Elsevier

The Lancet

Volume 377, Issue 9782, 11–17 June 2011, Pages 2023-2030
The Lancet

Articles
Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial

https://doi.org/10.1016/S0140-6736(11)60607-7Get rights and content

Summary

Background

Whether addition of corticosteroids to antibiotic treatment benefits patients with community-acquired pneumonia who are not in intensive care units is unclear. We aimed to assess effect of addition of dexamethasone on length of stay in this group, which might result in earlier resolution of pneumonia through dampening of systemic inflammation.

Methods

In our double-blind, placebo-controlled trial, we randomly assigned adults aged 18 years or older with confirmed community-acquired pneumonia who presented to emergency departments of two teaching hospitals in the Netherlands to receive intravenous dexamethasone (5 mg once a day) or placebo for 4 days from admission. Patients were ineligible if they were immunocompromised, needed immediate transfer to an intensive-care unit, or were already receiving corticosteroids or immunosuppressive drugs. We randomly allocated patients on a one-to-one basis to treatment groups with a computerised randomisation allocation sequence in blocks of 20. The primary outcome was length of hospital stay in all enrolled patients. This study is registered with ClinicalTrials.gov, number NCT00471640.

Findings

Between November, 2007, and September, 2010, we enrolled 304 patients and randomly allocated 153 to the placebo group and 151 to the dexamethasone group. 143 (47%) of 304 enrolled patients had pneumonia of pneumonia severity index class 4–5 (79 [52%] patients in the dexamethasone group and 64 [42%] controls). Median length of stay was 6·5 days (IQR 5·0–9·0) in the dexamethasone group compared with 7·5 days (5·3–11·5) in the placebo group (95% CI of difference in medians 0–2 days; p=0·0480). In-hospital mortality and severe adverse events were infrequent and rates did not differ between groups, although 67 (44%) of 151 patients in the dexamethasone group had hyperglycaemia compared with 35 (23%) of 153 controls (p<0·0001).

Interpretation

Dexamethasone can reduce length of hospital stay when added to antibiotic treatment in non-immunocompromised patients with community-acquired pneumonia.

Funding

None.

Introduction

The mainstays of treatment for community-acquired pneumonia are early diagnosis and initiation of appropriate antibiotic therapy.1 Despite preventive measures such as vaccination and advances in antibiotic treatments, community-acquired pneumonia has a high rate of mortality and morbidity and is associated with significant health-care costs.2 Adjunctive therapy for community-acquired pneumonia might help to reduce disease severity.

In community-acquired pneumonia, locally produced pulmonary cytokines are needed to control and eliminate the primary infection. However, organ dysfunction can result from a systemic inflammatory response.3 Therefore, a balanced cytokine response needs to be sufficient to control the local infection but not be excessive, to prevent systemic effects. An ideal intervention would reduce the systemic complications of the inflammatory response without affecting the resolution of local inflammation.

Corticosteroids are very potent inhibitors of inflammation.4 They switch off genes that encode proinflammatory cytokines and switch on genes that encode anti-inflammatory cytokines. Treatment with low-dose corticosteroids downregulates proinflammatory cytokine transcription, which prevents an extended cytokine response and might accelerate the resolution of systemic and pulmonary inflammation in the early phase of community-acquired pneumonia.5, 6

Although not all studies show a beneficial effect of corticosteroids, these hormones are widely given as adjunctive therapy in patients with sepsis and septic shock.7 By contrast with the large number of studies about sepsis and septic shock, there are few controlled trials of corticosteroids as adjunctive treatment to antibiotics in pneumonia, and these trials have produced variable results.8, 9, 10

We postulated that adjunctive treatment of community-acquired pneumonia with intravenous dexamethasone might change the immune response and thereby reduce morbidity, leading to a decrease in patients' length of stay in hospital. Dexamethasone has potent anti-inflammatory effects and weak mineralocorticoid effects compared with other corticosteroids, thus avoiding interference with sodium reabsorption and water balance. Moreover, dexamethasone has a long-lasting effect, allowing for a once-a-day regimen.

We aimed to assess the effect of intravenous dexamethasone compared with placebo on length of hospital stay in non-immunocompromised patients who were admitted to hospital with community-acquired pneumonia.

Section snippets

Study design and patients

We undertook a randomised, double-blinded, placebo-controlled trial at the 880-bed St Antonius Hospital in Nieuwegein and the 500-bed Gelderse Vallei Hospital in Ede in the Netherlands (both teaching hospitals). Patients were prospectively enrolled if they were aged 18 years or older and had confirmed community-acquired pneumonia. Diagnosis of pneumonia was confirmed when a new pulmonary infiltrate on a chest radiograph was present in combination with at least two of the following criteria:

Results

From November, 2007, to September, 2010, we enrolled 304 patients (figure 1, table 1). 133 (44%) patients had comorbidities, with more patients having renal disease in the dexamethasone group than in the control group (table 1). 79 (52%) of 151 patients in the dexamethasone group were in pneumonia severity index risk classes 4 and 5 compared with 64 (42%) of 153 in the placebo group (table 1). Baseline characteristics of patients did not differ between the two hospitals (data not shown).

For the

Discussion

In our trial, we noted an overall reduction in median length of hospital stay of 1 day in patients with community-acquired pneumonia who were given intravenous dexamethasone compared with controls. In a secondary analysis, patients in the dexamethasone group had a better quality of life than did controls with respect to social functioning by day 30 after admission to hospital.

These findings support our hypothesis that early administration of dexamethasone changes the immune response and thereby

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