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Original Investigation
Caring for the Critically Ill Patient
February 17, 2015

Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory Response: A Randomized Clinical Trial

Author Affiliations
  • 1Servei de Pneumologia, Institut Clínic del Torax, Hospital Clínic, Barcelona, Spain
  • 2Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
  • 3Centro de Investigación Biomédica En Red-Enfermedades Respiratorias, Islas Baleares, Spain
  • 4University of Barcelona, Barcelona, Spain
  • 5Servei de Pneumologia, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  • 6Institut d´Investigació Biomèdica Sant Pau, Barcelona, Spain
  • 7Servicio de Neumologia, Hospital Universitario La Fe, Valencia, Spain
  • 8Servei de Malalties Infeccioses, Hospital Clinic, Barcelona, Spain
  • 9University of Texas Health Science Center, San Antonio
  • 10South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio
  • 11VERDICT, San Antonio, Texas
  • 12Winthrop-University Hospital, Mineola, New York
JAMA. 2015;313(7):677-686. doi:10.1001/jama.2015.88
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 community-acquired 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 150 mg/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 0.5 mg/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 outcome was 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 mortality was a secondary outcome and adverse events were 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

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