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Guidelines for Management of Severe Sepsis/Septic Shock
Bekele Afessa, MD
™ Slide 3
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&pubmedid=18058085
Surviving Sepsis Campaign: Guidelines for Management of Severe Sepsis/Septic Shock
™ Slide 4
Sepsis-induced Tissue Hypoperfusion
• Persistent hypotension
• Elevated lactate
• Hypoxemia
• Oliguria or increase in creatinine
• Coagulation abnormalities
• Ileus
• Thrombocytopenia
• Elevated bilirubin Levy MM et al. CCM 2003;31:1250
™ Slide 5
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™ Slide 7
A Melting Pot of Shock Etiologies
• Hypovolemic
• Distributive
• Cardiogenic
• Obstructive
• Cytotoxic
Dellinger RP. CCM 2003;31:946
™ Slide 8
Figure B, page 948, reproduced with permission
from Dellinger RP. Cardiovascular
management of septic shock. Crit Care Med.
2003;31:946-955.
Pre-Fluid Resuscitation
™ Slide 9
Diastolic Size of Ventricles
10 days post-shock
Diastole Systole
Diastole Systole
Images used with permission from Joseph E. Parrillo, MD
™ Slide 10
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™ Slide 12
Early Goal Directed Therapy
Rivers E et al. NEJM 2001;345:1368
™ Slide 13
Importance of Early Goal for Hypoperfusion
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.
In-hospital mortality
(all patients)
0
10
20
30
40
50
60 Standard therapy
EGDT
28-day mortality
60-day mortality
NNT to prevent 1 event (death) = 6-8
Mo
rtal
ity
(%)
™ Slide 14
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™ Slide 16
Fluid Therapy
• 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
™ Slide 17
Bicarbonate Therapy
• Bicarbonate therapy not recommended to improve hemodynamics in patients with lactate-induced pH >7.15
Cooper et al. Ann Intern Med. 1990;112:492-498.Mathieu et al. Crit Care Med. 1991;19:1352-1356.
™ Slide 18
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™ Slide 20
Vasopressors for Septic Shock
• Indications
• Drug of choice Norepinephrine or dopamine
• No place for “low dose” dopamine
™ Slide 21
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™ Slide 23
Effects on Splanchnic Circulation
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.
™ Slide 24
Vasopressin in Septic Shock
• Elevated in early septic shock, normal later
• Indication
• Dose 0.03 units/min. It may decrease stroke volume.
• Watch for side effects
™ Slide 25
Changing pH Has Limited Value
Treatment Before After
NaHCO3 (2 mEq/kg)
pH 7.22 7.36
PAOP 15 17
Cardiac output 6.7 7.5
0.9% NaCl
pH 7.24 7.23
PAOP 14 17
Cardiac output 6.6 7.3
Cooper DJ et al. Ann Intern Med. 1990;112:492-498.
™ Slide 26
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™ Slide 28
Resuscitation in Septic Shock
• 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)
™ Slide 29
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™ Slide 31
Looking for a Source
• Identify common causes of ICU-acquired infections
• Obtain cultures before antibiotics
• Testing Procedures
™ Slide 32
Antibiotics
• 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
™ Slide 33
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™ Slide 35
Infection Source Control
Dellinger RP. Crit Care Med 2004;32:858
™ Slide 36
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™ Slide 38
Steroid Therapy
Figure 2A, page 867, reproduced with permission from Annane D, Sébille 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.
™ Slide 39
P = .045
Figure 2 and Figure 3, page 648, reproduced with permission from Bollaert PE, Charpentier C, Levy B, et al. Reversal of late septic shock with supraphysiologic doses 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, single-center study. Crit Care Med. 1999;27:723-732.
P = .007
™ Slide 40
CORTICUS Study
Sprung CL et al. NEJM 2008;358:111
Kaplan-Meier Curves Hydrocortisone Vs Placebo
™ Slide 41
Steroids
• 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
™ Slide 42
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™ Slide 44
Results: 28-day All-cause Mortality
35
30
25
20
15
10
5
0
30.8%
24.7%
Placebo
(n - 840)
Drotrecogin alfa
(activated) (n = 850)
Mo
rtal
ity
(%)
6.1% absolute reduction in
mortality
Primary analysis results2-sided p-value 0.005Adjusted relative risk reduction 19.4%Increase in odds of survival 38.1%
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.
™ Slide 45
Patient Criteria for Recombinant Human Activated Protein C
• Full support patient
• High risk of death – Any of the following:
– APACHE II 25
– Sepsis-induced multiple organ failure
– Septic shock
™ Slide 46
Recombinant Human Activated Protein C: Contraindications
• 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
™ Slide 47
Sepsis Resuscitation Bundle
• 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
™ Slide 48
Sepsis Management Bundle
• 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.
™ Slide 49
Copyright restrictions may apply.
Ferrer, R. et al. JAMA 2008;299:2294-2303.
The Impact of Sepsis Resuscitation and Management Bundles
™ Slide 50
www.survivingsepsis.org
™ Slide 51
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 52
Self Assessment
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™ Slide 53
References
• 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 54
References
• 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.
™ Slide 55
References
• 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