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European Dexamethasone Study

"Dexamethasone in Adults with Bacterial Meningitis". The New England Journal of Medicine. PMID 12362006. Full text. PDF.

Links to original sources: Wiki Journal Post Full Journal Article

Clinical Question


Does early treatment with dexamethasone improve outcomes in adults with acute bacterial meningitis?

Bottom Line


Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of gastrointestinal bleeding.

Major Points


Studies in animals suggest that inflammation from bacterial lysis, induced by antibiotic treatment for bacterial meningitis, may contribute to an unfavorable outcome. Trials in children with meningitis showed mixed effects of dexamethasone, but suggested benefits if given early. This study's goal was to determine if early dexamethasone treatment improves outcomes in adults with bacterial meningitis.

Guidelines


Use of dexamethasone in adult bacterial meningitis was not previously routine due to lack of data. This study leads to recommendations for the use of dexamethasone in adult cases of bacterial meningitis.

Design


Prospective, randomized, double-blind, multicenter trial.

Population


301 adults with suspected bacterial meningitis based on either cloudy cerebrospinal fluid, bacteria present in cerebrospinal fluid on Gram's stain, or a leukocyte count of more than 1000 per cubic millimeter.

Interventions


Dexamethasone 10 mg IV or placebo given 15 to 20 minutes before or with the first dose of antibiotics, every 6 hours for four days.

Outcomes


Primary: Score on the Glasgow Outcome Scale at eight weeks. Secondary: Death, focal neurologic abnormalities, hearing loss, gastrointestinal bleeding, fungal infection, herpes zoster, and hyperglycemia.

Major Points


Treatment with dexamethasone resulted in a significant reduction in unfavorable outcomes (15% for dexamethasone group vs. 25% for placebo, P=0.03). Mortality was also reduced (7% dexamethasone vs. 15% placebo, P=0.04), especially notable in pneumococcal meningitis.

Criticisms


- Selection bias concern due to comparison with a nationwide cohort. - Delay in antibiotic therapy as a potential confounding factor, especially if CT scan was performed prior to lumbar puncture. - Duration and timing of dexamethasone therapy could be further researched.

Funding


Partially funded by NV Organon, which also supplied the study medication.

Further Reading


De Gans J, van de Beek D; European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002 Oct 10;347(15):1549-56. doi: 10.1056/NEJMoa021334. PMID: 12362006.