Effect of hydrocortisone-fludrocortisone combination on mortality in septic shock: a systematic review and meta-analysis

This study assessed the effect of hydrocortisone-fludrocortisone combination therapy on the mortality of patients with septic shock.

A literature search was conducted using Medline, Embase, the Cochrane Library, ClinicalTrials.gov, and other databases for articles published until October 1, 2023. Only clinical studies that assessed the clinical efficacy and safety of hydrocortisone-fludrocortisone therapy for the treatment of septic shock were included. The primary outcome was the in-hospital mortality rate.

Seven studies with a total of 90, 756 patients were included. The study group exhibited lower in-hospital mortality rates (40.8% vs. 42.8%; OR, 0.86; 95% CI, 0.80–0.92). Compared to the control group, the study group also had lower intensive care unit (ICU) mortality (OR, 0.77; 95% CI, 0.63–0.95), 28-day mortality (OR, 0.85; 95% CI, 0.72–1.00), 90-day mortality (OR, 0.85; 95% CI, 0.71–1.01), 180-day mortality (OR, 0.82; 95% CI, 0.68–0.90), and one-year mortality (OR, 0.70; 95% CI, 0.42–1.16). Subgroup analyses showed a similar trend, particularly prominent in the pooled analysis of randomized clinical trials, multicenter studies, and ICU patients, the study drug regimen involved hydrocortisone at a dose of 50 mg every 6 h in combination with fludrocortisone at 50 µg daily, with the control group receiving either placebo or standard care. Hydrocortisone-fludrocortisone also increased vasopressor-free days and reduced vasopressor duration, without elevating the risk of adverse events.

This study emphasizes the potential survival benefits of hydrocortisone-fludrocortisone combination therapy for patients with septic shock and its additional advantages, including reduced vasopressor use.