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Dexamethasone, glycerol fail to prevent hearing loss in kids with meningitis

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – In children with bacterial meningitis, age and presenting neurologic status are the most important predictors of hearing loss, and neither dexamethasone nor glycerol help alleviate the risk, a new study shows.

The randomized multicenter trial, reported in a December 14 online publication in Pediatrics, was headed by Dr. Heikki Peltola, from Helsinki University Central Hospital, Finland. He and his co-authors note that hearing loss accompanies up to 50% of cases of pediatric bacterial meningitis and that dexamethasone and glycerol have reputations for protecting children’s hearing.

“The basic problem is that not a single study has shown the clinical benefits of dexamethasone in pediatric meningitis, not even in cases caused by Haemophilus influenzae type b (Hib),” Dr. Peltola told Reuters Health. “With biochemical parameters, the advantages are demonstrated, but this does not necessarily translate into improvement in the prognosis.”

He continued: “All meta-analyses to date, which ‘demonstrate’ the benefits of dexamethasone, combine very dissimilar patient series, lump together retrospective and prospective studies, various ages, etc. And they completely neglect the two most important predictors of outcomes: the child’s presenting condition (which can be measured with Glasgow Coma Scale), and the age.”

Their study, which they describe as “the largest in pediatrics,” included 383 children, ages 2 months to 16 years, with bacterial meningitis. All were treated with IV ceftriaxone for 7 to 10 days, and in addition, they were randomly assigned to one of four groups:
— IV dexamethasone 0.15 mg/kg every 6 hours for 48 hours, started 15 minutes before ceftriaxone if possible, plus oral placebo (n = 101);
— oral glycerol 1.5 g/kg every 6 hours for 48 hours, maximum 25 mL, plus IV placebo (n = 92);
— both active agents (n = 95); or
— only placebos (n = 95).

Impairment was classified on the basis of hearing threshold in the patient’s better ear: mild impairment, from 40 to 59 dB; moderate hearing loss, 60 to 79 dB; and severe impairment, >/= 80 dB.

Audiology testing showed mild impairment in 44 patients (11%), at least moderate impairment in 46 (12%), and severe impairment in 27 (7%). Fifteen patients (4%) became totally deaf.

“Regardless of the threshold level, no treatment differed from each other or placebo,” Dr. Peltola’s group reports. Outcomes were similar regardless of etiology.

On multivariate analysis, only the child’s initial Glasgow Coma Scale score and age were independent predictors of audiological outcome. Specifically, starting from the maximum Glasgow score, each lower point increased the risk of hearing impairment by 15% to 21%. Each increasing month of age decreased the risk by 2% to 6%.

“Although glycerol — but not dexamethasone — statistically significantly prevented severe neurological sequelae (and almost significantly prevented death), neither glycerol nor dexamethasone, or their combination, was effective against hearing impairment caused by bacterial meningitis,” Dr. Peltola said.

“It has become very clear that hearing impairment develops via other mechanisms than those leading to the neurological sequelae and/or death,” the researcher added. “Therefore, these outcomes should not be lumped together but examined separately.”

“The best solution would be to implement large-scale Haemophilus influenzae type B and Streptococcus pneumoniae vaccinations,” the authors write, “but globally, few children are privileged to those.”

They conclude: “To save a child from hearing loss in meningitis, better agents than dexamethasone or glycerol should be sought.”

Until such agents are found and proven, Dr. Peltola advises clinicians, “Do not give dexamethasone, because no data show its benefits and animal studies suggest that it may be harmful. Instead, give oral glycerol, because it is the first agent since effective antibiotics were developed that has demonstrated efficacy in preventing severe neurological sequelae in children; dexamethasone has never done this.”

Pediatrics 2009.