Corticosteroids Effective in Community-Acquired Pneumonia

Ricki Lewis, PhD

August 11, 2015

Corticosteroid treatment was associated with approximately 3% lower mortality, 5% reduction in need for mechanical ventilation, and a 1-day shorter hospital stay for adults with community-acquired pneumonia (CAP), according to a meta-analysis published online August 11 in the Annals of Internal Medicine.

CAP is common and costly worldwide and is associated with considerable morbidity. It may lead to acute respiratory distress syndrome (ARDS) and require mechanical ventilation.

Because inflammation may initially clear bacteria but ultimately contribute to sepsis and end-organ failure, systemic corticosteroid treatment may be effective. However, use of corticosteroid therapy is controversial because several randomized controlled clinical trials have had conflicting results. It is currently not part of clinical practice guidelines.

Therefore, Reed A. C. Siemieniuk, MD, from McMaster University and colleagues conducted a meta-analysis to evaluate the use of corticosteroid therapy in CAP. They searched the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE from 2010 through 2015 for relevant studies, restricting their analysis to randomized controlled trials that compared oral or intravenous corticosteroids vs placebo or no treatment. For inclusion, the trials had to have at least one of the following outcomes: length of hospitalization stay, time to clinical stability, mortality, mechanical ventilation, development of ARDS, or intensive care unit admission.

The investigators ultimately included 13 trials with 2005 patients. Approximately 60% of patients were male, and median age was in the 60s.

Use of corticosteroids was associated with "moderate certainty" of reductions in mortality, need for mechanical ventilation, and development of ARDS. Decrease in intensive care unit admission paralleled a decrease in need for ventilation. Treatment also shortened time to clinical stability and shortened hospital stays with high certainty.

Specifically, among 1974 patients enrolled in 12 clinical trials, corticosteroids were associated with possible reductions in all-cause mortality (risk ratio [RR], 0.67 [95% confidence interval (CI), 0.45 - 1.01]; risk difference [RD], 2.8%).

Among 1060 patients in five clinical trials, treatment was associated with need for mechanical ventilation (RR, 0.45 [95% CI, 0.26 - 0.79]; RD, 5.0%). Among 945 patients participating in four clinical trials, development of ARDS was associated with a RR of 0.24 (95% CI, 0.10 - 0.56; RD, 6.2%).

The meta-analysis also revealed increased frequency (about 4%) of hyperglycemia requiring treatment, but did not find increased frequency of gastrointestinal hemorrhage, rehospitalization, or neuropsychiatric symptoms.

The authors found that benefit may be greater among severely ill patients, but they caution that the apparent benefit may be spurious. That is, risk for ARDS and need for ventilation was not greater in studies enrolling sicker patients.

"The apparent benefits of systemic corticosteroids in CAP are large enough — a decrease in hospital stay of approximately 1 day and an absolute reduction in risk for mechanical ventilation of 5% — to be considered important by many. Given the frequency of CAP, and thus the associated economic burden, routine use of corticosteroids for CAP could result in considerable cost savings," the researchers conclude.

A limitation of the meta-analysis was the heterogeneity of the evaluated clinical trials for drugs, dosages, and routes of administration. However, the US Department of Veterans Affairs is sponsoring the Extended Steroid in CAP(e) (ESCAPe) study, which is randomly assigning hospitalized patients with CAP to receive a week of full-dose methylprednisolone, a week of half-dose, 6 days of tapering doses, or placebo, write Marcos I. Restrepo, MD, from the University of Texas Health Science Center at San Antonio, and colleagues in an accompanying editorial.

The editorial writers suggest use of a biomarker, such as C-reactive protein, to identify hospitalized patients with CAP who have a strong inflammatory response that would respond to corticosteroid therapy. They conclude, "As clinicians, we need to balance the benefits and harms of systemic corticosteroid therapy to provide optimal care for patients with severe CAP."

The authors and editorialists have disclosed no relevant financial relationships.

Ann Intern Med. Published online August 10, 2015. Abstract

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