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Brouwer MC, McIntyre P, de Gans J, Prasad K, van de Beek D. Corticosteroids for Acute Bacterial Meningitis. Cochrane Database of Systematic Reviews 2010, Issue 9.

Van de Beek D, Farrar JJ, de Gans J, et al. Adjunctive dexamethsone in bacterial meningitis: a meta-analysis of individual patient data. Lancet 2010;9;254-63.

Efficacy Endpoints

Mortality, hearing loss, neurological sequelae

Harm Endpoints

Recurrent fever, persistent fever, gastrointestinal bleeding, herpes zoster, fungal infection, or reactive arthritis

Narrative

Acute bacterial meningitis (ABM) carries a high morbidity and mortality. As bacteria enter the meninges there is a dramatic inflammatory response that potentiates the infectious process and initiates a cascade of events that can culminate in cerebral edema and a rise in intracranial pressure. This can result in neurologic damage and/or death. Giving steroids to patients with bacterial meningitis would theoretically decrease this inflammatory response, reducing neurologic sequelae and death.

This review included 24 studies (4041 patients) and compared the effects of steroids with placebo. Twenty-one of the studies used dexamethasone with a range of dosing from 0.4-1.5mg/kg/day for two to four days. About two-thirds of included patients were children and a third were adults.

Benefits: Overall, there was no statistically significant difference in mortality rate between patients who received steroids and those who received placebo (18% vs 20%, p = 0.18).

Only 19/24 studies looked at hearing loss as a complication of ABM. The administration of steroids led to an absolute risk reduction of hearing loss by approximately 5% (NNT=20.5). Seventeen studies differentiated between any hearing loss and severe hearing loss, showing a three percent reduction (NNT=31).

Excluding hearing loss there were thirteen studies (1756 patients) showing a decreased risk of short term neurological sequelae (NNT=26.9), though no difference in long term sequelae was observed.

Results were also subdivided by pathogen. S. pneumoniae was the etiologic agent in about 1100 subjects and was the most deadly (mortality 32.8%). H. influenzae and N. meningitidis had mortality rates of 10.5 and 4.3 respectively. There was a decrease in mortality for the subgroup of patients with S. pneumoniae (NNT=17.5). Children with H. influenzae also had decreased rates of hearing loss (NNT=12.5).

One further subgroup analysis examined differences in high and low income countries. Results for high income countries were similar to those reported previously in the analysis. On the contrary, results for low income countries had significant heterogeneity and found no statistically significant differences.

Harms: Adverse events were recorded in nineteen studies. The steroid group had an increase in recurrent fever (NNH=16.3).

Caveats

There is an updated meta-analysis of ‘patient-level data’ for dexamethasone in bacterial meningitis, which tends to offer a slightly more nuanced and detailed look at the possibility of a benefit (Van de Beek, 2010). In patient-level data analyses data from individual patients in each trial are analyzed, rather than analyzing aggregated blocks of data from each trial. This meta-analysis included 5 large, high quality trials and found no mortality benefit to dexamethasone, results consistent with the Cochrane review. However, the authors also found no benefit in terms of severe neurologic problems, other than hearing loss among adult survivors. They conclude that the benefits of dexamethasone remain unproven. An accompanying editorial points out that there did seem to be benefit in trials from industrialized settings and that this may have been neutralized by lack of benefit in other settings where meningitis may present later or be associated with poorer outcomes. The editorialist supports steroid administration in industrialized settings but concedes small benefits and a lack of certainty (Brewer, 2010).

Author

Patricia Van Leer, MD

Published/Updated

April 22, 2011