Hydrocortisone was associated with lower all-cause mortality among patients with severe community-acquired pneumonia, whereas dexamethasone, methylprednisolone, and prednisolone were not, according to a network meta-analysis.
Researchers analyzed 11 randomized controlled trials involving 2,042 patients with severe community-acquired pneumonia (CAP). Severe CAP was defined as CAP requiring intensive care unit admission, meeting American Thoracic Society/Infectious Diseases Society of America criteria, PaO2/FiO2 less than 300, or pneumonia severity index score of IV or higher. All included trials compared a corticosteroid with placebo.
Among the evaluated corticosteroids, only hydrocortisone was associated with statistically lower mortality compared with placebo. The network estimate suggested an approximately 65% relative reduction in mortality risk with hydrocortisone. Hydrocortisone also was associated with reduced need for mechanical ventilation.
The findings build on prior evidence from the CAPE COD trial, which reported lower 28-day mortality with hydrocortisone among critically ill patients with severe CAP.
The researchers noted, however, that the analysis relied entirely on indirect comparisons because all included studies compared corticosteroids with placebo rather than with one another. The resulting “star-shaped” network prevented direct head-to-head comparisons among corticosteroids, and the researchers found no evidence that any corticosteroid was superior to another.
Subgroup analyses suggested that low-to-moderate corticosteroid doses and short-course treatment were associated with lower mortality and reduced need for mechanical ventilation compared with placebo. However, these exploratory subgroup findings should be interpreted cautiously because of limited statistical power and heterogeneity across studies.
The researchers reported no statistically significant differences in serious adverse events between corticosteroid-treated groups and placebo. Reported adverse events included opportunistic infections, cardiac events, neuropsychiatric symptoms, acute renal failure, gastrointestinal bleeding, and hyperglycemia. However, the included trials did not consistently report secondary infections, fungal infections, or antibiotic-resistant pathogens.
The certainty of evidence for mortality, mechanical ventilation, and serious adverse events was rated very low to low. According to the researchers, the low certainty ratings were driven largely by imprecision, heterogeneity, and reliance on indirect comparisons.
Additional limitations included variability in severe CAP definitions, corticosteroid dosing strategies, treatment duration, adverse-event reporting, comorbidities, and intensive care unit admission status across studies. Sensitivity analyses were not feasible because of the limited number of randomized trials and the network structure.
“Hydrocortisone significantly reduced mortality, whereas methylprednisolone, dexamethasone, and prednisolone did not exhibit the same effect,” wrote lead study researcher Liangdong Zhu, of The First Hospital of Changsha, Changsha, China, and colleagues. The researchers added that the findings were “not yet robust enough to warrant immediate changes to current treatment guidelines.”
The researchers reported no competing interests.
Source: BMC Pulmonary Medicine
