title: Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial.
abstract: 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; P=.010) and 0.39 (95% CI, 0.17-0.93; P=.033), respectively. For neurological sequelae and death, the odds ratios were 0.44 (95% CI, 0.25-0.76; P=.003) and 0.55 (95% CI, 0.32-0.93; P=.027), 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; P=.014).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Helsinki University Central Hospital, Hospital for Children and Adolescents, Helsinki, Finland. heikki.peltola@hus.fi
authors.forename: Heikki
authors.initials: H
authors.lastname: Peltola
authors.forename: Irmeli
authors.initials: I
authors.lastname: Roine
authors.forename: Josefina
authors.initials: J
authors.lastname: Fernández
authors.forename: Inés
authors.initials: I
authors.lastname: Zavala
authors.forename: Silvia González
authors.initials: SG
authors.lastname: Ayala
authors.forename: Antonio González
authors.initials: AG
authors.lastname: Mata
authors.forename: Antonio
authors.initials: A
authors.lastname: Arbo
authors.forename: Rosa
authors.initials: R
authors.lastname: Bologna
authors.forename: Greta
authors.initials: G
authors.lastname: Miño
authors.forename: José
authors.initials: J
authors.lastname: Goyo
authors.forename: Eduardo
authors.initials: E
authors.lastname: López
authors.forename: Solange Dourado
authors.initials: SD
authors.lastname: de Andrade
authors.forename: Seppo
authors.initials: S
authors.lastname: Sarna
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use; D002443:Ceftriaxone / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D003638:Deafness / Q000517:prevention & control; D003643:Death; D003907:Dexamethasone / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005990:Glycerol / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007843:Latin America; D008297:Male; D016920:Meningitis, Bacterial / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D008583:Meningitis, Haemophilus / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D008585:Meningitis, Meningococcal / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D009422:Nervous System Diseases / Q000517:prevention & control*; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D010919:Placebos; D002443:Ceftriaxone; D003907:Dexamethasone; D005990:Glycerol