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Three Part Question

In [adults presenting with signs and symptoms suggestive of acute meningitis] is [early medication with dexamethasone] useful at [improving outcome]?

Clinical Scenario

A 38-year-old previously fit and well insulin-dependent diabetic presents to the emergency department with a fever, vomiting and reduced Glasgow Coma Score. He has obvious signs of meningism and is suspected to have acute bacterial meningitis. He is appropriately managed with antibiotics and is subsequently intubated and transferred to the intensive care unit. His initial CT brain scan is unremarkable, but the LP is turbid and subsequently grows Neisseria meningitidis C, as do his throat swabs. You have read about the use of steroids in meningitis but are unsure of the evidence in acute bacterial meningitis and decide to look it up.

Search Strategy

MEDLINE via OVID 1950 to October week 3 2007
The Cochrane Library, Issue 4, 2007
Medline: {exp Meningitis, Haemophilus/or meningitis.mp. or exp Meningitis, Cryptococcal/or exp Meningitis, Listeria/or exp Meningitis, Pneumococcal/or exp Meningitis, Bacterial/or exp Meningitis, Meningococcal/or exp Meningitis, Aseptic/or exp Meningitis, Escherichia coli/or exp Meningitis/or Meningitis, Viral/or exp Meningitis, Fungal/AND exp Dexamethasone Isonicotinate/or exp Dexamethasone/or dexamethasone.mp or dexamethazone.mp. or corticosteroids.mp. or steroids.mp. or Steroids/} limit to (humans and English language).
Cochrane: MeSH descriptor Dexamethasone explode all trees AND (bacterial meningitis): ti,ab,kw 39 records. None unique.

Search Outcome

A total of 801 articles were found of which one was an up-to-date Cochrane review. No relevant papers found postdated this review

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
van de Beek et al, 2006,	Eighteen studies involving 2750 people (adults and children) were included	Systematic Review	Overall Mortality	RR 0.83, 95% CI 0.71 to 0.99	Patient Group: Some studies included trials in children, resulting in exceptionally low mortality rates causing a selection bias and thereby, possibly causing an underestimation of the beneficial effect of corticosteroids Treatment Drug: 17/28 studies used dexamthasone as the treatment drug; while 1 used hydrocortisone, prednisolone or a combination Timing of administration: In only 9/18 studies the drug was administered before or with the first dose of antibiotic. Heterogenecity: Only on RCT (as assessed by the Jadad scale )was included. First study published in 1963, last two in 2002. Adverse Events: Definitions of adverse events used in the studies were heterogeneous and most studies had no specified criteria in advance, so under ascertainment is possible.
			Overall severe hearing loss	RR 0.65, 95% CI 0.47 to 0.91
			Overall long-term neurological sequelae	RR 0.67, 95% CI 0.45 to 1.00
			Adults death	RR 0.57, 95% CI 0.40 to 0.81
			Adults short-term neurological sequelae	RR 0.42, 95% CI 0.22 to 0.87
			Subgroup analysis for Streptococcus pneumoniae mortality	RR 0.59, 95% CI 0.45 to 0.77)
			Subgroup analysis for Meningiococcal meningitis mortality	Nonsignificant favourable trend RR 0.71, 95% CI 0.31 to 1.62

Comment(s)

The evidence merits the use of dexamethasone prior to or together with the first dose of antibiotics. The results show a benefit in reducing unfavourable outcome, reducing neurological sequelae and preventing death in adults suspected of having acute bacterial meningitis. This was particularly beneficial in those patients who were subsequently found to have pneumococcal meningitis. The regime used in the randomised controlled trial was 10 mg dexamethasone four times a day for 4 days.

Editor Comment

Glasgow Outcome Scale as assessed by the physician. 1=death 2=vegetative state; unable to interact with the environment 3=severe disability; unable to live independently 4=moderate disability; unable to return to work/school 5=mild/no disability RR = Relative Risk CI = Confidence Interval ARR = Absolute risk Reduction NNT = Numbers Needed to Treat

Clinical Bottom Line

Dexamethasone should be given prior to or with the first dose of antibiotics in adults suspected of having acute bacterial meningitis. A regime of 10 mg dexamethasone four times a day for 4 days should be followed.

Level of Evidence

Level 2 - Studies considered were neither 1 or 3.

References

1. van de Beek D, de Gans J, McIntyre P, Prasad K Corticosteroids for acute bacterial meningitis The Cochrane Database of Systematic Reviews 2007 Issue 1 November 10. 2006