Diazepam for treating tetanus

Background

Clinical management of the muscle spasms and rigidity of tetanus poses a difficult therapeutic problem to physicians everywhere, especially in resource poor countries. There are wide variations in therapeutic regimens commonly used in clinical practice due to uncertainties about effectiveness of conventional drugs. Diazepam compared to other drugs (eg phenobarbitone and chlorpromazine) may have advantages because of combined anticonvulsant, muscle relaxant, sedative and anxiolytic effects.

Objectives

To compare diazepam to other drugs in treating the muscle spasms and rigidity of tetanus in children and adults.

Search strategy

We searched the Cochrane Neonatal Group trials register (June 2004), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to June 2004), EMBASE (1980 to June 2004), LILACS (2004), CINAHL (June 2004), Science Citation Index, African Index Medicus, conference abstracts and reference lists of articles. We contacted researchers, experts and organizations working in the field and used personal communication.

Selection criteria

Randomized and quasi-randomized controlled trials.

Data collection and analysis

We independently identified eligible trials, assessed trial methodological quality and extracted data.

Main results

Two studies met the inclusion criteria. Method of generation of allocation sequence, concealment of allocation and blinding were unclear in both studies. A total of 134 children were allocated to three treatment groups comprising diazepam alone, phenobarbitone and chlorpromazine, or phenobarbitone and chlorpromazine and diazepam.

Meta-analysis of in-hospital deaths indicates that children treated with diazepam alone had a better chance of survival than those treated with combination of phenobarbitone and chlorpromazine (Relative Risk for death 0.36; 95% confidence interval 0.15 to 0.86; Risk Difference -0.22; 95% CI -0.38 to -0.06).

Giving diazepam alone, or supplementing conventional anticonvulsants (phenobarbitone and chlorpromazine) with diazepam, was reported in one study to be associated with a statistically significantly milder clinical course and shorter duration of hospitalization.

Authors' conclusions

Although this review suggests that diazepam alone compared with combination of phenobarbitone and chlorpromazine may be more effective in treating tetanus, the small size, methodological limitations and lack of data on drug safety from available trials preclude definite conclusions to support change in current clinical practice. The application of this observation should be moderated by local needs and circumstances, pending the availability of better evidence. We recommend a reinforcement of preventive measures against tetanus infection and it is hoped that in the light of clear evidence about the preventive efficacy of tetanus toxoid immunization, concerted efforts should be made towards preventive interventions and ultimate eradication such that there will not be enough case materials for a trial. In the event of a need for a trial, a large prospective, multicenter, randomized controlled trial, which compares diazepam alone with combinations of other drugs (excluding diazepam) will be ideal.