Chapter 59. Regional Anesthesia in the Patient with Preexisting Neurologic Disease

Patients with preexisting neurologic disease present a unique challenge to the anesthesiologist. Knowledge of the pathophysiology of the disease and the effect of anesthetic drug therapy on the disease process is essential for the safe management of anesthesia for these patients. Both active and dormant neurologic diseases may worsen in the perioperative period, independent of the chosen anesthetic method. However when regional techniques are used, the cause of postoperative neurologic deficits may be difficult to evaluate as neural injury can be related to a wide variety of reasons, ie, surgical trauma, tourniquet pressure, improper positioning, or anesthetic technique.1 The possibility of needle-induced trauma, local anesthetic toxicity, or neural tissue ischemia or damage during regional anesthesia has led many anesthesiologists to avoid regional techniques in patients with underlying neurologic diseases.

Many of these patients can benefit from regional techniques. Greater autonomic stability, the ability to provide selective anesthesia and analgesia, greater hemodynamic stability (especially with peripheral nerve block anesthesia in patients with concurrent cardiomyopathy), and the avoidance of side effects related to general anesthetics and opioids are a few of the advantages.2,3 Careful preoperative neurologic evaluation, evaluation of the risk/benefit ratio, and a comprehensive discussion with the patient about the anesthetic plan and the possibility of worsening neurologic signs and symptoms unrelated to the anesthetic technique is important for successful implementation of regional techniques in this patient population.

Although perioperative nerve injuries have been well recognized as a complication of spinal and epidural anesthesia, severe or disabling neurologic complications occur relatively rarely. In 1999, Cheney and colleagues examined the American Society of Anesthesiologists Closed Claims database to determine what percentage of the claims were related to nerve damage in malpractice cases.4 Of the 4183 claims reviewed, 670 (16%) were anesthesia-related nerve injuries. Ulnar neuropathies were the most frequently reported, followed by other injuries to the brachial plexus, lumbosacral nerve roots, and spinal cord. The injuries were bilateral in 14% of the ulnar injuries and in 12% of the brachial plexus injuries. The important factor in this analysis is that the incidence of ulnar and brachial plexus injuries was greater with general anesthesia than with regional anesthesia.5,6 Horlocker and coworkers examined the cause of perioperative nerve injury in a review of 607 patients undergoing 1614 axillary blocks for upper extremity surgery. Various surgical variables (direct trauma, stretch, hematoma, vascular compromise, case or tourniquet ischemia) were thought to be the cause of neurologic complications in the majority of the cases (89%).7

In the Closed Claims Analysis 189 (4%) involved either the lumbosacral root or the spinal cord. Injuries to these areas were more frequently associated with regional anesthesia. The lumbosacral root injuries were thought to be related to paresthesias during needle or catheter placement or pain on injection of local anesthetic. The spinal cord injuries were related to blocks for chronic pain or neuraxial blocks on patients receiving systemic anticoagulation. These injuries were not related to the presence of preexisting neurologic disease. In another review of over 50,000 spinal and epidural anesthetics, the incidence of persistent peripheral neuropathy, including paresthesia and sensory or motor dysfunction ranged from 0% to 0.16% for spinal anesthetics and 0% to 0.06% for epidural anesthetics, still appreciably lower than the incidence of nerve injuries reported with general anesthetic cases.8–11

Although the reported incidence of nerve injuries with regional anesthesia is very low, the use of regional techniques in patients with preexisting neuropathies is often considered controversial. The possibility of needle- or catheter-induced nerve trauma, neural ischemia, or local anesthetic toxicity placing the patient with an underlying neurologic deficit at greater risk has limited the use of regional techniques in this patient population. In a retrospective study of over 300 patients with preexisting ulnar neuropathy undergoing ulnar nerve transposition, it was demonstrated that anesthetic technique did not affect neurologic outcome in the immediate postoperative period or up to 6 weeks after surgery.6 The authors did not find any evidence that the use of a peripheral nerve block increased the risk of new or worsening neurologic symptoms in patients with preexisting ulnar nerve neuropathy. They concluded that regional anesthesia is as safe as general anesthesia in these patients with mononeuropathy.

In patients with other serious neurologic diseases, regional anesthesia is often avoided for a variety of reasons, including lack of understanding of the disease process, the risk of unknown or unpredicted effects of local anesthetics in abnormal nervous tissue, concerns regarding possibly worsening preexisting symptoms, limited experience using regional techniques, and limited data to support its utilization.

The following paragraphs discuss many of the neurologic conditions the anesthesiologist may encounter. The approach to the management of anesthesia is included with a discussion of various regional techniques that can be safely used in these patients. When information in the literature is sparse, suggestions for anesthetic techniques are included based on available neurologic research, case reports, and experience of clinicians in institutions performing large volume regional anesthesia techniques.

Degenerative Diseases

Parkinson's Disease

Parkinson's disease is a disabling neurologic disease affecting 3% of the population older than age 65 years. The peak onset is in the sixth decade, but the disease can begin to manifest from age 20 to age 80 with the male to female ratio of 3:2. Parkinson's disease is caused by loss of dopamine-containing nerve cells in the substantia nigra.13 The presence of Lewy bodies, eosinophilic cytoplasmic inclusions in pigmented neurons, are a characteristic feature. The cause of the disease is unknown although multiple theories have been proposed, including a defect in the gene for α-synuclein, mitochondrial dysfunction, excitotoxicity secondary to persistent activation of N-methyl-d-aspartate (NMDA) receptors, and oxidative stress secondary to catabolism of dopamine.12,13

Four clinical features are characteristic of Parkinson's disease: rigidity “cogwheel,” bradykinesia, resting tremor, and postural instability.

These patients may have depression and dysautonomia. Patients with Parkinson's disease may suffer from orthostatic hypotension and urinary dysfunction. Clinical assessment should include an evaluation of these systems to identify potential problems. Measurements of blood pressure in the lying and standing position should be obtained to assess the degree of autonomic dysfunction as evidenced by orthostatic hypotension.

Treatment is directed at increasing dopamine levels in the brain.12 The mainstay of treatment is levodopa or dopamine receptor agonists. Monoamine oxide inhibitors are used to prolong the action of dopamine in the striatum. Catechol-O-methyl transferase (COMT) inhibitors are used to inhibit the breakdown of dopamine in the periphery and increase its bioavailability. Anticholinergics are effective in treating tremor, but because of many side effects (worsening dementia, psychosis, dry mouth, constipation), they are reserved for younger patients in the early phase of disease.

Anesthetic Considerations

Patients with Parkinson disease most commonly present for urologic, ophthalmologic, or orthopedic procedures. In addition to the routine history, physical examination, and preoperative testing, assessment of systems specifically affected by Parkinson disease should be evaluated. See Table 59–1 for specific systems affected.

Regional Anesthesia in Parkinson's Disease

Autonomic dysfunction is exacerbated by inhalational anesthetics, resulting in more hemodynamic instability.14 Halothane, although less commonly used today, sensitizes the heart to catecholamines and should be avoided in patients on levodopa.14 Isoflurane and sevoflurane are less arrhythmogenic; however, hypotension from catecholamine depletion, autonomic dysfunction, and the coadministration of other medications remains a concern.14 Muscle relaxants and positive pressure ventilation can lead to prolonged postoperative ventilatory support in a patient with respiratory impairment, common in the Parkinson patient.15 There are numerous reports of opioid-induced muscle rigidity in patients with an established diagnosis of Parkinson's disease.15 Postoperative nausea and vomiting related to opioids, reversal agents, and inhalation anesthetics may be more common.17 Patients with Parkinson's disease are more prone to postoperative confusion and hallucinations.17

Regional anesthesia may have advantages over general anesthesia as the effects of inhalation anesthetics, muscle relaxants, high-dose opioids, and anesthetic medications that may exacerbate the symptoms of Parkinson's disease are eliminated. By utilizing peripheral nerve block anesthesia or appropriate segmental epidural anesthesia with limited sedation, the autonomic instability can be controlled, the incidence of nausea and vomiting limited, and muscle rigidity resulting from doses of narcotics used for general anesthesia can be avoided. Careful titration of sedation with limited use of opioids is suggested in this patient population.

Alzheimer's Disease

Alzheimer's disease is the major cause of dementia in the United States.16 If affects 10% of people older than age 65 with the female to male ratio of 2:1. Risk factors include female sex, advanced age, family history, Down syndrome, and African American or Hispanic descent. Patients with a history of brain trauma may have an increased risk of developing the disease.16

The cause is unknown. Pathologic changes in the brain include the accumulation of tau protein with formation of neurofibrillary tangles, deposition of β-amyloid with formation of neuritic plaques, and selective loss of cholinergic neurons, leading to cortical atrophy. It is theorized that these changes may arise as a result of excitotoxicity involving the NMDA receptor. Current drug therapy is directed at increasing the levels of acetylcholine, cholinesterase inhibition, cholinergic receptor stimulation, and blocking NMDA receptors with the intent of reducing excitotoxicity.16

The clinical features of the patient with Alzheimer's disease are a gradual decline of intellectual function, progressive loss of short-term memory, disorientation, language and speech problems, and seizures in 10% of the patients. Paranoid delusions with hallucinations and personality changes are common.16

Anesthetic Considerations

The choice of anesthetic technique for patients with Alzheimer's disease should be guided by the patient's general physiologic condition, the degree of neurologic deterioration, and the potential for drug interactions between the anesthetics and the patient's treatment. Detection of early symptoms may be difficult. Administration of sedatives or anticholinergics could precipitate delirium. Inhalation agents must be administered with care as the elderly patient is more sensitive to the depressant cerebral and cardiovascular effects of these agents.17 Anesthetics with short durations of action and rapid recovery are advantageous.

Regional Anesthesia in Alzheimer Disease

Regional anesthesia can be a challenge because these patients are often uncooperative preoperatively. The advantage of regional techniques is the ability to selectively anesthetize the area of interest without subjecting the patient to systemic effects of general anesthetic agents. For block placement, a short-acting sedative/hypnotic, such as propofol or midazolam, at a low dose is effective. Depending on the type of block, a short-acting narcotic (eg, alfentanil) may be administered just before the block placement. Avoiding postoperative confusion and delirium caused by inhalation agents, narcotics, muscle relaxants, and reversal agents may be beneficial to this patient population.17 Postoperative pain control without narcotics may be an even greater benefit of peripheral nerve blocks. Educating the staff and the caregivers about protection of the insensate extremity, requiring assistance with mobilization, and the duration of the block is a necessary part of the anesthetic management. Although these patients can be challenging to treat without general anesthesia, they can benefit from regional techniques.

Amyotrophic Lateral Sclerosis (Lou Gehrig Disease)

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease of motor cells throughout the central nervous system (CNS). It involves destruction of cortical, brainstem, and spinal motor neurons. Progression of the disease is relentless. Death occurs within 3 to 5 years of the diagnosis, most commonly precipitated by aspiration. The onset is usually after the age of 50 with a male to female ration of 2:1. The cause is unknown, but theories include glutamate excitotoxicity, oxidative stress, mitochondrial dysfunction, paraneoplastic tumors, autoimmune disease, and viral infection.18 The prevalence of the disease is 6:100,000, making it a rare but profound disease.

Initially, the disease presents as atrophy, weakness, and fasciculations in the intrinsic hand muscles. As the disease progresses, atrophy and weakness develop in all skeletal muscles including those of the tongue, pharynx, larynx, and respiratory muscles of the chest. Patients lose the ability to cough, increasing the risk of aspiration. Eventually, respiratory failure ensues, requiring mechanical ventilation. Autonomic dysfunction may be evident and is manifested by orthostatic hypotension and an increased resting heart rate. The cause of death is usually related to respiratory failure.18

Anesthetic Considerations

Patients with ALS present a challenge to the anesthesiologist. Neuromuscular transmission is markedly abnormal leading to the up-regulation of nicotinic acetylcholine receptors (nAChRs).19 The up-regulation makes these patients vulnerable to hyperkalemia in response to succinylcholine.20 They have presynaptic impairment of neuromuscular transmission, making them hypersensitive to nondepolarizing muscle relaxants.21 If general anesthesia is used, intubation with a deep inhalation agent without the administration of muscle relaxants is recommended.22 As the disease progresses, respiratory muscles weaken, placing these patients at high risk for respiratory depression and aspiration. They can be exquisitely sensitive to sedatives and anesthetic drugs. Postoperative ventilatory support after general anesthesia is usually necessary.23

Regional Anesthesia in ALS

Regional anesthesia has been used on patients with ALS. There have been several case reports of successful epidural anesthesia for abdominal surgeries, ie, hysterectomy, bowel obstruction, and orthopedic procedures.24–26 Case studies and reports of the use of peripheral nerve blocks in patients with ALS are not available, probably because the condition is so rare. Given the importance of preserving the laryngeal reflexes and respiratory failure due to the weakness of the respiratory muscles, the judicious use of selective peripheral nerve blocks may be beneficial for these patients. In patients with advanced weakness of the respiratory muscles, interscalene nerve block should be used with caution due to the resultant diaphragmatic paralysis.

Spinal Cord Injury

Spinal cord injury after trauma affects over 10,000 Americans each year. Of these, approximately one half occur at the cervical level. Complete neurologic deficit occurs in about 3500 patients per year, and partial deficits in another 4500 patients per year.27 The majority of the injuries are secondary to blunt trauma, with a smaller percentage the result of penetrating injuries. Advances in the care of patients with acute spinal cord injury have reduced the mortality rate to less than 7% per year.28

The clinical presentation varies depending on the chronicity, the magnitude, and the level of the injury. Acutely, the patient appears flaccid with spinal shock. Hypotension, bradycardia, dysrhythmias, hypoxemia, and alveolar hypoventilation are common presenting symptoms. There is high risk of aspiration. When the injury becomes chronic, as manifested by the return of spinal reflexes, multiple complications arise including involuntary skeletal muscle spasms, overactivity of the sympathetic nervous system, chronic respiratory and genitourinary infections, altered thermoregulation, and pain.29

A major problem that appears after the resolution of spinal shock is autonomic dysreflexia. It is a life-threatening syndrome resulting from cutaneous or visceral stimulation below the level of the spinal cord injury and leading to extreme vascular instability. The syndrome has been shown to develop if the level of injury is at T7 or above, although some cases have been reported in patients with lesions below T7.30 The trigger for the syndrome is a cutaneous, proprioceptive, or visceral stimulus below the level of the spinal cord injury lesion, ie, a full bladder or bowel. Activation of sympathetic nerves cause vasoconstriction and subsequent hypertension. The increase in the blood pressure is sensed in the aortic bodies and carotid sinus, resulting in vagal hyperactivity. Exaggerated vagal stimulation causes bradycardia, heart block, and ventricular dysrhythmias. Reflex vasodilation can be observed above the level of the lesion causing flushing in the head and neck. Hypertension can be so severe that subarachnoid hemorrhage, seizures, and acute left ventricular failure can occur.29 In the obstetric patient, it can result in significant maternal–fetal morbidity including hypertensive encephalopathy, stroke, intraventricular hemorrhage, and death. It may occur in up to 85% of pregnant women with spinal cord lesions at or above T6 to T7.31

Other abnormalities occur with spinal cord injury. Retention of urine and feces are common. Abdominal distension can be severe enough to impair respiration. Acute spinal cord injury is associated with the highest risk of venous thromboembolism among all hospital admissions. If there is no DVT prophylaxis or the patient is noncompliant with prophylactic therapy, DVTs will occur in more than half (40–100%) of the patients within the first 3 months after injury.32

Anesthetic Considerations

The care of the patient with spinal cord injury depends on the timing, the location, and any associated injuries the patient may have. In the acute phase, the spinal cord is vulnerable to secondary injury from hypotension and hypoxia. Thermoregulation is impaired. Prompt recognition and treatment with early intubation and oxygenation, vasopressor therapy, and warming measures is indicated. During the acute phase, well-controlled general anesthesia is usually the best option as an anesthetic plan if there is any indication of respiratory compromise. Because of the high risk of deep venous thrombosis in the acute injury phase, most patients will be on prophylactic medication, either low-molecular-weight heparin or unfractionated heparin subcutaneously, which serves as a potential contraindication to neuraxial anesthesia. Most urgent orthopedic trauma cases are often performed under general anesthesia because the majority of these patients are already intubated, the mental status is altered by the trauma, or multiple procedures are going to be performed at one time involving multiple areas of the body. The use of succinlycholine should be avoided after the first 24 h of injury to avoid the massive hyperkalemic response that has been well documented.33

Patients with either quadriplegia or paraplegia may be hemodynamically unstable acutely as a result of initial spinal shock or occult injury. Computed tomographic scans, radiographs, and laboratory studies should be reviewed prior to surgery and blood samples drawn for either type and screen or type and cross match. Invasive monitoring, such as arterial lines, may be necessary to manage blood pressure changes. Vasopressors may be necessary to stabilize the blood pressure. Complicating the hemodynamic picture at this time with neuraxial anesthesia may not be the best option.

Regional Anesthesia in Patients with Spinal Cord Injuries

Regional anesthesia techniques can be a valuable tool in the treatment of patients with chronic spinal cord injury. Central neuraxial anesthesia has been used successfully for extracorporeal shockwave lithotripsy, for gynecologic procedures to prevent autonomic hyperreflexia, and in obstetrics for labor and delivery.34–36 Peripheral nerve blocks have been used successfully to facilitate lithotomy positioning required for gynecologic or urologic examinations in spastic paraplegics.37

Lesions below T7

For patients with lesions below T7, the risk of hemodynamic instability from autonomic dysreflexia is reduced, but not eliminated. The incidence has been reported for lesions as low as T10.38 In obstetrics, spinal or epidural anesthesia for labor, delivery, and cesarean section is preferred after the period of spinal shock has passed to attempt to avoid the complications associated with autonomic dysreflexia, as the occurrence is reduced with regional techniques.35,36

Pulmonary dysfunction, although more prevalent in lesions above T7, is still a concern with the paraplegic patient.39 Peripheral nerve blocks on the lower extremities may be an excellent anesthetic choice in these patients, providing adequate anesthesia while avoiding the known effects of general anesthesia, ie, respiratory compromise, overall muscle relaxation, nausea, and sedation from narcotics. Because of the uncertain risk of autonomic hyperreflexia in lesions below T7, peripheral nerve block or central neuraxial blocks reduce the risk of its occurrence by blocking the sensory limb of the reflex. An added advantage to peripheral nerve blocks is prevention of chronic pain, common in patients with spinal cord injuries.40 Patients with spinal cord injury are prone to the development of spasticity. In the dysreflexive spinal cord of a paraplegic patient, pain has been shown to increase the level of spasticity.40 Pain from surgical procedures may, therefore, precipitate spasticity. Utilizing peripheral nerve block anesthesia may prevent this from occurring. Nerve blocks must be performed with a nerve stimulator or ultrasound rather than paresthesia techniques as the patient with paraplegia may not have sensory (paresthesia) perception.

Upper extremity blocks can be performed safely in the paraplegic patient, as spinal cord functions above the lesion is intact and normal. Careful evaluation of the patient for coexisting medical problems or to ascertain the absolute level of the lesion is recommended. The development of syringomyelia has been reported in these patients, creating deficits above the established lesion which can cause unforeseen problems for the anesthesiologist.

Lesions above T7

The risk of autonomic hyperreflexia has been reported to be 85% or higher in this patient population.41 Light general anesthesia does not offer protection against its occurrence. Deep general anesthesia is effective, but the associated hemodynamic instability associated may not be tolerated in many of these patients. Pulmonary dysfunction is common and accounts for the largest percentage of morbidity in this population. General anesthesia with intubation may result in prolonged mechanical ventilation with increased risk of pulmonary infection. These patients are prone to the development of neurogenic pulmonary edema. It has been reported that certain anesthetic agents, ie, barbiturates, can provoke its occurrence.42 General anesthesia-induced bowel and bladder dysfunction can compound the preexisting dysfunction associated with the disease.

Regional anesthesia, eg, spinal and epidural blockade, are effective in preventing autonomic hyperreflexia and have been used successfully in obstetrics for spinal cord-injured patients, even with high cord lesions.36,43 However, concerns about the ability to determine the anesthetic level, exaggerated hypotension, and difficulties with placing the block secondary to spinal deformities from injury or prior surgery make many clinicians reluctant to use neuraxial anesthesia in this setting.

Peripheral nerve blocks, especially on the lower extremities, are a theoretically acceptable form of anesthesia for the properly evaluated patient with a high-level spinal cord injury. Selective nerve blocks on the lower extremities, ie, femoral-sciatic or ankle blocks, are an effective alternative to exposing the patient to general anesthesia. Providing adequate anesthesia is even more important with a high spinal cord lesion to avoid the stimulus for autonomic hyperreflexia. Avoiding systemic hypotension with general anesthesia or an exaggerated hypotensive response with neuraxial anesthesia is possible with selective nerve blocks. Again, paresthesia techniques cannot be used; nerve stimulation or ultrasound-guided technique are required for proper localization of the nerve(s) to be blocked.

Upper extremity peripheral nerve blocks should be approached on an individual basis. For a patient with a low cervical injury, who is not ventilator-dependent, performing an interscalene block with subsequent unilateral phrenic nerve paresis and up to 30% reduction in pulmonary function volumes, may create the need for respiratory support. However, an infraclavicular or axillary block may be beneficial both for surgical anesthesia and for reducing spasticity without creating further respiratory compromise in the appropriate patient.

Demyelinating Central Nervous System Diseases

Multiple Sclerosis

Multiple sclerosis (MS) is the most common demyelinating disease of the CNS, affecting over a million people worldwide.44 Of the people affected, 75% are women in young adulthood (ages 20–40). It is characterized by random, multiple sites of demyelination in the brain and spinal cord. The peripheral nervous system is not involved. The cause of the disease is unknown, but is thought to involve a complex series of immunologic events in a genetically susceptible person. Infectious agents (especially viral), may predispose the disease.44,45 The autoimmune mechanism is supported by laboratory findings in many patients. Often, cerebrospinal fluid (CSF) in patients with MS have elevated IgG with oligoclonal bands. Sodium channels are also redistributed along the demyelinated axon, leading to an increase in the influx of sodium and sodium-calcium exchange and ultimately destruction of axons.46,47

The presentation of the disease can vary. The symptoms of MS depend on the sites of demyelination. The most common clinical signs and symptoms are visual disturbances, ataxia, limb paresthesias and weakness, and autonomic disturbances including bowel and bladder dysfunction. The course of the disease is characterized by recurrent exacerbations of the symptoms (relapsing remitting MS). After a period of approximately 20 years, patients do not fully recover from the symptoms. Deficits persist and disability progresses (secondarily progressive MS). In severe cases, some patients may be wheelchair-bound or develop respiratory failure.48–50 Pregnancy is associated with an improvement in symptoms, but relapses generally occur in the first 6 months postpartum.51

Treatment consists of corticosteroids, interferon, glatiramer, and mitoxantrone used to modulate the immunologic and inflammatory responses.44 Side effects of the treatment therapy include adrenal suppression, liver function test abnormalities, anemia, leukopenia, and dose-related cardiotoxicity.44

Anesthetic Considerations in Patients with MS

Autonomic dysfunction can be seen in patients with MS.49 They exhibit an increased sensitivity to sympathomimetics used to manage hypotension.52 Preload should be adequately maintained for hemodynamic stability. Increases in temperature as well as metabolic and hormonal changes associated with surgery are thought to be responsible for exacerbation of symptoms that may occur postoperatively.48 A temperature change of as little as 0.5°C may block impulse conduction in demyelinated fibers.48 Stress dose steroids may be necessary, depending on the dose and length of time steroids have been used preoperatively. Although the effect of surgery and anesthesia on the course of MS is controversial, (ie, reports support and refute the exacerbation of symptoms from anesthesia), the patient should be advised that regardless of the anesthetic technique, there is a possibility that a relapse of symptoms may occur after surgery.54

Regional Anesthesia in Patients with MS

The use of regional anesthesia, ie, central neuraxial blocks, in patients with MS is controversial. Both spinal and epidural anesthesia have been used safely, but unpredictable progression of the neurologic symptoms has been observed.54 The mechanism by which spinal anesthesia may exacerbate MS is unknown, but it is speculated that demyelinated areas of the spinal cord might be more sensitive to the effects of local anesthetics.55 In fact, it has been suggested that lidocaine can be used to unmask silent demyelinating lesions in MS, making it a diagnostic tool.56 Epidural anesthesia has been found to be innocuous in obstetric analgesia and anesthesia. However, in one study, patients who received concentrations of bupivacaine greater than 0.25% experienced postpartum relapses.55,57

Because MS is a disorder of the central nervous system, peripheral nerve block anesthesia should be a more appropriate choice then spinal anesthesia. Peripheral nerve block anesthesia may be considered the technique of choice for patients with MS when the surgical procedure allows it.58

Although not contraindicated, lumbar plexus blocks and paravertebral blocks may have a prolonged duration of action in patients with MS. In one report, a patient who received a paravertebral block for an inguinal hernia repair developed a flaccid paralysis of both lower extremities. The block regressed slowly, with full recovery, in 12.5 h. It was postulated that in peripheral blocks near the central neuraxis, uptake of local anesthetics into the spinal cord may cause a prolonged duration or unpredictable response in patients with MS, similar to spinal anesthetics.59

Peripheral neuropathies involve motor, sensory, and autonomic fibers outside of the CNS. They produce variable motor, sensory, and autonomic symptoms. They can be divided into disorders producing focal (ie, mononeuropathy) or widespread (ie, polyneuropathy) nerve dysfunction. The polyneuropathies may be symmetrical [ie, the distribution of deficits is symmetrical and usually distal (Guillain–Barré)] or asymmetrical (ie, diabetic, uremic, or vasculitic).

The causes of peripheral neuropathies are multiple, ie, metabolic, vasculitic, hereditary, infectious, neoplastic, paraneoplastic, trauma, toxins, or medication-induced. The most common cause is diabetic neuropathy, affecting nearly 100% of patients with long-standing disease.60 Diabetic neuropathy is discussed in Chapter 58.

Treatment for peripheral neuropathies involves identification of the cause and attempting to mitigate or remove it. Painful neuropathies have been treated with many agents, including antiepileptic drugs, antidepressants, sodium channel-blocking agents, tramadol, and capsaicin ointment.61 It is important for the anesthesiologist to understand the disease process, the potential interaction of anesthetic agents with chronic treatment medications, and the differences in response to local anesthetics or nerve stimulation if regional anesthetics are to be employed.

Inherited Peripheral Neuropathies

Charcot–Marie–Tooth Disease

Charcot–Marie–Tooth (CMT) disease is the most common inherited peripheral neuropathy. The incidence is 1:2500. It is both a motor and sensory peripheral neuropathy, classically presenting as distal skeletal muscle weakness and wasting (quadriceps muscle wasting, peroneal muscle atrophy). Peroneal nerve atrophy causing weakness in the anterior and lateral compartments of the leg is the most common presentation, but considerable variations in the presentation are common. The sensory deficit is usually milder than the motor deficits. Exacerbations of the disease during pregnancy is thought to be related to hormonal changes.62 A variety of respiratory problems, including respiratory insufficiency and vocal cord paresis, have been associated with CMT disease.62 Cardiac conduction defects can occur, although they are not common.62

Anesthetic Considerations

Primary concerns with anesthesia include responses to muscle relaxants, increased incidence of malignant hyperthermia, and postoperative respiratory failure. There is no evidence of a prolonged response to muscle relaxants, and these patients seem to tolerate anesthesia without incident. However, because episodes of malignant hyperthermia have been reported, agents that trigger this life-threatening problem should be avoided.63,64 Respiratory function, including a review of pulmonary function studies, blood gases, or evaluations by consultants should be evaluated prior to the initiation of anesthesia. A history of hospital admissions requiring mechanical ventilation or frequent exacerbations of pneumonia will alert the anesthesiologist to the risk of postoperative respiratory complications.

Regional Anesthesia for Patients with CMT Disease

The main advantage of regional anesthesia over general anesthesia in the patient with CMT disease is in eliminating the triggers for malignant hyperthermia. Subjecting the patient with a tendency toward respiratory failure to general anesthesia is avoided. Further vocal cord damage is also avoided by eliminating the need for airway manipulation. Even though pregnancy may cause exacerbations, epidural anesthesia for labor and delivery have been performed successfully without adverse effects.65

There is very little data in the literature about peripheral nerve block anesthesia or analgesia in patients with this disease. Upper extremity blocks avoid exposing the patient to potentially harmful anesthetic agents, intubation, and mechanical ventilation. It is prudent to remember that in patients with respiratory dysfunction, interscalene blocks will result in a 30% reduction in pulmonary volumes. Probably this block should be avoided in the presence of severe pulmonary dysfunction. Lower extremity blocks are more controversial. In the presence of peroneal and quadriceps muscle wasting, lower extremity blocks are probably best avoided, although they can be used with for selective cases.

Inflammatory-Immune Peripheral Neuropathies

Guillain–Barré Syndrome

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculoneuropathy. The incidence is 4 in 10,000, with men affected slightly more often than women. The disease is rare in pregnancy with only 29 reported cases in the literature from 1986 to 2002, but the risk of GBS increases for the mother during the postpartum period.67,68 Death from Guillain-Barré syndrome is usually secondary to respiratory failure or autonomic nervous system dysfunction (ie, labile systemic blood pressure, cardiac conduction disturbances, sudden death).

The cause of GBS is unknown. It has been associated with a variety of bacterial and viral infections in two thirds of the cases. Other possible precipitants include vaccinations (polio, rabies), malignancies (most commonly Hodgkin lymphoma), hyperthyroidism, and drugs (heroin).66,69,70 It is theorized that an infection triggers an immune response that targets myelin components of the nerve cells, resulting in macrophage-induced demyelination. In addition to the demyelination seen in GBS, channelopathies have been identified.70 A sodium channel-blocking factor, similar to that seen in MS, has been found in the cerebrospinal fluid of patients with GBS, possibly contributing to the paralysis seen in this syndrome.71

The most common clinical presentation is an acute onset of progressive, symmetrical motor weakness, paralysis, and areflexia.70 It usually begins in the legs, then ascends cephalad. Intercostal and pharyngeal muscle weakness may require intubation and mechanical ventilation. The incidence of dull, aching, burning low back or lower extremity pain occurs in approximately 90% of these patients. The condition worsens for several days to a peak at approximately 4 weeks. A period of stability follows for 1 to 2 weeks, then gradual improvement to normal or nearly normal function. Complications include aspiration pneumonia, respiratory and cardiac arrest, deep vein thrombosis, pulmonary embolism, and persistent motor weakness. The mortality rate ranges from 3% to 12%. Treatment is primarily supportive. Plasmapheresis or intravenous immunoglobulin (IVIG) therapy has been used successfully to reduce the duration of symptoms, but there is no cure.70

Anesthetic Considerations

It is highly recommended that patients with Guillain–Barré syndrome have a complete neurologic evaluation both before and after anesthesia is administered. A knowledge of the course of the disease, associated medical conditions, and expected time and quality of recovery will aid the anesthesiologist in choosing the anesthetic technique that best meets the needs of the patient. A thorough preoperative discussion with the patient, when possible, should include the risk/benefit ratio of general anesthesia vs regional anesthesia.

Up-regulation of the acetylcholine postsynaptic receptor occurs as a result of demyelination or axonal degeneration of nerve fibers.72 Succinylcholine should be avoided due to the increased risk of a hyperkalemic response leading to cardiac arrest.72 The response to nondepolarizing muscle relaxants varies from extreme sensitivity to resistance, depending on the phase of the disease.

Autonomic dysfunction, occurring in approximately 60% of the patients with GBS, indicates that the compensatory mechanisms for cardiovascular stability are defective.72 Postural changes, blood loss, or positive pressure ventilation may result in an exaggerated hypotensive response. Asystole has been reported with eyeball pressure and tracheal suctioning in patients with GBS.73 Systemic hypertension with noxious stimulation (ie, laryngoscopy), and an exaggerated response to indirect-acting vasopressors can occur.52

Respiratory and pharyngeal muscle involvement may predispose a loss of airway patency, decrease cough response, and increase risk of aspiration following general anesthesia.73,74 The need for postoperative mechanical support should be anticipated when general anesthesia is provided.

Regional Anesthesia in Patients with GBS

Regional anesthetics may be beneficial for the patient with GBS.

In the pregnant patient, regional analgesia has been utilized to limit the exaggerated hemodynamic response to labor pain.73 Sensitivity to local anesthetics may occur, possibly secondary to the sodium channel-blocking factor found in the CSF of these patients.46,74,75 Because of the increased autonomic instability, epidural anesthesia may be preferable over spinal anesthesia because of its slower onset and more stable hemodynamic profile.74,75 Theoretically, smaller doses of local anesthetics may be required and higher levels may be achieved secondarily to the effects of denervation.53 Complications associated with neuraxial anesthesia in GBS patients, such as worsening neurologic symptoms, prolonged duration of action of local anesthetics, triggering underlying disease, and cardiac arrest after low subarachnoid block have been reported in the literature.74–76

The use of peripheral nerve block anesthesia in the patient with Guillain-Barré syndrome has not been reported. Theoretical advantages of regional anesthetic include the ability to provide excellent selective anesthesia, minimize sedation, eliminate the need for general anesthetic medications, and avoid intubation and ventilation. The hemodynamic instability associated with central neuraxial blocks is also avoided. The block should be performed utilizing a nerve stimulator or ultrasound technique. Objective monitoring of injection pressures may also be useful to prevent injection into a tight compartment space (eg nerve fascicle) and for objective procedure documentation.

Entrapment Neuropathies

Carpal Tunnel Syndrome

Carpal tunnel syndrome is the most common entrapment neuropathy.77 Causes include wrist trauma, diabetes, hypothyroidism, rheumatoid arthritis, oral contraceptives, repetitive motion of the wrist, and pregnancy.77 It results from compression of the median nerve between the transverse carpal ligament (flexor retinaculum) and the carpal bones of the wrist. Either a reduction in the size of the space in the carpal tunnel or an increase in the volume of its contents leading to an increased carpal tunnel pressure engenders the symptoms commonly associated with the disease.77 The common clinical presentation is tingling; numbness; and pain in the thumb, index finger, long finger, and radial side of the ring finger.69,77 Patients may complain of pain and paresthesias spreading to the affected arm and shoulder. Thenar weakness and loss of two-point discrimination may be observed.77

Treatment is directed at immobilization of the wrist when the cause is transient or related to a medically treatable disease, such as pregnancy or hypothyroidism. Splinting keeps the wrist in a neutral position, decreasing pressure on the carpal tunnel. Other treatments (ie, physical therapy, diuretics, steroid injection) have been tried with varying levels of success. Definitive treatment is surgical decompression of the median nerve by dividing the flexor retinaculum.77

Anesthetic Considerations in CTR

Anesthetic options for carpal tunnel release (CTR) surgery are numerous.78 General anesthesia, local anesthetic infiltration, intravenous regional anesthesia, and peripheral nerve blocks of the brachial plexus or more distally at the peripheral nerves are some of the options. The choice of anesthetic technique is the same as with any type of surgical procedure. The goal is to provide the safest, most efficient anesthesia that affords the greatest benefit to the patient while offering coverage for the operative procedure. Because a bloodless operative field is required to enable clear identification of the anatomy to avoid damage to surrounding nerve fibers, an arm tourniquet is usually required. If the tourniquet is inflated longer than 30 min, however, intolerable tourniquet pain may occur and must be addressed.78

Local anesthetic infiltration is the simplest method of anesthesia, but it does not limit tourniquet pain, and may cause anatomic distortion of the surgical site from the infiltrating solution.79 Intravenous regional anesthesia is another simple technique, but if the tourniquets are not applied properly, venous engorgement after tourniquet inflation can distort surgical exposure.80 General anesthesia fulfills all of the surgical requirements for carpal tunnel release, but with the risk/benefit ratio for a relatively minor surgical procedure it may not be warranted, especially for ambulatory surgery.81

Regional Anesthesia for CTR

Peripheral nerve block anesthesia is an excellent means of anesthesia for CTR. Several peripheral block options are available to meet the anesthetic requirements for CTR surgery. At the brachial plexus, infraclavicular and axillary blocks provide excellent anesthesia as well as tourniquet tolerance beyond 30 min. Surgical site distortion does not occur. The disadvantage of a brachial plexus block is that both motor and sensory block occurs. If the surgeon is not concerned about an intraoperative sensory block, then a short-acting local anesthetic can be used that would allow return of motor–sensory function prior to the patient's discharge home.80

Peripheral blocks can be performed at or distal to the elbow for CTR surgery. The advantage of this technique is that selective sensory blocks can be performed while limiting the motor block (most motor fibers have already divided at this level). The disadvantages to selective lower peripheral nerve blocks is that multiple nerves must be located and blocked. Although the median nerve provides the predominant innervation of this area, there is overlap from the ulnar and radial nerves. To provide complete anesthesia, all three terminal branches of the brachial plexus should be blocked. If the incision is extended to the forearm, cutaneous branches of the musculocutaneous nerve are involved. Tourniquet pain is still an issue with distal peripheral nerve blocks, but most of these procedures do not extend beyond 30 min. The administration of additional light sedation is usually adequate for patient comfort.82

Ulnar Nerve Entrapment

Ulnar nerve entrapment can occur either at the elbow or at the wrist. Ulnar-sided wrist pain is often vague and chronic in nature, has an insidious onset, and its symptoms are often intermittent. Diagnosis can be frustrating both for the patient and for the physician. Ulnar wrist pain is usually related to acute traumatic injuries, chronic overuse injuries, or chronic degenerative problems.83 Depending on the nature and timing of the injury, treatment includes rest, immobilization, nonsteroidal antiinflammatory drugs (NSAIDs), steroids, or surgical decompression.84

Ulnar nerve entrapment at the elbow, “cubital entrapment syndrome,” is the second most frequent upper extremity compression neuropathy.85 The ulnar nerve is at increased risk because of its superficial location in the regional of the medial elbow. Injury to the nerve may occur as a result of acute trauma, compression, repetitive traction, subluxation of the nerve, osteoarthritis, gout, or following surgical treatment of an upper extremity injury. The initial symptoms include intermittent hypersthesia in the ulnar nerve distribution, elbow pain, and paresthesias in the ring and small fingers. These symptoms are often intermittent and may occur for months or years. In the later stages of the disease, weakness of the intrinsic muscles of the hand with or without visible atrophy may be observed.85 Initial treatment of closed injuries to the ulnar nerve include physical therapy and NSAIDs. Open injuries with evidence of ulnar nerve disruption associated with fractures or lacerations are commonly treated with early surgical repair or grafting. Surgical decompression has a high success rate if performed prior to the occurrence of chronic signs and symptoms.86

Anesthetic Considerations for Ulnar Nerve Entrapment Surgery

General, regional, or local anesthesia can be used for surgical decompression of an entrapped ulnar nerve. The choice of anesthetic depends on the surgical procedure, whether nerve function will be tested intraoperatively, and the extent of injury accompanying the nerve injury. The most conservative approach is local anesthesia with sedation (in selective cases). General anesthesia is often used for more involved procedures.6

Regional Anesthesia for Ulnar Nerve Entrapment

The use of regional anesthetic techniques in patients with preexisting neuropathies is controversial, but is gaining acceptance as a safe method of anesthesia in centers that perform large numbers of regional blocks. The primary concern in these patients is that needles or catheters used for regional blocks may place the patient at a greater risk of nerve injury from trauma, local anesthetic toxicity, or neural ischemia, especially in the face of preexisting neurologic derangements.6 In a 2001 study of 360 patients with preexisting ulnar neuropathy undergoing ulnar nerve transposition, Hebl and colleagues found that anesthetic technique did not affect the neurologic outcome immediately after surgery or 2–6 weeks postoperatively in patients undergoing ulnar nerve transposition surgery.6 Depending on the surgical site, a supraclavicular, infraclavicular, or axillary block will provide effective anesthesia for the procedure. The block may be performed using a nerve stimulator, with the understanding that the ulnar distribution may be impaired. If the inner aspect of the upper extremity is part of the operative site (T1, T2 distribution), local infiltration by the surgeon or additional sedation is usually all that is required for patient comfort. A preoperative discussion with the surgeon to determine the intraoperative plan, specific concerns related to the patient's disease process, and the extent of the operative field (to determine the coverage required with a peripheral nerve block) will assist the anesthesiologist in making the most appropriate choice of anesthetic.

The neuromuscular junction is an area of primary interest for the anesthesiologist because it holds the key to skeletal muscle function. The large number of nAChRs (1–10 million) in the postsynaptic muscle membrane (the motor end-plate) is critical for maintaining normal neuromuscular function. Under normal circumstances, only a small portion of the available receptors must bind to acetylcholine to trigger a muscle contraction. Therefore, there is an excess of receptors available providing a “wide margin of safety” for muscle contraction in the event that the postsynaptic receptors are blocked, damaged, or destroyed.

Neuromuscular blocking agents that interact with the nicotinic cholinergic receptor to prevent muscle contraction are commonly used during many surgical procedures. A large number of receptors must be occupied by neuromuscular blocking agents before muscle paralysis occurs. In the patient with a neuromuscular junction defect the effects of these anesthetic agents are markedly altered.

Skeletal muscle relaxation can also be produced by deep inhalational anesthesia or by local anesthetics. The mechanism of action is different. Inhaled anesthetics produce muscle relaxation by altering physiology of the brain and spinal cord, as well as the nAChRs.87 Local anesthetics produce muscle relaxation by their effect on voltage-dependent sodium channels on nerve and muscle membranes.88 When a neuromuscular junction defect is present, as is the case in the myasthenic syndromes, the anesthesiologist must carefully choose the anesthetic agent that will provide the greatest benefit without potentiating the skeletal muscle weakness or causing a myasthenic crisis.

Myasthenia Gravis

Myasthenia gravis (MG) is a chronic, acquired autoimmune disease caused by antibodies that destroy or inactivate the nAChRs at the neuromuscular junction. The antibodies specifically target the α-subunit of the receptor in 80% of the cases of the disease. In the other 20% of the patients (seronegative patients), autoantibodies target a muscle-specific tyrosine kinase (MuSK).89 Weakness and easy fatigability are the hallmark symptoms, with either discrete muscle groups affected (ie, ocular MG), or generalized weakness with life-threatening respiratory muscle dysfunction (ie, myasthenia crisis).90 The antibodies do not affect the nAChRs in the autonomic nervous system or the CNS because of differences in protein structure, therefore limiting autonomic and CNS symptoms in the disease process.91

MG has a prevalence of 14 per 100,000, without an ethnic predominance. The most common age at onset is the second and third decade in women (childbearing age) and the sixth to seventh decade in men. Family members of patients with MG are 1000 times more likely to have the disease than the general population. The effects of pregnancy on MG are variable; symptoms can remain unchanged, worsen, or improve. Of the 30–40% of patients whose symptoms worsen with pregnancy, primigravidas usually experience exacerbations in the first trimester. In subsequent pregnancies, exacerbations in the third trimester and in the postpartum period are more common.92

Skeletal muscles innervated by cranial nerves are especially vulnerable. In 70% of the cases, the initial complaint is diplopia, with over 90% of the patients demonstrating extraocular muscle weakness during the course of the disease. The vast majority will have bulbar muscle involvement (laryngeal, pharyngeal muscles), leading to airway compromise, dysphagia, and the increased risk of aspiration. Other signs and symptoms of the disease include asymmetrical skeletal muscle weakness with exercise, myocarditis (leading to cardiomyopathy, atrial fibrillation and heart block), hypothyroidism, and isolated respiratory failure from diaphragmatic and thoracic intercostal muscle weakness.90

The clinical course of the disease is marked by periods of exacerbations and remissions. Most patients whose initial symptoms are limited to ptosis or diplopia will develop generalized muscle weakness within the first 3 years.93 Muscle strength characteristically improves with rest but deteriorates rapidly with exertion. The life-threatening result of the disease is called a myasthenic crisis. It is a severe exacerbation of weakness often associated with respiratory compromise precipitated by menses, infection, noncompliance with treatment, or the introduction of new medications (ie, aminoglycosides to treat infection, beta-blockers).93

Treatment for MG can be medical or surgical, depending on the patient's age, the presence of a thymoma, and the extent of the disease. Medical treatment is aimed at (1) enhancing neuromuscular transmission by anticholinesterases, (2) suppressing the immune system with corticosteroids, immunosuppressants (cyclosporine/azathioprine), and (3) modulating the circulating antibody level with plasmapheresis or IVIG. Elective thymectomy is the preferred treatment for patients with generalized MG, those younger than 60 years of age, and in all patients with a thymoma (33% risk of malignancy). MG patients undergoing thymectomy are twice as likely to attain a medication-free remission and 1.7 times as likely to have an improvement in symptoms.94 Beneficial effects of thymectomy may be delayed for months or years, and most patients will continue to have symptoms to a varying degree. Prior to surgery, effective immunosuppressant therapy must be used to make the patient asymptomatic to reduce postoperative morbidity and mortality.70

Anesthetic Considerations for Patients with MG

Anesthetic management of the patient with MG is complicated because the response to commonly used drugs is variable.95,96 Cautious use of sedatives, muscle relaxants, and general anesthetics must be considered for all patients with a diagnosis of MG.

A thorough preoperative evaluation is necessary for the safe delivery of anesthesia for these patients. Preoperative evaluation should include (1) consultation with the patient's neurologist to review the course of the patient's disease, treatment, and any recent changes in status, (2) review of the patient's preoperative drug therapy, changes in dose or type of medication, and response to medications as well as potential interactions with anesthetic agents, (3) counseling the patient and the family about the potential for postoperative mechanical ventilation.

Optimizing the patient's condition preoperatively can improve outcome. Anticholinesterase agents are usually discontinued preoperatively unless the patient is physically dependent on them. Preoperative plasmapheresis has been used successfully to optimize the patient's condition and reduce perioperative morbidity and mortality.96

The most important preoperative factor predicting the need for postoperative mechanical ventilation is the degree and severity of bulbar involvement, especially when associated with a prior history of respiratory failure.97 Other factors that have been identified as predictors for postoperative respiratory support include disease duration of >6 years, concomitant pulmonary disease, peak inspiratory pressure of –25 cm H2O, and vital capacity of <4 mL/kg.97

Anesthetic medications need to be used with caution. Because of the reduced number of nAChRs, myasthenic patients are resistant to succinylcholine.98 However, they are exquisitely sensitive to nondepolarizing muscle relaxants.99 Short- and intermediate-duration nondepolarizing muscle relaxants can be used with careful titration and monitoring with a nerve stimulator. Long-acting muscle relaxants should be avoided. If the patient has been on pyridostigmine therapy, the response to muscle relaxants changes. The patient will be less sensitive to nondepolarizing muscle relaxants, the response to succinylcholine or mivacurium will be prolonged (plasma cholinesterase effect), and reversal of the block at the end of the case is unpredictable.98,99

General anesthesia has been provided with total intravenous anesthesia (remifentanil) and high thoracic epidural, or inhaled anesthetic without neuromuscular blockers.100 It is important to remember that these patients are more sensitive to inhaled anesthetics (leading to a slower recovery from anesthesia), and to the neuromuscular depressant effects of isoflurane and halothane.100 Drugs that interfere with neuromuscular transmission (ie, aminoglycoside antibiotics, antiarrhythmics, beta-blockers, phenytoin) should be limited or avoided when possible. Usually, opioids are avoided or limited. During the postoperative period, abrupt reduction in skeletal muscle strength may occur, necessitating the need for mechanical ventilation. Diligent postoperative monitoring in the surgical intensive care unit is therefore necessary for the myasthenic patient.

Regional Anesthesia in Patients with MG

Because of the numerous problems associated with perioperative sedation, general anesthetic agents, and muscle relaxants, regional anesthesia may be a better choice for anesthesia in the myasthenic patient. Because local anesthetics do not directly affect the nAChRs, regional anesthesia offers greater predictability with fewer complications.

Epidural anesthesia has been used in myasthenic patients. High thoracic epidural with either total intravenous anesthesia or a balanced general anesthesia provides excellent anesthesia for the MG patient undergoing thymectomy.101,102

In the pregnant patient with MG, epidural anesthesia has been used successfully to reduce the physical and emotional stress that may potentiate a crisis.103 Many of the drugs used to treat the disease are continued during pregnancy to avoid a crisis, but these may have an effect on platelet function and number. Prior to placing a central neuraxial block, it is important to obtain a coagulation profile as well as a platelet count.103 Amide local anesthetics may be a better choice than ester local anesthetics because the metabolism of amides is not dependent on cholinesterase activity.103

Very little data are available on the use of peripheral nerve blocks in the patient with MG. The successful use of a paravertebral block for inguinal hernia surgery, infraclavicular block for a dislocated elbow, and various central neuraxial blocks for surgery on the lower extremities have been reported.104,105

Interscalene blocks should be avoided in patients with bulbar or respiratory compromise because the phrenic nerve can be blocked during the procedure. Infraclavicular or axillary blocks in selected cases will provide anesthesia for the upper extremity without compromising respiratory function. Isolated digital nerve blocks for injuries to the fingers, hand, wrist, or ankle are excellent methods for providing anesthesia without involving other muscle groups. Lumbar plexus blocks should probably be avoided in patients with dysfunctional platelet function. The anesthesiologist should be prepared for the possibility of epidural spread causing a more profound motor block. Femoral, popliteal sciatic, and ankle blocks are effective blocks for surgery on the lower extremities. Reduced doses of sedatives and opioids during block placement are necessary due to the sensitivity of the myasthenic patient to these medications.

Lambert–Eaton Myasthenic Syndrome

Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune disease in which autoantibodies target voltage-gated calcium channels.106 Sixty-six percent of the cases are associated with carcinomas (usually small cell carcinomas of the lung), but the symptoms of LEMS may precede the discovery of the cancer by as much as 5 years. The autoantibodies are directed at calcium channels in the tumor, but because of antigenic similarity, they cross-react with calcium channels at the presynaptic neuromuscular junction responsible for the release of acetylcholine. Consequently, acetylcholine release is reduced.106

The typical patient is a male, smoker, 50–70 years of age, who presents with slowly progressive proximal muscle weakness and fatigue that affects gait and the ability to stand and climb stairs.106 Muscle pain and paresthesias can occur, although the sensory examination is usually normal. Over 75% of the patients with LEMS have symptoms of autonomic dysfunction, including dry mouth, constipation, blurred vision, orthostatic hypotension, and impotence.106 Ocular and bulbar symptoms (ptosis, dysphagia, diplopia) are less prominent than in MG, but may occur in up to 30% of the patients. Unlike in MG, exercise improves strength.106

Treatment of LEMS is geared toward identification and treatment of the underlying neoplasm, medications that enhance neuromuscular transmission, and alteration of the autoantibodies. Early and successful treatment of the lung cancer usually results in clinical improvement.70,107 Treatment includes 3,4-diaminopyridine (enhances acetylcholine release by blocking potassium channels), pyridostigmine (inhibits acetylcholinesterase, resulting in more available acetylcholine), immunosuppresants, plasmapheresis or IVIG.107

Medications that interfere with neuromuscular transmission can worsen the symptoms of LEMS should be avoided. These include aminoglycoside antibiotics, beta-blockers, neuromuscular blocking agents, quinidine, and iodinated contrast agents.107

Anesthetic Considerations

Patients with LEMS are sensitive to the effects of both depolarizing and nondepolarizing muscle relaxants. Therefore, doses of these drugs should be reduced.108 Neuromuscular function should be carefully assessed with a nerve stimulator. Because the syndrome is difficult to diagnose, it may be unmasked perioperatively when the patient demonstrates prolonged paralysis after receiving the usual dose of neuromuscular blockers.108 In patients with LEMS, antagonism with anticholinesterases may be inadequate.108 The possibility of postoperative mechanical ventilation must be considered. Because of the autonomic dysfunction related to the syndrome, hemodynamic instability may occur with inhaled anesthetics.108 Anticipating and preparing for orthostatic changes is prudent.

Regional Anesthesia for Patients with Lems

LEMS is a rare disease, much less common than MG. Literature regarding the use of regional anesthesia in these patients is absent. Given the complications associated with general anesthesia, selective nerve blocks may be advantageous in specific cases.

The current literature regarding regional anesthesia in patients with preexisting neurologic disease is limited. Many neurologic conditions pose a risk to patients undergoing general anesthesia. Problems could arise with autonomic dysfunction, airway and respiratory complications, abnormal responsiveness to anesthetic drugs, and delirium. For these reasons, the use of regional techniques should be considered after careful evaluation of the patient's disease processes, neurologic evaluation, consideration of the risk/benefit ratio, and the surgical procedure. Peripheral nerve blocks may be the safest and most appropriate method of anesthesia. However, the risk of nerve block-related neurologic complications has prevented many from employing regional anesthesia in these patients. Practitioners of regional anesthesia have been particularly vulnerable to the blame for postoperative neurologic impairment. However, recent developments in nerve localization with ultrasound-assisted nerve blocks, and injection pressure monitoring have decreased the risk of causing nerve damage. With these developments, regional anesthesia will have an increasingly important role in management of patients with preexisting neurologic conditions.