Comparative efficacy and safety of hydrocortisone-based regimens in septic shock: A network meta-analysis
In brief
High-dose hydrocortisone linked to 47% lower odds of 28-day death
In a network meta-analysis of 21 trials and 7,908 adults with septic shock, hydrocortisone at 300 mg/day or more was associated with 47% lower odds of 28-day death than placebo; hydrocortisone plus fludrocortisone was also linked to lower odds. Higher hydrocortisone doses carried more superinfection risk, and gastrointestinal bleeding estimates were imprecise, so dose-specific trials are still needed.
- Journal
- Journal of critical care (Q1)
- Published
- 22 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Sehyun Kwon, Sang Gyu Kwak, Hyo-Lim Hong
- PMID
- 42784878
- DOI
- 10.1016/j.jcrc.2026.155750
Why clinicians should know about it
- Picked for Critical Care and Intensive Care Medicine (top studies of the week, 27 September 2026): Network meta‑analysis of hydrocortisone regimens in septic shock
Abstract
BACKGROUND: The optimal corticosteroid regimen for septic shock, particularly the dosing and combination of hydrocortisone and fludrocortisone, remains uncertain due to inconsistent mortality findings across trials. METHODS: We conducted a PRISMA-compliant systematic review and network meta-analysis of randomized controlled trials evaluating hydrocortisone and/or fludrocortisone in adults with septic shock (PubMed, Embase, CENTRAL; inception-May 1, 2025; PROSPERO CRD420251015672). Interventions were grouped into six regimens (including placebo), and outcomes were analyzed using a frequentist random-effects model; the primary outcome was 28-day mortality. RESULTS: A total of 21 trials involving 7908 patients were included. Hydrocortisone ≥300 mg/day and hydrocortisone 200-299 mg/day combined with fludrocortisone 50 μg/day were associated with reduced 28-day mortality compared with placebo (OR 0.53, 95% CI 0.29-0.96; OR 0.78, 95% CI 0.64-0.96, respectively), with higher fludrocortisone doses showing numerically greater point estimates of benefit, though estimates were not statistically significant. Higher hydrocortisone doses were associated with increased superinfection risk, while fludrocortisone appeared to attenuate this effect. An increased risk of gastrointestinal hemorrhage was observed across regimens, although estimates were imprecise. CONCLUSIONS: Higher-dose hydrocortisone was associated with improved survival but also increased adverse events, whereas adjunctive fludrocortisone may provide additional benefit without substantially increasing complications. These findings should be interpreted with caution and highlight the need for further dose-specific trials.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.