Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo, a study found.
To specifically target a population with high requirements for vital organ support (use of mechanical ventilation and at least four hours of vasopressor therapy before randomization) and a substantial risk of death, researchers randomly assigned patients with septic shock to receive 200 mg of hydrocortisone per day or placebo for seven days or until death or discharge from the ICU, whichever came first. Results were published online by the New England Journal of Medicine on Jan. 19.
From March 2013 through April 2017, 3,800 patients were enrolled. Status with respect to the primary outcome, death from any cause at 90 days, was determined in 3,658 patients (1,832 of whom had been assigned to the hydrocortisone group and 1,826 of whom had been assigned to the placebo group). At 90 days, 27.9% of patients in the hydrocortisone group had died, compared to 28.8% in the placebo group (odds ratio, 0.95; 95% CI, 0.82 to 1.10; P=0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients assigned to receive hydrocortisone had faster resolution of shock than those on placebo (median duration, 3 days [interquartile range, 2 to 5 days] vs. 4 days [interquartile range, 2 to 9 days]; hazard ratio [HR], 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group also had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18 days] vs. 7 days [interquartile range, 3 to 24 days]; HR,1.13; 95% CI, 1.05 to 1.22; P<0.001). However, when episodes of recurrence of ventilation were taken into account, no significant differences were seen in the number of days alive and free from mechanical ventilation. Blood transfusion was less common in the hydrocortisone group than in the placebo group (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P=0.004).
No significant between-group differences were seen in mortality at 28 days, rate of shock recurrence, number of days alive and out of the ICU, number of days alive and out of the hospital, recurrence of mechanical ventilation, rate of renal replacement therapy, and incidence of new-onset bacteremia or fungemia.
The researchers wrote, “Although we did not observe a significant difference between the hydrocortisone group and the placebo group with regard to 90-day mortality, some secondary outcomes were better in the group that received the active treatment. Our observation of the hemodynamic effects of hydrocortisone is consistent with those in previous studies. These hemodynamic effects may represent a beneficial role of hydrocortisone.”