Anesthesia for children with myopathy and for children who undergo muscle biopsy

INTRODUCTION — Myopathies are a heterogeneous group of disorders with diverse etiologies that affect muscle structure or muscle metabolism. Both skeletal muscle and cardiac muscle may be affected, as well as other organ systems. Children with myopathy present for anesthesia as part of the diagnostic process, for treatment of the direct complications of the disorder, or for unrelated surgery. Children with myopathy are surviving to adulthood and may present for anesthesia care with advanced, multisystem disease, including severe cardiorespiratory dysfunction. Certain myopathies present life-threatening risks that are specific to anesthesia. These are malignant hyperthermia (MH), anesthesia-induced rhabdomyolysis (AIR), and propofol toxicity.

This topic will discuss general considerations and anesthetic management for children with myopathy with a focus on children with muscular dystrophy (MD), and the anesthetic management of children presenting for diagnostic muscle biopsy.

The manifestations, diagnosis and treatment of muscle diseases are discussed in topic reviews of individual disorders.

●(See "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis".)

●(See "Duchenne and Becker muscular dystrophy: Management and prognosis".)

●(See "Approach to the metabolic myopathies".)

●(See "Myotonic dystrophy: Etiology, clinical features, and diagnosis".)

●(See "Myotonic dystrophy: Treatment and prognosis".)

Anesthesia for children with myotonia is also discussed separately. (See "Myotonic dystrophy: Treatment and prognosis", section on 'Risk of anesthesia'.)

MULTIORGAN SYSTEM EFFECTS OF MYOPATHY — Myopathies are associated with multiple organ system abnormalities that may be present at birth or develop with disease progression. The abnormalities that may affect anesthetic care and perioperative risk are discussed briefly here, and in more depth in topics on individual disorders.

●Respiratory problems – Respiratory failure is usually multifactorial, and may include the following:

•Weakness of the muscles of respiration, including the diaphragm and the intercostal muscles.

•Increase in chest wall compliance early in the course of the disease, decrease in chest wall compliance with disease progression [1].

•Musculoskeletal abnormalities (eg, scoliosis), which contribute to a restrictive respiratory defect with reduced total lung capacity and reduced forced vital capacity.

•Recurrent aspiration and poor cough, which lead to frequent episodes of pneumonia and further compromise of respiratory function.

•Sleep disordered breathing, which may include nocturnal hypoventilation, nocturnal hypoxemia, and obstructive sleep apnea (OSA), with associated alterations in respiratory drive and marked central sensitivity to respiratory depressant drugs, and if severe, pulmonary hypertension and right heart failure. (See "Cardiovascular consequences of obstructive sleep apnea in children", section on 'Pulmonary hypertension' and "Anesthesia for tonsillectomy with or without adenoidectomy in children", section on 'Sensitivity to opioids'.)

Respiratory failure can be exacerbated by generalized weakness and malnutrition, cardiomyopathy, and an increased metabolic demand. Perioperative pulmonary risks for patients with Duchenne muscular dystrophy (DMD) are discussed separately. (See "Duchenne and Becker muscular dystrophy: Management and prognosis", section on 'Surgery and anesthesia'.)

●Cardiovascular disorders – Cardiovascular disorders commonly associated with myopathies include cardiomyopathy, arrhythmias, and autonomic dysfunction. Cardiomyopathy may occur as a direct result of the muscle disease, or secondary to respiratory failure. In patients with DMD, the incidence of cardiomyopathy increases gradually during the teenage years, such that one-third of patients have clinically apparent cardiomyopathy by age 14, and one-half by age 18. (See "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis", section on 'Cardiomyopathy'.)

The severity of cardiac involvement is not predicted by the severity of muscle involvement. As an example, patients with Becker dystrophy and Emery-Dreifuss muscular dystrophy can have severe cardiac disease but only mild muscular symptoms [1,2]. Cardiorespiratory dysfunction may be asymptomatic or underestimated because of impaired mobility, intellectual disability, and an inability to communicate. (See "Inherited syndromes associated with cardiac disease", section on 'Neuromuscular disorders'.)

●Central nervous system effects – Some myopathies are associated with encephalopathy, seizures, or developmental delay. Most patients with myopathies are sensitive to opioids and sedatives, compared with patients without these disorders.

●Gastrointestinal disorders, bulbar dysfunction, and malnutrition – Bulbar dysfunction is a common feature of muscle diseases and may result in dysphagia and recurrent aspiration. Gastroesophageal reflux and gastrointestinal dysmotility further increase the risk of aspiration [3,4].

Feeding difficulties coupled with an increased metabolic demand from respiratory and cardiac failure can lead to a poor nutritional state with some patients becoming cachectic [4,5]. Malnutrition may predict pulmonary complications after surgery in patients with neuromuscular disorders [6,7].

●Musculoskeletal effects – Myopathies may be associated with craniofacial abnormalities that can cause difficulty with airway management. Myopathy is also associated with progressive contractures, and joint or spine deformities, such as kyphosis or scoliosis. These deformities are a common indication for surgery and can create difficulty in performing regional anesthesia techniques and intraoperative positioning.

●Endocrine and metabolic dysfunction – The metabolic myopathies are a group of rare diseases that includes the mitochondrial disorders, disorders of glycogen metabolism, disorders of lipid metabolism, or other rare metabolic defects. Along with myopathy, there can be involvement of other systems and endocrine dysfunction, such as diabetes. Organ dysfunction can include encephalopathy, renal dysfunction, and hepatic dysfunction. There can be baseline metabolic derangement, such as lactic acidosis, and patients with metabolic myopathy may tolerate fasting poorly. Lactated intravenous (IV) fluids should be avoided [8,9], and continuous dextrose infusion may be required during fasting.

●Intercurrent illness – Childhood illnesses may be poorly tolerated by children with some myopathies. In particular, minor illnesses can cause metabolic decompensation in children with mitochondrial diseases [10]. We defer elective surgery for children with metabolic myopathy who have a current or recent acute illness, however minor.

PREANESTHESIA EVALUATION — Wherever possible, patients with myopathy should have preanesthesia consultation prior to the day of surgery. Our approach to preoperative evaluation for patients with myopathy is shown in a table (table 1).

A medical history and review of systems should be elicited, including the time course and severity of the myopathy, other organ system abnormalities, and review of patient medications. Evaluation always includes an anesthesia-directed physical examination, including airway assessment. (See "Preoperative evaluation for anesthesia for noncardiac surgery".)

Management decisions must be individualized and multidisciplinary, often after input from a neurologist or metabolic medicine specialist.

We agree with the American College of Chest Physicians recommendation that a preoperative nutritional assessment should be performed, nutrition should be optimized, and strategies should be employed to manage dysphagia for children with DMD [11]. This may require insertion of a gastrostomy tube and supplemental feeding prior to major surgery.

The preoperative visit is an opportunity to discuss specific anesthesia risks and the risk of prolonged ventilation or failure to extubate. Advanced care directives should be discussed if appropriate, including directives specific to the perioperative period. Clinical ethicists can be invaluable in complex cases [12]. (See "Preoperative evaluation for anesthesia for noncardiac surgery", section on 'Consent and decision making'.)

Preoperative testing — Preoperative testing for patients with myopathy should include the following (table 1):

●Cardiac testing – Recommendations for preoperative cardiac testing reflect the high incidence of cardiac disease in patients with myopathies. We agree with recommendations from the American College of Chest Physicians and the Anesthesia in Neuromuscular Disorders group that patients with muscle diseases should be evaluated by a cardiologist in anticipation of anesthesia [11,13]. This allows documentation of baseline function, optimization, planning for intraoperative monitoring and inotrope therapy, and postoperative management in intensive care.

Baseline preanesthesia testing should include an electrocardiogram and an echocardiogram if it has not been performed in the past year, or if there has been a change in cardiac symptoms since the last echocardiogram. Further testing may include a dobutamine stress echocardiogram and/or Holter monitor [14,15].

●Pulmonary testing – We perform preoperative pulmonary function testing for patients with myopathies, to predict preoperative risk of pulmonary complications [5], and to guide the use of perioperative noninvasive ventilation, particularly for major surgery (table 1). These issues are discussed separately [11] (see "Duchenne and Becker muscular dystrophy: Management and prognosis", section on 'Surgery and anesthesia'). We agree with recommendations from the American College of Chest Physicians consensus statement for respiratory care for patients with DMD that blood or end tidal carbon dioxide should be measured for patients with oxygen saturation <95 percent (table 2).

We screen all children for obstructive sleep apnea (OSA), and perform polysomnography for patients with myopathy who screen positive for OSA. Polysomnography can guide perioperative optimization and suggest the need for preoperative training in the use of noninvasive ventilation, and perioperative precautions to prevent worsened airway obstruction [4]. Evaluation of children for OSA is discussed separately. (See "Evaluation of suspected obstructive sleep apnea in children".)

●Laboratory testing – We perform a complete blood count and measure serum electrolytes, lactate, and creatine kinase (CK) before anesthesia for patients with myopathy. Other laboratory tests are performed as indicated by comorbidities.

ANESTHETIC MANAGEMENT — This section will focus primarily on anesthesia for patients with Duchenne muscular dystrophy (DMD), the most common pediatric myopathy. The general principles may be applicable to management of other more rare types of myopathy.

The literature regarding anesthetic management of patients with myopathies consists mostly of case reports and small case series. For many rare diseases, there is little or no literature on anesthetic management and insufficient literature on which to base recommendations for or against the use of specific anesthetic agents. There are several published consensus statements on anesthesia and perioperative care for patients with more common neuromuscular disorders, based on review of existing literature and primarily on expert opinion [10,11,13,16].

Premedication — Premedication should be administered judiciously and only when necessary. Sedatives should be titrated to effect. All children who receive sedative premedication should do so in a monitored environment. (See "General anesthesia in neonates and children: Agents and techniques", section on 'Prevention and treatment of preoperative anxiety'.)

Preparation for anesthesia — For patients who are at risk for malignant hyperthermia (MH) or anesthesia induced rhabdomyolysis (AIR), the anesthesia machine should be prepared to eliminate traces of inhalation agents. (See "Susceptibility to malignant hyperthermia: Evaluation and management", section on 'Equipment preparation' and 'Anesthesia-induced rhabdomyolysis and myopathy' below.)

Choice of anesthetic technique — The choice of anesthetic technique should be based on the surgical or diagnostic procedure and patient factors. Regional anesthesia avoids the need for airway management, reduces or eliminates the need for anesthetic and sedative medications, and reduces the need for postoperative opioid analgesics. Thus, regional anesthesia has distinct advantages and may be optimal in some children. Despite these advantages, in practice general anesthesia is often required for children, and for patients with cognitive or behavioral problems. Regional anesthesia is the exception rather than the norm for pediatric patients with myopathy.

Regional anesthesia — The decision to use regional anesthesia should be individualized. There is little available evidence to guide the use of regional anaesthesia in patients with primary muscle disorders. Prior to performing regional anesthesia, a thorough neurologic examination should be performed, with documentation of existing deficits. The risks and benefits of a regional technique must be considered and discussed with the patient and family or caregiver.

Regional anesthesia in children often requires the use of sedation; children with myopathy may require ventilatory support during regional anesthesia with sedation. The American College of Chest Physicians Consensus Statement on respiratory management of patients with DMD undergoing general anesthesia or sedation states that patients with a forced vital capacity (FVC) <50 percent of predicted, and especially those with FVC <30 percent predicted, are at risk for requiring assisted ventilation during procedural sedation, as well as during induction and recovery from general anesthesia [10].

Patients with mitochondrial myopathies may be at increased risk for local anesthetic systemic toxicity, which may be of concern if high volume or continuous regional anesthesia or analgesia techniques are used. (See "Local anesthetic systemic toxicity", section on 'Patient risk factors'.)

Regional anesthesia for muscle biopsy is discussed below. (See 'Regional anesthesia for muscle biopsy' below.)

General anesthesia

Monitoring — Standard anesthesia monitors are always employed during anesthesia (table 3). Advanced monitors (eg, invasive arterial blood pressure monitoring, transesophageal echocardiography) and central venous catheterization may be indicated based on the surgical procedure, expected blood loss, and patient comorbidities (see "Basic patient monitoring during anesthesia"). We use a processed electroencephalogram monitor to guide administration of intravenous (IV) anesthetics. (See "Accidental awareness during general anesthesia", section on 'Brain monitoring'.)

Choice of anesthetic agents — Children with certain myopathies may be at risk for MH, AIR, or possibly propofol infusion-like syndrome. The choice of anesthetic agents for induction and maintenance of anesthesia should be based on these patient specific risks, which are discussed here, as well as patient comorbidities, particularly cardiac status.

Patients with myopathy are more sensitive to the respiratory and cardiovascular depressant effects of anesthetic agents, sedative agents, and opioids. Thus doses should be reduced and when appropriate, titrated to effect. The physiologic effects of these agents are discussed separately. (See "General anesthesia: Intravenous induction agents" and "Inhalation anesthetic agents: Clinical effects and uses" and "General anesthesia in neonates and children: Agents and techniques", section on 'Intravenous induction medications'.)

Malignant hyperthermia and myopathy — Some muscle diseases are associated with susceptibility to malignant hyperthermia (MHS); association with MHS depends on the specific diagnosis and the underlying genetic defect, and is shown in a table (table 4). Testing, genetics, and management of MHS are discussed separately. (See "Susceptibility to malignant hyperthermia: Evaluation and management".)

Anesthesia-induced rhabdomyolysis and myopathy — Anesthesia-induced rhabdomyolysis (AIR) is a syndrome that involves skeletal muscle breakdown, resulting in release of myoglobin, elevated serum creatine kinase (CK), and potentially life-threatening hyperkalemia after exposure to succinylcholine or volatile anesthetic agents, primarily in patients with muscular dystrophy (MD).

●Pathogenesis – AIR is thought to occur as a result of muscle contraction in the presence of an unstable sarcolemma. The succinylcholine induced depolarization of muscle membranes is thought to cause membrane damage in susceptible patients, but the mechanism by which halogenated anesthetic agents precipitate this reaction is unclear [1]. AIR has been reported in patients with MD after administration of halogenated anesthetic agents without administration of succinylcholine [17-22], and does not appear to be dose-related. AIR has occurred after a brief exposure to volatile anesthetic (<10 minutes) for induction of anesthesia [23], and cardiac arrest has occurred in the recovery room [18-22], when remaining anesthetic concentrations are low. AIR can resemble MH, but is a distinct entity [24], and unlike MH, AIR is not associated with hypermetabolism [17].

●Incidence – The incidence of AIR in patients with myopathy is unknown. DMD and Becker muscular dystrophy (BMD) are the most common myopathies that have been associated with AIR. Patients with other muscular dystrophies caused by an abnormality in one of the many dystrophin-associated proteins are also at risk for AIR. Susceptibility to rhabdomyolysis may change with age; older children may have fewer remaining muscle fibers that are susceptible to breakdown [25]. This may explain why most reported cases of AIR were in preadolescent patients with DMD, or older patients with BMD, which progresses more slowly [26]. (See "Duchenne and Becker muscular dystrophy: Clinical features and diagnosis", section on 'Clinical phenotypes'.)

●Choice of anesthetic agents – Succinylcholine is contraindicated in patients with MD. The Food and Drug Administration (FDA) of the United States has issued a boxed warning for succinylcholine for children, except for emergency airway management, over concerns for acute rhabdomyolysis and hyperkalemia in children with undiagnosed muscular dystrophies [27].

Some expert recommendations have stopped short of declaring halogenated agents contraindicated in patients with MD [1,26,28,29]. Often the case series upon which recommendations are made include older children. There have been many case reports of death from AIR even after a brief (<10 minute) exposure to volatile anesthetic to secure IV access. This often occurs in younger pediatric patients (<8 years) who still have significant muscle bulk. Older patients with little remaining muscle mass may not be as susceptible to AIR, but the degree of risk cannot be predicted. Thus we avoid halogenated anesthetics in all patients with MD. If necessary, we sedate patients for IV catheter placement for induction.

We agree with experts who feel that the volatile anesthetics should be avoided for patients with DMD and BMD, and for patients with elevated CK as a result of other forms of MD [1,26,28,29]. Whereas AIR occurs in only a small minority of children with MD exposed to volatile anesthetics, this syndrome is life threatening and may be prevented by avoiding volatile agents. We prepare the anesthesia machine to remove traces of anesthetic gases, as for patients with known MHS, and avoid halogenated anesthetic agents, even for induction of anesthesia. (See 'Preparation for anesthesia' above.)

●Management of an AIR event – Anesthesia-induced rhabdomyolysis (AIR) can be acute, resulting in hyperkalemic cardiac arrest, or subacute with delayed myoglobinuria and elevated serum CK. If intraoperative AIR is suspected, all volatile anesthetics should be discontinued, and anesthesia equipment should be changed to a clean anesthetic circuit with charcoal filters or a clean anesthesia machine. Treatment includes cardiorespiratory support, rapid correction of hyperkalemia, volume resuscitation, and diuresis. Dantrolene is unlikely to help if MH has been ruled out. After an episode of AIR, patients should be monitored in an intensive care unit until stable.

Propofol and myopathies — Children with mitochondrial disorders may be more susceptible to adverse cardiac and metabolic effects of propofol than other children. All anesthetic agents, including volatile agents, barbiturates, ketamine, etomidate, benzodiazepines, and propofol, have been shown to affect mitochondrial function in vitro [30,31]. All of these drugs, including propofol [8,18], have been used safely in patients with mitochondrial disorders. However, propofol is of particular interest because it is often administered by infusion, with the possibility of high cumulative doses. Propofol at high doses can cause propofol infusion syndrome (PRIS) which may include acute refractory bradycardia, severe metabolic acidosis, cardiovascular collapse, and rhabdomyolysis. PRIS is thought to result from inhibition of mitochondrial enzymes in mitochondria and on mitochondrial membranes [32]. (See "Sedative-analgesia in ventilated adults: Medication properties, dose regimens, and adverse effects", section on 'Propofol-related infusion syndrome'.)

PRIS generally occurs in children who receive high doses of propofol (>4 mg/kg per hour) for prolonged periods (>48 hours). However, children with mitochondrial disorders may be more susceptible to PRIS, which may occur at lower doses and after shorter durations of infusion [10,18,29,33].

A safe threshold dose or duration of propofol administration cannot be predicted, given the large number of genotypes and expressed phenotypes of mitochondrial myopathies, although a single induction dose of propofol is probably safe. We suggest avoiding propofol for total IV anesthesia or prolonged sedation in patients with known mitochondrial disease [34].

Airway management — (See "Airway management for pediatric anesthesia" and "Management of the difficult airway for pediatric anesthesia".)

Neuromuscular blocking agents — Succinylcholine is contraindicated for all patients with myopathies, as it can cause life threatening hyperkalemia, and in susceptible patients, can trigger MH or AIR. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Adverse effects of succinylcholine'.)

Alternatives to succinylcholine for rapid sequence induction and intubation, or for short procedures that require muscle relaxation (eg, rocuronium followed by reversal with sugammadex) are discussed separately. (See "General anesthesia in neonates and children: Agents and techniques", section on 'Rapid sequence induction and intubation' and "Rapid sequence induction and intubation (RSII) for anesthesia", section on 'Alternatives to succinylcholine'.)

The response to nondepolarizing neuromuscular blocking agents (NMBAs) is unpredictable in patients with myopathies because of variable loss of muscle mass, and possible upregulation of acetylcholine receptors [35,36]. Thus, NMBAs should be avoided when possible, and if used, doses should be reduced and guided by quantitative train-of-four neuromuscular monitors. (See "Monitoring neuromuscular blockade".)

Opioid sparing analgesia — A multimodal opioid-sparing strategy for postoperative analgesia may begin in the preoperative period with administration of acetaminophen and other oral analgesics. The choice of nonopioid analgesics should be individualized based on patient factors, such as renal and hepatic function, and the risk of surgical bleeding if nonsteroidal antiinflammatory drugs are considered. Regional anesthesia or analgesia can reduce or eliminate the need for opioids. If opioids are required, reduced doses should be administered and doses should ideally be titrated to effect. (See "Pharmacologic management of acute perioperative pain in infants and children".)

Positioning for surgery — Positioning during surgery for patients with contractures may be challenging. Pressure points should be well padded to avoid nerve, skin, or tissue injuries. (See "Patient positioning for surgery and anesthesia in adults", section on 'General considerations'.)

Avoidance of hypothermia — Patients with myopathy are at increased risk of hypothermia. Active warming and temperature monitoring should be used in all but the very shortest procedures. (See "Perioperative temperature management".)

Emergence and extubation — We have a low threshold to delay extubation in patients who undergo prolonged surgery, have poor preoperative respiratory function (ie, FVC <30 percent of predicted), reduced cardiac function, sleep disordered breathing, or persistent oxygen desaturation or hypoventilation. In one retrospective review of patients who underwent spinal fusion for non-idiopathic scoliosis using delayed extubation criteria similar to ours, 6 of 15 patients with DMD required postoperative ventilation, and none of the patients who were extubated at the end of surgery required reintubation [37]. In this study, the anesthetic strategy included the use of ultrashort-acting anesthetics, medications to minimize blood loss, and epidural analgesia with regularly scheduled acetaminophen as well as IV morphine.

In patients with DMD with poor preoperative pulmonary function (ie, FVC <50 percent of predicted), extubation or removal of a supraglottic device directly to noninvasive positive pressure ventilation may prevent the need for delayed extubation [11], and may be facilitated by preoperative training in the use of the device. These issues are discussed in more detail separately. (See "Duchenne and Becker muscular dystrophy: Management and prognosis", section on 'Surgery and anesthesia'.)

POSTOPERATIVE CARE — Patients with myopathies often require intensive postoperative respiratory and cardiac monitoring, even after relatively minor surgery. In general, patients with myopathy are not candidates for ambulatory surgery for all but the most minor procedures. Patients with compromised pulmonary function (ie, forced vital capacity [FVC] <50 percent of predicted) may benefit from noninvasive ventilation during recovery from anesthesia. (See "Duchenne and Becker muscular dystrophy: Management and prognosis", section on 'Surgery and anesthesia'.)

Respiratory compromise is an important postoperative concern. The use of respiratory depressant drugs should be minimized. If opioid analgesia is required, respiratory monitoring should be instituted with invasive or noninvasive ventilatory support readily available. Patients who use noninvasive ventilation and/or cough assist devices at home should use them immediately postoperatively.

ANESTHESIA FOR DIAGNOSTIC MUSCLE BIOPSY — Anesthetic concerns for muscle biopsy are similar to those discussed above for patients with myopathy. Regional anesthesia is preferred when possible. The optimal choice of anesthetic agents for general anesthesia for diagnostic muscle biopsy depends on the most likely diagnosis, balancing the patient specific risk of malignant hyperthermia (MH) or anesthesia-induced rhabdomyolysis (AIR), if halogenated agents are used, against the risk of propofol infusion syndrome (PRIS)if propofol is used. The most difficult conundrum is the situation in which there is no likely diagnosis, and therefore the patient-specific risks of these complications is unknown. These patients often have multiple specimens taken at the time of biopsy. (See 'No clear suspected diagnosis' below.)

There may be anesthetic requirements related to the testing performed on the biopsy specimen, and also management decisions based on the end organ effects of the patient's underlying disease. (See 'Multiorgan system effects of myopathy' above.)

Open muscle biopsy is performed in most cases with a 1 to 2 cm incision in the quadriceps or deltoid muscle, or rarely with a percutaneous needle biopsy. Biopsy in vitro contracture testing requires a larger incision and specimen [38]. (See "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Muscle biopsy'.)

Likely diagnosis — Muscle biopsy may be performed for a variety of indications, including myopathic and neurodegenerative diseases. In most myopathic children, the diagnosis is uncertain, and the plan for anesthesia must be based partly on estimated risk of rare but potentially life threatening complications (ie, MH, AIR, metabolic decompensation), which are discussed above (see 'Choice of anesthetic agents' above). The anesthesia clinician should discuss the most likely diagnosis and the reason for the biopsy with the patient's neurologist or referring clinician. Consultation with an MH expert and/or a metabolic specialist may be required.

Requirements for processing of muscle biopsy specimens — The choice of anesthetic agents depends partly on the type of biopsy specimen, separate from the patient specific concerns.

●Standard anatomical muscle biopsy – There are no anesthetic requirements specific to the specimen if standard anatomical muscle biopsy is performed.

●Contracture test – For patients who undergo in vitro contracture testing for MH, a non-triggering anesthetic should be administered, both to avoid an MH episode and to avoid effects on the contracture test. (See "Susceptibility to malignant hyperthermia: Evaluation and management", section on 'Contracture test'.)

●Mitochondrial enzyme analysis biopsy – Some metabolic clinicians or pathologists request avoidance of propofol if biochemical and enzyme testing is to be performed. However, all anesthetics affect mitochondrial function in vitro, and can theoretically affect muscle enzyme assays [16,39-45], and there is no basis in the literature for avoiding propofol in particular.

Preanesthesia assessment — Preanesthesia assessment prior to muscle biopsy is similar to assessment described for all patients with myopathies. (See 'Preanesthesia evaluation' above.)

Choice of anesthetic technique for muscle biopsy

Regional anesthesia for muscle biopsy — For cooperative adults and older children, regional anesthesia with or without sedation can be used, though more often general anesthesia is required. In a single center review of 877 pediatric patients who underwent muscle biopsy for neuromuscular disorders, regional anesthesia (mostly spinal) was used in only 13 percent of patients [46]. In our institution, spinal anesthesia may be used for muscle biopsy in infants below 5 kg and in mature young adults. However, spinal anesthesia in infants under 5 kg is technically challenging, with a failure rate as high as 20 percent even in expert hands [47], and a back-up plan for general anesthesia is required.

In older children, local anesthetic infiltration can be used to provide anesthesia without direct infiltration at the site. In very small children the volumes of local anesthetic used may risk contaminating the specimen site. Local anesthesia cannot be used for contracture testing, which requires a larger sample, and local anesthetic infiltration around the muscle can interfere with the test. Infiltration at the surgical site can be performed after specimen collection to provide postoperative analgesia.

General anesthesia for muscle biopsy — For children and for patients with developmental disabilities, general anesthesia is usually required. The optimal choice of anesthetic agents for general anesthesia (volatile anesthetics versus propofol) for the undiagnosed child with myopathy is debated. (See 'Choice of anesthetic agents' above.)

Patients who undergo muscle biopsy may be divided into four groups according to the likely diagnosis, as follows:

Patients at risk for malignant hyperthermia — Patients who are suspected of having a congenital myopathy associated with malignant hyperthermia susceptibility (MHS) or who are scheduled for in vitro contracture testing to rule out MH should receive a non-triggering anesthetic (ie, avoid succinylcholine and volatile inhaled anesthetics, use anesthesia machine cleaned of inhalation agents). (See "Susceptibility to malignant hyperthermia: Evaluation and management", section on 'Management of anesthesia in malignant hyperthermia-susceptible patients'.)

Patients at risk for anesthesia-induced rhabdomyolysis — We suggest that patients with high preoperative creatine kinase (CK), or suspected of having Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or muscular dystrophy (MD) caused by an abnormality in one of the many dystrophin-associated proteins should receive a non-triggering anesthetic (ie, avoid succinylcholine and volatile inhaled anesthetics, anesthesia machine cleaned of inhalation agents). (See 'Anesthesia-induced rhabdomyolysis and myopathy' above.)

Metabolic myopathy suspected — Volatile anesthetics may be administered, anticipating increased sensitivity to these agents. We suggest avoiding propofol because of small, unquantifiable risk of propofol infusion-like syndrome. (See 'Propofol and myopathies' above.)

No clear suspected diagnosis — We suggest avoiding volatile inhaled anesthetics for this category of patients, and instead using intravenous (IV) anesthesia with or without nitrous oxide, if regional anesthesia is not appropriate. This approach is based upon the rationale that the risk of MH or AIR with inhaled anesthetics may be greater in susceptible patients than the unknown, likely very small risks associated with propofol in one category of patients (ie, patients with mitochondrial myopathy). The best estimate of the risk of MH or AIR comes from a retrospective study of 274 undiagnosed children who received volatile anesthetics during general anesthesia for muscle biopsy [48]. There were no cases of MH or rhabdomyolysis that were thought to be related to the anesthetic, and the estimated risk of MH or rhabdomyolysis was ≤1.09 percent (ie, the upper bound of the 95% CI for the result was 1.09). We believe that a risk of approximately 1 percent is too high for a potentially life-threatening event, and that these data support avoidance of volatile anesthetics in children with undiagnosed myopathy. If the pathologist or the referring clinician requests the exclusion of propofol, sedation with ketamine, remifentanil, nitrous oxide, midazolam, or dexmedetomidine, with or without regional anesthesia (eg, spinal, caudal, epidural, or regional nerve block) is a rarely used option. (See 'Regional anesthesia' above.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Mitochondrial disorders" and "Society guideline links: Malignant hyperthermia" and "Society guideline links: Muscular dystrophy" and "Society guideline links: Pediatric anesthesia".)

SUMMARY AND RECOMMENDATIONS

●Preoperative evaluation

•Myopathies are multiorgan system diseases with widespread implications for anesthesia. (See 'Multiorgan system effects of myopathy' above.)

•We perform the following preoperative testing for patients with myopathies, in addition to any testing indicated by comorbidities (table 1) (see 'Preoperative testing' above):

-Pulmonary function testing

-Electrocardiogram

-Echocardiogram if not performed in the past year

-Complete blood count, serum electrolytes, lactate, and creatine kinase (CK)

●Risks of anesthesia – Children with certain myopathies may be at risk for malignant hyperthermia (MH), anesthesia-induced rhabdomyolysis (AIR), or possibly propofol infusion-like syndrome (table 4). (See 'Choice of anesthetic agents' above.)

AIR is a syndrome that involves skeletal muscle breakdown and potentially life threatening hyperkalemia after exposure to succinylcholine or volatile anesthetic agents, primarily in patients with muscular dystrophy (MD). (See 'Anesthesia-induced rhabdomyolysis and myopathy' above.)

●Choice of anesthetic technique – Regional anesthesia may be a safer option for some children. (See 'Regional anesthesia' above and 'Regional anesthesia for muscle biopsy' above.)

●Anesthetic agents

•Patients at risk for MH – For general anesthesia in patients with a known or suspected congenital myopathy associated with MH, or for those who undergo muscle biopsy for caffeine contracture testing, volatile anesthetics should be avoided, and instead, intravenous (IV) anesthetics should be used with or without nitrous oxide. Succinylcholine should be avoided, and the anesthesia machine should be cleaned of volatile agents. (See 'Malignant hyperthermia and myopathy' above and 'Patients at risk for malignant hyperthermia' above.)

•Patients at risk for AIR – For general anesthesia in patients with known or suspected conditions associated with AIR (ie, MD, or with a high preoperative CK), we suggest avoiding volatile inhaled anesthetics, and instead using IV anesthesia with or without nitrous oxide. The anesthesia machine should be cleaned of volatile agents. (See 'Preparation for anesthesia' above and 'Anesthesia-induced rhabdomyolysis and myopathy' above and 'Patients at risk for anesthesia-induced rhabdomyolysis' above.)

•Patients with mitochondrial myopathy – For general anesthesia in patients with known or suspected mitochondrial myopathy, we suggest avoiding propofol beyond an induction dose, and instead using volatile inhalation anesthetics, anticipating increased sensitivity to these agents (Grade 2C). (See 'Metabolic myopathy suspected' above and 'Propofol and myopathies' above.)

●Neuromuscular blocking agents – Succinylcholine is contraindicated for any patient with myopathy. The response to nondepolarizing neuromuscular blocking agents (NMBAs) is unpredictable in patients with myopathy. Thus, NMBAs should be avoided when possible, and if used, doses should be reduced and guided by quantitative train-of-four neuromuscular monitors. (See 'Neuromuscular blocking agents' above.)

●Postoperative care – Patients with myopathy, particularly those with poor preoperative pulmonary function (ie, forced vital capacity [FVC] <30 percent of predicted), may require delayed extubation after general anesthesia, or extubation directly to noninvasive positive pressure ventilation. Patients with myopathies often require intensive postoperative respiratory and cardiac monitoring, even after relatively minor surgery. (See 'Emergence and extubation' above and 'Postoperative care' above.)

●Anesthesia for muscle biopsy

•For general anesthesia for muscle biopsy, the choice of anesthetic agents depends on the likely diagnosis, with concerns similar to those that apply to other surgical procedures for patients with myopathy. (See 'Choice of anesthetic agents' above.)

•For general anesthesia for muscle biopsy in patients without a clear suspected diagnosis we suggest avoiding volatile inhaled anesthetics, and instead using IV anesthesia with or without nitrous oxide (Grade 2C). (See 'No clear suspected diagnosis' above.)