Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial.
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.
Peltola
Heikki
H
Helsinki University Central Hospital, Hospital for Children and Adolescents, Helsinki, Finland. heikki.peltola@hus.fi
Roine
Irmeli
I
Fernández
Josefina
J
Zavala
Inés
I
Ayala
Silvia González
SG
Mata
Antonio González
AG
Arbo
Antonio
A
Bologna
Rosa
R
Miño
Greta
G
Goyo
José
J
López
Eduardo
E
de Andrade
Solange Dourado
SD
Sarna
Seppo
S
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
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D010919:Placebos; D002443:Ceftriaxone; D003907:Dexamethasone; D005990:Glycerol