Stress doses of hydrocortisone reverse hyperdynamic septic shock: A prospective, randomized, double-blind, single-center study

Objective: To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock. Design: Prospective, randomized, double-blind, single-center study. Setting: Twenty bed multidisciplinary intensive care unit in a 1400 bed uni versity hospital. Patients: Forty consecutive patients who met the ACCP/SCCM criteria for sep tic shock. An additional criterion for inclusion in the study was vasopress or support and high-output circulatory failure with a cardiac index of >4 L /min/m(2) after fluid resuscitation (pulmonary capillary wedge pressure: 12 -15 mm Hg) and without the use of positive inotropes such as dobutamine or dopexamine. The primary study end point was the time to cessation of vasopr essor support (norepinephrine or epinephrine in any dose, dopamine greater than or equal to 6 ug/kg/min). Secondary study end points were the evolutio n of hemodynamics and the multiple organ dysfunction syndrome (MODS). The s everity of illness at recruitment was graded using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems. MOBS was described by the Sepsis related Organ Failure Ass essment score. Interventions: All eligible patients were prospectively randomized to recei ve either stress doses of hydrocortisone or placebo. Hydrocortisone was sta rted with a loading dose of 100 mg given within 30 mins and followed by a c ontinuous infusion of 0.18 mg/kg/hr. When septic shock had been reversed, t he dose of hydrocortisone was reduced to 0.08 mg/kg/hr. This dose was kept constant for 6 days. As soon as the underlying infection had been treated s uccessfully or sodium serum concentrations had increased to >155 mmol/L, th e hydrocortisone infusion was tapered in steps of 24 mg/day. Physiologic sa line solution was the placebo. Measurements and Main Results: Hemodynamic and oxygen-derived variables wer e measured at previously defined time points over a study period of 5 days. Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction. Baseline da ta at recruitment did not differ between the two groups. Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of th e 20 patients treated with placebo. Hydrocortisone significantly reduced th e time to cessation of vasopressor support. The median time of vasopressor support was 2 days (1(st) and 3(rd) Quartiles, 1 and 6 days) in the hydroco rtisone treated group and 7 days (1(st) and 3(rd) Quartiles, 3 and 19 days) in the placebo group (p =.005 Breslow test). There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group. Conclusions: Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock. This was associate d with a trend to earlier resolution of sepsis induced organ dysfunctions. Overall shock reversal and mortality were not significantly different betwe en the groups in this low sized single-center study.