Perioperative Management of Neuromuscular Disorders
The term neuromuscular disorder encompasses a number of different disease processes, including myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), Duchenne muscular dystrophy (DMD), and hypokalemic periodic paralysis. Each of these conditions has its own characteristics and specific anesthetic considerations; however, there are certain shared considerations, most notably the concern regarding perioperative respiratory complications associated with the administration of neuromuscular blocking agents.
Key points in the management of these disorders in the perioperative setting include the following:
Neuromuscular disorders pose several potential issues for the anesthesiologist. It is important to note that there is no single global approach to these disorders in the perioperative setting: Each one has its own characteristics and considerations that must be specifically taken into account. Accordingly, it is always necessary to familiarize oneself with the specific disease process affecting the patient in question. There are, however, some shared considerations.
One of the primary concerns the anesthesiologist should have when caring for a patient with a neuromuscular disorder is the increased risk of perioperative respiratory complications, including aspiration and the need for postoperative mechanical ventilation. Because these patients are often at higher risk for such complications, one must be aware of the potentially negative effects neuromuscular blocking agents can have on the perioperative course. One must also be able to recognize when a patient requires medical optimization before elective surgery.
Myasthenia gravis (MG) is an autoimmune disorder caused by the development of immunoglobulin G (IgG) antibodies that bind to and destroy postsynaptic nicotinic acetylcholine receptors. This leads to fewer receptors present at the neuromuscular junction.
The end result of this process is fatigable skeletal muscle weakness that most commonly affects the ocular muscles, leading to ptosis and diplopia. Less common symptoms include bulbar muscle weakness and proximal limb weakness. In the most severe cases, patients with MG can ultimately develop respiratory muscle weakness, which results in respiratory failure that necessitates mechanical ventilation. 
Patients with MG experience unpredictable effects with both depolarizing and nondepolarizing neuromuscular blocking agents. Patients are generally resistant to depolarizing agents (eg, succinylcholine) and sensitive to nondepolarizing agents. This can make the perioperative administration of these drugs challenging, in that they can increase the likelihood that the patient will require postoperative ventilatory support.
The symptoms of MG can be exacerbated by a number of factors, leading to myasthenic crisis, a state characterized by the acute worsening of skeletal muscle weakness necessitating intubation and mechanical ventilation. These exacerbating factors include the following  :
Pharmacologically, these patients are managed with anticholinesterases (eg, pyridostigmine) and steroids. Other interventions that can benefit patients with MG include intravenous (IV) immunoglobulin (IVIg) and plasmapheresis. 
Like MG, Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder, but it is far less common than MG (incidence, ~0.5 per million). LEMS is frequently associated with small cell lung carcinoma and other malignancies (eg, paraneoplastic syndrome) and is characterized by the development of IgG antibodies that bind to and destroy presynaptic voltage-gated calcium channels. This leads to decreased release of acetylcholine from the presynaptic terminal and a consequent decrease in acetylcholine within the neuromuscular junction.
Patients with LEMS frequently experience proximal limb weakness that is worsened with inactivity. Repeated muscle activity increases the release of acetylcholine from the presynaptic terminal, thereby alleviating the weakness experienced by the patient. 
Duchenne muscular dystrophy (DMD) is an X-linked recessive hereditary disorder characterized by the progressive degeneration of smooth and skeletal muscle. The mutation in question affects the gene that codes for the muscle-stabilizing protein dystrophin.
Patients with DMD often experience profound, progressive muscle weakness that leaves them wheelchair-bound. Proximal muscles are most often involved. Disease progression can lead to restrictive pulmonary disease, cardiac manifestations (eg, dilated cardiomyopathy and associated congestive heart failure [CHF], valvular insufficiency, and arrhythmia), and contractures that can make intraoperative positioning a challenge. 
Hypokalemic periodic paralysis is a rare autosomal dominant hereditary disorder that is characterized by abnormal voltage-gated ion channels and consequent transient weakness or paralysis associated with a low serum potassium level. The weakness or paralysis generally resolves when the serum potassium level normalizes. 
Patients with MG who are undergoing elective procedures should be medically optimized beforehand. Medical optimization includes an appropriate anticholinesterase dose (eg, pyridostigmine). One can also consider the addition of a glucocorticoid for immunosuppression. It should be kept in mind that patients receiving more than 5 mg of prednisone daily for more than 3 weeks may require stress dose glucocorticoids perioperatively secondary to iatrogenic adrenal suppression.
Other potentially beneficial interventions in MG patients include IVIg and plasmapheresis. These will decrease the likelihood that the patient will require postoperative ventilation.
Preoperative evaluation of an MG patient undergoing elective surgery should focus on the following:
A number of risk factors may increase the likelihood of postoperative ventilation, including the following:
If appropriate, avoidance of general anesthesia and associated airway manipulation is preferable. Monitored anesthesia care using short-acting sedatives and analgesics should be provided whenever possible, and regional or neuraxial techniques should be considered when appropriate for the planned procedure.
It should be kept in mind, however, that a neuraxial technique may affect the accessory muscles of respiration. Accordingly, neuraxial anesthesia should be approached cautiously and is probably ill-advised if a mid-to-high thoracic sensory level is necessary for surgical anesthesia. Similarly, certain brachial plexus blocks (eg, interscalene or supraclavicular) can result in diaphragmatic hemiparesis and therefore are best avoided.
If general anesthesia is necessary for the proposed procedure, avoidance of neuromuscular blocking agents is preferable if feasible and safe. If nondepolarizing agents are necessary, reduced doses of short- or intermediate-acting agents should be given; MG patients are typically sensitive to the effects of these drugs. Sugammadex should be considered to reverse neuromuscular blockade with rocuronium before extubation, this may reduce the risk of postoperative respiratory complications, including reintubation. 
The use of succinylcholine at induction also poses potential issues, in that patients are often resistant to the effects of the drug. For this reason, an increased dose is frequently required to achieve adequate relaxation for the purposes of intubation.
Avoidance of certain pharmacologic agents, avoidance of extremes of temperature, and providing effective analgesia can help prevent perioperative exacerbations of MG (eg, myasthenic crisis).
Unlike patients with MG, patients with LEMS are sensitive to the effects of both depolarizing and nondepolarizing neuromuscular blocking agents. Compared with MG patients, LEMS patients are relatively unresponsive to acetylcholinesterase inhibitors (eg, pyridostigmine) alone but are more responsive to a combination of an anticholinesterase and a pharmacologic agent that induces the release of acetylcholine from the presynaptic nerve terminal (eg, amifampridine phosphate [3,4-diaminopyridine], which is awaiting US Food and Drug Administration [FDA] approval for LEMS).
Plasmapheresis can lead to an improvement in some LEMS patients who are experiencing an acute exacerbation, but it is typically less effective than it is in MG patients. 
Succinylcholine and inhalational agents are best avoided in patients with DMD, secondary to the proposed risk of malignant hyperthermia and anesthetic-induced rhabdomyolysis, complications that carry an associated mortality of 30%. 
Because glucocorticoids are commonly prescribed for management of DMD, it is important to determine the dose and duration preoperatively; these patients may require stress-dose glucocorticoids perioperatively.
Because patients with DMD often have restrictive pulmonary disease, general anesthesia should be avoided if possible. This underlying lung pathology, in association with residual neuromuscular blockade, can predispose these patients to perioperative pulmonary complications, including reintubation and prolonged mechanical ventilation. Moreover, general anesthesia poses an additional risk if the patient has dilated cardiomyopathy. 
Regional techniques, if appropriate for the planned procedure, are advantageous in that they allow avoidance of sedative medications and analgesics that may depress the patient’s respiratory drive. If sedative agents are necessary, reduced doses of shorter-acting agents are preferred. However, certain brachial plexus blocks (eg, interscalene or supraclavicular) are ill-advised because they can temporarily lead to diaphragmatic hemiparesis. 
Several factors that can precipitate an episode of periodic paralysis, and the patient is at increased risk for such an episode during the perioperative period. Exacerbating factors include stress, hypothermia, hyperglycemia, respiratory or metabolic alkalosis, and infection. Avoidance of these factors, along with prompt recognition and treatment of hypokalemia during the perioperative period, will make an episode of periodic paralysis less likely. 
An 87-year-old man is scheduled to undergo emergency laparotomy secondary to a perforated sigmoid diverticulum. He was diagnosed with MG 3 years previously, and he is being medically managed with pyridostigmine 240 mg/day orally (PO) and prednisolone 12 mg/day PO.
Three years ago, just before receiving his diagnosis of MG, the patient underwent general anesthesia for surgical management of an esophageal pouch. At emergence, he was reversed with neostigmine and glycopyrrolate and was subsequently extubated. He was ultimately reintubated in the postanesthesia care unit (PACU) because of hypercapnic respiratory failure. On the following day, he was successfully extubated in the intensive care unit (ICU). 
Because of the emergency nature of the surgical procedure, medical optimization of this patient’s MG is not an option and should not be allowed to delay the operation. If an MG patient requires a rapid-sequence induction, an increased succinylcholine dose should be considered because these patients are unpredictably resistant to this medication. If a nondepolarizing neuromuscular blocking agent is necessary to facilitate intubation, the surgical procedure, or both, reduced doses are prudent because patients with MG are unpredictably sensitive to these agents. 
The patient underwent general endotracheal anesthesia and received a reduced rocuronium dose (25 mg) at the time of induction. Intraoperative train-of-four (TOF) ratio monitoring was used to determine the status of the neuromuscular blockade. The patient received 5 mg of rocuronium each time the TOF ratio exceeded 50%. Reversal was accomplished by administering sugammadex 4 mg/kg, with a documented return of four twitches on the TOF count.
Immediately after the surgical procedure, the patient was successfully extubated. He did not require reintubation and ventilatory support at any time during hospitalization. Perioperatively, his outpatient medication regimen (ie, pyridostigmine and prednisolone) was continued. 
A 34-year-old primigravida nullipara presents at 36 weeks’ gestation complaining of a 2-week history of dysphagia and proximal upper-limb weakness.  Physical examination, nerve conduction studies, pulmonary function tests, and laboratory testing result in a diagnosis of seronegative MG. The patient is admitted to the inpatient neurology unit and starts pharmacologic therapy in the form of pyridostigmine 60 mg PO three times daily and prednisolone 20 mg/day.
In addition, the patient has preeclampsia, diagnosed at 33 weeks’ gestation on the basis of persistently elevated blood pressure values and elevated transaminase levels. 
Pregnancy is one of several factors that can exacerbate MG. IV magnesium sulfate, which is often used in the management of preeclampsia, can also exacerbate myasthenic symptoms. Spinal anesthesia should be approached with caution in MG patients undergoing cesarean section because a mid-to-high thoracic sensory level is necessary for surgical anesthesia. This can affect the accessory muscles of respiration. It is important to be aware that spinal anesthesia can exacerbate respiratory impairment in some patients.
In addition, it should be noted that the neonate is at risk for myasthenia for approximately 3 weeks after birth because the mother’s IgG antibodies undergo transplacental transfer. 
Because the patient had also been diagnosed with preeclampsia at 33 weeks’ gestation, the decision was ultimately made to proceed with cesarean delivery at 37 weeks out of concern for possible deterioration of the patient’s myasthenic or preeclamptic symptoms. The patient underwent primary cesarean section under spinal anesthesia with few intraoperative issues. The neonate was observed for signs of neonatal myasthenia in the neonatal ICU (NICU) for 48 hours.
Postoperatively, the patient developed progressively worsening upper-extremity weakness. This weakness was reduced with a course of IVIg and an increase in the pyridostigmine dose. 
A 25-year-old man with DMD that is complicated by moderate restrictive pulmonary dysfunction presents for open cholecystectomy under general anesthesia. 
The providers had difficulty establishing peripheral access, and central venous access was established.  The patient underwent rapid sequence induction with propofol, fentanyl, and a reduced dose of rocuronium (10 mg). Anesthesia was maintained with sevoflurane, fentanyl, oxygen, air, and rocuronium. Rocuronium was redosed in 5-mg increments approximately every 45 minutes, as the TOF ratio exceeded 25%.
Immediately before emergence, the TOF ratio was noted to be 25%. The patient received sugammadex 150 mg, and 10 minutes later, the TOF ratio had reached 90%. The patient was then extubated without issue. 
A 22-year-old man presents with a left femur fracture that necessitates treatment with open reduction and internal fixation (ORIF).  He was diagnosed with DMD at the age of 5 years and has needed to use a wheelchair since the age of 13 years. At the age of 17 years, he developed dyspnea necessitating noninvasive positive-pressure ventilation (PPV). Pulmonary function tests reveal evidence of severe restrictive lung disease.
In view of the patient’s increased levels of risk for malignant hyperthermia, anesthetic-induced rhabdomyolysis, and perioperative pulmonary complications, it was determined that he would benefit from avoidance of general anesthesia.  The patient consented to undergo preoperative sacral plexus, femoral nerve, and lateral femoral cutaneous nerve blocks for the purpose of surgical anesthesia. The three blocks were performed with a total of 40 mL of 0.375% ropivacaine. No sedation was administered before block placement.
After the effectiveness of the blocks was confirmed with pinprick tests, surgery took place without any significant issues. The patient did not require any sedatives or analgesics during the procedure. He was subsequently discharged from the facility without complications. 
A 44-year-old man presents for hepaticojejunostomy secondary to a common bile duct (CBD) stricture, which occurred after he underwent cholecystectomy and choledocholithotomy 4 years previously.  He has a documented history of hypokalemic periodic paralysis associated with vitamin D deficiency and consequent secondary hyperparathyroidism (the vitamin D deficiency is believed to be related to his CBD stricture and inability to absorb the fat-soluble vitamin D). He has been managed with oral potassium supplementation, oral spironolactone, and calcitriol supplementation.
The patient underwent the hepaticojejunostomy under general endotracheal anesthesia with an epidural catheter in place as an adjunctive measure.  A hot air warmer, an IV fluid warmer, and a heat and moisture exchanger (HME) filter for humidification of inhaled gases were utilized to prevent hypothermia. In addition, the patient received 20 mEq of potassium chloride IV to prevent hypokalemia.
An intraoperative arterial blood gas analysis showed no evidence of respiratory or metabolic alkalosis. Intraoperative serum potassium levels were noted to be within normal limits on two occasions (3.9 mEq/L and 4.0 mEq/L). The patient was extubated after the procedure without complications.
Postoperatively, the patient received daily IV potassium supplementation. The lowest measured serum potassium level during hospitalization was 3.3 mEq/L. The patient did not experience any episodes of paralysis during hospitalization. He was discharged home on postoperative day 6 with instructions to resume oral potassium supplementation and daily oral spironolactone. 
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Thomas J Rayl, MD Assistant Professor of Anesthesiology, University of Minnesota Medical School
Thomas J Rayl, MD is a member of the following medical societies: American Society of Anesthesiologists
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Sheela Pai Cole, MD Clinical Associate Professor of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine
Sheela Pai Cole, MD is a member of the following medical societies: American Medical Association, American Society of Anesthesiologists, American Society of Echocardiography, California Society of Anesthesiologists, International Anesthesia Research Society, Pennsylvania Society of Anesthesiologists, Society of Cardiovascular Anesthesiologists, Society of Critical Care Anesthesiologists, Society of Critical Care Medicine
Disclosure: Nothing to disclose.
Perioperative Management of Neuromuscular Disorders
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