Sepsis Guidelines International guidelines for management of severe sepsis and septic shock: 2008 Critical Care Medicine 2008 Vol.36 (1)

Septic Shock Mortality

Dellinger: Crit Care Med, Vol 31(3).March 2003.946-955

Definitions SIRS: 2 or more of the following: Ø Ø Ø Ø

Core T >=38 or =90 RR >=20 or PaCO2 =12,000 or = 4 ACCP / SCCM Consensus Panel, 1992

Organ Dysfunction CV: SBP = 8 (>= 12 if mech vent) n Initial bolus: Crystalloids: ~1000 cc; Colloids 300 – 500 cc over 30 min; repeat based on response and tolerance n

Fluid Therapy Reduce rate of fluids when CVP or PCWP increase without concurrent hemodynamic improvement n Venodilation and capillary leak: need for continuing aggressive treatment with fluids n I >> O is typical; can’t use to judge fluid resuscitation during the first 24h n

Vasopressors Hypotensive pt: loss of autoregulation and dependence of perfusion on pressure n May need to start before correction of hypovolemia n Titration of norepinephrine to MAP 65 has been shown to preserve tissue perfusion n Baseline BP should be considered n

Vasopressors Initial pressor of choice: norepinephrine or dopamine n Vasopressin 0.03 U/min may be added n Epinephrine in cases of poor response to norepi or dopa n Central and A-lines n

ScvO2 or SvO2 below target Transfuse RBC to achieve Hct >= 30 n Dobutamine up to 20 mcg/kg/min n

CORTICUS Study n n n n

50 mg hydrocortisone q 6h x 5d with 6-day taper vs. placebo Primary outcome: death at 28 days in ACTH stimulation test nonresponders No mortality difference in responders or nonresponders Faster shock reversal in hydrocortisone group

Corticosteroids IV hydrocortisone: cases of septic shock when BP is poorly responsive to fluid resuscitation and vasopressors. Do not exceed 300 mg hydrocortisone / day n No need in ACTH stimulation test n Wean steroids when vasopressors are no longer required n

Other Issues Diagnosis n Antibiotics n Source control n Activated Protein C n

Supportive Therapy Transfuse for Hgb < 7 once tissue hypoperfusion resolved n Mechanical ventilation n Glucose control n Nutrition n DVT and stress ulcer prophylaxis n

Activated Protein C Approved for patients with severe sepsis and increased risk of death n APACHE II > = 25 or dysfunction of 2 or more organs: absolute decrease in mortality 13% (6) v Not effective in patients with low risk of death (7) n

Vasopressin Consider in patients with refractory shock despite fluid resuscitation and high-dose conventional vasopressors. n Dose 0.01 – 0.03 u/min n May decrease stroke volume n Not the first choice n

Vasopressin Low VP levels (3.1 pg/ml) were found in a study of 19 patients with vasodilatory septic shock as compared to patients with cardiogenic shock (22.7pg/ml). n VP 0.04 u/min increased measured VP level and improved BP. n

Landry DW et al Circulation 1997; 95(5): 1122-5 Columbia University

Vasopressin n n n n

n

Prospective study of 239 mixed critically ill SICU patients and 70 healthy volunteers Study pts had higher AVP than healthy controls No correlation between serum AVP level and the incidence of shock. 4/239 patients met criteria for absolute (