Mitochondrial myopathies are a large heterogeneous group of diseases with an incidence of 1 in 4000. They have a varied aetiology and clinical picture but all result from mitochondrial abnormalities. The age of onset of symptoms varies from birth to adult, although most cases have presented by the age of 20 . The cells affected tend to be those with the highest energy requirements for example, neurones and muscle fibres. All body systems can be affected. Presenting symptoms include skeletal muscle weakness, ptosis, opthalmoplegia and exercise intolerance [2–4]. Other symptoms include dementia, movement disorders, deafness, blindness, seizures and stroke-like episodes [5,6]. Cardiac, respiratory and hepatic involvement are common and necessitate thorough anaesthetic care.
We report successful general anaesthesia in a patient without cardiac or gross metabolic involvement but with significant muscle weakness.
A 49-year-old man with mitochondrial myopathy presented for cataract extraction and insertion of an artificial lens. He gave a history of progressive muscle weakness developing from the age of 12 years. At first, only his eyelids were involved resulting in ptosis. Other muscles began to be affected and by his thirties he developed ophthalmoplegia, bilateral facial weakness, sternocleidomastoid weakness, mild proximal arm muscle weakness and moderate weakness of his legs. There was progressive bulbar muscle involvement and by 45 years old, he was losing weight with increasing dysphagia. He also had mainly nocturnal aspiration, resulting in frequent chest infections. A percutaneous gastrostomy feeding tube was inserted, improving his nutritional state and chest problems significantly. His diagnosis was confirmed with a muscle biopsy showing the typical appearance of mitochondrial myopathy with multiple deletions of mitochondrial DNA.
At admission he weighed 57 kg; he was generally wasted and weak, with an exercise tolerance of only a few meters. His medication consisted of coproxamol for analgesia and nitrazepam for night sedation. He had dysarthria and dysphonia. Auscultation of his chest was clear, as was his chest radiograph. Reflexes and sensation were normal. Full blood count, liver and renal profile, arterial blood–gas analysis, electrocardiogram (ECG) and echocardiogram were normal.
The patient insisted on general anaesthesia, and the operation was scheduled for the next morning. Premedication consisted of a dose of ranitidine 150 mg orally the night before and on the morning of surgery. PEG feeding was stopped at midnight.
Prior to induction, the percutaneous gastrostomy tube was aspirated. Venous access was difficult to obtain but eventually a 22-gauge cannula was sited in a vein in the left wrist. Monitoring with a pulse oximeter, non-invasive arterial pressure and ECG was initiated, and anaesthesia induced with a propofol target-controlled infusion at 4.5 µg mL−1 (IVAC® TCI/TIVA Diprifusor™ Alaris Medical Systems, San Diego, CA, USA). A nerve stimulator (Life-Tech MiniStim MS-III) was applied to the left lateral popliteal nerve using surface electrodes. This nerve was used because the patient's leg was the most accessible limb. The unit was set to train-of-four mode and four supra-maximal, square wave impulses of 0.2 ms duration at 2 Hz were administered. Nasopharygeal temperature monitoring was also established. A size 4 laryngeal mask was used to maintain his airway but was changed to a size 5 to allow a better seal for ventilation.
A dose of vecuronium 4 mg (70 µg kg−1) abolished the train-of-four response and intermittent positive pressure ventilation of the lungs with oxygen and air (FIO2 0.6) instituted via a Bain circuit and Penlon Nuffield 200 ventilator. Anaesthesia was maintained with propofol and alfentanil infusions. Surgery was uneventful and lasted 50 min. The patient was haemodynamically stable throughout the procedure with a heart rate of around 70 beats per min, a SpO2 of 99%, a systolic arterial pressure of between 100 and 110 mmHg and a temperature of 35.8°C.
The train-of-four nerve stimulator did not elicit any twitches until 40 min after the dose of vecuronium, but by 50 min four twitches had returned. Neuromuscular block was then antagonized with neostigmine 2.5 mg and glycopyrronium 0.5 mg, and after 60 min spontaneous respiration returned. Anaesthesia was discontinued and the patient rapidly regained consciousness. Postoperative recovery was also uneventful.
The mitochondrial myopathies can be divided into three groups depending upon the underlying mitochondrial abnormalities. The first group are due to respiratory chain deficiencies and these include deficiency of complex I–V. The second group are due to mitochondrial DNA (mtDNA) mutations and these include mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) and myoclonus epilepsy with ragged-red fibres (MERRF). The third group are due to mitochondrial deletions, e.g. Kearns–Sayre syndrome [5–7]. Skeletal muscle biopsy reveals structural mitochondrial abnormalities and when stained with Gomori tricolour they have the appearance of red-ragged fibres . Specific diagnosis involves mitochondrial DNA analysis. Mitochondrial DNA is maternally inherited and few affected males transmit the diseases . There are no specific treatments for any of the mitochondrial myopathies.
The anaesthetic implications are numerous. Metabolic dysfunction due to hepatic involvement may result in altered glucose, lactate and protein metabolism . There may be altered drug pharmacokinetics and dynamics . Cardiac involvement can lead to cardiomyopathies and conduction dysfunction . Respiratory function is often poor before surgery and patients will be at higher risk of postoperative respiratory complications . If there is bulbar muscle involvement aspiration is more likely. Malignant hyperpyrexia (MH) is a risk, with one case reported , although there are other case reports in which volatiles were used without triggering MH . Patients with mitochondrial myopathies have also previously been reported as being sensitive to non-depolarizing neuromuscular blocking drugs [14,15].
The choice of anaesthetic for this patient was limited by his insistence for a general anaesthetic. Local anaesthesia would have been very suitable for this procedure. There are case reports of local and regional anaesthetics in patients with mitochondrial myopathies and they appear to be safe [16,17]. This patient's risk of aspiration was reduced by premedication with ranitidine, cessation of the PEG feeding 9 h preoperatively and the aspiration of the PEG prior to induction. A total intravenous technique was chosen to exclude any drugs that may have precipitated malignant hyperpyrexia. The patient was paralysed and ventilated in view of his skeletal muscle weakness. A laryngeal mask airway was used as it was less stimulating for the patient compared with an endotracheal tube and as such the depth of anaesthesia could be lighter and less muscle relaxant used. Interestingly, a larger laryngeal mask airway was required for a satisfactory seal with the hypopharynx, presumably due to the bulbar involvement in this patient. Sensitivity to non-depolarizing muscle relaxants was anticipated and the bolus dose was reduced to 70 µg kg−1. Despite this, the train-of-four nerve stimulator did not elicit any twitches until 40 min after this dose. The usual time to 25% recovery of the first twitch with vecuronium 100 μg kg−1 is 20 to 30 min . The duration of action can be increased in hepatic or renal disease, but this patient's renal and hepatic function tests were normal. This suggests an increased sensitivity to non-depolarizing muscle relaxants, at least in some patients with mitochondrial myopathies.
In summary total intravenous anaesthesia with propofol and alfentanil, air and oxygen, was a safe technique in this patient with mitochondrial myopathy. However, he did appear to be more sensitive to non-depolarizing neuromuscular blockade.
The authors would recommend careful preoperative investigation and preparation in these patients, to enable anticipation of potential cardiorespiratory, aspiration and metabolic complications.
We thank Mr B Garston, Consultant Ophthalmologist, for his help.
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