Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis

Abstract

IMPORTANCE Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial. OBJECTIVE To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. DESIGN, SETTING,ANDPARTICIPANTS Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trialwas performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. INTERVENTIONS Patientswere randomly allocated 1:1 either to receive a continuous infusion of 200mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). MAIN OUTCOMES AND MEASURES The primary outcomewas development of septic shock within 14 days. Secondary outcomeswere time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscleweakness, and hyperglycemia (blood glucose level >150mg/dL [to convert to millimoles per liter, multiply by0.0555]). RESULTS The intention-to-treat population consisted of 353 patients (64.9%male; mean [SD] age, 65.0[14.4] years). Septic shock occurred in 36 of 170patients (21.2%) in the hydrocortisone group and 39 of 170patients (22.9%) in the placebo group (difference, −1.8%; 95%CI, −10.7%to 7.2%; P = .70). No significant differenceswere observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference,0.5%; 95%CI, −5.6%to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95%CI, −5.1%to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95%CI, −4.6%to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5%vs 16.9%had secondary infections, 8.6%vs 8.5%hadweaning failure, 30.7%vs 23.8% had muscleweakness, and 90.9%vs 81.5%had hyperglycemia. CONCLUSIONS AND RELEVANCE Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients. TRIAL REGISTRATION clinicaltrials.gov Identifier:NCT00670254