Objective: To evaluate the efficacy and safety of low-dose hydrocortisone therapy in patients with septic shock.
Design: Multicentre, randomized, double-blind, placebo-controlled trial.
Setting: Nine centres (including 52 intensive care units) in Europe and the Middle East.
Patients: Patients with clinical evidence of infection, evidence of systemic response to infection and onset of shock within the previous 72 hours (defined by systolic blood pressure < 90 mm Hg despite adequate fluid replacement or a need for vasopressors for at least 1 hour) and hypoperfusion or organ dysfunction attributable to sepsis.
Intervention: INTERVENTION group (n = 251) was randomly assigned to receive 50 mg of hydrocortisone intravenously, and the control group (n = 248) was randomly assigned to receive placebo every 6 hours for 5 days; the dose was tapered during a 6-day period.
Main outcome measure: Death at 28 days in patients who did not have a response to corticotrophin.
Results: In all, 233 (46.7%) patients did not have a response to corticotrophin (125 in the treatment group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the 2 groups who did not have a response to corticotropin (39.2% in the treatment group and 36.1% in the placebo group, p = 0.69) or between those who had a response to corticotropin (28.8% in the treatment group and 28.7% in the placebo group, p = 1.00). At 28 days, 86 of 251 (34.3%) patients in the treatment group and 78 of 248 (31.5%) in the placebo group had died (p = 0.51). In the treatment group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock.
Conclusion: Hydrocortisone cannot be recommended as general adjuvant therapy for septic shock (vasopressor responsive), nor can corticotrophin testing be recommended to determine which patients should receive hydrocortisone therapy.