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Bekele Afessa, MD
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Surviving Sepsis Campaign: Guidelines for
Management of Severe Sepsis/Septic Shock
Dellinger RP, Levy MM, Carlet JM, et al. for the
International Surviving Sepsis Campaign Guidelines Committee
Crit Care Med. 2008;36:296-327
Intensive Care Med. 2008;34:423-430
Available free online at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&p ubmedid=18058085
Slide 3

• Persistent hypotension
• Elevated lactate
• Hypoxemia
• Oliguria or increase in creatinine
• Coagulation abnormalities
• Ileus
• Thrombocytopenia
• Elevated bilirubin
Levy MM et al. CCM 2003;31:1250
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• Hypovolemic
• Distributive
• Cardiogenic
• Obstructive
• Cytotoxic
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Slide 7
Dellinger RP. CCM 2003;31:946

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Slide 8
Figure B, page 948, reproduced with permission from Dellinger RP.
Cardiovascular management of septic shock. Crit Care Med.
2003;31:946-955.

Diastole Systole
10 days post-shock
Diastole
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Images used with permission from Joseph E. Parrillo, MD
Slide 9
Systole

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Slide 12
Rivers E et al. NEJM 2001;345:1368

60
50
40
30
20
10
NNT to prevent 1 event (death) = 6-8
Standard therapy
EGDT
0
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In-hospital mortality
(all patients)
28-day mortality
Slide 13
60-day mortality
Adapted from Table 3, page 1374, with permission from Rivers E, Nguyen B, Havstad
S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock.
N Engl J Med. 2001;345:1368-1377.

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• Boluses of 1,000 mL crystalloid or 300 to 500 mL colloid every 30 minutes
• Target CVP 8 mm Hg
• Target higher CVP of 12 mm Hg in certain conditions
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Slide 16

• Bicarbonate therapy not recommended to improve hemodynamics in patients with lactate-induced pH >7.15
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Cooper et al. Ann Intern Med. 1990;112:492-498.
Mathieu et al. Crit Care Med. 1991;19:1352-1356.
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• Indications
• Drug of choice Norepinephrine or dopamine
• No place for “low dose” dopamine
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Figure 2, page 1665, reproduced with permission from De Backer D,
Creteur J, Silva E, Vincent JL. Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: Which is best? Crit Care Med. 2003;31:1659-1667.
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• Elevated in early septic shock, normal later
• Indication
• Dose 0.03 units/min. It may decrease stroke volume.
• Watch for side effects
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Slide 24

Treatment
NaHCO3 (2 mEq/kg) pH
PAOP
Cardiac output
0.9% NaCl pH
PAOP
Cardiac output
Before
7.22
15
6.7
7.24
14
6.6
Cooper DJ et al. Ann Intern Med. 1990;112:492-498.
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Slide 25
After
7.36
17
7.5
7.23
17
7.3

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• Fluid to achieve CVP 8 – 12 mm Hg
• If central venous oxygen saturation < 70% or mixed venous oxygen saturation < 65% despite fluid and CVP 8
– 12 mm Hg,
– PRBC to keep Hct > 30%
– Dobutamine infusion (up to a maximum of 20 μg·kg-
1·min-1)
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• Identify common causes of ICU-acquired infections
• Obtain cultures before antibiotics
• Testing Procedures
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Slide 31

• IV antibiotic within the first hour (premixed supply)
• Initially (adequate and appropriate)
• Observe for adverse consequences
• De-escalate within 48 – 72 hours
• Be aware of non-infectious causes
• Be aware of negative blood cultures
• Duration of therapy 7-10 days for most
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Dellinger RP. Crit Care Med 2004;32:858
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Figure 2A, page 867, reproduced with permission from Annane D,
™
S ébille V, Charpentier C, et al. Effect of treatment with low doses with septic shock. JAMA. 2002;288:862-871.

P = .045
P = .007
Figure 2 and Figure 3, page 648, reproduced with permission from Bollaert PE, Charpentier C, Levy B, et al.
Slide 39 of hydrocortisone. Crit Care Med. 1998;26:645-650.
Figure 2 and Figure 3, page 727, reproduced with permission from Briegel J, Forst H, Haller M, et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: A prospective, randomized, double-blind, singlecenter study. Crit Care Med. 1999;27:723-732.

Kaplan-Meier Curves
Hydrocortisone Vs
Placebo
Sprung CL et al. NEJM 2008;358:111
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Slide 40

• For septic shock poorly responsive to fluid and vasopressors
• ACTH stimulation not recommended
• If non-hydrocortisone corticosteroid is used, fludrocortisone 50 μg daily is added
• Dose of hydrocortisone 200-300 mg/day, which can be weaned off when vasopressors are no longer needed
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35
30
25
20
15
10
5
0
Primary analysis results
2-sided p-value
Adjusted relative risk reduction
Increase in odds of survival
30.8%
24.7%
0.005
19.4%
38.1%
6.1% absolute reduction in mortality
Placebo
(n - 840)
Drotrecogin alfa
(activated) (n
= 850)
Adapted from Table 4, page 704, with permission from Bernard GR, Vincent
JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis.
N Engl J Med. 2001;344:699-709.
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Slide 44

• Full support patient
• High risk of death – Any of the following:
– APACHE II 
25
– Sepsis-induced multiple organ failure
– Septic shock
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Slide 45

• Risk of bleeding
• Hemorrhagic stroke
• Head trauma, intracranial or spinal surgery
• Intracranial mass or herniation
• Presence of epidural catheter
• Recent surgery
• Intracranial lesion
• Low APACHE II score
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Slide 46

• Serum lactate measured.
• Blood cultures obtained prior to antibiotic administration.
• At presentation, broad-spectrum antibiotics administered
• Management of hypotension
• Management of persistent arterial hypotension refractory to volume resuscitation
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Slide 47

• Low-dose steroids administered for septic shock in accordance with a standardized ICU policy.
• Drotrecogin alfa (activated) administered in accordance with a standardized ICU policy.
• Glucose control maintained > lower limit of normal, but
<150 mg/dL (8.3 mmol/L).
• For mechanically ventilated patients, inspiratory plateau pressures maintained <30 cm H2O.
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Slide 48

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Copyright restrictions may apply.
Ferrer, R. et al. JAMA 2008;299:2294-2303.
Slide 49

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Slide 50

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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.
Slide 51

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Slide 52

• Levy MM et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International
Sepsis Definition Conference. Crit Care Med 2003;31:1250-1256
• Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med.
2001;345:1368-1377.
• Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J
Med. 2001;344:699-709.
• Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862-871.
• Dellinger RP. Cardiovascular management of septic shock. Crit
Care Med. 2003;31:946-955.
™
Slide 53

• Bochud PY, Bonten M, Marchetti O, et al. Antimicrobial therapy for patients with severe sepsis and septic shock: an evidence-based review. Crit Care Med. 2004;32:S495-S512.
• Marshall JC, Maier RV, Jimenez M, et al. Source control in the management of severe sepsis and septic shock: an evidence-based review. Crit Care Med. 2004;32:S513-S526.
• Annane D, Vignon P, Renault A, et al. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomized trial. Lancet 2007;370:676-684
• Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. NEJM
5008;358:877-887.
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Slide 54

• Sprung CL, Annane D, Keh D, et al. Hydrocortisone therapy for patients with septic shock. NEJM 2008;358;11-124
• Dellinger RP et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock:2008.
Crit Care Med. 2008;36:296-327.
• Ferrer R, Artigas A, Levy MM, et al. Improvement in process of care and outcome after multicenter severe sepsis educational program in
Spain. JAMA 2008;299:2294-2303
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Slide 55