• Ryo Yamamoto, Isao Nahara, Mitsunobu Toyosaki, Tatsuma Fukuda, Yoshiki Masuda, and Seitaro Fujishima.
• Department of Emergency and Critical Care Medicine Keio University School of Medicine Tokyo Japan.
• Acute Med Surg. 2020 Jan 1; 7 (1): e563.

AimCombined hydrocortisone and fludrocortisone therapy for septic shock has not been evaluated with an independent systematic review. We aimed to elucidate the beneficial effects of a dual corticosteroid treatment regime involving both hydrocortisone and fludrocortisone for adult patients with septic shock on mortality.MethodsWe searched the Medline, Cochrane CENTRAL, and ICHUSHI databases for reports published before April 2019. We included randomized controlled trials that compared the use of both hydrocortisone and fludrocortisone with either corticosteroid-free or hydrocortisone-only treatments on adult patients with septic shock. Three researchers independently reviewed the studies. The meta-analyses were undertaken to assess primary outcome (28-day mortality) and secondary outcomes (in-hospital mortality, long-term mortality, shock reversal, and adverse events).ResultsAmong the four studies eligible for data synthesis, we included 2,050 patients from three studies for quantitative synthesis. All studies used similar regimens (hydrocortisone and fludrocortisone for 7 days without tapering). The 28-day mortality rate was reduced after dual corticosteroid treatment (risk ratio, 0.88; 95% confidence intervals [CI], 0.78-0.99). The heterogeneity between the studies was low (I2 = 0%). Patients who underwent dual corticosteroid treatment had lower long-term mortality rates (risk ratio, 0.90; 95% CI, 0.83-0.98) and higher rate of shock reversal after 28 days (odds ratio, 1.06; 95% CI, 1.01-1.12) than control patients. Adverse events (except for hyperglycemia) were similar among the treatment groups.ConclusionsThe available evidence suggests that a combination of fludrocortisone and hydrocortisone is more effective than adjunctive therapy and could be recommended for septic shock.© 2020 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.

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