Limb-girdle muscular dystrophies (LGMDs) are a clinically and genetically heterogeneous group of muscle diseases resulting from genetic mutation. These gene defects affect various sites throughout the muscle fibre, including the nuclear envelope, sarcomere, sarcoplasm and sarcolemma.1 LGMDs have been mapped to 15 different chromosomal loci: five autosomal-dominant (LGMD1A to E) and 10 autosomal-recessive (LGMD2A to J).2 The autosomal-dominant forms are much less common (<10% of all LGMDs) than autosomal-recessive LGMD and usually show adult onset. They are characterised by progressive weakness and wasting in the pelvic and shoulder girdles2 and may be complicated by respiratory insufficiency and myocardial conduction abnormalities.1 Anaesthetic management of these patients is challenging and rarely reported in the literature.3 We report the successful anaesthetic management for cholecystectomy of a patient with LGMD and severe restrictive lung disease.
A 57-year-old man (70 kg) with LGMD1 diagnosed in 1985 by muscle biopsy was admitted for laparoscopic cholecystectomy. He had a severe restrictive lung disease on pulmonary function tests with chronic hypercapnia (PaCO2 = 62 mmHg) and was on intermittent non-invasive positive pressure ventilation (NIPPV) overnight and 4 h during the day. The pre-operative ECG showed right bundle branch block. Chest X-ray and transthoracic echocardiography were normal except for cardiomegaly. Laboratory tests were adequate except for creatine kinase of 2240 U l−1.
The patient received adequate explanations about the increased risk for anaesthesia and gave his informed consent. He was pre-medicated with 150 mg of ranitidine. Intra-operative monitoring included 5-lead electrocardiography, pulse oximetry, end-tidal capnography, invasive arterial pressure, rectal temperature probe and bispectral index (BIS). The anaesthesia machine (Aestiva/5; Datex-Ohmeda, Helsinki, Finland) was prepared by using a disposable circuit, a fresh CO2-absorbent, disconnecting the vaporisers and flushing with O2 at a rate of 10 l min−1 for 20 min before use. General anaesthesia was induced with remifentanil infusion 1 μg kg−1 min−1 for 1 min during which the patient was pre-oxygenated followed by propofol 3 mg kg−1 without myorelaxant.
Laryngoscopy and intubation were performed successfully without any increase in blood pressure or heart rate. Mechanical ventilation with 40% oxygen in air was begun, maintaining PaCO2 (according to arterial blood gases done at 10 and 30 min after induction) close to the patient's pre-operative values. Anaesthesia was maintained with continuous infusion of remifentanil 0.1–0.4 μg kg−1 min−1 to keep haemodynamic parameters within normal limits and propofol 6–9 mg kg−1 h−1 to provide a BIS number between 40 and 50. No volatile anaesthetic agents were used. Temperature was maintained between 36.5 and 37°C using forced air-warming blankets. The cholecystectomy was performed in 45 min, using low-pressure pneumoperitoneum. Forty millilitre of bupivacaine 0.125% were aerosolised intra-peritoneally and 1 g of paracetamol was given intravenously to provide post-operative analgesia. Recovery time from anaesthesia was 12 min and the patient was extubated after being fully awake with a tidal volume of more than 5 ml kg−1, a respiratory rate of more than 12 per min and an adequate cough reflex. He was transferred to the ICU for 24 h and put on intermitent NIPPV and on paracetamol and tramadol for post-operative analgesia. Peri-operative course was uneventful with no rhabdomyolysis, respiratory or cardiac complications and the patient left the hospital 48 h after surgery.
Sensitivity of patients with LGMD to sedative, anaesthetic and myorelaxant may result in intra-operative and early post-operative cardiovascular and respiratory complications, as well as prolonged recovery from anaesthesia.4 The risk of malignant hyperthermia susceptibility in these patients is not increased compared with the general population, except if there is a positive familial history.4 However, LGMD patients who are exposed to inhaled anaesthetics may develop disease-related cardiac complications, or rarely, a malignant hyperthermia-like syndrome characterised by acute rhabdomyolysis (such as in Duchenne progressive muscular dystrophy) which can also occur post-operatively. As in any muscle disease, succinylcholine administration could be associated with life-threatening hyperkalemia and should be avoided.4 LGMDs belong to the group of progressive muscular dystrophies and are characterised by mutation of transmembrane proteins (dystroglycans, sarcoglycans) with dystrophin. This lack of dystrophin–glycoprotein complex (linking the intra-cellular sarcolemma to the extra-cellular matrix) results in instability and increased muscle membrane fragility, inflammatory reactions and necrosis followed by fibrosis. Exposure to inhalation anaesthetics or succinylcholine stresses the muscle cell membrane and further increases its instability and permeability and, therefore, could predispose LGMD patients to rhabdomyolysis.5 The safest anaesthetic technique for patients with LGMD is still to be established, but probably includes avoiding halogenated agents. That is why the anaesthetic machine was flushed with O2 before the anaesthetic procedure as recommended when exposure to even traces of halogenated agents, particularly when a patient at risk for malignant hyperthermia is scheduled.
This is, to our knowledge, the first case reporting the use of an anaesthetic protocol based on propofol and remifentanil without myorelaxant or volatile anaesthetics in a patient with LGMD1. The potency and the rapid onset of action of remifentanil potentiated anaesthesia, decreased the risk of intra-operative awareness and blunted the haemodynamic changes associated with laryngoscopy and surgery. Because the metabolism of remifentanil is independent of hepatic and renal function, our patient benefited from its analgesic properties without the risk of drug accumulation. In addition, its short duration of action prevented prolonged post-operative respiratory depresssion and sedation. We found that the combination of propofol and remifentanil infusions was successful for our patient with LGMD undergoing surgery. The PaCO2 was maintained close to the pre-operative level to avoid alterations of physiological compensatory mechanisms against acute respiratory alcalosis. In patients with chronic hypercapnia, accepting an intra-operative elevated PaCO2 is mandatory to improve survival and reduce complications.6 The insufflation pressure used for laparoscopic cholecystectomy (12–15 mmHg) has significant effects on both cardiovascular and respiratory function and may be dangerous in American Society for Anethesiologists physical status classification III and IV patients with severe restrictive disease. The use of low-pressure pneumoperitoneum at 6–8 mmHg has been shown to reduce adverse haemodynamic effects.7
Use of ultra-short agents (propofol and remifentanil), use of BIS monitoring to titrate the anaesthetic drugs and avoid awareness, avoidance of myorelaxant together with maintaining of hypercapnia and use of low-pressure pneumoperitoneum resulted in a non-complicated course of anaesthesia in this patient.
In conclusion, the combination of propofol and remifentanil infusions appears to be a suitable anaesthetic technique for patients with LGMD undergoing laparoscopic surgery, because of very little risk of triggering rhabdomyolysis, rapid awakening, minimal effects on the respiratory system and ease of controlling anaesthetic depth. More cases are required to evaluate this anaesthetic technique in patients suffering from LGMD undergoing different types of surgery, including major abdominal or thoracic surgery.
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. The most common mutation in FKRP causing limb girdle muscular dystrophy type 21 (LGMD21) may have occurred only once and is present in Hutterites and other populations. Hum Mutat 2005; 25:38–44.
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. ‘Low-pressure’ laparoscopic cholecystectomy in high risk patients (ASA III and IV): our experience. Chir Ital 2004; 56:71–80.