Anaesthesia and neuromuscular disorders: what a neurologist needs to know

Abstract

Neurologists are often asked for specific advice regarding patients with neuromuscular disease who require general anaesthesia. However, guidelines on specific neuromuscular disorders do not usually include specific guidelines or pragmatic advice regarding (regional and/or general) anaesthesia or procedural sedation. Furthermore, the medical literature on this subject is mostly limited to publications in anaesthesiology journals. We therefore summarise general recommendations and specific advice for anaesthesia in different neuromuscular disorders to provide a comprehensive and accessible overview of the knowledge on this topic essential for clinical neurologists. A preoperative multidisciplinary approach involving anaesthesiologists, cardiologists, chest physicians, surgeons and neurologists is crucial. Depolarising muscle relaxants (succinylcholine) should be avoided at all times. The dose of non-depolarising muscle relaxants must be reduced and their effect monitored. Patients with specific mutations in RYR1 (ryanodine receptor 1) and less frequently in CACNA1S (calcium channel, voltage-dependent, L type, alpha 1S subunit) and STAC3 (SH3 and cysteine rich domain 3) are at risk of developing a life-threatening malignant hyperthermia reaction.

Keywords: Anaesthetics; muscle disease; muscular dystrophy; myasthenia.

Figure 1

The mode of action of depolarising and non-depolarising muscle relaxants. With depolarising muscle relaxants, a significant depolarisation and muscle contraction occurs before relaxation starts. The depolarising muscle relaxant succinylcholine works very fast (about 30–60 s) and has a short (10 min) duration of action. Non-depolarising muscle relaxants lead to relaxation by reversible competitive inhibition of the acetylcholine receptor. Rocuronium is the fastest working non-depolarising muscle relaxant. Relaxation is achieved approximately 90 s after administration. Ach, acetylcholine; Ch, choline ●, depolarising muscle relaxants; l, non-depolarising muscle relaxants.

Figure 2

Increased sensitivity to non-depolarising muscle relaxants. Increased sensitivity to non-depolarising muscle relaxants is represented by a leftward shift of 30–50% of the amount of relaxant needed to completely or partially suppress the first twitch of the train-of-four.

Figure 3

Intraoperative neuromuscular monitoring. Neuromuscular function monitoring is a technique that involves the electrical stimulation of a motor nerve and monitoring the response of the muscle supplied by that nerve. The necessary equipment should be part of the standard equipment in the operating theatre and may be used to monitor depth of neuromuscular blockade. Importantly in patients with an underlying neuromuscular disorder, it is used to confirm recovery from the ‘blocking’ effect of neuromuscular blocking agents. The response of the muscles to electrical stimulation of the supplying nerves is recorded and preferably quantified. The main reason for measuring muscle relaxation is to prevent residual relaxation in a patient who is awakening and has an aspiration risk after removal of the endotracheal tube. Residual relaxation leads to acute respiratory events after extubation such as airway obstruction and hypoxaemia and an increased risk of postoperative (aspiration) pneumonia. In most neuromuscular disorders, muscle relaxants have a delayed action time and longer duration of action. Therefore, the dose of these agents should be reduced in such cases, applying neuromuscular monitoring to allow titration of the correct dose. There are different ways of stimulation and relaxation measurement: (1) a ‘single twitch’ of 0.1 Hz used to measure the effect of the relaxant; (2) a ‘TOF’, consisting of 4 stimuli of 2 Hz every 30 s which is used to measure the effect of the relaxant; (3) and post-tetanic contraction counts with stimulation of 50 Hz followed 3 s later by 15 single twitches, to measure the depth of blockage when TOF is 0.

Figure 4

Malignant hyperthermia. Succinylcholine and volatile anaesthetics directly and indirectly cause the ryanodine receptor 1 (RyR1) channel to remain open. In case of certain mutations in the RYR1 gene, the RyR1 channel is abnormally sensitive, causing a massive flow of calcium ions from the sarcoplasmic reticulum to the cytoplasm. This is reinforced by the increase in calcium concentration itself (‘calcium-induced calcium release’), causing an abnormally sharp increase in the intracellular calcium concentration, and ultimately resulting in a clinically relevant muscle contracture, manifesting as massive muscle cramps, hyperthermia, rhabdomyolysis, hypercapnia, renal failure, cardiac arrhythmias and eventually death. The precise mechanism(s) in the implicated in rarer genetic backgrounds— CACNA1S and STAC3—may be slightly different but clinical manifestations are the same.

Figure 5

Counselling following a malignant hyperthermia episode. This flow chart summarises the recommended diagnostic approach in a patient with a suspected malignant hyperthermia episode. Genetic screening of family members can only be performed in case of an RYR1 or CACNA1S mutation for which the pathogenicity for malignant hyperthermia has been proven. CACNA1S, calcium channel, voltage-dependent, L type, alpha 1S subunit; RYR1, ryanodine receptor 1. Currently, this applies to 50 mutations (48 RYR1 and 2 CANA1S mutations), referred to as ‘diagnostic mutations’. Mutations should fulfil several requirements to be classified as a diagnostic mutation. In vitro functional studies demonstrating a gain of function effect of the mutation on intracellular calcium release are the highest level of evidence. The results of functional studies must be supported by other investigations such as studies demonstrating segregation of the malignant hyperthermia phenotype and genotype in at least two unrelated families or computational modelling of the effect of the mutation on the receptor. A list of ‘diagnostic mutations’ can be found on the website of the European Malignant Hyperthermia Group (https://www.emhg.org/diagnostic-mutations).

Figure 6

In vitro contracture test. Despite advances in genetics, the in vitro contracture test is still the gold standard to test for malignant hyperthermia susceptibility. During the test four, fresh biopsied muscle strips (length 20–25 mm and 2–3 mm thick) from the quadriceps femoris muscle are exposed to a tissue bath with an increasing concentration of halothane and caffeine. The muscle strips are electrically stimulated with a supramaximal stimulus. The test is positive when one of the muscle strips develops a contracture after exposure to halothane and/or caffeine and electrical stimulation, suggesting the tested person is malignant hyperthermia–susceptible. When the muscle strips do not develop a contracture after exposure to caffeine and/or halothane and electrical stimulation, the test is negative and the tested individual is malignant hyperthermia normal. The in vitro contracture test is the only test able to conform or rule out malignant hyperthermia susceptibility. The standardised in vitro contracture test protocol of the European Malignant Hyperthermia Group can be found at https://www.emhg.org/testing-for-mh/2017/12/28/in-vitro-contracture-testing-ivct.

Figure 7

Medical alert cards, apps and warnings in electronic patient files. International and national patient organisations (such as the Muscular Dystrophy Campaign of the United Kingdom, which has provided the example shown in the figure) have also taken the initiative to send out medical alert cards to patients with neuromuscular disorders and health professionals. Neurologists should repeatedly inform their patients with neuromuscular disorders about these cards and emphasise the importance of using them. In addition, electronic patient files should contain alerts regarding anaesthesia in the specific disorder, to ensure easy visibility to other healthcare provider accessing the patient file. For myotonic dystrophy this could, for example, include the following: ‘perioperative complications can develop in patients with myotonic dystrophy, both children and adults. General anaesthesia is associated with an increased risk of perioperative complications and should be avoided whenever possible, especially in patients with advanced disease. Where possible, local anaesthesia should be chosen’.