Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial

Antoni Torres, Oriol Sibila, Miquel Ferrer, Eva Polverino, Rosario Menendez, Josep Mensa, Albert Gabarrús, Jacobo Sellarés, Marcos I. Restrepo, Antonio Anzueto, Michael S. Niederman, Carles Agustí

Research output: Contribution to journalArticlepeer-review

259 Scopus citations

Abstract

Importance: In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial. Objective: To assess the effect of corticosteroids in patients with severe communityacquired pneumonia and high associated inflammatory response. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012. Interventions: Patients were randomized to receive either an intravenous bolus of 0.5mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission. Main Outcomes and Measures: The primary outcomewas treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortalitywas a secondary outcome and adverse eventswere assessed. Results: There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, -6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34). Conclusions and Relevance: Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population. Trial Registration: clinicaltrials.gov Identifier: NCT00908713.

Original languageEnglish (US)
Pages (from-to)677-686
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume313
Issue number7
DOIs
StatePublished - Feb 17 2015

ASJC Scopus subject areas

  • Medicine(all)

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