade 2B
Combo therapy for neutropenic fever Grade 2B
Beta-lactam and macrolide for Strep pneumonia
Grade 2B
ABX, Contd
Reassess routinely
Grade 1B
Grade 2B
Grade 2C
Source Control
Seek, diagnose or exclude potential anatomical
infections and treat expectantly
Within the first 12 hrs
Grade 1C
Corticosteroids
Hydrocortisone
200 mg/day
Only with persistent hypotension/poorly
responsive to vasopressor therapy Grade 2C
Consider a continuous infusion Grade 2D
Do not do an ACTH stimulation test Grade 2B
No Dexamethasone Grade 2B
Fludrocortisone if other steroid than HCT
Wean steroids when off pressors Grade 2D
Grade 2C
Corticosteroids, Contd
Annane D. JAMA 2002; 288:862871
Cosyntropin Stim Test delta < 9 = non-responders
10% decrease in mortality if treated with steroids
17% decrease in pressor requirements
CIRCI
(Critical Illness Related Corticosteroid Insufficiency)
CIRCI, Contd
Mechanical Ventilation
Target tidal volume = 6 mL/Kg Grade 1A
Plateau pressure goal < 30 cmH2O Grade 1B
Allow permissive hypercapnia Grade 1C
Use PEEP to decrease FiO2 Grade 1B
Higher PEEP vs lower
Grade 2C
ARDS
ARMA Trial
The Acute Respiratory Distress Syndrome
Network. N Engl J Med 2000;342:1301-08.
Alveoli Trial
Brower RG. N Engl J Med 2004;351:327-36
Grade 2C
HOB elevated
Grade 1B
Grade 1B
Grade 2B
Grade 2B
Beta-Agonists
No recommended for routine use
Grade 1B
Intravenous (Salbutamol)
Increased mortality
Grade 1B
Grade 1B
Grade 1C
Without ARDS
With ARDS (Sepsis-induced and P:F <150)
< 48 hours
Grade 2C
Glucose Control
Use intravenous insulin to control blood
sugars Grade 2C
If 2 consecutive BSs > 180
Grade 1B
Grade ? 1A
Bicarbonate Therapy
Avoid NaHCO3 in patients with a pH > 7.15
and lactic acidemia for the purpose of
improving hemodynamics or to reduce
vasopressor requirements
Grade 2B
Thromboembolism Prophylaxis
LMWH daily vs Low dose UFH BID
LMWH daily vs Low dose UFH TID
Grade 1B
Grade 2C
Grade 2C
or UFH
Grade 1A
Grade 1A
Mechanical prophylaxis if
contraindications to heparin
products
Grade 2C
PPI over H2
Grade 2C
Grade 2B
Nutrition
Oral or enteral nutrition in the 1 st 48 hrs vs
complete fasting or just glucose Grade 2C
Avoid full caloric feeding for the 1 st full
week Grade 2B
Low dose feeding up to 500 Kcal/day and
advance as tolerated (60-70%)
Bundles
Point/Counterpoint Editorials
Are the best patient outcomes achieved when
ICU bundles are rigorously adhered to?
Pros: Dr. Delinger
Not perfect/have flaws, but are based on the best
available evidence.
1. Yes
2. No
1. Yes
2. No
Benefits of the
Surviving Sepsis Campaign
Surviving Sepsis Campaign Improvement
Program
Resuscitation Bundle - First 6 hours
Compliance increase linearly from 10.9% to 31.3% over two
years ( p = 0.0001)
THE END
?? QUESTIONS ??