CHAPTER 39 EARLY GOAL-DIRECTED THERAPY IN SEPSIS

Early Goal-directed Therapy in the Treatment of Severe Sepsis and Septic Shock

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

BACKGROUND

Severe sepsis and septic shock are deadly diseases, with up to 25% mortality. In the late 1990s, small human and animal studies showed potential benefit from early resuscitation to hemodynamic goals to reverse systemic inflammatory response syndrome (SIRS) before deterioration to organ dysfunction and death, mainly in the ICU setting. Rivers et al. postulated that early hemodynamic assessment and aggressive, goal-directed resuscitation of septic patients while still in the ED might improve mortality.

OBJECTIVES

To evaluate the efficacy of early goal-directed therapy (EGDT) in patients with severe sepsis or septic shock in the ED.

METHODS

Prospective, randomized controlled trial conducted in a single American academic ED between 1997 and 2000.

Patients

Two hundred and sixty-three adult patients with at least two SIRS criteria and SBP <90 mm Hg after a 20 to 30 mL/kg crystalloid challenge or a lactate >4 mmol/L. Select exclusion criteria: Patients presenting with noninfectious etiologies of shock (acute coronary syndrome, ischemic or hemorrhagic stroke, drug overdose) or immunosuppression.

Intervention Evaluated

EGDT for 6 hours vs. standard therapy. Both groups received an arterial and central venous catheterization, blood and urine cultures.

EGDT Protocol

500-cc crystalloid boluses targeting central venous pressure (CVP) between 8 and 12 mm Hg. Vasopressors/vasodilators targeting a mean arterial pressure (MAP) of greater than 65 and less than 90. Red cell transfusion to target a hematocrit greater than 30% for central venous oxygen (CVO₂) of less than 70%. If CVO₂ remained less than 70%, dobutamine was given and titrated up unless the MAP was less than 65 or the heart rate was greater than 120 beats per minute. Patients who could not achieve hemodynamic optimization were intubated, mechanically ventilated, and sedated.

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