Clinical question: Does hydrocortisone and fludrocortisone reduce all-cause mortality among patients with septic shock due to community-acquired pneumonia (CAP)?
Background: A meta-analysis of 17 studies looking at corticosteroids in CAP suggested the effects of corticosteroids varied with the severity of CAP. A trial of 795 adults with severe CAP without shock found that IV hydrocortisone reduced 28-day all-cause mortality, the incidence of intubation, and the need for vasopressor therapy compared with placebo.
Study design: A priori, planned, exploratory, subgroup analysis of the phase 3 double-blinded, randomized, controlled trial.
Setting: 34 centers in France
Synopsis: 562 adults with septic shock from CAP were randomized to receive corticosteroids (279 patients) or placebo (283 patients). 648 patients with non-CAP-related septic shock were randomized to receive corticosteroids (319 patients) or placebo (329 patients). The treatment involved seven days of IV hydrocortisone 50 mg every six hours and oral fludrocortisone 50 mcg every 24 hours.
For CAP patients, the treatment group had fewer deaths at day 90 compared to the placebo group (39% versus 51%, odds ratio [OR] 0.60; 95% CI, 0.43 to 0.83). There was no difference in death for non-CAP patients (OR, 0.95; 95% CI, 0.70 to 1.29). Among patients with CAP, fewer deaths occurred in the treatment group at day 28 (OR, 0.60; 95% CI, 0.43 to 0.87) and day 180 (OR, 0.59; 95% CI, 0.42 to 0.83). Significant differences were also seen in ICU discharge (OR, 0.64; 95% CI, 0.46 to 0.90), and hospital discharge (OR, 0.62; 95% CI, 0.44 to 0.87).
The primary limitation of the study was that a large subset of patients with CAP-related septic shock also met the criteria for acute respiratory distress syndrome (ARDS), but the subgroup analysis was underpowered to discriminate between ARDS and CAP.
Bottom line: Hydrocortisone plus fludrocortisone reduced mortality among patients with CAP-related septic shock but did not benefit patients with non-CAP-related septic shock.
Citation: Heming N, et al. Hydrocortisone plus fludrocortisone for community-acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial. Lancet Respir Med. 2024; 12:366-74.
Dr. Ha
Dr. Ha is a hospitalist in the division of hospital medicine at the Mount Sinai Health System and an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York.