septic shock.ppt

Current Management of Severe Sepsis and Septic Shock

Isabel C. Mira-Avendano, M.D.Isabel C. Mira-Avendano, M.D.

PGY-3 ResidentPGY-3 Resident

Department of MedicineDepartment of Medicine

Current Management of Severe Sepsis and Septic Shock l September 8, 2010 l 2

Current Management of Severe Sepsis and Septic Shock

OBJECTIVESOBJECTIVES

• Review the Septic Shock Management Review the Septic Shock Management GuidelinesGuidelines

• Know the main trials which are the base Know the main trials which are the base for that Guidelinesfor that Guidelines

• Discuss the level of evidence for each Discuss the level of evidence for each recommendationrecommendation

IntroductionIntroduction

• Severe Sepsis and Septic Shock are major Severe Sepsis and Septic Shock are major healthcare problemshealthcare problems

• High mortalityHigh mortality

• Increasing in incidenceIncreasing in incidence

• APPROPRIATED AND RAPID APPROPRIATED AND RAPID MANAGEMENT INFLUENCE THE MANAGEMENT INFLUENCE THE OUTCOMEOUTCOME

SYSTEMIC INFLAMMATORY RESPONSE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SRIS):SYNDROME (SRIS):

2 o more of:2 o more of:

• Fever: oral temperature >38C or Fever: oral temperature >38C or hypothermia (<36C)hypothermia (<36C)

• Tachypnea: >24 breaths/minTachypnea: >24 breaths/min

• Tachycardia: heart reat >90 beats/minTachycardia: heart reat >90 beats/min

SYSTEMIC INFLAMMATORY RESPONSE SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SRIS):SYNDROME (SRIS):

2 o more of:2 o more of:

• Leukocytosis: WBC >12.000/ul, leukopenia Leukocytosis: WBC >12.000/ul, leukopenia <4000/ul, or >10% bands<4000/ul, or >10% bands

SEPSIS:SEPSIS:

SIRS in response to documented infectionSIRS in response to documented infection

SEVERE SEPSIS:SEVERE SEPSIS:

Sepsis with evidence of acute organ dysfunctionSepsis with evidence of acute organ dysfunction

• CV: SBP CV: SBP <<90 mmHg or MAP 90 mmHg or MAP <<70 mmHg70 mmHg

• RENAL: urine output <0.5 ml/kg/hrRENAL: urine output <0.5 ml/kg/hr

• RESPIRATORY: PaO2/FIO2 RESPIRATORY: PaO2/FIO2 <<250250

• HEMATOLOGIC: platelet count <80.000/ulHEMATOLOGIC: platelet count <80.000/ul

• METABOLIC ACIDOSIS: pH METABOLIC ACIDOSIS: pH <<7.30 or plasma 7.30 or plasma lactate >2mmol/Llactate >2mmol/L

SEPTIC SHOCK:SEPTIC SHOCK:

Severe Sepsis with refractory hypotension: Severe Sepsis with refractory hypotension: MAP <60 mmHg after fluid resucitation MAP <60 mmHg after fluid resucitation (30-50cc/Kg crystalloids)(30-50cc/Kg crystalloids)

• Guidelines have been created to improve Guidelines have been created to improve outomes in severe sepsis and septic outomes in severe sepsis and septic shockshock

• These Guidelines are evidence-based These Guidelines are evidence-based medicine methodology systemmedicine methodology system

HOW THESE GUIDELINES WERE CREATED?HOW THESE GUIDELINES WERE CREATED?

Phase 1 Barcelona declarationPhase 2 Evidence based guidelines

Phase 3 Implementation and education

Surviving Sepsis

Evidence-Based-GuidelinesEvidence-Based-Guidelines

Surviving Sepsis Campaign (SSC) Guidelines for Management of Severe

Sepsis and Septic Shock

Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM,

Ramsay G, Zimmerman JL, Vincent JL, Levy MM and the

SSC Management Guidelines Committee

Crit Care Med 2004;32:858-873Intensive Care Med 2004;30:536-555

available online at www.springerlink.com

www.sccm.orgwww.sepsisforum.com

Updated International GuidelinesUpdated International Guidelines

Crit Care Med 2008; 36:296-327

International Guidelines – SepsisInternational Guidelines – Sepsis

Initial ResuscitationInitial Resuscitation

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

Central Venous Central Venous O2 Saturation:O2 Saturation:

SVO2 ?SVO2 ?

NEJM 2001; 345:1368-77NEJM 2001; 345:1368-77

Early-Goal Directed Therapy in SepsisEarly-Goal Directed Therapy in Sepsis

NEJM 2001; 345:1368-77NEJM 2001; 345:1368-77

Early-Goal Directed Therapy in SepsisEarly-Goal Directed Therapy in Sepsis

The Importance of Early Goal-DirectedTherapy for Sepsis Induced 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 Med2001; 345:1368-1377

I n-hospi tal mor talit y

(all pat ients)

60 St andard therapyEGDT

28-day mor t alit y

60-day mort alit y

NNT t o pr event 1 event ( deat h) = 6-8M

IF TIME IS MUSCLE IN CASE OF CARDIAC IF TIME IS MUSCLE IN CASE OF CARDIAC

ISCHEMIC DISEASE. ISCHEMIC DISEASE.

TIME IS TIME IS L I F EL I F E IN CASE OF SEPSIS IN CASE OF SEPSIS

During the first 6 hours, goals are:During the first 6 hours, goals are:

• CV pressure 8-12 mmHg. In mechanical ventilated CV pressure 8-12 mmHg. In mechanical ventilated patients or patients with known preexisting patients or patients with known preexisting decreased ventricular compliance, target will be decreased ventricular compliance, target will be 12 – 15 mmHg12 – 15 mmHg

• MAP MAP >> 65 mmHg 65 mmHg

Grade 1-BGrade 1-B

• Urine output > 0.5 ml/kg/hUrine output > 0.5 ml/kg/h

• Central venous saturation (SVO2) Central venous saturation (SVO2) >> 70% 70% Intermitent or continuous measurements of O2 Intermitent or continuous measurements of O2 are the sameare the same

Grade 1-BGrade 1-B

• If SVO2 is not achieved with fluid resuscitation, If SVO2 is not achieved with fluid resuscitation, through the CVC target, then transfusion of red through the CVC target, then transfusion of red blood cells to achieve Ht of 30%blood cells to achieve Ht of 30%

• After that, if no goal SVO2 is achieved, start After that, if no goal SVO2 is achieved, start Dobutamine Dobutamine

Grade 1-BGrade 1-B

DiagnosisDiagnosis

• Obtain appropriate cultures before Obtain appropriate cultures before antimicrobial therapy is initiated, if such antimicrobial therapy is initiated, if such cultures do not cause delay in antibiotic cultures do not cause delay in antibiotic administration. administration. Grade 1-CGrade 1-C

• Imaging studies should be performed Imaging studies should be performed promptly in attempts to confirm a potential promptly in attempts to confirm a potential source of infectionsource of infection

Antibiotic TherapyAntibiotic Therapy

Critical Care Medicine 2006. 34, 6Critical Care Medicine 2006. 34, 6

• Retrospective Cohort studyRetrospective Cohort study

• 2731 patients with Septic Shock2731 patients with Septic Shock

• 50% of them received effective 50% of them received effective antimicrobial administration within the antimicrobial administration within the first hour of documented hypotensionfirst hour of documented hypotension

• Increased survival was seen among themIncreased survival was seen among them

• IV antibiotic therapy must be started as early as IV antibiotic therapy must be started as early as possible and within the first hour of recognition possible and within the first hour of recognition of severe sepsis or septic shockof severe sepsis or septic shock

• Broad spectrum therapy until the causative Broad spectrum therapy until the causative organisms and susceptibilities are knownorganisms and susceptibilities are known

Evidence 1-CEvidence 1-C

Source of ControlSource of Control

• Specific anatomical diagnosis of infection Specific anatomical diagnosis of infection requiring consideration of emergent requiring consideration of emergent source of control, should be sought and source of control, should be sought and diagnosed as rapidly as possible and diagnosed as rapidly as possible and within the first 6 hours following within the first 6 hours following presentationpresentation

Grade 1-CGrade 1-C

Photograph used with permission from Janice L. Zimmerman, MD

EKG tracing reproduced with permission from Janice L. Zimmerman, MD

Fluid TherapyFluid Therapy

Fluid Management in SepsisFluid Management in Sepsis

Fluid TherapyFluid Therapy

• Fluid resuscitation could be done with Fluid resuscitation could be done with either crystalloids or colloids. either crystalloids or colloids.

Grade 1-BGrade 1-B

Vasopressor Support in Vasopressor Support in Septic ShockSeptic Shock

Below a certain MAP, autoregulation is lost Below a certain MAP, autoregulation is lost and perfusion becomes linearly depend on and perfusion becomes linearly depend on pressurepressure

• MAP should be maintained over 65 mmHgMAP should be maintained over 65 mmHg

• Vasopresor therapy is required to maintain Vasopresor therapy is required to maintain perfusion in the face of life-threatening perfusion in the face of life-threatening hypotension, even when hypovelemia has hypotension, even when hypovelemia has been not resolvedbeen not resolved

Evidence C-1Evidence C-1

• Use either Norepinephrine (NE) or Use either Norepinephrine (NE) or Dopamin (Dopa) as the first choice Dopamin (Dopa) as the first choice vasopressor agent to correct hypotensionvasopressor agent to correct hypotension

• Epinephrine (Epi), Phenylephrine or Epinephrine (Epi), Phenylephrine or vasopressin should not be administered vasopressin should not be administered as the initial vasopressor in septic shockas the initial vasopressor in septic shock

Effects of Dopamine, Norepinephrine,and Epinephrine on the Splanchnic

Circulation in Septic Shock

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

Vasopressin in SepsisVasopressin in Sepsis

• In physiologic doses: 0.01-0.04 U/min, is In physiologic doses: 0.01-0.04 U/min, is synergistic with exogenous synergistic with exogenous cathecholamines, yielding a pressor cathecholamines, yielding a pressor response without evidence of organ response without evidence of organ hypoperfussionhypoperfussion

• In pharmacologic doses: >0.04 U/min, the In pharmacologic doses: >0.04 U/min, the vasopressor effect is associated with vasopressor effect is associated with vasoconstriction of renal, mesenteric, vasoconstriction of renal, mesenteric, pulmonary and coronary vasculaturepulmonary and coronary vasculature

• Vasopressin 0.03 – 0.04 U/min may be Vasopressin 0.03 – 0.04 U/min may be added to NE, to raise BP in patients with added to NE, to raise BP in patients with refractory Septic Shockrefractory Septic Shock

• Low dose Dopa not be used for renal Low dose Dopa not be used for renal protection protection

Evidence 1-AEvidence 1-A

• All patients requiring vasopressors must All patients requiring vasopressors must have an arterial catheter placed have an arterial catheter placed

Inotropic Support in Inotropic Support in Septic ShockSeptic Shock

During Septic Shock

10 Days Post Shock

Diastole Systole

Images used with permission from Joseph E. Parrillo, MD

Inotropic Support in Inotropic Support in Septic ShockSeptic Shock

• Consider Dobutamine as first choice Consider Dobutamine as first choice Inotrope for patient with measured or Inotrope for patient with measured or suspected low cardiac output, in the suspected low cardiac output, in the presence of adequate left ventricular filling presence of adequate left ventricular filling pressure and adequate MAPpressure and adequate MAP

Corticoid Therapy in Septic ShockCorticoid Therapy in Septic Shock

Corticoid Therapy in SepsisCorticoid Therapy in Sepsis

• Use Hydrocortisone only after confirm that BP is Use Hydrocortisone only after confirm that BP is poorly responsive to fluid resuscitation and poorly responsive to fluid resuscitation and vasopressor therapyvasopressor therapy

• Use no more that 300 mg/day, which will be wean Use no more that 300 mg/day, which will be wean when vasopressors are no longer requiredwhen vasopressors are no longer required

• Not use ACTH stimulation testNot use ACTH stimulation test

Evidence 2-BEvidence 2-B

Recombinant Activated Protein-C in Recombinant Activated Protein-C in Severe Sepsis and Septic ShockSevere Sepsis and Septic Shock

NEJM 2001; 344:699-709NEJM 2001; 344:699-709

Activated Protein C in Severe SepsisActivated Protein C in Severe Sepsis

Thrombin

Thrombomodulin

Protein C (Inactive)

Protein C Activity

Blood VesselBlood Flow ⇒

Protein C Receptor

ProteinS

Human Activated Protein CEndogenous Regulator of Coagulation

NEJM 2001; 344:699-709NEJM 2001; 344:699-709

Placebo

(n-840)

Drotrecoginalfa

(activated) (n=850)

6.1% absolute reduction in

mortality

Results: 28-Day All-Cause MortalityPrimary analysis results

2-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

NEJM 2005; 353:1332-41NEJM 2005; 353:1332-41

• Use its in patients with high risk of death, Use its in patients with high risk of death, multiple organ failure, APACHE multiple organ failure, APACHE >> 25, if its, is not 25, if its, is not contraindicatedcontraindicated

• Patients with severe sepsis and low risk of death, Patients with severe sepsis and low risk of death, most of who will have APACHE < 25 or one organ most of who will have APACHE < 25 or one organ failure, should not receive Activated Protein Cfailure, should not receive Activated Protein C

Evidence 1-AEvidence 1-A

SUPPORTIVE THERAPY OF SEVERE SEPSISSUPPORTIVE THERAPY OF SEVERE SEPSIS

Mechanical Ventilation of Sepsis-induced Mechanical Ventilation of Sepsis-induced ALI/ARDSALI/ARDS

Mechanical Ventilatory Support in ARDSMechanical Ventilatory Support in ARDS

Mechanical Ventilatory Support in Mechanical Ventilatory Support in ARDSARDS

Peak Airway Pressure

Inspiratory Plateau Pressure

PEEP (5 cm H2O

NEJM 2000; 342:1301-8NEJM 2000; 342:1301-8

Mechanical Ventilatory Support in ARDSMechanical Ventilatory Support in ARDS

6 ml/kg

12 ml/kg

ARDSnet Mechanical Ventilation Protocol

Results: Mortality

Adapted from Figure 1, page 1306, with permission from The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000;342:1301-1378

Mechanical Ventilatory Support in Mechanical Ventilatory Support in ARDSARDS

• Target a tidal volume of 6 ml/kg of PBWTarget a tidal volume of 6 ml/kg of PBW

• Upper limit goal for Plateau Pressure less than 30 Upper limit goal for Plateau Pressure less than 30 cmH2OcmH2O

• Permissive hypercapnia be allowed in the Permissive hypercapnia be allowed in the patients if neededpatients if needed

• Raising PEEP keeps lung units open Raising PEEP keeps lung units open

Sedation, Analgesia, and Neuromuscular Sedation, Analgesia, and Neuromuscular blockade in Sepsisblockade in Sepsis

• Use sedation protocols with sedation goalUse sedation protocols with sedation goal

• Daily interruption of continuous infusion Daily interruption of continuous infusion sedation with awakening and retitration if sedation with awakening and retitration if necessary necessary

• Neuro Muscular blockage agents (NMBA) Neuro Muscular blockage agents (NMBA) should be avoided if possible in the septic should be avoided if possible in the septic patientpatient

Grade 1-BGrade 1-B

Glucose ControlGlucose Control

Tight Glucose Control in SepsisTight Glucose Control in Sepsis

NEJM 2001; 345:1359-67NEJM 2001; 345:1359-67

The Role of IntensiveInsulin Therapy in the Critically Ill

At 12 months, intensive insulin therapy reduced mortality by 3.4% (P<0.04)

Adapted from Figure 1B, page 1363, with permission from van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345:1359-67

Intensive treatment

Conventional treatment

Days after admission

50 100 150 200 250

P=0.01

NEJM 2006; 354:449-61NEJM 2006; 354:449-61

• Maintain Glucose levels less than 150, Maintain Glucose levels less than 150, using validated protocol for insulin dose using validated protocol for insulin dose adjustments (enteral preferred)adjustments (enteral preferred)

Renal Replacement TherapyRenal Replacement Therapy

• Continuous Renal Replacement Therapies Continuous Renal Replacement Therapies and Intermitent Hemodialysis are and Intermitent Hemodialysis are equivalent in patients with severe sepsis equivalent in patients with severe sepsis and ARFand ARF

• Use Continuous therapies to facilitate Use Continuous therapies to facilitate management of fluid balance in management of fluid balance in hemodynamically unstable septic patientshemodynamically unstable septic patients

Evidence 2-Evidence 2-BB

Bicarbonate TherapyBicarbonate Therapy

• Recommendation is against the use of Recommendation is against the use of Sodium-Bicarbonate therapy for the Sodium-Bicarbonate therapy for the purpose of improving hemodynamics or purpose of improving hemodynamics or reducing vasopressor requirements in reducing vasopressor requirements in patients with hypotension-induced lactic patients with hypotension-induced lactic acidemia with pH acidemia with pH >> 7.15 7.15

Crit Care Med 2004; 320:Suppl S595-7 Crit Care Med 2004; 320:Suppl S595-7

ConclusionConclusion

septic shock.ppt

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