TREATMENT Tetanus
If possible, the entry wound should be identified, cleaned, and debrided of necrotic material in order to remove anaerobic foci of infection and prevent further toxin production. Metronidazole (400 mg rectally or 500 mg IV every 6 h for 7 days) is the preferred antibiotic. An alternative is penicillin (100,000–200,000 IU/kg per day), although this drug theoretically may exacerbate spasms. Failure to remove pockets of ongoing infection may result in recurrent or prolonged tetanus.
Antitoxin should be given early in an attempt to deactivate any circulating tetanus toxin and prevent its uptake into the nervous system. Two preparations are available: human tetanus immune globulin (TIG) and equine antitoxin. TIG is the preparation of choice, as it is less likely to be associated with anaphylactoid reactions. Recommended therapy is 3000–5000 IU of TIG as a single IM dose, a portion of which should be injected around the wound. Equine-derived antitoxin is available widely and is used in low-income countries at a dosage of 10,000–20,000 U administered IM as a single dose or as divided doses after testing for hypersensitivity. Some evidence indicates that intrathecal administration of TIG inhibits disease progression and leads to a better outcome. The results of relevant studies have been supported by a meta-analysis of trials involving both adults and neonates, with TIG doses of 50–1500 IU administered intrathecally.
Spasms are controlled by heavy sedation with benzodiazepines. Chlorpromazine and phenobarbital are commonly used worldwide, and IV magnesium sulfate has been used as a muscle relaxant. A significant problem with all these treatments is that the doses necessary to control spasms also cause respiratory depression; thus, in resource-limited settings without mechanical ventilators, controlling spasms while maintaining adequate ventilation is problematic, and respiratory failure is a common cause of death. In locations with ventilation equipment, severe spasms are best controlled with a combination of sedatives or magnesium and relatively short-acting, cardiovascularly inert, nondepolarizing neuromuscular blocking agents that allow titration against spasm intensity. Infusions of propofol have also been used successfully to control spasms and provide sedation.
It is important to establish a secure airway early in severe tetanus. Ideally, patients should be nursed in calm, quiet environments because light and noise can trigger spasms. Tracheal secretions are increased in tetanus, and dysphagia due to pharyngeal involvement combined with hyperactivity of laryngeal muscles makes endotracheal intubation difficult. Patients may need ventilator support for several weeks. Thus tracheostomy is the usual method of securing the airway in severe tetanus.
Cardiovascular instability in severe tetanus is notoriously difficult to treat. Rapid fluctuations in blood pressure and heart rate can occur. Cardiovascular stability is improved by increasing sedation with IV magnesium sulfate (plasma concentration, 2–4 mmol/L or titrated against disappearance of the patella reflex), morphine, or other sedatives. In addition, drugs acting specifically on the cardiovascular system (e.g., esmolol, calcium antagonists, and inotropes) may be required. Short-acting drugs that allow rapid titration are preferred; particular care should be taken when longer-acting β antagonists are administered, as their use has been associated with hypotensive cardiac arrest.
Complications arising from treatment are common and include thrombophlebitis associated with diazepam injection, ventilator-associated pneumonia, central-line infections, and septicemia. In some centers, prophylaxis against deep-vein thrombosis and thromboembolism is routine.
Recovery from tetanus may take 4–6 weeks. Patients must be given a full primary course of immunization, as tetanus toxin is poorly immunogenic and the immune response following natural infection is inadequate.