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Reference - Ann Intern Med 2015 Oct 6;163(7):519 (level 2 [mid-level] evidence)
- Community-acquired pneumonia requiring hospitalization accounts for 24.8 cases per 10,000 adults in the United States each year.
- Adjunctive corticosteroid therapy reduced the risk of mechanical ventilation and acute respiratory distress syndrome in some patients with community-acquired pneumonia.
- In patients with severe pneumonia, adjunctive corticosteroid therapy was associated with improved mortality.
- Clinical heterogeneity in trial design and patient populations may limit the generalizability of these findings.
Community-acquired pneumonia is a major cause of morbidity and mortality worldwide. In the United States, the annual incidence of community-acquired pneumonia requiring hospitalization is 24.8 cases per 10,000 adults. This incidence sharply increases for adults ≥ 65 years old (N Engl J Med 2015 Jul 30;373(5):415). Current guidelines recommend empiric antibiotic therapy as the mainstay of treatment for community-acquired pneumonia (Clin Infect Dis 2007 Mar 1;44 Suppl 2:S27). However, a growing body of evidence, including two recent randomized trials, has suggested adjunctive corticosteroids may provide additional benefit in some populations (JAMA 2015 Feb 17;313(7):677, Lancet 2015 Apr 18;385(9977):1511, EBM focus 2015 Apr:10(16)). To further examine this potential benefit, a recent systematic review and meta-analysis compared adjunctive corticosteroid therapy vs. placebo or no treatment in 2,005 adults with community-acquired pneumonia in 13 randomized trials. Trials including patients with ventilator-associated pneumonia, aspiration pneumonia, or Pneumocystis jiroveci pneumonia and trials limited to patients with chronic obstructive pulmonary disease were excluded.
There was a great deal of clinical heterogeneity among the 13 included trials. The mean patient age ranged from 36-72 years and most trials had a higher proportion of men than women. The corticosteroid studied, dosage, and length of follow-up also varied widely. Most trials excluded patients who were at an increased risk of corticosteroid-related adverse events, including patients with gastrointestinal hemorrhage in the prior 3 months, immunosuppressed patients, and pregnant women. Overall, adjunctive corticosteroids were associated with a reduced risk of mechanical ventilation (risk ratio [RR] 0.45, 95% CI 0.26-0.79) in an analysis including 5 trials with 1,060 patients and a reduced risk of acute respiratory distress syndrome (RR 0.24, 95% CI 0.1-0.56) in an analysis including 4 trials with 945 patients. In the analysis of 6 trials including 388 patients with severe pneumonia, adjunctive corticosteroids were associated with a significant decrease in mortality (RR 0.39, 95% CI 0.2-0.77), however this outcome did not reach significance in the overall analysis including 12 trials with 1,974 patients (RR 0.67, 95% CI 0.45-1.01). Time to clinical stability and length of hospitalization were also reduced with corticosteroids, but these outcomes may be confounded by a reduction in fever caused by corticosteroid therapy independent of clinical wellness. It is therefore difficult to determine how corticosteroids improve this composite outcome. In the analyses of adverse events, only the risk of hyperglycemia was increased with adjunctive corticosteroid therapy.
While this systematic review suggests adjunctive corticosteroid therapy reduces the risk of mechanical ventilation and may reduce mortality, one of the limitations of these analyses is the heterogeneity of the included trials. Trials with at least 70% of patients fulfilling criteria for severe pneumonia, as well as trials where mortality in the control group was at least 15%, were classified as trials of severe pneumonia. In analyses segregating trials by pneumonia severity, adjunctive corticosteroids had a greater reduction in mortality in trials of severe pneumonia compared to trials including patients with less severe pneumonia. These results are consistent with previous reports from individual trials suggesting patients with severe pneumonia may derive the greatest benefit from corticosteroid treatment. However, the limited number of mortality events and differences in trial methodology, such as patient populations and treatments used, make the generalizability of these findings problematic. Underlying comorbidities may impact the effect of corticosteroid therapy and in some patients, corticosteroid use has the potential to be deleterious. For example, another recent systematic review evaluated corticosteroid treatment in patients hospitalized with respiratory failure due to influenza A infection and found corticosteroid therapy was associated with an increased risk of death (Crit Care 2015 Feb 20;19(1):46).
These results suggest that while patients with more severe infection generally benefit from corticosteroid treatment, further examination is needed to determine the precise population that may most benefit from corticosteroid therapy. The optimal dose and duration of therapy is also unknown, though an ongoing trial by the United States Department of Veteran Affairs evaluating corticosteroids in critically ill patients (ESCAPe trial) will hopefully provide more information on the best treatment regimen.
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