Therapeutics

Dexamethasone reduced length of hospital stay in patients with communityacquired pneumonia

Question
Does IV dexamethasone reduce length of stay (LOS) in nonimmunocompromised patients hospitalized with communityacquired pneumonia (CAP)?

Meijvis SC, Hardeman H, Remmelts HH, et al. Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial. Lancet. 2011;377:2023-30.

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Median LOS was shorter in the dexamethasone group than the placebo group (Table). Mortality, pleural effusion or empyema, ICU admissions, and hospital readmissions within 30 days did not differ between groups; hyperglycemia was more frequent in the dexamethasone group (Table).

Methods
Design: Randomized placebo-controlled trial. ClinicalTrials.gov NCT00471640. Allocation: Concealed.* Blinding: Blinded (patients, clinicians, outcome assessors, monitoring committee, {data collectors, data analysts, and manuscript writers}).* Follow-up period: To hospital discharge or death. Setting: 2 teaching hospitals in the Netherlands. Patients: 304 patients 18 years of age (mean age 64 y, 56% men), who were hospitalized with CAP (new pulmonary infiltrate on chest radiograph with 2 of cough, sputum production, temperature > 38C or < 35C, auscultatory findings consistent with pneumonia, C-reactive protein level > 15 mg/L, white blood cell count > 10 x 109 cells/L or < 4 x 109 cells/L, or > 10% rods in leukocyte differentiation). Exclusion criteria were congenital or acquired immunodeficiency, chemotherapy, oral corticosteroids or immunosuppressive drugs in the past 6 weeks, hematologic cancer, diagnosis of pneumonia > 24 hours after admission, need for corticosteroid therapy or immediate admission to an intensive care unit (ICU), and pregnancy or breast-feeding. Intervention: IV bolus of dexamethasone disodium phosphate, 5 mg (1 mL) (n = 151), or sterile water (n = 153) in the emergency department within 12 hours of admission, and then once daily for 3 days. All patients received antibiotics within 4 hours of admission and before study treatment began. Outcomes: Primary endpoint was LOS until discharge or death. Secondary outcomes included in-hospital mortality, development of empyema or pleural effusion, hyperglycemia, ICU admission, and hospital readmission. Patient follow-up: 100%.

Conclusion
A 4-day course of IV dexamethasone reduced length of hospital stay in patients with community-acquired pneumonia.
*See Glossary. Information provided by author.

Source of funding: No external funding. For correspondence: Ms. S. Meijvis, St. Antonius Hospital, Nieuwegein, The Netherlands. E-mail s.meijvis@antoniusziekenhuis.nl. I

Commentary
Many clinical trials have assessed the use of corticosteroids as adjunctive treatment for various infectious diseases, with conflicting results. High-dose steroids seem to be harmful in sepsis and septic shock, but low doses may improve survival (1). Results have been conflicting for treatment of bacterial and tuberculous meningitis. However, there seems to be agreement that steroids are beneficial in patients with HIV infection and hypoxemic Pneumocystis pneumonia. Unfortunately, the trial by Meijvis and colleagues does not resolve the question in terms of treating CAP. The large, well-designed, well-conducted trial found that 4 days of IV dexamethasone added to antibiotics resulted in similar clinical outcomes and reduced LOS but increased hyperglycemia compared with placebo. A recent Cochrane review of 6 smaller trials of adults and children with pneumonia found weak evidence that was suggestive of clinical benefit (2). A literature search identified 2 additional placebocontrolled trials in adults with CAP that were published after the Cochrane review: One (n = 56) reported faster resolution with steroids (3), whereas a larger trial of 213 patients found more late failures with steroids (4). So, the problem for practitioners is not a lack of good evidence, but conflicting results among good studies. This may be due in part to different corticosteroid regimens (e.g., oral vs IV, 4 vs 7 d, tapering vs abrupt stopping) or differences in such factors as patient populations and ancillary treatments. The results of ongoing trials may help to clarify this question. However, at present, providers are left to form their own interpretations of the data and can justify adding or withholding adjunctive steroids for their patients with CAP. Henry S. Sacks, MD, PhD Mount Sinai School of Medicine New York, New York, USA
References 1. Annane D, Bellissant E, Bollaert PE, et al. JAMA. 2009;301:2362-75. 2. Chen Y, Li K, Pu H, Wu T. Cochrane Database Syst Rev. 2011;(3): CD007720. 3. Fernndez-Serrano S, Dorca J, Garcia-Vidal C, et al. Crit Care. 2011;15:R96. 4. Snijders D, Daniels JM, de Graaff CS, van der Werf TS, Boersma WG. Am J Respir Crit Care Med. 2010;181:975-82.

Dexamethasone vs placebo for patients with communityacquired pneumonia

Outcomes
Median length of stay (d)

Dexamethasone Placebo
6.5 7.5

Difference (95% CI)

1.0 (0 to 2)

Event rates
In-hospital mortality Empyema or pleural effusion Hospital readmission within 30 d Hyperglycemia ICU admission 5.3% 4.6% 4.6% 44% 4.6% 5.2% 3.3% 4.6% 23% 6.5%

RRI (CI) at discharge or death

1.3% (60 to 155) 42% (51 to 316) 1.3% (62 to 171) 94% (39 to 174)

RRR (CI)
29% (76 to 71)

ICU = intensive care unit; other abbreviations defined in Glossary. RRI, RRR, and CI calculated from event rates in article. Hazard ratio for time to discharge (adjusted for baseline characteristics) based on Cox proportional hazard regression model was 1.46, CI 1.13 to 1.89, favoring earlier discharge with dexamethasone.

JC3-6

2011 American College of Physicians

20 September 2011 | ACP Journal Club | Volume 155 Number 3