Intensive Care Med (1990) 16:75-80 IntensiveCare Medicine 9 Springer-Verlag 1990 Review article Management of autonomic dysfunction in severe tetanus: the use of magnesium sulphate and clomdine D.N. Sutton, M.R. Tremlett, T.E. Woodcock and M.S. Nielsen Shackleton Department of Anaesthetics, Southampton General Hospital, Southampton, UK Received: 12 August 1989; accepted: 22 November 1989 Abstract. The treatment of severe tetanus with autonomic dysfunction is discussed, with emphasis on the use of magnesium sulphate. An exemplary case is reported, de- scribing the inadequate response to magnesium, but the previously unreported and successful use of clonidine to control sympathetic overactivity. The properties of clonidine are reviewed. Clonidine is felt to be a logical and appropriate drug for the treatment of autonomic dysfunction in severe tetanus. Key words: Tetanus - Autonomic dysfunction - Mag- nesium sulphate - Clonidine hydrochloride Tetanus is the result of a wound infection by the bacteri- um Clostridium tetani, and its clinical manifestations of spasms and rigidity are caused by the organism's neuro- toxin, tetanospasmin [1- 3]. Severe tetanus is classified as having frequent and severe spasms interfering with swal- lowing and respiration [1, 3], and the mainstay of treat- ment since the 1950s has been sedation, neuromuscular blockade and controlled ventilation. Half or more of this group with severe tetanus develop cardiovascular instabil- ity [1, 2] secondary to sympathetic overactivity and raised catecholamine levels [3, 4], and this complication has been associated with a mortality of over 50% [5, 6]. Vari- ous therapeutic regimens have been used to control this autonomic dysfunction, including beta-adrenergic block- ade [7], vasodilatation [8-11], heavy sedation [5, 7, 12], and combined alpha/beta-adrenergic blockade with labetolol [13, 14]. These regimens have not all convinc- ingly reduced mortality [5, 6,19, 15, 16] but, more recent- ly, effective use has been made of magnesium sulphate [5, 17]. We have reviewed the management of autonomic dysfunction in severe tetanus and report a case that illus- trates the problems involved. This patient did not respond adequately to magnesium sulphate infusion in addition to heavy sedation, neuromuscular blockade and ventila- tion, and we describe the first reported use of clonidine to control the sympathetic overactivity. Case report A 45-year-old male was involved in a road traffic accident during which he sustained a compound fracture of his right elbow. There was no re- cord of tetanus toxoid or immunoglobulin being given following the in- jury, and the patient had received no active immunisation for over 30 years. His only significant past medical history was of asthma treated with salbutamol inhalers. On the 3rd day post-injury he developed localised spasms in his right hand, and by the 7th day had trismus and generalised, severe spasms. The diagnosis of tetanus was made, and he was admitted to the intensive care unit (ICU). On admission to ICU, he was fully conscious, apyrexial but sweating and peripherally vasoconstricted. He had marked trismus and was hav- ing painful spasms, but had no dysphagia or respiratory distress. His blood pressure (BP) was 140/90 and he had a sinus tachycardia of 130bpm. Antibiotic therapy was started, and human tetanus im- munoglobulin (300 IU/kg) was given intramuscularly. Sedation was giv- en initially as a midazolam infusion at 5 mg/h and morphine for anal- gesia at 3 mg/h, with boluses of diazepam as required. The arm wound was explored and debrided under general anaesthesia. Twenty-four hours after admission he had markedly worsened, with severe and frequent spasms, uncontrolled with increased sedation, and associated with high systolic blood pressures (SBP). A tracheostomy was performed, and thereafter ventilation continued with increased se- dation. Despite 50 mg/h of midazolam, he continued to have spasms when stimulated, and vecuronium was given. By day 2 of his 1CU admission the spasms were well controlled, but autonomic instability was developing, with high SBP on minimal stimu- lation despite steady sinus rythm at a rate of 100 bpm. By day 3 there was increasing cardiovascular instability, with SBP varying from 100 to 180 mmHg, and heart rate from 60 to 120 bpm. These variations were not always related to stimulation and occurred despite increasing amounts of sedation. He was well perfused peripherally, but developed a persistent pyrexia with a core temperature of up to 39 ~ At this point we began to collect twice daily samples for plasma cat- echolamine determination, once during stimulation and once when un- disturbed; these were assayed for adrenaline and noradrenaline [18]. Heavy sedation failed to provide adequate control of the sympathet- ic overactivity and the BP became increasingly labile. In view of the pa- tient's bronchospasm, and reported problems with beta-adrenergic blockade in severe tetanus [5, 15, 16], on day 4 we started a magnesium sulphate infusion. The dosage was based on that used by James and Manson [5], namely a loading dose of 70 mg/kg, followed by a continu- ous infusion of between 1 and 4 g/h to maintain the suggested level of 2.5 to 4 mmol/1. Plasma magnesium was assayed 4 hourly until these