Adjuvant Glycerol and/or Dexamethasone to Improve the Outcomes of Childhood Bacterial Meningitis: A Prospective, Randomized, Double‐Blind, Placebo‐Controlled Trial
1Helsinki University Central Hospital, Hospital for Children and Adolescents, and 2University of Helsinki, Department of Public Health, Helsinki, Finland; 3University Diego Portales, Faculty of Health Sciences, Santiago, Chile; 4Clinica Infantil Dr. Robert Reid Cabral, Santo Domingo, Dominican Republic; 5Hospital de Niños Dr. Roberto Gilbert, and 6Hospital del Niño Dr. Francisco de Icaza Bustamante, Guayaquil, Ecuador; 7Hospital de Niños Sor María Ludovica, La Plata, and 8Hospital de Pediatría Dr. Juan P. Garrahan and 9Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires, Argentina; 10Hospital Pediatrico Dr. Agustin Zubillaga, Barquisimeto, and 11Hospital Universitario de los Andes, Mérida, Venezuela; 12Instituto de Medicina Tropical, Universidad Nacional de Asunción, Asunción, Paraguay; and 13Fundação de Medicina Tropical do Amazonas, Institute for Tropical Diseases, Manaus, Brazil
Background.
Despite favorable meta‐analyses, no study involving third‐generation cephalosporins for the treatment of childhood bacterial meningitis has documented a benefit of adjuvant dexamethasone therapy if the outcomes are examined individually.
Methods.We conducted a prospective, randomized, double‐blind trial comparing adjuvant dexamethasone or glycerol with placebo in children aged from 2 months through 16 years in Latin America. Ceftriaxone was administered to all children; children were randomized to also receive dexamethasone intravenously, glycerol orally, both agents, or neither agent. Primary end points were death, severe neurological sequelae, or deafness, with the first 2 end points forming a composite end point. A subgroup analysis for Haemophilus influenzae type b meningitis was undertaken. Intention‐to‐treat analysis was performed using binary logistic regression models.
Results.H. influenzae type b, pneumococci, and meningococci were the main agents found among 654 patients; dexamethasone was given to 166, dexamethasone and glycerol were given to 159, glycerol was given to 166, and placebo was given to 163. No adjuvant therapy significantly affected death or deafness. In contrast, glycerol and dexamethasone plus glycerol reduced severe neurological sequelae, compared with placebo; the odds ratios were 0.31 (95% confidence interval [95% CI], 0.13–0.76; 
) and 0.39 (95% CI, 0.17–0.93; 
), respectively. For neurological sequelae and death, the odds ratios were 0.44 (95% CI, 0.25–0.76; 
) and 0.55 (95% CI, 0.32–0.93; 
), respectively. Dexamethasone therapy prevented deafness in patients with H. influenzae type b meningitis only if patients were divided grossly into dexamethasone recipients and nonrecipients and if timing between dexamethasone and ceftriaxone administration was not taken into account (odds ratio, 0.27; 95% CI, 0.09–0.77; 
).
Conclusion.Oral glycerol therapy prevents severe neurological sequelae in patients with childhood meningitis. Safety, availability, low cost, and oral administration also add to its usefulness, especially in resource‐limited settings.
Received 2 March 2007; accepted 24 July 2007; electronically published 15 October 2007.
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(See the editorial commentary by Saez‐Llorens and McCracken on pages 1287–9)
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