Management of Tetanus on the ICU Dr John Griffiths DICM MRCP FRCA MA CriticalCareUK Editor

Focus on tetanus Tetanus is characterised clinically by rigidity, muscle spasms and autonomic instability. It has become a rare disease in developed countries following the introduction of widespread immunisation programmes. Approximately 10 cases are reported each year in the UK. Those at high risk of developing tetanus are immigrants, the elderly and intravenous drug abusers. Modern intensive care management has achieved a dramatic reduction in mortality. In one series, all-age mortality from tetanus fell from 44% to 15% after the introduction of an ICU. However, mortality remains high in patients over 60 years of age, and can exceed 50%. In the developing world, tetanus remains endemic.

Focus on prevention of tetanus The immunisation programme in the UK was introduced in 1961, and assigns a total of five injections of adsorbed tetanus toxoid to every child. Every person who has received this full course is regarded as having life-long immunity against tetanus. A course of three injections in adulthood provides 5 to 10 years protection, two injections only 6 months protection. Patients with open wounds should be given a dose of adsorbed tetanus toxoid if not fully immunised or if the immunisation status is unclear. This initial dose should be followed by further doses (at 4-week intervals) to complete a course of 3 injections. Wounds that are infected or necrotic, or contaminated by soil or manure are especially susceptible to tetanus. In these high-risk cases, tetanus immunoglobulin (250 to 500 units intramuscularly) should be administered in addition to tetanus toxoid. Contaminated wounds need to be cleaned thoroughly. Necrotic or infected areas should be surgically debrided.

Focus on the management of tetanus The lack of randomised controlled trials assessing treatment options for tetanus limits the evidence-based approach to its management. One key aspect of treatment is the provision of adequate sedation. This is commonly provided by benzodiazepines (often in high doses), often in combination with opiates. Additional benefit may be provided by anticonvulsants, (particularly phenobarbitone), chlorpromazine, clonidine or dantrolene. If the control of rigidity and muscle spasms is inadequate, then neuromuscular blocking agents and mechanical ventilation are often necessary. Recently, remifentanil has been used successfully to control muscle spasms refractory to other recognised treatments. If further control of sympathetic overactivity is required, then beta-adrenergic blocking agents are useful adjuncts. However, the use of these drugs in tetanus has been associated with profound bradycardia, hypotension and sudden death.

Magnesium sulphate may offer another treatment modality to reduce spasms, rigidity and autonomic instability. Magnesium acts as a presynaptic neuromuscular blocker and vasodilator, reduces catecholamine release and catecholamine receptor responsiveness, and antagonises the effects of calcium in the myocardium. Magnesium also possesses anticonvulsant properties. The largest case series of the management of patients with tetanus comes from Sri Lanka. In this series of 40 patients, the tetanic spasms and muscle rigidity were controlled with an infusion of magnesium as the sole agent. This required an average plasma magnesium concentration of 2-4 mmol/L. Interestingly, control of spasms was not followed by hypertension or tachycardia. In six patients, hypotension (systolic blood pressure below 70 mmHg) and bradycardia (heart rate below 40/min) occurred, which was reversed in four patients by reducing the infusion rate. In this case series, all patients underwent early tracheostomy initially to facilitate endotracheal suctioning. However, subsequent respiratory complications or magnesium-related muscle paralysis meant that 30% of patients under 60 years of age and 60% over 60 years eventually required mechanical ventilation. A reduced level of consciousness was found in four patients with plasma magnesium concentrations above 3.5 mmol/L. All patients developed hypocalcaemia, which normalised after discontinuation of magnesium. The authors of this case series recommend magnesium as a first-line treatment for severe tetanus. However, potential side effects of magnesium, especially respiratory muscle paralysis and cardiovascular depression, remain a matter of concern.