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Three Part Question

In [children with meningococcal meningitis] does [early treatment with dexamethasone] [reduce the frequency of sensorineural hearing loss or other neurologic sequelae]?

Clinical Scenario

A six-month-old boy was admitted to the Paediatric ward with history of fever, non-blanching petechial rash, shrill cry and poor capillary refill. He required 20 ml/kg of fluid bolus. After a full sepsis screening including a lumbar puncture, he was started on IV Cefotaxime for a presumed diagnosis of meningococcal meningitis. Next day on the ward round the Specialist Registrar wondered if a short course of dexamethasone should have been started with the first dose of antibiotic to improve neurological outcome in this child.

Search Strategy

Cochrane Database and Medline using PubMed interface.
Search words: "meningitis" AND "steroids"; "meningococcal" AND "steroids"; "meningitis" AND "dexamethasone".
Limits (in PubMed): study type: randomised control trial; language: English.

Search Outcome

32 hits: 5 directly relevant to the question; no systematic reviews. Relevant papers are shown in the table.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
McIntyre PB et al, 1997,	848 children with bacterial meningitis with mean age in studies 1.2 to 7 yrs	Meta-analysis of 11 randomised controlled trials. Nonrandomised studies assessed for adverse effects (1a)	Hearing loss and neurological outcome other than hearing loss	In H influenzae meningitis dexamethasone reduced severe hearing loss (OR 0.31, 95% CI 0.14 to 0.69). Pneumococcal meningitis OR 0.52 (95% CI 0.17 to 1.46). Protection against other neurological deficits was not statistically significant (OR 0.59, 95% CI 0.34 to 1.02)	Authors do not report a method for assessing validity Difference between subgroups may be observed by chance Potential publication bias
Thomas R et al, 1999,	60 adult patients with bacterialmeningitis	Multicentre, doubleblind, randomised trial (1b)	Rate of patients cured without clinical neurologic sequelae at 30 days	Rate of cured patients without neurological sequelae was not significant (p=0.071) between the 2 groups. RRR of severe neurologic sequelae following dexamethasone therapy was 44% (95% CI –57 to 100)	Adult patient groups First dose of dexamethasone was given within 3 hr of first antibiotic dose rather than with or before the dose
Syrogiannopoulos GA et al, 1994,	118 children aged 2.5 mo to 15 yrs with suspected or proven bacterial meningitis	Single-blinded randomised control trial (1b)	Neurological and audiological assessment at 6 weeks and 4-24 months	No difference in the rate of neurologic and/or audiologic sequelae between 2 groups; RRR –135% (95% CI –11 to 100)	Both groups received dexamethasone
Schaad UB et al, 1995	115 children (age 3 mo to 16 yr) with suspected or confirmed bacterial meningitis	Double-blinded randomised control trial (1b)	Neurologic and audiologic test at 3, 9 and 15 months	16% of 55 placebo recipients and 5% of 60 dexamethasone recipients had 1 or more neurologic/audiologic sequelae (p=0.066); the relative risk of sequelae was 3.27 (95% CI 0.93 to 11.47)	55% of children in control group and 62% in experimental group had H influenzae meningitis
Odio CM et al, 1991	101 children aged 6 weeks to 13 years with suspected or proven bacterial meningitis	Double-blind randomised controlled trial (1b)	Neurological follow-up up to 12 months, audiologic follow-up up to 24 months	Favourable neurological outcome in dexamethasone treated group; RRR 68% (95% CI 11 to 100) with NNT 6. No difference in audiologic sequelae between two groups; RRR 63% (95% CI –13 to 100)	Only 2 patients (4%) in dexamethasone group and none in control group had meningococcal meningitis

Comment(s)

There appears to be a paucity of studies on the effects of adjunctive therapy with steroids in children specifically with meningococcal meningitis. Earlier studies (5,7) done in children with bacterial meningitis, suggest improved neurological outcome with dexamethasone. However, majority of children in these studies had H influenzae meningitis and hence these could not be considered as being representative studies for meningococcal meningitis. These results were reflected in a meta-analysis of randomised control trials assessing improved neurological outcome with dexamethasone in bacterial meningitis (8). The later study on adults by Thomas et al (9), which had a mix of patients with pneumococcal and meningococcal meningitis, was inconclusive regarding systematic use of dexamethasone as an adjunctive therapy for bacterial meningitis. Meningococcal meningitis appears to have the lowest risk of major neurological sequelae compared with pneumococcal and H. influenzae meningitis (1,8). In a multicentre prospective study on 124 children with bacterial meningitis by Richardson et al(2), the children treated with steroids actually had a higher incidence of hearing loss (relative risk 1.70). In this population of children, hearing loss was more common in children who had been ill for more than 24 hours (relative risk 2.72; 95% CI 0.93 to 7.98) and hence the authors hypothesise that there is a critical period around second day of illness, during which hearing loss can be reversed, provided appropriate antimicrobial and supportive treatment is commenced. Pollard and colleagues (3) recommend a 2-day course of dexamethasone as an adjunctive treatment for children with bacterial meningitis, but admit that no data were available for meningococcal meningitis. None of the studies have stratified their results according to serotype of the causative organism or age group of patients, but the subjects in the paediatric studies were outside the neonatal period. It appears, hence, from the review of current best evidence, that use of dexamethasone as an adjunctive therapy could improve neurological outcome in children with suspected H influenzae meningitis and possibly pneumococcal meningitis. However, its use cannot be routinely recommended in cases of suspected meningococcal meningitis or in any case where the aetiology is uncertain (4).

Clinical Bottom Line

Currently there is not sufficient published evidence to recommend early use of dexamethasone in order to improve neurological outcome in children with meningococcal meningitis. In fact, there is some evidence that its use in such a situation might be disadvantageous as far as hearing is concerned.

References

1. McIntyre PB, Berkey CS, King SM et al. Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomised clinical trials since 1988. JAMA 1997:278;925-31.
2. Thomas R, Le Tulzo Y, Bouget J, et al. Trial of dexamethasone treatment for severe bacterial meningitis in adults. Intensive Care Med 1999;25:475-80.
3. Syrogiannopoulos GA, Lourida AN, Theodoridou MC, et al. Dexamethasone therapy for bacterial meningitis in children: 2- versus 4-day regimen. J Infect Dis 1994;169:853-8.
4. Schaad UB, Lips U, Gnehm HE, et al. Dexamethasone therapy for bacterial meningitis in children. Lancet 1993;342:457-61.
5. Odio CM, Faingezicht I, Paris M, et al. The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. N Engl J Med 1991;324:1525-31.
6. Bedford H, de Louvois J, Halket S, et al. Meningitis in infancy in England and Wales: follow up at age 5 years BMJ 2001;323:533-6.
7. Richardson MP, Reid A, Tarlow MJ, et al. Hearing loss during bacterial meningitis. Arch Dis Child 1997;76:134-8.
8. Pollard AJ, Britto J, Nadel S, et al. Emergency management of meningococcal disease. Arch Dis Child 1999;80:290-6.
9. Davies EG, Elliman DAC, Hart CA, et al. . In Manual of Childhood Infections. WB Saunders Company 2001;50-54.