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Dexamethasone improves meningitis outcomes

Dexamethasone improves outcome in bacterial, and particularly s. pneumoniae, meningitis.

Level of Evidence: 1⁺ (RCT with a low risk of bias)

Citation/s:De Gans J, et al. Dexamethasone in Adults with Bacterial Meningitis. NEngl J Med 2002; 347: 1549-56

Lead author's name and email: Dr Jan de Gans. j.degans@amc.uva.nl

Three-part Clinical Question: Does the use of dexamethasone in patients with acute bacterial meningitis improve outcome?

Search Terms: meningitis, therapy, steroids, dexamethasone, outcome

The Study: Double-blinded concealed randomised controlled trial with intention-to-treat.

The Study Patients: Inclusion: >17yrs old, suspected meningitis in combination with: cloudy CSF, bacteria in CSF or CSF WCC> 1000 per ml. Exclusion: allergy to B lactams or steroids, pregnancy, CSF shunt, treated with antibiotics in the previous 48 hours, history of TB or fungal infections; recent head trauma, neurosurgery, or peptic ulcer disease or if they were enrolled on another study.

Control group (N = 157; 157 analysed): (N=157; 157 analysed): Placebo rather than steroid. Otherwise identical.

Experimental group (N = 144; 144 analysed): (N=144; 144 analysed): Dexamethasone 10mg six hourly for four days. Initially the steroid was given 15-20 mins prior to the administration of the first dose of antibiotics. After interim analysis the protocol was amended to allow administration of steroid with the antibiotics. Initially treated with amoxycillin 2g six hourly for 7 to 10 days, depending on the cause of the meningitis and clinical response.

The Evidence:

Outcome	Time to Outcome	CER	EER	RRR	ARR	NNT
Death	8 weeks	0.146	0.070	52%	0.076	13
Death	95% Confidence Intervals:			4% to 100%	0.006 to 0.146	7 to 171
Unfavourable outcome (unable to return to work or school)	8 weeks	0.250	0.146	42%	0.104	10
	95% Confidence Intervals:			6% to 77%	0.014 to 0.194	5 to 70

S.Pneumoniae patients only:

Outcome	Time to Outcome	CER	EER	RRR	ARR	NNT
Death	8 weeks	0.340	0.138	59%	0.202	5
Death	95% Confidence Intervals:			13% to 100%	0.044 to 0.360	3 to 23
Unfavourable outcome (unable to return to work or school)	8 weeks	0.520	0.259	50%	0.261	4
	95% Confidence Intervals:			16% to 85%	0.082 to 0.440	2 to 12

EBM Questions

1. Do the methods allow accurate testing of the hypothesis? Yes

2. Do the statistical tests correctly test the results to allow differentiation of statistically significant results? Yes.

3. Are conclusions valid in light of the results? Yes

4. Did results get omitted, and why? No

5. Did they suggest areas of further research? No

6. Did they make any recommendations based on the results and were they appropriate? Yes. Recommendation for the use of Dexamethasone 10mg 6hrly for 4 days in all patients with acute bacterial meningitis, which seems appropriate in view of the study results.

7. Is the study relevant to my clinical practice? Yes, as bacterial meningitis continues to cause significant morbidity and mortality

8. What level of evidence does this study represent? 1+

9. What grade of recommendation can I make on this result alone? B

10. What grade of recommendation can I make when this study is considered along with other available evidence? B

11. Should I change my practice because of these results? Yes, although the recommendations made may be difficult to follow in practice, particularly relating to timing of antibiotic administration

12. Should I audit my current practice because of these results? Yes, although this would also need to apply to acute medical and emergency physicians

Appraised by: Dr Chris Cairns, Consultant Stirling Royal Infirmary, UK and Dr Celia Bygrave, SHO, Stirling Royal Infirmary ; 14 December 2005
Email: Chris.Cairns@fvah.scot.nhs.uk

Kill or Update By: December 2010

Reviewed & Edited by FM.

Citation: EBM Critical Appraisals. Scottish Intensive Care Society EBM Group. 2006. Bygrave C, Cairns CJS. De Gans J, et al. Dexamethasone in Adults with Bacterial Meningitis. NEngl J Med 2002; 347: 1549-56.

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