Early Administration of Hydrocortisone Replacement After the Advent of Septic Shock: Impact on Survival and Immune Response

Objectives: To investigate the impact of early initiation of hydrocortisone therapy on the clinical course of septic shock and on cytokine release. Design: Prospective study in patients with septic shock treated with low doses of hydrocortisone. Setting: ICUs and general wards. Patients: Over a 2-year period, 170 patients with septic shock treated with low doses of hydrocortisone were enrolled. Blood was sampled from 34 patients for isolation of peripheral blood mononuclear cells and cytokine stimulation before and 24 hours after the start of hydrocortisone. Interventions: None. Measurements and Main Results: After quartile analysis, patients were divided into those with early initiation of hydrocortisone (< 9 hr after vasopressors, n = 46) and those with late initiation of hydrocortisone (> 9 hr after vasopressors, n = 124). After adjusting for disease severity and type of infection, a protective effect of early hydrocortisone administration against unfavorable outcome was found (hazard ratio, 0.20; p = 0.012). Time of discontinuation of vasopressors was earlier among patients with initiation of hydrocortisone within 9 hours. Production of tumor necrosis factor- was lower among patients who had had hydrocortisone early. Conclusions: In patients receiving hydrocortisone for septic shock, early initiation of treatment was associated with improved survival. This treatment was also associated with attenuated stimulation of tumor necrosis factor-.