Intrathecal vs. intramuscular administration of human antitetanus immunoglobulin or equine tetanus antitoxin in the treatment of tetanus: a meta-analysis

BACKGROUND: Mortality caused by tetanus is still a serious health problem in developing countries. Apart from immunization, early treatment with equine antitetanus serum (ATS) or human tetanus immunoglobulin (TIG) is the real treatment that can avoid death. On pathophysiological grounds intrathecal administration would be preferred because of high concentrations of the antiserum in cerebrospinal fluid and thus around the nerve roots. Many studies concluded on its effectiveness whereas others did not find any superiority of this method. However, most of those studies were not random and/or had no sufficient weight. OBJECTIVE: To assess the efficacy of intrathecal therapy with ATS in neonates and adults. METHODS: Meta-analysis: Clinical trials were identified by searching Medline, the Cochrane library and Current Contents. Published randomized studies in English or French comparing intrathecal therapy and intramuscular therapy (IMS) were analysed with Revman, R, and Stata software. Treatment effects were evaluated by relative risk (RR) between intrathecal vs. intramuscular administration. RESULTS: A total of 942 patients were included in 12 trials, 484 in the intrathecal group and 458 in the intramuscular one. The combined RR of mortality for intrathecal vs. IMS was 0.71 (95% CI, 0.62-0.81). The superiority of intrathecal therapy also emerged when the analysis was performed in subcategories of both adults and neonates and for high and low dose of intrathecal serotherapy. Intrathecal administration of ATS or TIG is more beneficial than intramuscular administration in the treatment of tetanus.