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 <= 36 HR >=90 RR >=20 or PaCO2 <=32 WBC >=12,000 or <=4,000

ACCP / SCCM Consensus Panel, 1992

1992 .Definitions • • • Sepsis: SIRS + known or suspected infection Severe sepsis: Sepsis with hypoperfusion or organ dysfunction (see next slide) Septic shock: ongoing tissue hypoperfusion = hypotension despite adequate fluid resuscitation or lactate >= 4 ACCP / SCCM Consensus Panel.

Metabolic: pH <=7. . delirium).0 mmol/L and plasma lactate >1. Hepatic dysfunction (eg. or the use of vasopressors to achieve the same goals. transaminitis) CNS: Acute alteration in mental status (eg.30 or base deficit >5. or acute renal failure Pulmonary: PaO2/FiO2 <= 250 if other organ dysfunction present or <= 200 if the lung is the only dysfunctional organ.Organ Dysfunction • <=70 mmHg for at least 1 hour despite adequate volume resuscitation. Hematologic: Platelet count <80.5 x upper limit of normal.5 mL/kg/h. or disseminated intravascular coagulation.000/mm3 or decreased by 50 percent over three days. hyperbilirubinemia. CV: SBP <=90 mmHg or MAP • • • • • • Renal: Urine output <0.

March 2003.Pathophysiology n Ø Ø Hypovolemia loss of cardiac filling Capillary leak (absolute hypovolemia) Venodilation (relative hypovolemia) n n n Ø Ø Cardiogenic decrease in contractility Obstructive rise in PVR Distributive hypoperfusion despite nl / incr CO Macrovascular (decreased splanchnic flow) Microvascular (shunting) n Cytotoxic cellular inability to utilize O2 despite adequate supply Dellinger: Crit Care Med.946-955 . Volume 31(3).

Multiorgan Dysfunction Host immunosupression (anergy. lymphopenia. hypothermia) n Apoptosis initiated by proinflammatory cytokines n Tissue injury and multiorgan dysfunction n NEJM 355(16):1699-1713 .

Septic shock: Hypodynamic state of O2 delivery dependency (high lactate and low ScvO2) hyperdynamic (O2 consumption is independent of O2 delivery. myocardial depression.Sepsis Progression n Early: systemic O2 supply / demand imbalance Hypovolemia. normal or increased lactate and high ScvO2) Otero. Elevated lactate. R et al EGDT in Severe Sepsis Revisited Chest 130(5) 1579-1595 . increased metabolic rate and vasoregulatory perfusion abnormalities. Can occur with normal vital signs. decreased ScvO2. • n Ø Ø Global tissue hypoxia: delivery dependent Transition to severe disease.

003(PaO2) n n n n n CaO2 in ml/dl arterial blood SaO2 expressed as decimal fraction HgB in g/dl 1.Oxygen Content Equation CaO2 = (SaO2 x Hgb x 1.003 = solubility constant (0.34 = O2-binding capacity of Hgb (ml O2/g Hgb) 0.003 ml O2/dl/mm Hg PaO2) .34) +0.

O. x CaO2 n Venous O2 delivery = C.O2 delivery Arterial O2 delivery = C. x CvO2 n If C.O. = 5 L/min and CaO2 = 20 ml O2/dl O2 delivery = 1000 ml/min n .O.

2 L O2/L – 0. x (CaO2 – CvO2) n VO2 = 5 L/min x (0.05 = 0.25 L = 250 ml n O2ER: VO2 / DO2 x 100% (Normal 20 .30%) .15 L O2/L) = 5 x 0.O.Oxygen uptake O2 uptake = art O2 – ven O2 delivery n VO2 = C.

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345:1368-1377 .Rivers. et al Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock NEJM 2001.

et al Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock NEJM 2001.Rivers. 345:1368-1377 .

345:1368-1377 . et al Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock NEJM 2001.Rivers.

Rivers. 345:1368-1377 . et al Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock NEJM 2001.

345:1368-1377.The Importance of Early Goal-Directed Therapy for Sepsis-induced Hypoperfusion NNT to prevent 1 event (death) = 6 . Havstad S. et al. 2001.8 60 50 Standard therapy EGDT Mortality (%) 40 30 20 10 0 In-hospital mortality (all patients) 28-day mortality 60-day mortality Adapted from Table 3. page 1374. N Engl J Med. . Nguyen B. with permission from Rivers E. Early goal-directed therapy in the treatment of severe sepsis and septic shock.

2001. Crit Care Med.32(Suppl):S445 Hercules Kills Cerberus. and organ dysfunction. hypoperfusion. Italy . Renato Pettinato. 2004.A clinician attacks the three heads of severe sepsis— hypotension.

5 ml/kg/h n ScvO2 >= 70% or SvO2 > = 65% n .Initial Resuscitation Protocolized resuscitation n CVP 8 – 12 n MAP > 65 n UO > = 0.

Fluid Therapy Crystalloids and colloids are equally effective n Target CVP >= 8 (>= 12 if mech vent) n Initial bolus: Crystalloids: ~1000 cc. repeat based on response and tolerance n . Colloids 300 – 500 cc over 30 min.

can’t use to judge fluid resuscitation during the first 24h 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.

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 .

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 .CORTICUS Study n n n n 50 mg hydrocortisone q 6h x 5d with 6-day taper vs.

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.03 u/min n May decrease stroke volume n Not the first choice n . n Dose 0.01 – 0.

95(5): 1122-5 Columbia University . n VP 0. n Landry DW et al Circulation 1997.04 u/min increased measured VP level and improved BP.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).Vasopressin Low VP levels (3.

34(2) 293 . 22% of septic shock patients had relative AVP deficiency Jochberger. S et al Crit Care Med 2006.83 pg/ml) and 32 patients met criteria for a relative AVP deficiency (AVP < 10 and MAP < 70).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 (<0.

All patients in the VP group survived and had other pressors withdrawn (maintained BP on VP only). 47(4): 699-703.Vasopressin 10 pts with vasodilatory septic shock admitted to a trauma ICU n Randomized to VP 0.04 u/min or placebo n 2 patients in the placebo group died of refractory hypotension. n Malay MB et al J Trauma 1999. Allegheny General Hospital Pittsburg .

04 u/min x 16h n BP. case-controlled study of 16 patients with septic shock who remained hypotensive despite pharmacologic doses of catecholamines. SVR and UO increased. Lactate decreased.Vasopressin Prospective. n Tsuneyoshi I et al Crit Care Med 2001 Mar. n VP 0. No side effects. 29(3): 487-93 .

Vasopressin n n n 48 patients with catecholamine –resistant vasodilatory shock randomized to NE or AVP 4 u/h + NE and followed for 48h. SV and LVSWI were higher in AVP group. 107: 2313 – 2319 30. AVP pts: significantly lower HR. NE requirements and incidence of new-onset tachyarrhythmias.2% incidence of ischemic skin ulcers Dunser Crit Care Med 2003. 31: 1394 – 1398 . but bilirubin was higher in the AVP group. Dunser Circulation 2003. MAP.GI perfusion was better (by gastric tonometry). CI.

4) Women 45.5 + 0. n TV 6 cc/kg IBW n Men 50 + 0.Ventilation ALI / ARDS is common n Lung protective ventilation decreases mortality (from 40 to 31% in ARDS Network Study)17. . lessens organ dysfunction and lowers levels of cytokines.4) n PEEP doesn’t improve mortality18.91(H cm – 152.91(H cm – 152.

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