Tetanus has been aptly described as a third world disease the treatment of which requires first world technology, as heavy sedation and ventilatory support (with or without muscle relaxants) are the mainstay of management, and these are not always available to tetanus patients in those developing countries in which the disease is prevalent. Even in the developed world the problems in the management of tetanus have yet to be solved.
The use of magnesium sulphate infusions in the management of tetanus enables one to minimise sedation and reduce the need for mechanical ventilation, and thereby greatly simplifying the care of the tetanus patient. Reported mortality for severe tetanus ranges between 15-40%, and depends on the availability and quality of intensive care. Deaths due to cardiovascular dysfunction have not been convincingly reduced by the various regimen of sedation, although with management guided by pulmonary artery catheterisation, mortality has been reduced to 6.5% in one study. The complications resulting from long term heavy sedation and artificial ventilation (pulmonary sepsis, bronchospasm, atelectasis, pressure sores, deep vein thrombosis, pulmonary embolism and gastric haemorrhage) also contribute significantly to morbidity and mortality. This is exemplified in Edmondson's series in which 6 out of 10 deaths were attributable to respiratory complications. There is, therefore, a continuing search for drugs which can control the spasms and the autonomic dysfunction of tetanus without the need for heavy sedation and artificial ventilation.
A role for magnesium in the management of tetanus has been postulated by many authors. As early as 1906 Blake described two cases of severe tetanus treated with intrathecal magnesium sulphate. James and Lipmann used it intravenously for the control of autonomic dysfunction, , but its efficacy in the control of spasms has not been investigated. Magnesium is a physiological calcium antagonist and there is a significant correlation between depression of neuromuscular transmission and serum magnesium concentrations. The fact that these magnesium producerseffects are dose dependent and controllable is a great advantage over muscle relaxants. Magnesium is utilized in the control of spasms in eclampsia and the safety of the therapeutic range (2-4 mmols/l) has been well established as areflexia only occurs at levels above 4 mmol/l and muscle paralysis above 6 mmol/l. It is therefore possible that would also control the tetanus without paralysis and the need for artificial ventilation.
The aim of this study was to investigate the efficacy and safety of magnesium sulphate i.v. in controlling the spasms of severe tetanus without the need for sedation and ventilatory support; efficacy to be assessed by the ability to control spasms and safety, by monitoring cardiovascular and respiratory function and serum magnesium concentrations.
All eight patients with severe tetanus admitted to the Anaesthetic Intensive Care Unit (ICU) of the National Hospital of Sri Lanka between March 1996 and 1997 were included in the study. The presence of severe trismus and dysphagia, generalized muscle rigidity, opisthotonus, an frequent spontaneous spasms embarrassing respiration on admission qualified them for inclusion to Grade III A of Ablett's classification. Exclusion criteria were defined as compromised renal function on the basis of blood urea > 6 mmol/l or urine output < 50 ml/hour and no patient qualified for exclusion.
Patients had been initially treated in the ward with antitoxin, toxoid, surgical debridement if the wound could be identified, and i.v. metronidazole and diazepam. Tracheostomy was performed in all eight patients as they had spasms sufficiently frequently and severe enough to interfere with respiration.
Magnesium therapy had to be continued for a few days after the cessation of spasms as attempts at withdrawal resulted in unacceptable rigidity in some patients and sustained tachycardia (> 120/min.) in others. The serum magnesium concentrations were found to be within the therapeutic range (2-4 mmol/l) throughout therapy. No patient needed supplementary therapy.
Rigidity was not completely abolished but reduced sufficiently in all patients to suppress trismus which allowed easy mouth care. Dysphagia was reduced and all but one patient could swallow saliva, three of them being able to swallow small quantities of semisolid diet. Lung and limb physiotherapy could be performed without difficulty.
Continuous magnesium therapy was interrupted in the following two patients. Patient 4 had magnesium therapy for the first 14 days but due to inability to obtain further stocks of magnesium sulphate sedation and paralysis (hourly diazepam 7.5 mg, and tubocurarine 3 mg to control spasms, and morphine 5 mg to control autonomic dysfunction) were introduced for the next 12 days. Patient 6 whose spasms were well controlled on the first two days was taken off magnesium therapy on the 3rd day, as he needed CMV for worsening aspiration pneumonia. He was given i.v. midazolam morphine and vecuronium for 60 hours. On the 6th day all drugs were discontinued and two hours later when spasms recurred magnesium therapy was recommenced. Spasms were then controlled but ventilatory support with SIMV and pressure support had to be continued for 21 days till the pneumonia resolved.
Spontaneous tidal volumes were adequate to maintain normocarbia. However patients 1, 2, 3 and 6 required ventilatory support, for the management of lung pathology. Bronchial secretions were markedly increased but often responded to nebulisation with ipratropium bromide. Cough was not sufficiently effective in the presence of increased bronchial secretions and patients required frequent tracheal suction. Vital capacity was low in all patients during therapy. Patients 5, 7, and 8 were sufficiently cooperative and able to enable us to measure vital capacity without stimulating spasms prior to magnesium therapy. Patient 5 & 7 had vital capacities of 2000 ml and 1000 ml respectively which fell further during the second week of therapy. Patient 7 had a vital capacity of 1000 ml after the commencement of therapy.
Source by: www.mgwater.com
Management of Tetanus on the ICU
Dr John Griffiths DICM MRCP FRCA MA
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 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.