1 Department of Anaesthesia, William Harvey Hospital, Kennington Road, Ashford, Kent TN23 3AQ, UK. 2 Department of Anaesthesia, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. 3 Malignant Hyperthermia Unit, University of Leeds, Leeds, UK
Corresponding author. E-mail: rrjohi@aol.com
Accepted for publication: July 2, 2003
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Abstract |
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Br J Anaesth 2003; 91: 7447
Keywords: complications, central core disease; complications, malignant hyperthermia; heart, coronary artery, bypass grafting; hormones, statins; protein, aprotinin; temperature, regulation, hypothermia
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Introduction |
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Case report |
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Two years previously, she had been referred for investigations after the diagnosis of central core disease and malignant hyperthermia susceptibility (MHS) in her sister and niece. Her skeletal muscle histology was typical of central core disease while the in vitro muscle contracture tests, carried out according to the protocol of the European Malignant Hyperthermia Group,9 were abnormal for both halothane (3 mN tension at halothane 2% v/v) and caffeine (6 mN at caffeine 2 mM) tests. None of the RYR1 mutations currently used for diagnostic purposes10 11 is present in this family. Our patient had undergone tonsillectomy and adenoidectomy as a child under general anaesthetic without any reported complications. Her myopathy was mild and restricted to minimal weakness of the legs. Her ventilatory function was normal, with an FVC (forced vital capacity) of 2.69 (88% predicted) and an FEV1 (forced expiratory volume in 1 s) of 2.10 (80% predicted). Preoperative full blood count, LFTs, serum creatinine kinase (CK), sodium, potassium, urea and creatinine were normal.
After ensuring full precautions to prevent and treat MH (Table 1) were in place, she was premedicated with i.m. morphine 15 mg and metoclopramide 10 mg and oral lorazepam 3 mg, 1 h before surgery. Anaesthesia was induced with midazolam 7 mg, fentanyl 20 µg kg 1 and pancuronium 16 mg. Anaesthesia was maintained using a propofol infusion at 300400 mg h1. Other infusions included dopamine 424 mg h1 and glyceryl trinitrate 110 mg h1. Aprotinin 2 000 000 U was given at sternotomy, followed by another 2 000 000 U during bypass. Anticoagulation was achieved with heparin (total dose 45 000 IU). The patient was cooled to 32°C on cardiopulmonary bypass and the aortic cross-clamp time was 45 min. After bypass, the residual effects of heparin were reversed with protamine 375 mg. Four units of platelets and two units of fresh frozen plasma were transfused perioperatively. The decision to transfuse blood products was made on account of increased microvascular bleeding. No allogenic blood was transfused at any time. After surgery, the patient was transferred to the intensive care unit and her trachea was extubated after 12 h. Postoperative recovery was uneventful. Our patient did not show any sign of muscle weakness at any time in the postoperative period and was discharged from hospital after 8 days. Lung function tests and determination of serum CK concentration were not repeated.
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Discussion |
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It is well known that statins can be associated with rhabdomyolysis and myopathy.14 The risk of myopathy is increased when statins are combined with drugs that inhibit hepatic cytochrome P450 enzymes (e.g. fibrates, cyclosporin, macrolide antibiotics and azole antifungals)15 and when high doses are given, or in the presence of acute viral infections, major trauma, surgery or hypothyroidism. The incidence of myopathy with individual statins varies widely. Simvastatin and cerivastatin are known to produce the highest incidences (35.8 and 31.9%, respectively), and the incidence with atorvastatin is 12.2%.14 The potential for a greater likelihood of rhabdomyolysis induced by statins in patients with pre-existing muscle disease is not known, but we are aware of a patient diagnosed as susceptible to malignant hyperthermia who presented with marked rhabdomyolysis after therapy with statins.16 It would seem prudent for patients receiving statins who have a known muscle disorder to have serum CK concentration measured routinely during their follow-up visits. Our patient, who was on long-term atorvastatin therapy, had had a normal serum CK concentration before cardiac surgery and also before muscle biopsy 2 yr earlier. She showed no sign of aggravation of her myopathy at any time during the perioperative period. However, in the postoperative period, CK measurements can cause diagnostic confusion as surgery itself can cause CK elevation. We did not measure CK concentration in the postoperative period.
This patient was obese and taking aspirin for its antiplatelet effect until the day before surgery. These factors are both associated with an increased risk of perioperative bleeding after coronary artery bypass grafting. Aprotinin is commonly used in these circumstances to reduce the risk of microvascular bleeding. This drug is known to have a relatively high incidence of anaphylaxis17 and its potential ability to trigger MH is unknown. Its use in MHS patients has not yet been reported.
Aprotinin is an antifibrinolytic, and can be used to decrease blood loss and reduce transfusion requirements in any surgical procedure in which profuse bleeding is anticipated. High-dose aprotinin is used extensively in adult and paediatric cardiac surgery, especially in high risk, re-do operations. Aprotinin has been shown to significantly reduce perioperative transfusion requirements and postoperative bleeding in non-cardiac operations, such as major thoracic surgery,18 complex maxillofacial surgery,19 orthotopic liver transplantation20 and complex adult reconstructive spinal surgery.21
For our patient, we considered the potential benefits of aprotinin administration to outweigh the risk of it triggering MH, despite no previous documentation of its use in MHS patients. Furthermore, we believed the risk of triggering MH to be sufficiently small. However, although an MH reaction was not triggered in our patient, we cannot conclude that aprotonin does not trigger MH in a susceptible individual. We recognize that exposure of susceptible individuals to triggering drugs does not always lead to an MH reaction. It is also conceivable that an MH reaction was prevented by the hypothermia (32°C) induced during cardiopulmonary bypass. Animal experiments, in susceptible pigs, have shown that hypothermia is protective against precipitating MH.22
In summary, although our patient had an uneventful procedure, there were many potential problems. It is recommended that patients suffering from a myopathy and on statin therapy should have their CK levels measured routinely as they are at risk of developing rhabdomyolysis. Hypothermia as a means of preventing an MH reaction needs more evaluation.
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References |
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