Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock
Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D., Suzanne Havstad, M.A., Julie Ressler, B.S., Alexandria Muzzin, B.S., Bernhard Knoblich, M.D., Edward Peterson, Ph.D., Michael Tomlanovich, M.D., for the Early Goal-Directed Therapy Collaborative Group
Background Goal-directed therapy has been used for severe sepsisand septic shock in the intensive care unit. This approach involvesadjustments of cardiac preload, afterload, and contractilityto balance oxygen delivery with oxygen demand. The purpose ofthis study was to evaluate the efficacy of early goal-directedtherapy before admission to the intensive care unit.
Methods We randomly assigned patients who arrived at an urbanemergency department with severe sepsis or septic shock to receiveeither six hours of early goal-directed therapy or standardtherapy (as a control) before admission to the intensive careunit. Clinicians who subsequently assumed the care of the patientswere blinded to the treatment assignment. In-hospital mortality(the primary efficacy outcome), end points with respect to resuscitation,and Acute Physiology and Chronic Health Evaluation (APACHE II)scores were obtained serially for 72 hours and compared betweenthe study groups.
Results Of the 263 enrolled patients, 130 were randomly assignedto early goal-directed therapy and 133 to standard therapy;there were no significant differences between the groups withrespect to base-line characteristics. In-hospital mortalitywas 30.5 percent in the group assigned to early goal-directedtherapy, as compared with 46.5 percent in the group assignedto standard therapy (P=0.009). During the interval from 7 to72 hours, the patients assigned to early goal-directed therapyhad a significantly higher mean (±SD) central venousoxygen saturation (70.4±10.7 percent vs. 65.3±11.4percent), a lower lactate concentration (3.0±4.4 vs.3.9±4.4 mmol per liter), a lower base deficit (2.0±6.6vs. 5.1±6.7 mmol per liter), and a higher pH (7.40±0.12vs. 7.36±0.12) than the patients assigned to standardtherapy (P0.02 for all comparisons). During the same period,mean APACHE II scores were significantly lower, indicating lesssevere organ dysfunction, in the patients assigned to earlygoal-directed therapy than in those assigned to standard therapy(13.0±6.3 vs. 15.9±6.4, P<0.001).
Conclusions Early goal-directed therapy provides significantbenefits with respect to outcome in patients with severe sepsisand septic shock.
Source Information
From the Departments of Emergency Medicine (E.R., B.N., J.R., A.M., B.K., M.T.), Surgery (E.R.), Internal Medicine (B.N.), and Biostatistics and Epidemiology (S.H., E.P.), Henry Ford Health Systems, Case Western Reserve University, Detroit.
Address reprint requests to Dr. Rivers at the Department of Emergency Medicine, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, or at erivers1{at}hfhs.org.
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