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Early Goal Therapy in Severe Sepsis & Septic Shock

Nabil Abouchala, MD, FCCP, FACPConsultant, Pulmonary and Critical Care Medicine

King Faisal Hospital & Research CenterRiyadh, Saudi Arabia

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Sepsis: Defining a Disease Continuum

A clinical response arising from a nonspecific insult, including 2 of the following:• Temperature 38oC or 36oC• HR 90 beats/min• Respirations 20/min• WBC count 12,000/mm3 or

4,000/mm3 or >10% immature neutrophils

SIRS = Systemic Inflammatory Response Syndrome

SIRS with a presumed or confirmed infectious process

SepsisSIRSInfection/Trauma Severe Sepsis

Adapted from: Bone RC, et al. Chest 1992;101:1644Opal SM, et al. Crit Care Med 2000;28:S81

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Sepsis: Defining a Disease Continuum

Bone et al. Chest 1992;101:1644; Wheeler and Bernard. N Engl J Med 1999;340:207

SepsisSIRSInfection/Trauma Severe Sepsis

Sepsis with 1 sign of organ failure

Cardiovascular (refractory hypotension)

RenalRespiratoryHepaticHematologicCNSMetabolic acidosis

Shock

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Mortality

Septic Shock

53-63%

20-53%Severe Sepsis300,000

7-17%Sepsis

400,000

Incidence

Balk, R.A. Crit Care Clin 2000;337:52

Mortality Increases in Septic Shock Patients

Serum Lactate Measured

Blood Culture Obtained Prior to Antibiotic Administration

Broad-Spectrum Antibiotics Administered within 1 Hour of ED Admission

Fluid Resuscitation (30 ML/Kg) for Hypotension or Lactate >4mmol/L

Vasopressors for Ongoing Hypotension

Maintain Adequate Central Venous Pressure (CVP ≥ 8)Maintain Adequate Central Venous Oxygen Saturation (ScvO2 ≥

70%)

Resu

scit

ati

on

Bu

nd

le

SEPSIS BUNDLE

Re-measure Serum Lactate

A. Initial Resuscitation

EARLY GOAL-DIRECTED THERAPY IN THE TREATMENT OF SEVERE SEPSIS AND SEPTIC SHOCKTo Examine whether Early Goal Directed Therapy (EGDT) before admission to the ICU is superior to standard hemodynamic therapy in patients with sever sepsis and septic shock

N Engl J Med, 2001;345:1368-77

#Citing

articles

2469

Central venous andarterial catheterization

CVP8 -12 mm Hg

MAP³65 and £90 mm Hg

ScvO2

³70%

Goals achieved

Hospital admission

PROTOCOL FOR EARLY GOAL-DIRECTED THERAPY

CrystalloidColloid

Vasoactive agents

Transf. of RBCuntil Hct ³30%

Inotropic agents

N Engl J Med, 2001;345:1368-77

Alternative of using mixed venous oxyhemoglobin saturation from pulmonary artery catheter instead of central venous O2 saturation from CVP catheter

Venous Oxygen Saturation

◦ If venous O2 saturation target not achieved: (2C)· Consider further fluid· Tansfuse packed red blood cells if required

to hematocrit of ≥30% and/or· Dobutamine infusion max 20 µg.kg−1 .min−1

Rivers E, Nguyen B, Havstad S, et al. 2001;345:1368-1377.

TREATMENT ADMINISTERED

5

3.5

8.62

10.6

13.44 13.35

0

5

10

15

0-6 h 7-72 h Total

Early GoalStandard

N Engl J Med, 2001;345:1368-77

MORTALITY

10-20%

Sudden

Death!

Rivers E, Nguyen B, Havstad S, et al. 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 - 8M

ort

alit

y (%

)

The Importance of Early Goal-DirectedTherapy for Sepsis-induced Hypoperfusion

RESULTS

MortalityEGT : 30.5 %Standard: 46.5 %

Absolute Risk Reduction

NNT =

N Engl J Med, 2001;345:1368-77

37 Observational studies showing improved

outcomes with early quantitative resuscitation

between 2001 and 2011

Multicenter trial of 314 patients with severe sepsis in eight Chinese centers (2010). This trial reported a 17.7% absolute reduction

16%

7

SEPSIS INDUCED VASODILATATION

Lower amount of fluid required to fill the tank

NE

VA

SO

CO

NS

TR

ICT

ION

Crit Care Med 2007; 35:1736–1740

Early NE + Fluids

Late NE + Fluids

Fluids

NE

LPS