Effects of Adjunctive Hydrocortisone on Mortality and Clinical Outcomes in Patients with Severe Community-Acquired Pneumonia: a Randomized, Double-Blind, Placebo-Controlled Trial at Nakhon Phanom Hospital, Thailand

Abstract

Pneumonia is a major global health problem, particularly severe pneumonia, which is associated with a markedly high mortality rate. Its pathophysiology involves a dysregulated inflammatory response, resulting in multiorgan dysfunction and death. This study aimed to compare all-cause in-hospital mortality between patients with severe community-acquired pneumonia receiving adjunctive hydrocortisone versus placebo. This was a single-center, randomized, double-blind, placebo-controlled trial conducted in patients with severe community-acquired pneumonia diagnosed according to the ATS/IDSA 2019 criteria, admitted to the medical intensive care unit and respiratory intensive care unit at Nakhon Phanom Hospital from January 1 to December 31, 2025. A total of 84 patients were enrolled and randomized to receive hydrocortisone (n = 42) or placebo (n = 42). The primary analysis was per-protocol (37 Adjunctive hydrocortisone therapy significantly reduced all-cause in-hospital mortality, reduced 28-day all-cause mortality, increased the rate of successful extubation within 14 days, and resulted in a greater reduction in C-reactive protein level (p<0.05), compared with placebo. No serious adverse events were observed, except for hyperglycemia (67.6% in the hydrocortisone group vs. 31.7% in the placebo group; p=0.05). In conclusion, adjunctive hydrocortisone therapy in patients with severe community-acquired pneumonia reduced in-hospital mortality and 28-day mortality, increased successful extubation rates, and decreased systemic inflammation, with hyperglycemia as a common adverse event. This study has several limitations, including its single-center design, relatively small sample size, and a lower-than-anticipated mortality rate in the control group compared with that used for sample size estimation. Therefore, larger multicenter randomized controlled trials are warranted to confirm these findings.