Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a degenerative disease involving the corticospinal tract and anterior horn cells. Loss of motor function is progressive, with development of asymmetric weakness of the limbs (lower motor neurons are affected first), spasticity, and muscle atrophy. Death usually occurs within 3 to 5 years of diagnosis, although approximately 10% of patients may live more than 10 years.23 The etiology of ALS is unknown, but possible causes include viral or prion infection, glutamate excitotoxicity, free radical stress, autoimmune response, and heavy metal exposures and other undefined mechanisms.24
Involvement of the bulbar region typically manifests as respiratory and pharyngeal muscular insufficiency. Pulmonary function tests reveal a decrease in vital capacity, maximal voluntary ventilation, and diminished expiratory muscle function.25 Ventilatory support will be necessary as the disease progresses because respiratory failure eventually develops in all patients. Indeed, the cause of death in most patients with ALS, as in most patients with neuromuscular disorders, is respiratory failure. Autonomic dysfunction may be present in patients with ALS, as evidenced by resting tachycardia, orthostatic hypotension, and increased concentrations of catecholamines.
The antiglutamate drug riluzole is approved specifically for treatment of ALS. Riluzole has been demonstrated to prolong survival and delay the need for tracheostomy.26 Anticholinergic agents usually are administered to decrease secretions and facilitate swallowing, whereas dantrolene sodium and benzodiazepines are commonly administered to relieve muscle cramps and spasticity. However, these agents may exacerbate respiratory and skeletal muscle weakness. Anticholinesterase therapy may transiently improve muscle function and therefore is sometimes administered to these patients.
Ventilatory and upper airway muscle impairment significantly affects anesthetic management. Aspiration is an ongoing risk, and the need for postoperative ventilatory support is high because the already decreased respiratory reserve is reduced even further postoperatively. In ALS patients, the response to muscle relaxants, either depolarizing or nondepolarizing, is altered and may be compounded by perioperative administration of anticholinesterase medication. As with other patients with muscle denervation and muscle wasting, ALS patients are susceptible to succinylcholine-induced hyperkalemia and cardiovascular arrest.27 Therefore, whenever possible, depolarizing and long-acting nondepolarizing muscle relaxants should be avoided. Autonomic dysfunction may produce exaggerated decreases in cardiovascular function in response to anesthesia. No evidence indicates that any one specific anesthetic drug or anesthetic technique is best for patients with ALS. Neuraxial anesthesia has been safely used in patients and can be considered.28 Concern has been raised regarding neuraxial anesthesia and acute or subacute worsening of symptoms postoperatively, but no scientific evidence has been forthcoming. Multiple novel avenues of investigation are developing new treatments as mechanistic targets are being identified.29
Multiple sclerosis is a chronic disease of the central nervous system (CNS) that is characterized by a demyelinating process of the brain and spinal cord with unpredictable intervals of exacerbations and remissions. The cause of the disease is multifactorial, involving immunologic-mediated events occurring in susceptible individuals. Initially, a virus or other agent triggers an inflammatory response that initiates an autoimmune response to myelin. Plaques in the white matter of the CNS are the fundamental lesions. The ability of the CNS to repair itself during the early phases of the disease accounts for the relapsing nature of the disease. Unfortunately, there is no curative treatment.
The symptoms of multiple sclerosis depend on the site(s) of demyelination. The most common presenting symptoms are sensory losses and ocular disturbances. Limb weakness and paresthesias may occur as a result of demyelination of motor neurons and sensory pathways. The lower extremities are affected more than the upper extremities. Brainstem involvement may produce cranial nerve deficits and abnormal ventilatory drive. Hypotension may reflect the presence of autonomic nervous system involvement. Bowel and bladder irregularities are frequent complaints. The course of multiple sclerosis is characterized by exacerbation of symptoms at unpredictable intervals over a prolonged period. Eventually, residual symptoms persist and lead to progressive disability. However, 10% to 20% of patients have a relatively benign course and trivial disability.30 Interestingly, pregnancy is associated with an improvement in symptoms, but relapse occurs postpartum.31
The diagnosis is based primarily on clinical signs and symptoms. Laboratory confirmation of the diagnosis may be made by analysis of the cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI). The CSF typically reveals increased concentrations of albumin and immunoglobulin G. MRI can detect CNS and spinal cord involvement and can be used as a measure to determine the effectiveness of various treatment modalities.32,33
Therapeutic modalities are directed at modulating the immunologic and inflammatory responses that damage myelin. Corticosteroids and interferon are used most commonly. Glatiramer is a polypeptide mixture that mimics the structure of myelin and serves as a distraction for autoantibodies. Mitoxantrone can be used to treat aggressive disease; however, it is cardiotoxic. Dantrolene, baclofen, and benzodiazepines can be used to treat spasticity. Carbamazepine can be used to treat painful dysesthesias, seizures, and paroxysmal symptoms. Antidepressants and anticholinergic drugs can be given for depression and urinary incontinence, respectively. Other promising new therapies are currently under investigation but are not currently approved for routine clinical use.34 Avoidance of emotional stress, fatigue, and hyperthermia is essential. Indeed, a 0.5°C increase in temperature can block impulse conduction in demyelinated fibers, resulting in an exacerbation or relapse.35
Surgery may be required more frequently in patients with multiple sclerosis because of orthopedic, urologic, and neurologic issues. Unfortunately, the effects of surgery and anesthesia on the course of this disease are controversial. Both regional and general anesthesias have been reported to exacerbate multiple sclerosis.36 However, factors other than anesthesia, such as emotional stress and hyperpyrexia, may increase the risk of an exacerbation as well. The patient should be adequately informed that, despite a well-managed anesthetic, a relapse might occur perioperatively. Patients with multiple sclerosis should undergo a comprehensive, well-documented neurologic examination aimed at identifying any existing deficits before anesthetic management. After surgery, the neurologic examination should be repeated in order to correlate preoperative and postoperative findings. Although patients may reveal no new symptomatology immediately after anesthesia, new symptoms may become present subacutely in the postoperative period.
Spinal anesthesia has been associated with exacerbation of multiple sclerosis, although the mechanism is unclear.36 Speculation is that lesions may cause the breakdown of the blood–brain barrier, and, in demyelinated areas of the spinal cord, the CNS is more sensitive to the effects of the local anesthetic, causing a relative neurotoxicity. Indeed, higher concentrations of local anesthetics are more likely to cause a relapse than are lower concentrations of local anesthetics. Interestingly, epidural analgesia has been used safely and does not appear to increase the incidence of disease relapse.31,36 General anesthetics do not appear to have any significant intrinsic adverse effect.
Consideration must be given to the potential interactions of anesthetics with medications patients may be taking for their disease. Patients receiving corticosteroids may require stress doses in the perioperative period. Immunosuppressants may produce subclinical cardiac dysfunction. Anticonvulsants produce resistance to nondepolarizing muscle relaxants,37-39 whereas baclofen may increase the sensitivity to nondepolarizing agents. Patients with significant muscle denervation or atrophy theoretically have an increased risk of a hyperkalemic response to succinylcholine, so it should be avoided. The hypotensive effects of volatile anesthetics may be exaggerated by autonomic dysfunction, so patients with severe disease may require invasive monitoring, possibly including transesophageal echocardiography. Respiratory dysfunction, when present, increases the likelihood of the need for postoperative mechanical ventilation.
Guillain-Barré syndrome, the most common cause of acute flaccid paralysis, is an autoimmune inflammatory polyneuropathy of motor, sensory, autonomic, and cranial nerves. The syndrome is triggered by an immune response to either a viral or bacterial infection that produces antibodies to an antigen of the infectious agent. The antigen mimics an epitope of the Schwann cell, and affected axons undergo lymphocytic infiltration and demyelination. A respiratory or gastrointestinal infection 3 to 4 weeks earlier usually precedes the onset of this disorder. Usually, the disease evolves over the course of 3 to 4 weeks, with complete recovery eventually occurring in fewer than 80% of patients. Unfortunately, 3% to 10% of patients die, and up to 20% may be permanently disabled.40
The clinical course is characterized by an ascending, usually symmetric muscle weakness of the lower extremities that develops over several days, followed by gradual recovery. Paresthesias often precede weakness and paralysis. Difficulty swallowing and impaired ventilation may occur if bulbar and respiratory muscles are involved. Respiratory insufficiency often is characterized by decreased forced exhalation and impaired cough.41 Rapid shallow breathing indicates inspiratory muscle weakness and usually develops later in the disease. Vital capacity should be measured frequently. When vital capacity is less than 15 to 20 mL/kg, mechanical ventilation often is required.42 In addition, tracheostomy may be required for management of ventilatory failure and for bulbar muscle weakness even after ventilatory function returns to normal. Autonomic dysfunction may be severe, especially in patients experiencing respiratory failure and quadriparesis. Blood pressure lability, tachycardia, and cardiac conduction abnormalities may be present. Physical stimulation may precipitate hypertension, tachycardia, and cardiac dysrhythmias.43
Management is primarily supportive and directed at intensive respiratory care and treatment of autonomic dysfunction. Plasmapheresis and IV immunoglobulin may hasten recovery and may alleviate the harmful effects of the immune response. Corticosteroids and immunosuppressive therapy have not been demonstrated to be effective.19
Anesthetic management of the patient with Guillain-Barré syndrome often is dictated by the severity of respiratory and autonomic nervous system dysfunction. Compensatory cardiovascular responses may be absent. Hypotension secondary to hypovolemia, positional changes, and positive-pressure ventilation is possible. Severe autonomic dysfunction may produce exaggerated responses in heart rate and blood pressure; thus invasive monitors may be necessary, and direct-acting vasopressors and antihypertensives must be readily available.
Succinylcholine should be avoided because it can precipitate hyperkalemic arrest.44 Interestingly, this risk may persist for some time after recovery from the disease. Depending on the phase of the disease, the sensitivity of patients to nondepolarizing muscle relaxants may vary from extreme sensitivity to resistance.45 Mechanical ventilation should be anticipated postoperatively. Profound sensory disturbance may be present, and patients will need adequate pain control. Although the use of regional anesthesia is limited, the use of epidural opioids has been reported and appears beneficial to patients experiencing intense sensory disturbance.46 Systemic opioid use must be judicious and closely monitored because these patients may be more sensitive to respiratory weakness or depression secondary to their underlying disease.
Familial Dysautonomia (Riley-Day Syndrome)
Familial dysautonomia is an inherited disease thought to be caused by a deficiency of dopamine-hydroxylase with a subsequent decrease in the level of norepinephrine. Patients with this disorder exhibit impaired temperature regulation, denervation supersensitivity, insensitivity to pain, vasomotor instability, and copious pulmonary secretions.
Riley-Day syndrome has numerous anesthetic implications, including excess secretions, pneumonia, decreased responsiveness to hypoxia and hypercarbia, labile blood pressure, intravascular volume depletion, postural hypotension, decreased gag reflex, corneal abrasions, and emetic crisis.47 Preparation of the patient for surgery includes achieving adequate pulmonary function and correcting fluid and electrolyte imbalance. Opioids should be used sparingly because pain, hypercapnic, and hypoxic responses are blunted. Because of a risk for aspiration, a nonparticulate antacid can be given. Invasive monitoring may be necessary, and vasopressors should be titrated carefully using direct-acting agents as needed.47 Profound bradycardia and hemodynamic collapse may occur, and the anesthesiologist should be prepared for hemodynamic support and resuscitation.
Porphyrias are a group of inherited disorders of heme synthesis that result in overproduction and accumulation of porphyrin compounds because of a specific enzyme deficiency in the production of heme. Porphyrias are classified as acute (inducible) or nonacute (noninducible) on the basis of clinical presentation. Several reviews contain more detailed discussions of porphyrias.48,49
Acute porphyria may affect the CNS and peripheral nervous system via direct neuronal damage, axonal degeneration, and demyelination. Generally, clinical manifestations of acute attacks occur after puberty. Severe abdominal pain, nausea and vomiting, autonomic dysfunction, mental status changes, electrolyte abnormalities, and peripheral neuropathy ranging from paresis to flaccid quadriplegia characterize acute attacks. Death may occur from respiratory muscle paralysis. The cause of neurologic involvement is unknown but may be related to metabolites of heme intermediates or result from deficiency of the heme pigment in the nerve cell. Factors known to precipitate acute porphyric crisis include fasting, dehydration, infection, emotional stress, excessive ethanol intake, and administration of certain drugs.50 Nonacute porphyrias are not associated with neurologic disorders or acute crisis.
Because the porphyrias are rare disorders, experience with the clinical use of many drugs, particularly anesthetics, is limited. Pharmacologic therapy of acute attacks is aimed at decreasing the activity of aminolevulinic acid synthetase, the rate-limiting step in heme production. Hematin and heme arginate are potent suppressors of aminolevulinic acid synthetase and markedly decrease the pain associated with acute crisis within 48 hours.51,52 Hydration and correction of electrolyte imbalance, glucose infusion to prevent starvation, and propranolol to control autonomic dysfunction and aminolevulinic acid suppression are several mainstays of treatment. Avoidance of precipitating factors is the foundation of therapy in the latent period.
Commonly used anesthetics rarely precipitate an acute attack during latent porphyria.53 Numerous anesthetics have been implicated to exacerbate an acute attack of porphyria and should be avoided. Propofol, ketamine, local anesthetics, muscle relaxants, nitrous oxide, isoflurane, and opioids are considered safe (Table 12-2). Drugs that induce cytochrome enzyme production may trigger a crisis and should be avoided (eg, barbiturates, ethyl alcohol, etomidate, nonbarbiturate sedatives, hydantoin anticonvulsants, hydralazine, and glucocorticoids).50 Although regional anesthetic techniques have been described in porphyria, most experts advise against them because of a risk for exacerbating preexisting neuropathy, which could create confusion if neurologic signs develop postoperatively.54 Perioperative glucose infusion should be administered. Careful positioning is necessary to protect fragile blisters and skin during surgery.
Table 12-2 Safe Anesthetic Drugs in the Presence of Acute Porphyria
Charcot-Marie-Tooth disease is the most frequent inherited peripheral neuropathy. Typically, the defect is restricted to the lower third of the legs, causing foot deformities and peroneal muscle atrophy; however, the disease may slowly progress and affect other areas. Patients typically have stocking-glove sensory loss. Sensory deficits usually are milder than are the motor disturbances.55 Pregnancy has been associated with exacerbations.56 Despite long-term disability, life expectancy is not decreased, and treatment usually is supportive.
The effects of nondepolarizing neuromuscular blocking agents appear to be predictable. Although succinylcholine has been used without untoward consequences, it seems prudent to avoid using this neuromuscular blocker given theoretical concerns about hyperkalemia and cardiac arrest.57 Respiratory insufficiency, vocal cord paresis, and cardiac conduction disturbances have been described.58-60
Myasthenia gravis is an autoimmune disorder involving the neuromuscular junction. Antibodies develop and are directed against postsynaptic acetylcholine receptors and other muscle membrane proteins.61,62 The thymus is abnormal in 90% of patients with this disorder (ie, thymic hyperplasia, thymoma, or thymic atrophy).63,64 Autoimmune disorders such as thyroiditis, pernicious anemia, and systemic lupus erythematosus are common in patients with myasthenia gravis.
The hallmark of this disorder is skeletal muscle weakness that is aggravated by exercise and improves with rest. Exacerbations and remissions are common. Any skeletal muscle may be affected, but the most common clinical presentation is ocular muscle weakness. Bulbar involvement may cause difficulty swallowing and respiratory insufficiency. When peripheral muscle groups are involved, ambulation may be difficult. Interestingly, the first manifestation of myasthenia gravis may occur when a patient is administered drugs that stabilize the muscle membrane, such as magnesium sulfate or local anesthetics. Myasthenic crisis occurs in approximately 20% of patients during the course of the disease and usually is precipitated by pulmonary infections.64
The diagnosis of myasthenia gravis is suggested by complaints of muscle weakness, particularly ocular and bulbar muscles. In addition to clinical history, the edrophonium tests (or challenge), electromyography, and detection of circulating antiacetylcholine receptor antibodies may confirm the diagnosis. Surprisingly, the extent of the disease is not proportional to the receptor antibody titer.
Treatment aims to improve function by increasing the amount of acetylcholine available at the neuromuscular junction. Cholinesterase inhibitors effectively increase the concentration of acetylcholine available at the neuromuscular junction. Because of its long duration of action, pyridostigmine is the drug of choice. Consistent control of myasthenia gravis with cholinesterase inhibitors may be a challenge. Underdosing results in worsening of the disease, and overdosing may cause cholinergic crisis. Circulating acetylcholine receptor antibodies are reduced by plasmapheresis, immunosuppressants, and corticosteroids. Thymectomy is controversial, but improvement occurs in the majority of patients with myasthenia gravis, especially if performed early in the course of the disease.65
Myasthenic crisis is a rapid deterioration of neuromuscular and respiratory function that may occur at any time perioperatively as a result of infection, stress, or an overdose with anticholinesterase drugs (cholinergic crisis). Cholinergic crisis typically presents with respiratory and bulbar muscle weakness, excessive salivation, miosis, bradycardia, and abdominal cramps. The diagnosis usually is made after a small dose of edrophonium is administered and worsening of these symptoms is observed. Control of a cholinergic crisis is achieved with supportive measures and administration of atropine or glycopyrrolate.
Preoperative preparation includes assessment of pulmonary function and optimization of medical therapy. Preoperative plasmapheresis has been shown to decrease ICU stay and the need for mechanical ventilation after thymectomy.66 Risk factors that have been identified to predict postoperative respiratory failure after transsternal thymectomy are disease duration greater than 6 years, history of chronic respiratory disease, pyridostigmine dose greater than 750 mg/d, and preoperative vital capacity less than 2.9 L.66 Transcervical thymectomy carries a lower incidence of prolonged postoperative mechanical ventilation than does transsternal thymectomy.67 Whether anticholinesterase medication should be continued up to and including the day of surgery is controversial.68
Volatile anesthetics can be used as the sole anesthetic to provide analgesia, amnesia, and muscle relaxation.69 Muscle relaxants should generally be avoided in most patients with myasthenia gravis. Anticholinesterase therapy should antagonize nondepolarizing muscle relaxants in theory, but in practice, patients with myasthenia gravis may be up to 100 times more sensitive to nondepolarizing relaxants than are unaffected patients.70 Increased sensitivity remains in patients who are asymptomatic. The need for careful titration of nondepolarizing neuromuscular blockers via monitoring with a peripheral nerve stimulator in all patients with a history of myasthenia gravis is confirmed by these findings. Also, anticholinesterase therapy prolongs the response to succinylcholine by impairing plasma cholinesterase activity. Phase II block may be seen after administration of low doses of succinylcholine.71 The decrease in the number of acetylcholine receptors also resists the action of succinylcholine.
Adjuvant drugs such as aminoglycoside antibiotics, magnesium, corticosteroids, loop diuretics, lithium salts, quinidine, and procainamide may exacerbate muscle weakness in myasthenic patients. Central respiratory depression is common in myasthenic patients, and the respiratory depressant effects of opioids and benzodiazepines may be enhanced.72
Epidural analgesia and anesthesia have been used in myasthenic patients.73,74 However, caution is necessary because the muscle relaxation induced by regional anesthesia may accentuate the inherent weakness of myasthenia. Amide local anesthetics are theoretically a better choice than are the ester local anesthetics because cholinesterase activity does not affect amide anesthetic metabolism (see Chapter 45 for a discussion of the local anesthetic structures). Pregnancy has an unpredictable affect on myasthenia, and exacerbations should be anticipated.
Myasthenic Syndrome (Eaton-Lambert Syndrome)
Myasthenic syndrome (Eaton-Lambert syndrome) is an acquired autoimmune disorder of the neuromuscular junction, often associated with carcinomas, in which release of acetylcholine from the nerve terminal is impaired despite normal production and processing of acetylcholine by the nerve cell. Onset of this disorder, when present, often precedes discovery of the malignancy by several years. Antibodies are produced against calcium channels, specific to tumor cells, but unfortunately cross-reactivity with calcium channels at the neuromuscular junction results in a decreased release of acetylcholine. Proximal extremity weakness is common, with the bulbar musculature less likely to be involved. In contrast to myasthenia gravis, muscle weakness is not consistently reversed by anticholinesterase administration, and exercise tends to improve muscle function (Table 12-3). Diagnosis may be made with electromyography or antibody assay. 3,4-Diaminopyridine is commonly administered and increases the presynaptic release of acetylcholine. Treatment of an underlying neoplasm, if present, usually improves symptoms. Immunosuppression, plasmapheresis, and immunoglobulin may be effective.75
Table 12-3 Myasthenia Gravis and Myasthenic Syndrome ||Download (.pdf)
Table 12-3 Myasthenia Gravis and Myasthenic Syndrome
|Myasthenia Gravis||Myasthenic Syndrome|
|Extraocular, bulbar, facial muscle weakness||Proximal limb (arms > legs) weakness|
|Fatigue with exercise||Improved strength with exercise|
|Female > male||Male > female|
|Thymoma||Carcinoma (small cell of the lung)|
|Resistant to succinylcholine||Sensitive to succinylcholine|
|Sensitive to nondepolarizing muscle relaxants||Sensitive to nondepolarizing muscle relaxants|
|Good response to anticholinesterases||Poor response to anticholinesterases|
Anesthetic management should focus on interactions with muscle relaxants. Patients with myasthenic syndrome are hypersensitive to the effect of depolarizing and nondepolarizing muscle relaxants. Doses should be reduced and titrated to effect with a peripheral nerve stimulator. Administration of 3,4-diaminopyridine should be continued perioperatively.76
Myopathies and Channelopathies
Muscular dystrophies are disorders associated with abnormalities of the muscle membrane, resulting in variable, and progressive, loss of skeletal muscle function (Table 12-4). Dystrophin is a major component of the muscle cell cytoskeleton, which provides structural support to the muscle membrane in normal muscle. Lack of dystrophin results in membrane instability and permeability, eventually leading to intracellular calcium accumulation, cell necrosis, and replacement of degenerated muscle by fibrous and adipose tissue.77 In addition to skeletal muscle dysfunction, cardiac and smooth muscles are affected. Indeed, in many types of muscular dystrophy, cardiac muscle involvement may be more significant than skeletal muscle involvement.
Table 12-4 Types of Muscular Dystrophies and Myotonias ||Download (.pdf)
Table 12-4 Types of Muscular Dystrophies and Myotonias
Hyperkalemic periodic paralysis
Hypokalemic periodic paralysis
Proximal myotonic dystrophy
Duchenne muscular dystrophy is the most common muscular dystrophy (1:3500 male births) and has the most severe clinical course.78 This disorder is a recessive, sex-linked genetic abnormality that is clinically evident in males, although female carriers may manifest subclinical abnormalities. Duchenne muscular dystrophy is characterized by painless skeletal muscle degeneration and atrophy. Muscle degeneration and weakness usually manifest in early childhood (age 2-5 years). Severe limitation in movement with development of contractures and kyphoscoliosis confine the child to a wheelchair by early adolescence. Marked increases in serum creatine kinase levels are present. Death commonly results from congestive heart failure or pneumonia. Although aggressive therapy for cardiopulmonary dysfunction has improved survival, afflicted individuals rarely survive beyond the third decade of life.79,80
As the patient ages and the disease progresses, cardiac muscle involvement typically is reflected by a progressive loss of R-wave amplitude in the lateral precordial leads of the ECG. Cardiomyopathy, ventricular dysrhythmias, and mitral regurgitation may develop as cardiac muscle is progressively lost and fibrous tissue replaces myocardial and conducting tissue. Treatment options include administration of angiotensin-converting enzyme inhibitors and β-adrenergic blockers to slow the deterioration of cardiac function.80 Pulmonary function testing reveals a restrictive pulmonary disease pattern. Ineffective cough, resulting from diminished respiratory muscle strength, causes retention of secretions, pneumonia, and oftentimes death.81 Many patients and families choose a tracheostomy and assisted ventilation, which may add years of life, but repetitive pulmonary infection contributes to a shortened life span.82 Intestinal tract hypomotility develops as a result of smooth muscle involvement. Supplemental feedings may slow the process of cachexia, but the disease continues.
Although the cause of Duchenne muscular dystrophy is known, specific genetic therapy is elusive. Therapy is supportive and focuses on improving cardiopulmonary function and better nutrition.
Becker muscular dystrophy is similar to Duchenne muscular dystrophy; however, it has a later onset in life and slower clinical progression. Typically, patients remain ambulatory past the age of 16 years, and cardiac failure caused by occult cardiomyopathy may be the presenting symptom.83 Any male with a persistent elevation in serum creatine kinase concentration should be evaluated for Becker muscular dystrophy.
Emery-Dreifuss X-linked muscular dystrophy is characterized by humeropectoral muscle weakness and contractures of the spine, elbows, and ankles. The autosomal-dominant type of this disorder is caused by a defect in the protein lamin, whereas the recessive form is caused by a defect in the protein emerin. Clinical manifestations of skeletal muscle weakness usually are mild, but cardiac conduction defects may manifest as sudden death. Patients with this disorder are candidates for implantable defibrillating pacemakers.84
Limb-girdle muscular dystrophy patients have weakness of the muscles of the shoulder and pelvic girdles. Most forms of this disorder are inherited in an autosomal-recessive fashion, although autosomal-dominant defects have been discovered. A defect in the sarcoglycan protein is the usual etiology of this abnormality.85 Cardiomyopathy and cardiac conduction defects may occur.
Fascioscapulohumeral muscular dystrophy is a disease with diverse clinical manifestations that is inherited in an autosomal-dominant fashion. Facial, scapulohumeral, anterior tibial, and pelvic-girdle muscle weakness are common. Cardiac conduction defects as well as deafness and retinal vascular disease may occur.
Oculopharyngeal muscular dystrophy primarily manifests with ptosis and dysphagia late in adulthood. Commonly, weakness of the head and neck develop in addition to dysphagia that is present from pharyngeal muscle weakness and esophageal dysmotility.
Merosin-deficient muscular dystrophy, Fukuyama muscular dystrophy, Walker-Warburg syndrome, Ulrich disease, muscle–eye–brain disease, nemaline myopathy, myotubular myopathy, and rigid spine muscular dystrophy are a group of muscular dystrophies that comprise congenital muscular dystrophy.85,86 Congenital muscular dystrophies are characterized by early onset of muscle weakness, feeding difficulties, and respiratory dysfunction, frequently with accompanying mental retardation.
Perioperative complications from anesthesia in patients with muscular dystrophies usually result from the effects of anesthetic drugs on myocardial and skeletal muscle. Preexisting myocardial dysfunction makes the patient with muscular dystrophy susceptible to the myocardial depressant effects of anesthetics. The abnormal muscle cell membrane predisposes patients with muscular dystrophy to hyperkalemia and rhabdomyolysis when subjected to volatile anesthetics alone or in combination with succinylcholine, as numerous case reports support. In light of the abnormal muscle membrane, succinylcholine administration may further damage the muscle membrane and cause the release of intracellular contents. Therefore, succinylcholine should be avoided in patients with muscular dystrophies. It has been speculated that volatile anesthetics cause the release of calcium from the sarcoplasmic reticulum and may elicit damage to the muscle cell membrane and cause rhabdomyolysis. Interestingly, sevoflurane appears to be a less potent stimulus for release of calcium from the sarcoplasmic reticulum than are other volatile agents.87
Nondepolarizing muscle relaxants may have a prolonged duration of action in patients with muscular dystrophy, although the response to mivacurium appears to be normal.88 Therefore, close monitoring of neuromuscular function is indicated. Although unpredictable, some patients with muscular dystrophies may be susceptible to developing malignant hyperthermia (MH). Without regard to specific etiology, patients who have chronically increased creatine phosphokinase levels may have a 40% to 45% risk of being MH susceptible.89 Therefore, careful consideration of anesthetic plan may be to avoid all MH-triggering agents until a patient has been evaluated by the caffeine–halothane contracture test on a muscle biopsy specimen. (A detailed discussion of malignant hyperthermia is provided in Chapter 87.)
Delayed gastric emptying and impaired swallowing increase the risk of perioperative aspiration. Postoperatively, patients with muscular dystrophies must be closely monitored for evidence of pulmonary dysfunction and retained secretions. Vigorous pulmonary toilet and mechanical ventilation are frequently required. Regardless of the need for postoperative mechanical ventilation, these patients should be placed in an advanced monitoring unit (ICU) for appropriate analgesic therapy and respiratory monitoring.
The myotonias are a diverse group of hereditary skeletal muscle disorders with a common clinical sign: myotonia (Table 12-1). Myotonia is the persistent contracture and delayed relaxation of skeletal muscle after cessation of voluntary contraction or stimulation of the muscle. One of the typical signs of myotonic dystrophy is the inability to relax the handgrip. Progressive muscle wasting, ptosis, and facial muscle weakness also are common in patients with myotonic dystrophy. Interestingly, in other myotonic syndromes, the most common finding is stiffness that improves with exercise. However, paramyotonia (cold-induced myotonia) is an exception, wherein exercise exacerbates symptoms. Recently, genetic defects in sodium, chloride, and calcium ion channels in the muscle membrane have been identified as the abnormalities responsible for myotonia. Therefore, drugs such as mexiletine, procainamide, tocainide, and quinine may relax myotonic contractures by altering ion channel activity and skeletal muscle membrane excitability.
The most common of the myotonic disorders is myotonic dystrophy (Steinert disease), although proximal myotonic myopathy, myotonic dystrophy type II, and proximal myotonic dystrophy are other myotonic diseases. Myotonic dystrophy is inherited in an autosomal-dominant pattern, and symptoms typically appear in the second or third decade of life. A defect on chromosome 19 produces a decrease in protein kinase that causes degeneration of the sarcoplasmic reticulum.90 This myotonic dystrophy is the only myotonic disorder to exhibit extramuscular manifestations. Cataracts, premature balding, diabetes mellitus, thyroid dysfunction, adrenal insufficiency, gonadal dysfunction, and cardiac conduction defects are common. Cardiac involvement does not correlate with the severity of skeletal muscle involvement.91 There is a progressive deterioration of the conduction system resulting in atrioventricular conduction delay. First-degree atrioventricular block, bundle-branch block, and widening of the QRS complex are common. Cardiomyopathy, cardiac failure, and sudden death may occur, and the incidences of septal defects, mitral valve prolapse, and valvular disease are increased.
Recurrent pulmonary infections and aspiration may result when bulbar musculature is affected. Pulmonary function testing demonstrates a restrictive lung disease pattern, mild arterial hypoxemia, and diminished ventilatory responses to hypercapnia and hypoxia. Gastric atony may develop as a result of alterations in smooth muscle function. Exacerbations of myotonic dystrophy often occur during pregnancy as a result of increased concentrations of progesterone. Congestive heart failure is common during pregnancy, and cesarean delivery is indicated because of uterine smooth muscle involvement. Labor typically is prolonged, and the incidence of postpartum hemorrhage is increased. Infants may have congenital myotonic dystrophy, which typically is characterized by hypotonia, respiratory insufficiency, and feeding difficulties.
Therapy for myotonic dystrophy is focused on treating coexisting diseases and cardiac dysrhythmias. Drugs that alter sodium channel function have been the most effective for managing myotonia (eg, mexiletine). Avoiding factors known to precipitate myotonia is important.
Anesthetic considerations for patients with myotonic dystrophy include the presence of coexisting diseases, abnormal responses to drugs, and avoiding factors that are associated with the development of perioperative myotonia. Perioperative myotonia has been precipitated by drugs (propofol and succinylcholine), physical factors (hypothermia), electrocautery, and surgical manipulation. Potassium administration worsens clinical myotonia. Succinylcholine produces an exaggerated contracture, and its use should be avoided. The myotonic response produced by succinylcholine may be so severe that ventilation and tracheal intubation are difficult and may be impossible. The typical presentation of succinylcholine-induced myotonic contracture includes jaw, abdominal, and chest rigidity. Perioperative myotonia may be difficult to differentiate from MH. A recent thorough review of the pathophysiology and clinical experience related to the myotonias concluded that MH is no more common in these patients than in the general population, despite the frequent suggestion of such a relationship (a minor theoretical concern remained for hypokalemic periodic paralysis, but no clinical episodes of MH have been reported in these patients).92 Nondepolarizing muscle relaxants and peripheral nerve blocks do not abolish myotonic contractures. Induction agents, volatile anesthetics, opioids (systemic and neuraxial), and sedatives may cause profound respiratory depression. Increased sensitivity to nondepolarizing muscle relaxants may occur, especially when there is muscle wasting. Prudence dictates the use of short-acting muscle relaxants when necessary, with careful monitoring of the response. Peripheral nerve stimulation may cause myotonia or be misinterpreted as sustained tetanus, even though significant neuromuscular blockade exists. Reversal of neuromuscular blockade may induce myotonia.
Although no specific anesthetic technique has been determined to be superior for patients with myotonic dystrophy, close monitoring of cardiac and pulmonary function is critical to ensure an optimal perioperative outcome. Mechanical ventilation should be used until muscle strength and function return to baseline.93 Regional anesthesia has been successfully performed in patients with myotonic dystrophy.94
Familial Periodic Paralysis
Periodic paralyses are skeletal muscle channelopathies, which include hyperkalemic and hypokalemic periodic paralysis, paramyotonia congenita, and potassium-aggravated myotonia.95-97 Periodic paralyses are characterized by acute reversible episodes of muscle weakness or paralysis of the extremities, with sparing of the respiratory muscles. Although these disorders are classified by changes in serum potassium concentrations during an acute episode, these changes are relative to the baseline potassium concentration and are not always abnormally increased or decreased (Table 12-5).
Table 12-5 Clinical Features of Hypokalemic and Hyperkalemic Familial Periodic Paralysis ||Download (.pdf)
Table 12-5 Clinical Features of Hypokalemic and Hyperkalemic Familial Periodic Paralysis
Potassium concentration >5.5 mEq/L (or normal) during crisis
- Potassium infusion
- Rest after strenuous exercise
- Metabolic acidosis
Duration of paralysis
- Minutes to hours (rarely a few days)
Potassium concentration <3 mEq/L during crisis
- High glucose intake
- Strenuous exercise
- Stress (including trauma or surgery)
- Glucose-insulin infusion
Duration of paralysis
Hyperkalemic periodic paralysis is inherited in an autosomal-dominant fashion. The dominant trait has been discovered as a mutation in the sodium ion channel on chromosome 17.90 As a consequence of this dysfunction, when the resting membrane potential becomes slightly more positive, the myofiber can more easily reach threshold and the muscle becomes hyperexcitable, which clinically manifests as myotonia.98 When the membrane potential becomes even more positive, the myofiber cannot fire an action potential because of the loss of a sufficient membrane potential, and the result is paralysis.98 Normokalemic periodic paralysis is rare and most likely is a variant of hyperkalemic paralysis in which the potassium concentration does not change during attacks.99
Attacks usually begin during childhood and vary in frequency from several times per week to once in a lifetime. These episodes of myotonia and paralysis may last several hours after exposure to a trigger. Triggering events include eating potassium-rich foods, IV infusion of potassium, fasting, cold exposure, and rest after strenuous exercise. Thiazide diuretics, acetazolamide and a low-potassium diet are the mainstays of preventive treatment. Glucose and insulin infusion, careful catecholamine infusions, and IV calcium administration can be used to manage acute attacks.
Hypokalemic periodic paralysis is usually inherited in an autosomal-dominant pattern. The dominant trait produces a defect in the calcium ion channel on chromosome 1.100 The dihydropyridine receptor is a voltage-gated ion channel that is responsible for attacks, but the mechanism by which this defect results in attacks of paralysis is under investigation.
Attacks usually begin during childhood or early adulthood and vary in frequency. In contrast to the hyperkalemic form, attacks last longer—from hours to days. Also, cardiac arrhythmias are more common, ventricular dilatation may be seen, myotonia is absent, and permanent muscle weakness eventually develops by the fifth decade of life. Paralysis is commonly triggered by ingestion of carbohydrates, strenuous exercise, glucose and insulin infusion, IV calcium, and exposure to cold. Paralysis often is incomplete, affecting the limbs and trunk but sparing the diaphragm. Rarely are respiratory muscles involved, but asphyxia has been reported. Treatment involves the administration of potassium, acetazolamide, and dichlorphenamide.
Maintenance of normal potassium concentrations and avoidance of events that precipitate weakness are the primary goals of the perioperative management of patients with hyperkalemic and hypokalemic periodic paralysis. Electrolyte abnormalities should be addressed and corrected as best as possible before surgery. Patients may be sensitive to nondepolarizing muscle relaxants; therefore, short-acting relaxants should be administered when necessary. The response should be monitored with a peripheral nerve stimulator. Reversal should be avoided because of concern that reversal agents may precipitate myotonia. However, adequate muscle strength must be assured before extubation.101 Succinylcholine should be avoided because it alters serum potassium concentrations and therefore may precipitate an attack. Reductions in serum potassium from metabolic changes or medications should be avoided because this situation may initiate an episode of paralysis. Perioperative potassium values should be monitored serially. The ECG should be continuously monitored for evidence of arrhythmia, and normothermia and normocapnia should be maintained. Volatile anesthetics have been administered without complication. Regional anesthesia has been used successfully, although there is concern that regional techniques can create confusion if neurologic signs develop postoperatively.102 MH has been associated with periodic paralyses.103
Central core disease is a hereditary, nonprogressive, congenital myopathy that typically is characterized by lower extremity muscle weakness. Increased lumbar lordosis, kyphoscoliosis, and hip dislocations may occur. Histologically, type I muscle fibers display amorphous central areas (cores). The underlying defect is thought to be associated with the ryanodine receptor gene, similar to MH.104 Susceptibility for MH is a great concern when anesthetizing patients with central core disease.105,106 MH precautions should be taken and nontriggering anesthetics used when anesthetizing patients with central core disease (see Chapter 87 for a thorough discussion of malignant hyperthermia).
Glycogen Storage Diseases
Glycogen storage diseases are inherited disorders characterized by a deficiency of enzymes involved in glucose metabolism. An enzyme deficiency results in a lack or excess of precursors and end-products of glycogen formation and breakdown. Type II (Pompe disease) glycogen storage disease is notable for the buildup of glycogen in smooth, skeletal, and cardiac muscle. Cardiac involvement typically leads to congestive heart failure. Anesthetic experience is limited.107,108 Skeletal muscle involvement predisposes patients to upper airway obstruction secondary to glycogen infiltration of the tongue. Aspiration is common secondary to neurologic involvement and subsequent impairment of cough, gag, and swallowing mechanisms. Volatile anesthetics may precipitate cardiovascular embarrassment or collapse. Administration of succinylcholine to these patients may not be prudent because theoretically it could result in myoglobinuria and perhaps hyperkalemia with subsequent cardiac arrest. Hypoglycemia and acidosis may develop perioperatively, and patients should be hydrated and receive exogenous glucose. Hepatic dysfunction usually is present, so judicious administration of drugs hepatically metabolized should be taken into consideration. Regional anesthesia has been performed in patients with glycogen storage disorders.109 Patients with type V (McArdle disease) glycogen storage disease are prone to developing myoglobinuria and rhabdomyolysis. Automated blood pressure readings should be performed cautiously, and tourniquets should be avoided to prevent muscle damage.110
Mitochondrial myopathies are a group of disorders that affect oxidative phosphorylation, resulting in impaired adenosine triphosphate production. These disorders have many manifestations, including CNS and muscle pathology. Exercise intolerance, fatigue, muscle pain, progressive weakness, and cardiomyopathy may be present. Respiratory depression is common after administration of general anesthesia. There does not appear to be an association with MH with most mitochondrial disorders.111-114 However, avoidance of succinylcholine seems prudent because of the potential for hyperkalemia.
Kearns-Sayre syndrome and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) are distinct mitochondrial disorders. The anesthetic concerns are similar to the general concerns previously stated, but, in addition, Kearns-Sayre syndrome is associated with heart block due to involvement of the cardiac conduction system. General anesthesia should be used with caution because it may increase the risk of myocardial depression and cardiac conduction defects.115 MELAS syndrome is characterized by stroke-like episodes, seizures, dementia, recurrent headaches, vomiting, and lactic acidosis. There is suspicion that MH susceptibility may be increased, and propofol-based anesthesia has been used successfully. Myocardial depression may occur with administration of volatile anesthetics, so they therefore should be used with caution. Additional precautions include maintenance of normothermia, avoidance of lactated solutions or acidosis, and careful attention to blood glucose control. A full discussion of this unusual syndrome is beyond the scope of this chapter, but a recent case report contains a useful review of overall anesthetic considerations.116