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To assess the impact of an algorithm defining resuscitation according to early goal-directed therapy, glycemic control, administration of stress doses of hydrocortisone, and use of recombinant human activated protein C (rhAPC) on measures of organ dysfunction and outcome in septic shock.Retrospective cohort study.Multidisciplinary ten-bed intensive care unit of a university hospital.Sixty patients were analyzed: 30 consecutive patients fulfilling criteria for diagnosis of septic shock, treated from September 2002 until December 2003 after implementation of a standard operating procedure (SOP) for severe sepsis and septic shock; and 30 patients with septic shock treated from January until August 2002 in the same unit, who served as controls.Data for blood gas analysis, lactate, glucose, serum creatinine, bilirubin, white blood cells, platelets, and C-reactive protein were obtained from patient files on admission or at time of diagnosis of septic shock and at 7:00 a.m. on days 2 and 4; Sequential Organ Failure Assessment scores were calculated and 28-day survival was assessed. With implementation of the SOP, use of dobutamine (12/30 vs. 2/30), insulin (blood glucose <150 mg/dL, day 4: 26/28 vs. 13/25), hydrocortisone (30/30 vs. 13/30), and rhAPC (7/30 vs. 0/30) significantly increased, whereas volume for resuscitation and use of packed red blood cells were unaffected. Mortality was 53% in the historical control group and 27% after implementation of the SOP (p < .05).The combined approach of early goal-directed therapy, intensive insulin therapy, hydrocortisone administration, and additional application of rhAPC in selected cases seems to favorably influence outcome. The implementation of a “sepsis bundle” can be facilitated by a standardized protocol while significantly reducing the time until the defined therapeutic measures are realized in daily practice.