Meta-analysis Of The Time,Effect And Adverse Effect Of Dexamethasone As Adjunctive Therapy Of Bacterial Meningitis In Children

Objective: To investigate the time,therapeutic and adverse effects of the adjunctive dexamethasone therapy in children with bacterial meningitis by comparing it with antibiotic therapy only.Methods: Using meta-analysis,documents of placebo-controlled randomized trials(RCT)relating to the treatment of bacterial meningitis in children with the adjunctive dexamethasone were retrieved from the databases of Cochrane Central,postgraduate,medical literature,abstracts,network science,China Biomedical Literature Database and China National Knowledge Infrastructure.References in RCT were retrieved by hand at the same time.Full texts on line were searched and given qualitative review by 3statisticians individually,and then,all RCT included were analyzed statistically by using Review Manger 5.2 software.Results: The search included 36 studies involving 3964 patients.Studies were divided into three categories of methodological quality: 3 in high,24 in medium and 9 in low according to the score in the ‘Risk of bias’ table.Dexamethasone was associated with a significant reduction in efficiency(risk ratio(RR)1.18,95% confidence interval(CI)1.12 to 1.25,P value<0.05),the duration of hospital stays(SMD=-4.45 d,95%CI-4.89 to-4.01,P<0.05)and recovery normal of blood and CSF(SMD=-2.46 d,SMD=-3.8d,P<0.05).Dexamethasone was also associated with lower rates of hearing loss(RR 0.67,95% CI0.51 to 0.90,P<0.05)and severe hearing loss(RR 0.66,95% CI 0.49 to 0.90,P<0.05),but no significant lower rates in short-term neurological sequelae,long-term neurological sequelae and mortality(P>0.05).We performed subgroup analyses for causative organisms(H.influenzae,Neisseria meningitis(N.meningitis)and S.pneumoniae)and time of administration of steroids.Dexamethasone was associated with a non-significant reduction in mortality in children with meningitis caused by them(P>0.05).For children with meningitis caused by H.influenzae,severe hearing loss was significantly reduced(RR 0.32,95% CI 0.18 to 0.57,P<0.05)by corticosteroids.No significant beneficial effect was seen in children with meningitis caused by bacteria other than H.influenzae(P>0.05).Subgroup analysis on timing of corticosteroids(before or with the first dose of antibiotics versus after the first dose of antibiotics)showed similar results for mortality(P>0.05),but hearing loss(RR 0.57,95% CI 0.39 to 0.84)and severe hearing loss(RR 0.35,95% CI 0.17 to0.73)were significantly reduced after the first dose of antibiotics(P<0.05).For subgroup analyses of severe hearing loss in children with meningitis caused by H.influenzae,administration after the first dose of antibiotics(RR 0.16,95% CI 0.06 to 0.44,P<0.05)had more favourable point estimates than studies with early administration of corticosteroids.Complications such as gastrointestinal bleeding,recurrent fever and arthritis occurred in similar proportions of the treatment and control groups(P>0.05).Conclusion: Evidence had proven that the adjunctive dexamethasone improved significantly the short-term and long-term prognosis of the children with bacterial meningitis.Adjuvant dexamethasone given after antibiotics was more effective in reduction of hearing loss and severe hearing loss but non-significant in neurological sequelae and mortality.Dexamethasone could not increase the risk of gastronintestinal bleeding,recurrent fever,arthritis and so on.