Perioperative care of the surgical patient with neurologic disease

INTRODUCTION — Important considerations for the perioperative care of patients with neurologic disease are the management of medications used to treat neurologic disorders, an understanding of the pathophysiologic mechanism of these disorders, prevention of adverse intraoperative events, and evaluation of new neurologic changes that occur perioperatively. Anesthesiologists are additionally concerned with understanding the impact of the neurologic disorder on anesthetic management, as well as minimizing perioperative physiologic changes that can impact the neurologic disorder and lead to an adverse perioperative event. The more commonly encountered neurologic disorders and their perioperative management are reviewed here.

Perioperative management of patients with traumatic brain injury, patients who undergo craniotomy and spine surgery, and patients with spinal cord injury are discussed separately. (See "Management of acute moderate and severe traumatic brain injury" and "Anesthesia for patients with acute traumatic brain injury" and "Anesthesia for craniotomy in adults" and "Anesthesia for adults with acute spinal cord injury" and "Anesthesia for adults with chronic spinal cord injury".)

SEIZURE DISORDERS — At least one million people in the United States have recurrent seizures or epilepsy [1]. Most patients with epilepsy are managed with antiseizure medications. (See "Overview of the management of epilepsy in adults".)

People with epilepsy appear to be at significant risk of postoperative complications, some of which are attributed to epilepsy and some to comorbidities associated with epilepsy. In one retrospective database study, 13,103 patients with epilepsy had a higher rate of postoperative complications compared with those without epilepsy (odds ratio [OR] 2.0, 95% CI 1.92-2.14) [2]. Stroke was identified as the most significant postoperative complication in patients with epilepsy.

Causes of seizures in perioperative patients

●Epilepsy – Patients with epilepsy may have a breakthrough seizure in the perioperative setting. In one retrospective review, 22 (3.4 percent) of 641 patients with epilepsy experienced a perioperative seizure [3]. The most prominent risk factors for perioperative seizure were related to poor seizure control prior to surgery: frequency of preoperative seizure and timing of most recent seizure. A lower seizure threshold and increase in risk for perioperative seizure in patients with epilepsy may be related to subtherapeutic drug levels or sleep deprivation.

●Anesthesia – Several anesthetic sedative-hypnotic drugs have both proconvulsant and anticonvulsant effects, which can depend on dose and physiologic situation [4-7]. In many instances, the putative proconvulsant effect of an anesthetic is evidenced only by an association with epileptiform activity on electroencephalography (EEG) and/or myoclonic activity during induction or emergence. Overt seizures caused by general anesthetic drugs are rare; most sedative-hypnotic drugs have been used to treat status epilepticus.

The incidence of general anesthesia-related seizures is unknown, but is more likely in patients with epilepsy than in patients without this predisposition [4,8]. In one series of 297 patients with epilepsy undergoing anesthesia for magnetic resonance imaging study, 2 percent of patients had a seizure that was temporally associated with the administration of an anesthetic agent [8].

Other causes of anesthesia-related seizures include local anesthetic systemic toxicity and meperidine in large doses or administered to patients receiving monoamine oxidase inhibitors. (See "Local anesthetic systemic toxicity".)

●Metabolic and systemic derangements – Most patients who have perioperative seizures in the absence of underlying epilepsy have a metabolic derangement. As examples, hyponatremia may occur following transurethral surgery, and hypocalcemia is seen after thyroid or parathyroid surgery. In addition, acute organ failure from any cause and rapidly developing malignant hyperthermia may cause seizures. Sepsis can cause seizures and should be considered in any trauma patient with an obvious source of infection.

●Drug and alcohol withdrawal – Seizures can occur following withdrawal from any sedative-hypnotic medication; alcohol and barbiturate withdrawal are common precipitants [8]. Thus, a toxicology screen is warranted in patients who suffer postoperative seizures without a history of previous seizure disorder.

Alcohol withdrawal seizures are predominantly seen in patients with a long history of chronic alcoholism. They are characteristically generalized tonic-clonic convulsions that occur within 48 hours after the last drink; they may occur after only two hours of abstinence. (See "Management of moderate and severe alcohol withdrawal syndromes".)

However, alcohol withdrawal does not preclude another cause for seizure. Such patients may benefit from further investigation. (See "Evaluation and management of the first seizure in adults", section on 'Acute symptomatic seizures'.)

●Intracranial and cerebrovascular surgery – The incidence of seizures following intracranial surgery depends upon the underlying pathologic conditions, location, and the degree of brain retraction required to perform the procedure [9,10]. The incidence of postoperative seizures is approximately 25 percent in surgical procedures requiring extensive retraction [9-11]. See individual topic reviews for a further description of risk in specific settings. (See "Seizures in patients with primary and metastatic brain tumors" and "Complications of carotid endarterectomy", section on 'Hyperperfusion syndrome' and "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis", section on 'Seizure prophylaxis'.)

●Perioperative stroke – Perioperative seizures may also be caused by other acute brain insults such as ischemic or hemorrhagic stroke. (See 'Cerebrovascular disease' below.)

●Others – Other causes of seizures are discussed in detail separately. (See "Evaluation and management of the first seizure in adults", section on 'Causes of seizures'.)

Evaluation of a new seizure — The cause of a new-onset seizure in the perioperative period should be determined. In this regard, a side effect of general anesthesia should not be assumed and if another etiology is not identified (local anesthetic toxicity, drug or alcohol withdrawal, intracranial surgery), then metabolic derangements and acute neurologic injury should be investigated. Patients with seizures postoperatively should be screened for electrolyte abnormalities as guided by the operative procedure and the preoperative laboratory values.

The evaluation of a patient with a new-onset seizure is described in detail separately. (See "Evaluation and management of the first seizure in adults", section on 'Initial evaluation'.)

Acute seizure management — Because major motor seizures that occur during or immediately after a surgical procedure can increase morbidity and mortality, an antiseizure medication is typically administered for a breakthrough or acute symptomatic seizure that occurs in the operating room or immediate postoperative period. Underlying metabolic disturbances should be quickly identified and treated. Patients with seizures that occur as a result of a reversible cause (metabolic disturbance, alcohol withdrawal) do not require long-term antiseizure medications.

Commonly used drugs in this setting include fosphenytoin, levetiracetam, lacosamide, and valproic acid. For patients taking one of these medications preoperatively, it seems reasonable to administer a bolus of that agent; otherwise, the choice is based upon physician experience or preference. As an example, propofol is readily available and is often used by anesthesiologists in the operating and recovery rooms.

●Fosphenytoin sodium is a water-soluble prodrug of phenytoin that can be administered intravenously and intramuscularly [9]. It is tolerated better than phenytoin. A loading dose of 15 to 20 phenytoin equivalents (PE)/kg can be given at a rate of 150 mg/minute [9]. Phenytoin must be administered in saline or lactated ringer solution at a rate no faster than 50 mg/minute to avoid hypotension and asystole. The loading dose is 15 to 20 mg/kg [10].

Regardless of the mode of administration, serum levels of phenytoin should be followed in all patients. A level of 10 to 20 mcg/mL is appropriate in patients with normal renal function.

●Levetiracetam can be administered intravenously. A dose of 1000 mg IV is typical for acute symptomatic seizures in this setting.

●Valproate sodium is available in a parenteral form [12]. Intravenous and oral forms are approximately dose equivalent. Valproic acid syrup also can be given rectally in the same dose as orally (10 to 15 mg/kg/day in divided doses). Suspensions of carbamazepine and valproic acid can be given via nasogastric tube.

●Phenobarbital can be administered in parenteral form. It is given in a 2 to 6 mg/kg loading dose and 1 to 5 mg/kg/day maintenance in divided doses [10]. It also can be given intramuscularly or orally.

●Lacosamide can be given as a loading dose of 200 mg either orally or intravenously, followed by 100 mg every 12 hours. In patients with known cardiac disease, first-degree heart block can occur [13].

●Intravenous diazepam, lorazepam, and midazolam (can be given intramuscularly) are other options for acute management of seizures, particularly those with alcohol withdrawal. (See "Management of moderate and severe alcohol withdrawal syndromes".)

●Small incremental doses of propofol (eg, 10 to 20 mg IV, titrated to effect) are used to halt seizures in the operating or recovery room.

There are no parenteral forms of carbamazepine, ethosuximide, gabapentin, topiramate, or lamotrigine.

Seizures that last longer than 5 to 10 minutes or serial clinical seizures without an interictal return to baseline consciousness meet the definition of status epilepticus. A prolonged postictal state after a seizure may represent nonconvulsive status epilepticus. The management of convulsive and nonconvulsive status epilepticus is discussed separately. (See "Convulsive status epilepticus in adults: Management" and "Nonconvulsive status epilepticus: Classification, clinical features, and diagnosis", section on 'Diagnosis' and "Nonconvulsive status epilepticus: Treatment and prognosis".)

Prevention of seizures — Patients with preexisting seizure disorders generally need to have antiseizure medications continued perioperatively either parenterally or with small sips of water as determined by the anesthesiologist or surgeon [7]. Pure absence seizures pose less threat perioperatively than do convulsive seizures; it is not as vital to continue antiseizure medications perioperatively in these patients. In general, routine drug levels are not required perioperatively in the absence of breakthrough seizures or other complications that would be expected to either lower seizure threshold or affect drug levels [7].

A number of options are available for patients who require antiseizure medications during the perioperative period and in patients who cannot take oral medications. Phenytoin, valproate, levetiracetam, and phenobarbital are available parenterally [7]. Some drugs are available in suspensions that can be administered via nasogastric tube. (See "Antiseizure medications: Mechanism of action, pharmacology, and adverse effects".)

Levetiracetam is increasingly administered rather than phenytoin for seizure prophylaxis during craniotomy, even if the patient has never had a seizure. In contrast with phenytoin and fosphenytoin, levetiracetam is not associated with hypotension during administration, has more reliable pharmacokinetics, does not require serum-level monitoring, and does not cause tissue injury with extravasation. A dose of 500 to 1000 mg IV is usually administered at the start of surgery. Levetiracetam can produce depression, agitation, and psychosis, especially in patients with an underlying psychiatric disorder [14].

Antiseizure medications are often maintained postoperatively. The duration of such treatment is individualized based upon the underlying intracranial pathology and other considerations. (See "Anesthesia for craniotomy in adults", section on 'Antiseizure drugs' and "Seizures in patients with primary and metastatic brain tumors", section on 'Postoperative prophylaxis'.)

PARKINSON DISEASE — Tremor, rigidity, bradykinesia, and impaired postural reflexes are cardinal manifestations of Parkinson disease. Another important clinical manifestation is autonomic dysfunction manifested by orthostatic hypotension, inability to control temperature, abnormal sweating, and sialorrhea. (See "Clinical manifestations of Parkinson disease".)

The major perioperative issues in patients with Parkinson disease are assessments of swallowing and pulmonary function, correct use of antiparkinsonian medications, and maintenance of volume status. Any person with Parkinson disease is susceptible to cognitive impairment after an operation, especially when opioids are used for pain relief. Early mobilization and physical therapy are important.

Retrospective reviews have found that Parkinson disease is associated with increased risks of mortality, medical and surgical complications, postoperative confusion, and increased length of hospital stay [15-18].

Swallowing impairment — Swallowing difficulty or dysphagia is common in Parkinson disease, due to bradykinesia and rigidity of the pharyngeal musculature; this may be exacerbated in the postoperative setting because of missed medication doses, and/or administration of other medications, and/or residual dysphagia from endotracheal intubation. (See 'Antiparkinsonian medications' below.)

All patients with moderate to severe Parkinson disease as well as patients who complain of swallowing difficulties are at risk of postoperative aspiration and can be taught preoperatively the voluntary airway protection technique in which they are instructed to hold their breath, tilt the chin to the chest, swallow, cough, and then swallow again. (See "Oropharyngeal dysphagia: Clinical features, diagnosis, and management", section on 'Swallowing rehabilitation and nutrition'.)

Other interventions to prevent aspiration pneumonia are discussed in detail separately. (See "Risk factors and prevention of hospital-acquired and ventilator-associated pneumonia in adults", section on 'Preventing aspiration' and "Aspiration pneumonia in adults", section on 'Prevention'.)

Pulmonary function — Rigidity and bradykinesia of the respiratory muscles put patients with Parkinson disease at risk for postoperative pulmonary complications. Kyphosis, pharyngeal dysfunction, and sialorrhea may further compound the restrictive dysfunction [11].

Preoperative pulmonary function tests and arterial blood gas determinations are not typically performed but may be obtained prior to high-risk surgery, either to establish a baseline or to assist with surgical risk assessment. Postoperative management includes incentive spirometry, postural drainage, percussion, early mobilization, and reinstitution of antiparkinsonian medications. An uncontrolled trial found that levodopa improved the minute ventilation and vital capacity in patients with Parkinson disease [19].

Cognitive impairment — Most patients with Parkinson disease have some degree of cognitive impairment, which can be substantial as the severity of the disease progresses. This places the patient at risk for postoperative delirium. Therefore, the anesthesiologist should be aware of the patient's baseline status in order to assess and to minimize the risk of postoperative delirium. This is discussed in detail separately. (See "Delirium and acute confusional states: Prevention, treatment, and prognosis", section on 'Prevention'.)

Perioperative medication management

Antiparkinsonian medications — Antiparkinsonian drugs should not be withheld in most circumstances. Abrupt withdrawal of antiparkinsonian drugs may to lead to flares of Parkinson symptoms with motor and bulbar symptoms that complicate anesthetic management and, rarely, the neuroleptic malignant syndrome or related withdrawal syndromes [20-23]. (See "Neuroleptic malignant syndrome", section on 'Antiparkinson medication withdrawal' and "Initial pharmacologic treatment of Parkinson disease", section on 'Parkinsonism-hyperpyrexia syndrome' and "Initial pharmacologic treatment of Parkinson disease", section on 'Dopamine agonist withdrawal syndrome'.)

Thus, medications should be continued up to the time of surgery and restarted as soon as possible after surgery. One exception is that antiparkinsonian drugs are often held the morning of surgery for deep brain stimulators. This is discussed separately. (See "Anesthesia for deep brain stimulator implantation", section on 'Preoperative evaluation and preparation'.)

●Carbidopa-levodopa has a short duration of action and can be given the night before surgery, and even on the day of surgery itself if the operation is scheduled for later in the day. For patients with postoperative dysphagia, orally disintegrating carbidopa-levodopa (Parcopa) is a potential treatment option. Levodopa tablets can be crushed and given through the tube.

●Dopamine agonists (pramipexole or ropinirole) can usually also be continued close to the time of surgery. They should be resumed as early as possible after the operation (with sips of water or by nasogastric tube). The dopamine agonist rotigotine is available as a transdermal patch.

●Benztropine and diphenhydramine are anticholinergic drugs that are available in parenteral form and can be used in patients who are unable to take oral medication, but they should be used in as low a dose as possible, as they may precipitate an acute confusional state, especially in older adults.

●Apomorphine and lisuride can be administered parenterally for acute symptom management but require special precautions. (See "Initial pharmacologic treatment of Parkinson disease", section on 'Dosing and titration' and "Initial pharmacologic treatment of Parkinson disease", section on 'Swallowing restrictions'.)

All antiparkinsonian medications are active in the central nervous system and can cause an alteration in mental status, as well as side effects such as involuntary movements (dyskinesias), dizziness, hallucinations, dystonia, confusion, somnolence, and insomnia. (See "Initial pharmacologic treatment of Parkinson disease".)

Other medication interactions, concerns — Treatment and prevention of postoperative nausea and vomiting should avoid phenothiazines, which are centrally acting dopamine antagonists and may exacerbate parkinsonism. There is a wide range of alternative medications, which are discussed in detail separately. (See "Postoperative nausea and vomiting", section on 'Antiemetics'.)

The use of meperidine (for postoperative analgesia) should be avoided in patients taking monoamine oxidase type B (MAO-B) inhibitors (selegiline, rasagiline).

Perioperative management of deep brain stimulators is discussed separately. (See "Anesthesia for deep brain stimulator implantation", section on 'Anesthesia for patients with pre-existing DBS'.)

CEREBROVASCULAR DISEASE — Patients with cerebrovascular disease are at risk for perioperative stroke. The assessment of a patient's risk for perioperative stroke and strategies to mitigate that risk are discussed separately. (See "Perioperative stroke following noncardiac, noncarotid, and nonneurologic surgery".)

Patients with cerebrovascular disease (including asymptomatic carotid stenosis) may also be at risk for major adverse cardiac events (MACE), including MACE after noncardiac surgery. (See "Management of asymptomatic extracranial carotid atherosclerotic disease", section on 'Risk of stroke and cardiovascular events' and "Overview of established risk factors for cardiovascular disease", section on 'Noncoronary atherosclerotic disease'.)

The assessment of a patient's cardiac risk prior to noncardiac surgery is discussed separately. (See "Evaluation of cardiac risk prior to noncardiac surgery".)

CHANGE IN MENTAL STATUS (DELIRIUM) — Delirium is a common postoperative complication, particularly in older patients. The two major considerations are the presence of structural central nervous system disease, metabolic derangement, and anesthetic and pain medications. Risk factors, causes, and the evaluation of patients with delirium are discussed separately. (See "Diagnosis of delirium and confusional states".)

Approaches to the prevention and treatment of delirium are discussed separately. (See "Delirium and acute confusional states: Prevention, treatment, and prognosis".)

MYASTHENIA GRAVIS — Perioperative management of patients with myasthenia gravis requires careful thought and planning. Myasthenic crisis with respiratory failure is the most concerning complication in the perioperative period. Perioperative management of myasthenia gravis is discussed in detail separately. (See "Anesthesia for the patient with myasthenia gravis".)

MULTIPLE SCLEROSIS — The signs and symptoms of multiple sclerosis (MS) may worsen in the postoperative period, because of the stress of surgery, perioperative fever, or infection. The choice of anesthetic technique for patients with MS is controversial, particularly with respect to neuraxial anesthesia (ie, spinal or epidural). (See "Obstetric and nonobstetric anesthesia for patients with neurologic disorders".)

Patients with MS who have weakness are at increased risk of life-threatening hyperkalemia with administration of the depolarizing neuromuscular blocking agent (NMBA) succinylcholine, and may have an unpredictable response to the effects of nondepolarizing NMBAs (eg, rocuronium, vecuronium, cisatracurium). (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Patient factors'.)

Temperature should be monitored closely and hyperthermia avoided during anesthesia and in the postoperative period to minimize the risk of temporary MS relapse. (See "Manifestations of multiple sclerosis in adults", section on 'Heat sensitivity'.)

AMYOTROPHIC LATERAL SCLEROSIS — Patients with amyotrophic lateral sclerosis (ALS) are at increased risk of aspiration during sedation and respiratory depression with administration of sedative and anesthetic medications. They are at risk for life-threatening hyperkalemia with administration of succinylcholine, and may have an unpredictable response to nondepolarizing neuromuscular blocking agents (NMBAs), because of the lower motor neuron pathology associated with ALS. (See "Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease" and "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Patient factors'.)

GUILLAIN-BARRÉ SYNDROME — The dysautonomia that occurs in most patients with Guillain-Barré syndrome (GBS) can increase the risk of cardiovascular instability during surgery. (See "Guillain-Barré syndrome in adults: Pathogenesis, clinical features, and diagnosis", section on 'Clinical features'.)

Patients with GBS may exhibit exaggerated hemodynamic responses to surgical stimuli, and orthostatic hypotension with surgical positioning. Succinylcholine should not be administered to patients with GBS because of the risk of severe hyperkalemia. (See "Clinical use of neuromuscular blocking agents in anesthesia", section on 'Adverse effects of succinylcholine'.)

SUMMARY AND RECOMMENDATIONS

●Seizures – Seizures that occur during the perioperative period may be due to metabolic derangements, drug and alcohol withdrawal, or intracranial surgery, or rarely may be anesthetic related. They may also arise from premorbid epilepsy, particularly when antiseizure medication therapy has been disrupted. (See 'Seizure disorders' above.)

•Seizures that occur during a surgical procedure can increase morbidity and mortality.

•Patients with preexisting seizure disorders generally need to have antiseizure medications continued perioperatively, with as little disruption as possible.

•Other patients with new-onset perioperative seizures should probably be treated with antiseizure medication therapy while the underlying cause is evaluated.

●Parkinson disease – The major perioperative issues in patients with Parkinson disease are impaired swallowing and pulmonary function potentially leading to pneumonia. The use of meperidine (for postoperative analgesia) should be avoided in patients taking monoamine oxidase type B (MAO-B) inhibitors (selegiline, rasagiline). Patients may also be at increased risk of postoperative delirium and other medical and surgical complications. (See 'Parkinson disease' above.)

●Cerebrovascular disease – Patients with cerebrovascular disease are at risk for perioperative stroke and for major adverse cardiac events. (See 'Cerebrovascular disease' above.)

●Postoperative delirium – Postoperative delirium may develop in the immediate postoperative period as the patient emerges from anesthesia, or it may follow lucid intervals for several days. Postoperative delirium may be caused by sepsis, medications, and a number of metabolic derangements. Delirium in hospitalized patients increases the length of stay, risk of complications, mortality, and postdischarge institutionalization. (See "Diagnosis of delirium and confusional states" and "Delirium and acute confusional states: Prevention, treatment, and prognosis".)

●Myasthenia gravis – For patients with myasthenia gravis, myasthenic crisis with respiratory failure is the most concerning complication in the perioperative period. The medication regimen should be disrupted as little as possible and medications that can exacerbate myasthenia should be avoided (table 1). (See "Anesthesia for the patient with myasthenia gravis".)

●Neuromuscular disorders – For patients with denervating neuromuscular disorders and neurologic disorders associated with muscle weakness, the depolarizing neuromuscular blocking agent (NMBA) succinylcholine should be avoided during anesthesia because of an increased risk of severe hyperkalemia. These patients may have a variable response to nondepolarizing NMBAs (eg, rocuronium, vecuronium, cisatracurium). (See 'Multiple sclerosis' above and 'Amyotrophic lateral sclerosis' above and 'Guillain-Barré syndrome' above.)