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The Ne w E n g l a nd Jour n a l o f Me d ic i ne

EARLY GOAL-DIRECTED THERAPY IN THE TREATMENT OF SEVERE SEPSIS AND SEPTIC SHOCK
EMANUEL RIVERS, M.D., M.P.H., BRYANT NGUYEN, M.D., SUZANNEHAVSTAD, M.A., JULIE RESSLER, B.S., ALEXANDRIA MUZZIN, B.S., BERNHARD KNOBLICH, M.D., EDWARD PETERSON, PH.D., AND MICHAEL TOMLANOVICH, M.D., FOR THE EARLY GOAL-DIRECTED THERAPY COLLABORATIVE GROUP*ABSTRACT
Background Goal-directed therapy has been used
for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractilityto balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit. Methods We randomlyassigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) beforeadmission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), endpoints with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups. Results Of the 263enrolled patients, 130 were randomly assigned to early goal-directed therapy and 133 to standard therapy; there were no significant differences between the groups with respect to base-linecharacteristics. In-hospital mortality was 30.5 percent in the group assigned to early goal-directed therapy, as compared with 46.5 percent in the group assigned to standard therapy (P=0.009). During the intervalfrom 7 to 72 hours, the patients assigned to early goaldirected therapy had a significantly higher mean (±SD) central venous oxygen saturation (70.4±10.7 percent vs. 65.3±11.4 percent), a lower...