Don’t forget the steroids when you give the cefotaxime…

De Gans J & Van de Beek D. Dexamethasone in adults with bacterial meningitis. New England Journal of Medicine 2002; 347: 1549-1556.

RHH Journal Club. January 10th, 2013. Dr Sireesha Aluri

Full-text article (if available)

Does adjunctive use of dexamethasone in adults with bacterial meningitis improve outcome?

Study design:

  • Randomised, double blind prospective trial with intention to treat.
  •  Multi centre European study (developed world) Jun 1993-Dec 2001.
  • Sub group analysis performed for patients with prospectively defined causes of meningitis.

Methodology:

Population: 301 patients randomly assigned. (Dex group 157, Placebo group 144)

Inclusion criteria: > 17 yrs of age, suspected meningitis with cloudy CSF, bacteria in CSF on gram staining, CSF WCC > 1000/cu mm.

Exclusion criteria: H/O hypersensitivity to B-lactams or corticosteroids, pregnant, had cerebrospinal shunt, Rx with oral/parenteral antibiotics in the previous 48 hrs, H/O active TB or fungal infection, recent H/O head trauma, neurosurgery, or peptic ulcer or enrolled in another trial.

Intervention:

Dexamethasone 10mg IV 6hrly for 4 days, started 15-20 min before antibiotics or along with first dose of antibiotics (changed after interim analysis, Jan 1997). Antibiotics: Amoxicillin 2gms IV 4hrly 7-10 days empirical, changed after sensitivities.

Control: Placebo, same volume, identical to active drug. Antibiotics: Amoxicillin 2gms IV 4hrly 7-10 days empirical, changed after sensitivities.

Outcomes:

Primary: Score on Glasgow Outcome Scale (1-5) at 8 wks post randomisation. Favourable outcome: GOS 5, unfavourable outcome: GOS 1-4.

Secondary: Death, focal neurological abnormalities, hearing loss, GI bleeding, fungal infection, herpes zoster, Hyper glycaemia (BM > 8 mmol/L)

Validity:

  • Baseline charecteristics in both groups same
  • Computer generated randomisation, Code not broken till the last patient to be enrolled finished 8 wk follow up.
  • Concealed to all, but access provided in case of emergency.
  • All patients included in analysis, with their last observation carried forward.

Results:

  • Dexamethasone group had less % of patients with unfavourable outcome (15% vs 25%, RR 0.59, P=0.03), less mortality (7% vs 15%, RR of death 0.48, P=0.04)
  • In patients with Pneumococcal meningitis: results more marked.

Unfavourable outcome – Dex vs placebo: 26% vs 52%, RR 0.50, P=0.006

mortality – Dex vs placebo:14% vs 34%.

  • In Meningococcal meningitis: Role of Dex not marked.
  • Adverse events: Not significant.
  • Dexamethasone group had less impairment of conciousness, less seizures and less cardiorespiratory failure.

Conclusions/ In practice.

  • Early adjuvant treatment with Dexamethasone reduces the risk of unfavourable outcomes and death in adults with bacterial meningitis, especially pneumococcal meningitis (Level 1B evidence).
  • Did not have beneficial effect on neurological sequelae, including hearing loss.
  • Does not show similar benefit in outcomes with other types of meningitis.
  • Dexamethasone does not increase risk of gastrointestinal bleeding.
  • Results can be extrapolated to developed world, but uncertain in developing world.

 

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