Tetanus in childhood: report of a therapeutic trial of diazepam.

The clinical management of tetanus poses a difficult therapeutic problem to physicians everywhere. Mortality from the disease remains high even in those medical centres endowed with the best facilities currently available. In many developing countries where the disease is prevalent, and medical services are inadequate for local needs, mortality figures are alarmingly high, especially among cases of neonatal tetanus (Tompkins, 1958; Loh Siew Gek, 1951). In these circumstances any innovation in treatment that offers some hope of reducing mortality from the disease is worthy of trial, especially if it is simple, relatively inexpensive, and safe. Diazepam (Valium) has two distinct pharmacological properties -tranquillizing and muscle-relaxant. In experimental work the drug has been shown to block spinal reflexes in anaesthetized cats (Randall et al., 1961), and it has been used with benefit in the management of the " stiff-man syndrome," which previously was unamenable to any form of treatment (Howard, 1963). These facts suggested that diazepam might be of value in the management of tetanus, and in October 1964 a therapeutic trial was started. Preliminary findings were encouraging (Hendrickse and Sherman, 1965). The trial has since been completed, and this report summarizes our findings. When the trial started in October 1964 all new cases of tetanus seen in the Department of Paediatrics were randomly allocated into one of three treatment groups designated A, B, and C. The following standard treatment was given to all groups: (1) paraldehyde by intramuscular injection for immediate control of spasms ; (2) anti-tetanus serum, 20,000 to 50,000 units, by intramuscular injection ; (3) penicillin, 150,000-300,000 units daily, for five days ; (4) as soon as initial sedation was secured with paraldehyde a gastric tube was passed through the nose, and subsequent medication was administered by this route during the early days of treatment ; and (5) additional antibiotics-for example, tetracycline-were used for complications such as bronchopneumonia. The following regimens of sedation were then employed in the different groups: Group A: Phenobarbitone, 4.4-6.6 mg./kg., and chlor-promazine 1.1-2.2 mg./kg. six-hourly. Group B: Phenobarbitone and chlorpromazine as in group A, plus diazepam, 0.44-1.1 mg./kg. six-hourly. Group C: Diazepam only; up to 1.1 mg./kg. six-hourly. The clinical course of all patients was recorded on a special form. The data recorded were summarized at the end of each 24-hour period, and sedation was modified, if necessary, in the light of the patient's progress. Routine administration of phenobarbitone, chlorpromazine, and diazepam was …