Steroids in meningitis Part B: Clinical commentary

You are called by the casualty officer (CO) in the emergency department for advice. He has just received a 10-month-old infant in transfer from a rural hospital. The child was feverish, lethargic and ill-looking at presentation, so the rural physician did a blood culture, started an intraveous drip, gave a dose of ceftriaxone and fluids, and transferred the infant. The CO has just performed a spinal tap, which yielded cloudy fluid. He wants to know if he should give steroids. What do you advise? Does this scenario sound familiar? It does to me! After considering the careful discussion in Part A, the important question, as in all evidence-based decision making, is, ‘Does the evidence apply to my patient/practice?’ The reality is that only a small minority of patients receive steroids for bacterial meningitis in Canada (1) and my patients are not among them! Is this because our clinical management is woefully lacking in evidence-based practice or are there other reasons? First of all, we are not alone in our lack of wholehearted support of this recommendation. The Canadian Paediatric Society (2), American Academy of Pediatrics (3) and Infectious Disease Society of America (4) all agree that there is controversy around the issue and the evidence is weak for a recommendation on steroid use. Although a pre-clinical animal study (5) documented a decreased inflammatory response with steroid pretreatment and a suggestion of decreased hearing loss, the benefit of the observed decrease in inflammation has not universally resulted in substantially improved clinical outcomes in human trials. If there are so many studies (as outlined in Part A), why is the evidence still not clear? The reason is that there is a large degree of variability in many characteristics of these studies. The antibiotics used in each study varied, with some being more effective for meningitis than others. The timing of steroid administration is quite variable, from before the administration of antibiotics (more effective) to well after antibiotics have been administered (ineffective). The patient population studied has also varied greatly. When studies are done in the developing world, the patients often have more advanced, severe disease with significant neurological morbidity at presentation and less adequate supportive care. However, the overall consensus is that for children in the developed world with Haemophilus influenzae type b (Hib) meningitis, steroids reduce hearing deficits if given before antibiotics. If steroids must be given before antibiotics to be effective, it poses another problem for the clinician. How often in clinical practice are patients started on antibiotics effective for sepsis and meningitis before a definitive diagnosis is made? How often does it happen that the lumbar puncture is delayed because the patient is unstable, there is concern about raised intracranial pressure, the procedure cannot be performed or the diagnosis is not suspected when the patient first presents? Sometimes, after the cerebrospinal fluid sample is obtained, it is not obviously cloudy, so a definitive diagnosis must await cell counts and Gram stains from the laboratory. Even then, the possibility of a nonbacterial etiology for the meningitis, especially during enterovirus season, may need to be considered and must await further diagnostic testing. Rather than delay antibiotic therapy, effective therapy is initiated and the definitive diagnosis of meningitis is ruled in or out later. Would it be practical for all of these children with possible meningitis to have empirical steroids given along with their empirical antibiotics? The answer is no, especially given the marginal benefit steroids appear to have. There is a final and most important reason why steroids will likely not be used routinely in the therapy of Canadian children with bacterial meningitis: the disease is disappearing! Hib invasive disease has declined dramatically in Canada with the introduction of the polysaccharide vaccine and later the conjugate vaccine in the early 1990s. This disease is now rare and seen primarily in infants who have not completed the primary series of vaccinations or are immunocompromised (6). Given that the benefit of steroids for bacterial meningitis has only been shown in children with Hib and this disease has all but disappeared, the findings of the studies have minimal relevance to children in Canada in the new millennium. What about pneumococcal meningitis? There was not significant evidence in the studies to recommend steroid therapy in pneumococcal meningitis, likely because the numbers were too small. However, this question is also likely to become less relevant as more Canadian provinces and territories institute universal routine infant immunization with conjugate pneumococcal vaccine. Given these changes in the epidemiology of bacterial meningitis, further clinical trials to assess the benefits of steroid therapy in bacterial meningitis will not be feasible in the developed world. So, what will you advise the CO in the emergency department? The case scenario described above is typical of children presenting with meningitis in Canada. Medical attention is reasonably prompt. The child in this case has received Hib vaccine, and he has been treated with antibiotics and referred to a tertiary care centre before having a definitive diagnosis made. I know what I would do; what would you do? In my clinical practice, I would only administer steroids to a child with meningitis if all of the following criteria were met: the child has not completed their primary series of Hib immunizations; the child has a clinical illness compatible with bacterial meningitis and has cloudy fluid at initial cerebrospinal fluid sampling; and the child has not yet received his or her first dose of antibiotic.

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