Systemic Corticosteroids in Severe Community-Acquired Pneumonia: Navigating Conflicting Signals in the ICU with REMAP-CAP Trial!
- Mazen Kherallah
- Nov 15
- 3 min read
The potential role of systemic corticosteroids in the management of severe community-acquired pneumonia (CAP) has garnered increasing attention, particularly following the CAPE-COD randomized controlled trial, which reported a significant reduction in 28-day mortality (absolute reduction of 5.6%) among ICU patients treated with hydrocortisone (1). These findings prompted an update to several clinical guidelines, including a strong recommendation (moderate certainty) for corticosteroid use in patients with severe CAP (2). Supporting this guidance, a 2023 meta-analysis reported a pooled risk ratio of 0.61 (95% CI 0.44–0.85) for mortality with corticosteroids in severe CAP (3). However, despite this evolving consensus, the REMAP-CAP trial introduced a new and cautionary perspective
The REMAP-CAP Trial: A Signal of Caution Amidst Optimism
REMAP-CAP, an international, adaptive platform trial, evaluated a 7-day fixed-dose hydrocortisone regimen (50 mg IV q6h) in ICU patients with severe CAP, randomizing 658 patients (4). Unlike conventional RCTs, this trial utilized response-adaptive randomization within a multifactorial design. It reported a higher 90-day mortality in the hydrocortisone group (15%) compared to control (9.8%), with adjusted odds ratios across subgroups ranging from 1.52 to 1.63. Bayesian analysis demonstrated low probabilities of benefit and high probabilities of harm, with futility triggered for a >20% mortality reduction.
The editorial by Pirracchio and Sprung outlined key limitations affecting the interpretation of the REMAP-CAP trial (5). These included heterogeneity across participating centers, enrollment of patients with influenza pneumonia (8.2%), and imbalances stemming from the adaptive trial design. Importantly, a potential signal of harm was observed even among patients with vasopressor-dependent shock—historically considered more likely to benefit from corticosteroids. Although the inclusion of influenza cases did not solely account for the findings, it highlighted the relevance of pathogen-specific treatment effects. Additional factors complicating interpretation included the trial’s open-label design, operational challenges, and early misclassification of treatment allocations due to a data handling error.
Updated Bayesian Meta-Analysis: Weighing the Totality of Evidence
To contextualize REMAP-CAP’s results, Lee et al. conducted a Bayesian meta-analysis incorporating twelve RCTs (N=2557), including REMAP-CAP, and focused exclusively on patients with severe CAP (6). The pooled odds ratio was 0.66 (95% credible interval [CrI] 0.48–0.92), with a 99.4% posterior probability of mortality benefit (OR <1.0) and 87.6% probability of ≥20% mortality reduction. The predicted odds ratio for future studies ranged from 0.37 to 1.17, reflecting heterogeneity but still favoring benefit. Subgroup analyses excluded older pre-2000 studies and adjusted for known confounders. Importantly, the inclusion of REMAP-CAP did not shift the pooled estimate substantially, underscoring its position as a potential outlier rather than a definitive refutation.
Clinical Implications & Practical Takeaways
Strong signal for benefit in high-severity CAP: Meta-analytic evidence supports corticosteroid use in patients requiring ICU-level care, particularly in the absence of viral co-infections.
Avoid routine corticosteroids in influenza pneumonia: Evidence from REMAP-CAP and prior influenza studies suggest a potential for harm.
REMAP-CAP limitations necessitate cautious interpretation: Adaptive randomization, site variability, and influenza inclusion may reduce generalizability.
ICU clinicians should individualize treatment: Consider etiology, severity (organ support), and comorbid risks before initiating corticosteroids.
Not a guideline reversal: While REMAP-CAP adds uncertainty, it does not override the broader evidence base supporting corticosteroid use in severe CAP.
Conclusion: A Nuanced Perspective for ICU Practice
The REMAP-CAP trial reintroduces complexity into the discussion around corticosteroids in severe CAP. However, the cumulative evidence, particularly from well-powered meta-analyses, continues to support their use in selected high-risk ICU patients. Future studies must refine definitions of severity, address heterogeneity, and identify phenotypes most likely to benefit. Until then, clinicians must synthesize trial data with bedside judgment, avoiding both reflexive use and outright dismissal of corticosteroids in severe CAP.
References
Dequin PF, Meziani F, Quenot JP, et al. Hydrocortisone in severe community-acquired pneumonia. N Engl J Med. 2023;388(20):1837–1847. doi:10.1056/NEJMoa2215145
Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45–e67. doi:10.1164/rccm.201908-1581ST
Wu J, Qian J, Wang H, et al. Systemic corticosteroids for hospitalized patients with community-acquired pneumonia: a meta-analysis. Crit Care. 2023;27(1):114. doi:10.1186/s13054-023-04517-w
Heming N, Berry L, Lorenzi E, et al. Effect of hydrocortisone on mortality in patients with severe community-acquired pneumonia: the REMAP-CAP corticosteroid domain randomized clinical trial. Intensive Care Med. 2025;51:665–680. doi:10.1007/s00134-025-07861-w
Pirracchio R, Sprung CL. REMAP-CAP corticosteroids: yet, another swing of the pendulum? Intensive Care Med. 2025;51:1135–1138. doi:10.1007/s00134-025-07957-3
Lee TC, Albuquerque AM, Lawandi A, et al. Systemic corticosteroids continue to reduce mortality in severe community-acquired pneumonia: an updated meta-analysis. J Gen Intern Med. 2025. doi:10.1007/s11606-025-09724-y