Corticosteroids for suspected bacterial meningitis in children – Status in 2005

Just after grand rounds, one of the senior residents comes up to you and asks, “I heard that there is some new evidence that steroids should be used in the therapy of suspected meningitis – is this true?” How do you respond? Whether recently published data support the use of corticosteroids in suspected bacterial meningitis in children illustrates a good example of the adage that, ‘children are not little adults’. Until the early 1990s, empirical corticosteroids were frequently used for cases of suspected bacterial meningitis in Canadian children (1). A meta-analysis of clinical trials concluded that corticosteroids were beneficial in preventing severe hearing loss in children with Haemophilus influenzae type b or Streptococcus pneumoniae meningitis if they are given before or with the first dose of antibiotics (2). However, when one study from Egypt (3) was excluded from the meta-analysis, no benefit was found for corticosteroids in S pneumoniae meningitis. The Egyptian study was very different from the other studies because hearing loss was not evaluated in children younger than five years of age, and the mortality was much higher than that of other studies (19% versus 1% in studies from developed countries) (3). By the end of the 1990s, with the near disappearance of H influenzae type b meningitis and inconclusive evidence for any benefit of corticosteroids in S pneumoniae meningitis (now the most common cause of bacterial meningitis), empiric corticosteroids were used in only 5% of cases (1). For S pneumoniae meningitis, the most recent Canadian Paediatric Society position statement (2001) (4) states that there is only fair to moderate evidence for the use of corticosteroids in suspected cases, and the American Academy of Pediatrics' 2003 Red Book: Report of the Committee on Infectious Diseases (5) states that, “data are not sufficient to demonstrate a clear benefit in children” of corticosteroids. What, then, is new on this subject? In 2002, a multicentre randomized placebo-controlled clinical trial (6) was published that compared dexamethasone with placebo given before or with the first dose of antibiotics in European adults with suspected bacterial meningitis. Their main finding was that, in adults with S pneumoniae meningitis, dexamethasone reduced mortality from 34% to 14% (P=0.02). However, mortality was not prevented in cases caused by Neisseria meningitidis or other pathogens, and neither hearing loss nor focal neurological sequelae were prevented in any cases. Is this dramatic effect to prevent mortality in S pneumoniae meningitis applicable to children? Likely it is not. The 34% baseline mortality in adults with S pneumoniae is far higher than the 5% mortality in Canadian children (1). A major factor in this difference is more frequent severe systemic disease in adults than in children. For example, in the European adult study (6), 20% in the placebo group had cardiorespiratory failure. Very recently, a secondary analysis of the European adult study was published that examined the particular issue of what kind of mortality was prevented by corticosteroids in S pneumoniae meningitis (7). By far, corticosteroids were most effective in preventing deaths in those with severe systemic disease (septic shock, multiorgan failure, respiratory failure or cardiac ischemia). The proportion of patients with deaths due to systemic disease was 16% in the placebo group compared with 2% in the corticosteroid group (P=0.04) (7). In contrast, deaths due to neurological causes did not differ between the groups (10% in the placebo group versus 7% in the corticosteroid group, P=0.56). The mechanism of action of the steroid benefit in adults is not known but is likely primarily related to the prevention of septic shock and respiratory failure (7). The results of the European meningitis study (6) brings new attention to another unresolved issue – the variable findings of studies of the impact of corticosteroids on sepsis in adults (7). For now however, for children with suspected bacterial meningitis, there is no new evidence to support the use of empirical corticosteroids. What is the bottom line on propofol and children? Should we be using steroids in children with meningitis? These and other questions from the front lines of child care are the subjects of a new feature in Paediatrics & Child Health, “Therapeutic Dilemmas”. The question should be a one or two line question on a therapeutic issue regarding child health. This question will then be addressed by experts in the field. Their response will undergo peer review and revision by the editors. How does this new feature fit with our Evidence for Clinicians articles? Regrettably, the majority of therapies in children have not had the benefit of evidence-based evaluation. This new feature will complement the outstanding work of Dr Klassen and others in establishing evidence-based practice by giving clinicians guidance on best current practice in areas of therapeutic uncertainty. You can submit questions to the Co-Editor-in-Chief (Dr Ford-Jones) or directly to Dr Rieder at mrieder@uwo.ca. The Editorial Board hopes that this provides an opportunity for residents, paediatricians and other child care workers on the front line to share their therapeutic questions with the readers of Paediatrics & Child Health.

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