Chapter 28: Anesthesia for Patients with Neurological & Psychiatric Diseases

Patients with vascular and nonvascular neurological diseases or psychiatric disorders are frequently encountered by anesthesia providers. Anesthesiologists must have a basic understanding of the major neurological and psychiatric disorders and their drug therapy. Failure to recognize potential adverse anesthetic interactions may result in avoidable perioperative morbidity.

Preoperative Considerations

Patients with diagnosed cerebrovascular disease typically have a history of transient ischemic attacks (TIAs) or stroke. Patients with TIAs undergoing surgery for other indications have an increased risk of perioperative stroke. Asymptomatic carotid bruits occur in up to 4% of patients older than age 40 years, but do not necessarily indicate significant carotid artery obstruction. Fewer than 10% of patients with completely asymptomatic bruits have hemodynamically significant carotid artery lesions. An asymptomatic carotid bruit may not increase the risk of stroke following surgery, but it increases the likelihood of coexisting coronary artery disease. Moreover, the absence of a bruit does not exclude significant carotid obstruction.

The risk of perioperative stroke increases with patient age and varies with the type of surgery. Although the overall risk of stroke associated with surgery is low, it is greater in patients undergoing cardiovascular or cerebrovascular surgery. Rates of stroke after general anesthesia and surgery range from 0.08% to 0.4%. Even in patients with known cerebrovascular disease, the risk is only 0.4% to 3.3%. Patients at greatest risk of postoperative stroke are those undergoing open heart procedures for valvular disease, coronary artery disease with ascending aortic atherosclerosis, and diseases of the thoracic aorta. Stroke following open heart surgery is usually attributed to embolism of air, clots, or atheromatous debris. In one study, 6% of patients experienced an adverse neurological outcome following cardiac surgery. Stroke following thoracic aortic surgery may be due to emboli or ischemia secondary to prolonged circulatory arrest or a clamp placed close to the origin of the carotid artery.

The pathophysiology of postoperative strokes following noncardiovascular surgery is less clear but may involve severe sustained hypotension or hypertension. Hypotension with severe hypoperfusion can result in so-called “watershed” zone infarctions or thrombosis of cerebral arteries, whereas hypertension can result in intracerebral hemorrhage (hemorrhagic stroke). Sustained hypertension can disrupt the blood–brain barrier and promote cerebral edema. Perioperative atrial fibrillation can likewise lead to atrial clot formation and cerebral embolism. The period of time during which anesthesia and surgery should best be avoided following a stroke is not clear. Abnormalities in regional blood flow and metabolic rate usually resolve after 2 weeks, whereas alterations in CO₂ responsiveness and the blood–brain barrier may require more than 4 weeks. However, urgent surgery is performed for acute intracranial hemorrhage, symptomatic carotid disease, and cardiac sources of emboli.

Patients with TIAs have a history of transient (<24 h) impairment, and, by definition, no residual neurological impairment. These attacks are thought to result from emboli of fibrin-platelet aggregates that form on plaques in extracranial vessels. Unilateral visual impairment, numbness or weakness of an extremity, or aphasia is suggestive of carotid disease, whereas bilateral visual impairment, dizziness, ataxia, dysarthria, bilateral weakness, or amnesia is suggestive of vertebral–basilar disease. Patients with TIAs have a 30% to 40% chance of developing a frank stroke within 5 years; 50% of these strokes occur within the first year. Patients with TIAs should not undergo any elective surgical procedure without an adequate medical evaluation that generally includes at least noninvasive (Doppler) flow and imaging studies. The presence of an ulcerated plaque of greater than 60% occlusion is generally an indication for endovascular intervention or less commonly an open carotid thromboendarterectomy.

PREOPERATIVE MANAGEMENT

Preoperative assessment requires neurological and cardiovascular evaluations. The type of stroke, the presence of neurological deficits, and the extent of residual impairment should be determined. Thromboembolic strokes usually occur in patients with generalized atherosclerosis. Most patients are elderly and have comorbid conditions, such as hypertension, hyperlipidemia, and diabetes. Coexisting coronary artery disease and renal impairment are common. Following nonhemorrhagic strokes or TIAs, many patients are placed on long-term anticoagulant or antiplatelet therapy, or both. Management of antiplatelet therapy and antithrombotic therapy should be reviewed by the anesthesia and surgical teams, often guided by the physician who prescribed the therapy, to determine the risks and benefits of discontinuation or maintenance of such therapy perioperatively. Other systemic diseases, such as diabetes, hypertension, coronary artery disease, heart failure, and chronic obstructive lung disease, frequently manifest in the patient with cerebrovascular disease.

INTRAOPERATIVE MANAGEMENT

Patients may present for surgery following embolic, thrombotic, and hemorrhagic strokes.

Management of the patient following acute embolic stroke is directed toward the embolic source. Cardiac surgery is performed to remove atrial myxomas. Systemic emboli can also be produced from endocarditic vegetations, as well as from degenerated heart valves and intracardiac thrombus.

Patients with acute strokes secondary to carotid and intracranial occlusive arterial disease present for carotid endarterectomy and endovascular procedures. When an awake procedure is undertaken, the patient serves as a monitor of the adequacy of cerebral blood flow during application of vessel clamps or placement of a stent. When general anesthesia is used, electroencephalography, evoked potentials, carotid stump pressure, near-infrared cerebral oximetry, or transcranial Doppler may be used to estimate the adequacy of cerebral oxygen delivery. During open carotid thromboendarterectomy the surgeon may place a shunt to deliver blood to the brain around the cross-clamped vessel. Despite adequate cerebral blood flow, perioperative stroke can occur during carotid surgery secondary to emboli.

Management of patients following thrombotic or hemorrhagic stroke for nonneurological surgery must be individualized. Cerebral autoregulation of blood flow may fail, leaving flow directly dependent upon cerebral perfusion pressure (Figure 28–1). The penumbra of potentially salvageable neurological tissue may therefore be very sensitive to injury from the effects of both hypotension and hypertension (Figure 28–2). We advocate tight control of blood pressure in these patients.

Patients taken to surgery following administration of thrombolytic therapy are at increased risk of cerebral hemorrhage, and tight blood pressure control may reduce the likelihood of cerebral bleeding.

Patients with major intracerebral hemorrhage or epidural or subdural hematomas after trauma typically undergo craniotomy and evacuation of hematoma. In these patients invasive arterial pressure monitoring is helpful given that cerebral autoregulation is deranged (see Figure 28–1). Hypertension is frequently treated with intravenous vasodilators and β-blockers. Subarachnoid hemorrhage is discussed in Chapter 27.

INTRACRANIAL TUMORS

Patients with intracranial mass lesions frequently present to their primary care physicians with complaints of headache, visual disturbances, or seizures. Families may have noticed behavioral changes in patients with frontal lobe masses. Imaging studies confirm the presence of a mass, and initial treatment with dexamethasone is aimed at decreasing cerebral edema. Electrolytes should be reviewed perioperatively in all patients undergoing cranial surgery, as both hyponatremia and hypernatremia can develop secondary to cerebral salt wasting, inappropriate antidiuretic hormone secretion, or central diabetes insipidus (Table 28–1; see also Chapter 49). Patients with altered mentation preoperatively may likewise be dehydrated. Hyperglycemia secondary to steroid use is frequently seen.

Preoperative Considerations

Seizures represent abnormal synchronized electrical activity in the brain. They may be a manifestation of an underlying central nervous system disease, a systemic disorder, or idiopathic. Up to 2% of the population may experience a seizure in their lifetime. Epilepsy is a disorder characterized by recurrent paroxysmal seizure activity. Healthy individuals who experience an isolated nonrecurrent seizure are not considered to have epilepsy.

Seizure activity may be localized to a specific area in the brain or may be generalized. Moreover, initially localized (focal) seizures can subsequently spread, becoming generalized. A simple classification scheme is presented in Table 28–2. Partial seizures (also called focal) are clinically manifested by motor, sensory, autonomic, or psychiatric symptoms, depending on the brain region affected. Focal seizures associated with impairment in consciousness are termed “complex partial” (psychomotor or temporal lobe) seizures. Generalized seizures characteristically produce bilaterally symmetric electrical activity without local onset. They may result in abnormal motor activity, loss of consciousness, or both. Absence (petit mal) seizures produce generalized activity resulting in isolated, transient lapses in consciousness. Other generalized seizures are usually classified according to the type of motor activity. Tonic–clonic (grand mal) seizures are most common and are characterized by a loss of consciousness followed by clonic and then tonic motor activity.

PREOPERATIVE MANAGEMENT

Anesthetic evaluation should focus primarily on the cause and type of seizure activity and the drugs with which the patient is being treated. Seizures in adults are most commonly due to structural brain lesions (head trauma, tumor, degeneration, or stroke) or metabolic abnormalities (uremia, hepatic failure, hypoglycemia, hypocalcemia, drug toxicity, or drug/alcohol withdrawal). Idiopathic seizures occur more often in children than in adults. Grand mal seizures are serious complicating factors in surgical patients and should be treated promptly to prevent musculoskeletal injury, hypoventilation, hypoxemia, and aspiration of gastrointestinal contents. If a seizure occurs, maintaining an open airway and adequate oxygenation are the first priorities. Propofol (50–100 mg) or a benzodiazepine such as diazepam (5–10 mg) or midazolam (1–5 mg) can be given intravenously to terminate the seizure.

Most patients with seizure disorders receive antiepileptic drugs preoperatively (Table 28–3). Antiseizure medications should be continued throughout the perioperative period to maintain therapeutic levels.

INTRAOPERATIVE MANAGEMENT

In selecting general anesthetic agents, we avoid those few drugs with consistent propensity to induce seizures, (eg, enflurane) when there are reasonable alternatives. Theoretically, ketamine and methohexital (in small doses) could precipitate seizure activity. Hypothetically, large doses of atracurium, cisatracurium, or meperidine may be relatively contraindicated because of the reported epileptogenic potential of their respective metabolites, laudanosine, and normeperidine. Hepatic microsomal enzyme induction should be expected from chronic antiseizure therapy. Enzyme induction may increase the dose requirement and frequency of intravenous anesthetics and nondepolarizing neuromuscular blockers (NMBs) and may increase the risk for hepatotoxicity from halothane.

PARKINSON DISEASE

Preoperative Considerations

Parkinson disease (PD) is a common movement disorder that typically afflicts individuals aged 50 to 70 years; it has a prevalence of 3% in the United States and Canada. This neurodegenerative disease is characterized by bradykinesia, rigidity, postural instability, and resting (pill-rolling) tremor. Additional frequently occurring findings include facial masking, hypophonia, dysphagia, and gait disturbances. Increasing problems with freezing, rigidity, and tremor eventually result in physical incapacitation. Early in the course of the disease, intellectual function is usually preserved, but the disease may progress to Lewy body dementia. PD is caused by a progressive loss of dopamine in the nigrostriatal pathway. Concurrent with the loss of dopamine, the activity of the γ-aminobutyric acid (GABA) nuclei in the basal ganglia increases, leading to an inhibition of thalamic and brainstem nuclei. Thalamic inhibition, in turn, suppresses the motor system in the cortex, resulting in the characteristic signs and symptoms.

Medical treatment is directed at controlling the symptoms. A variety of drugs may be used for mild disease, including levodopa, dopamine receptor agonists, monoamine oxidase (MAO) B inhibitors, anticholinergic agents, amantadine, and catechol-O-methyltransferase (COMT) inhibitors.

Moderate to severe disease is typically treated pharmacologically with dopaminergic agents, either levodopa (a precursor of dopamine) or a dopamine-receptor agonist. COMT inhibitors are also used to prevent the decarboxylation of levodopa. Levodopa side effects include nausea, vomiting, dyskinesias, sudden sleepiness, cardiac irritability, and orthostatic hypotension. Dopamine receptor agonists include both ergot derivatives (bromocriptine, cabergoline, lisuride, and apomorphine) and nonergot derivatives (pramipexole and ropinirole). The nonergot derivatives have been shown to be beneficial when used as monotherapy in early PD; all dopamine receptor agonists are effective when given as combination therapy with levodopa in the treatment of moderate to severe PD. Side effects are similar to those found with the use of levodopa alone, and, in addition, include headache, confusion, and hallucinations. Pulmonary, cardiac, and retroperitoneal fibrosis; pleural effusion and thickening; Raynaud syndrome; and erythromelalgia are more common side effects with the use of ergot derivatives than with nonergot derivatives.

The surgical treatment of PD formerly included ablative procedures (thalamotomy and pallidotomy), but implantation of electrodes for deep brain stimulation is currently the most common approach. Stimulation of the subthalamic nucleus improves all of the primary symptoms of PD and results in a greater decrease in the amount of medication required for symptom relief, when compared with stimulation of the globus pallidus pars internus. However, globus pallidus pars internus stimulation may produce greater improvement in dyskinesia as compared with stimulation of the subthalamic nucleus.

Anesthetic Considerations

Medications for PD should be continued perioperatively, including the morning of surgery, because the half-life of levodopa is short. Abrupt withdrawal of levodopa can cause worsening of muscle rigidity and may interfere with ventilation. Phenothiazines, butyrophenones (droperidol), and metoclopramide can exacerbate symptoms as a consequence of their antidopaminergic activity and should be avoided. Anticholinergics (atropine) or antihistamines (diphenhydramine) may be used for acute exacerbation of symptoms. Diphenhydramine may be used for intraoperative sedation in patients with tremor. Induction of anesthesia in patients receiving long-term levodopa therapy may result in either marked hypotension or hypertension. Relative hypovolemia, catecholamine depletion, autonomic instability, and sensitization to catecholamines are probably contributory. Hypotension should be treated with small doses of a direct-acting vasopressor, such as phenylephrine, rather than ephedrine. The response to NMBs is generally normal. As mentioned previously, patients who fail medical treatment are candidates for surgical intervention—for example, implantation of a deep brain stimulator of the subthalamic nucleus, the ventral intermediate nucleus, or the globus pallidus internus. Because general anesthesia alters the threshold for stimulation, correct placement of the electrodes can be affected. Awake craniotomy has been the norm for epilepsy surgery and is being used increasingly for deep brain stimulation procedures. Two techniques are advocated: (1) a true awake craniotomy with heavy sedation (we recommend dexmedetomidine), and (2) an approach in which the patient receives a general anesthetic, usually a total intravenous anesthetic with propofol and remifentanil and a laryngeal mask airway for control of the airway. Following appropriate surgical exposure, the intravenous infusions are discontinued and the laryngeal mask airway is removed. The patient can be reanesthetized once the implantation of leads is complete.

ALZHEIMER DISEASE & OTHER COMMON DEMENTIAS

Preoperative Considerations

Neurodegenerative diseases often lead to dementia. The incidence of dementia varies by population but seems to double every decade of life, starting at age 60. Alzheimer disease (AD) is the most common neurodegenerative disease, causing more than half of all cases of dementia; dementia with Lewy bodies (most often associated with PD) and vascular dementia comprise most of the rest. Slow, progressive impairment of memory, judgment, and decision making, as well as emotional lability, are hallmarks of AD. Late in the course of the disease, severe extrapyramidal signs, apraxias, and aphasia are often present. Patients with AD usually show marked cortical atrophy with ventricular enlargement; the pathological hallmarks of AD seen at necropsy include neurofibrillary tangles that contain the phosphorylated microtubular protein tau, neuritic plaques, and excessive brain concentrations of amyloid β-peptides.

Anesthetic Considerations

Anesthetic management of patients with moderate to severe dementia is often complicated by disorientation and uncooperativeness. New onset of temporary cognitive impairment is frequent in elderly patients and often persists for 1 to 3 days following surgery. Such patients require repeated reassurance and explanation. Legally incompetent patients cannot provide informed consent for anesthesia or surgery. We avoid premedication if at all possible. Centrally acting anticholinergics, such as atropine and scopolamine, may contribute to postoperative confusion. Glycopyrrolate, which does not cross the blood–brain barrier, may be the preferred agent when an anticholinergic is required. Patients having dementia with Lewy bodies often will have PD and thus the anesthetic issues with PD that were addressed earlier in the chapter would apply.

Animal studies have shown that conventional general anesthetic agents are associated with neuronal injury and cell death. The outcome implications of general anesthesia in both the elderly and small children are currently the subject of much investigation and debate. Apoptotic neurodegeneration has been linked to the use of GABA receptor modulators and N-methyl-D-aspartic acid receptor antagonists, mechanisms by which common general anesthetics produce their effects. Moreover, increased β-amyloid production is associated with anesthetic exposure; tau protein phosphorylation increases after general anesthesia; and hypothermia transiently increases tau protein phosphorylation. Despite concerns about anesthetic exposure in patients with or at risk for AD, current studies do not support avoiding needed surgery in this group.

MULTIPLE SCLEROSIS

Preoperative Considerations

Multiple sclerosis (MS) is characterized by demyelination at multiple sites in the brain and spinal cord; chronic inflammation eventually produces scarring (gliosis). Most investigators believe that the disease is an autoimmune disorder; however, the definitive cause has not been identified. MS primarily affects patients between 20 and 40 years of age, with a 2:1 female predominance, and typically follows an unpredictable course of attacks and remissions. With time, remissions become less complete, and the disease progresses to incapacitation; almost 50% of patients will require help with walking within 15 years of diagnosis. Clinical manifestations depend on the sites affected but frequently include sensory disturbances (paresthesias), visual problems (optic neuritis and diplopia), and motor weakness. Symptoms develop over the course of days and remit over weeks to months. Early diagnosis of exacerbations can often be confirmed by analysis of cerebrospinal fluid and magnetic resonance imaging. Remyelination is limited and often fails to occur. Moreover, axonal loss can develop. Changes in neurological function seem to be related to changes in axonal conduction. Conduction can occur across demyelinated axons, but seems to be affected by multiple factors, particularly temperature. In patients with MS, increases in body temperature cause exacerbation of symptoms.

The treatments of MS focus separately on symptoms and attempts to arrest the disease process. Diazepam, dantrolene, or baclofen, and, in refractory cases, an intrathecal delivery system for baclofen are used to control spasticity; bethanechol and other anticholinergics are useful for urinary retention. Painful dysesthesia may respond to carbamazepine, phenytoin, or antidepressants. Glucocorticoids may decrease the severity and duration of acute attacks. Corticosteroid-resistant relapses may respond to five to seven courses of plasma exchange offered on alternate days. Interferon has also been used to treat MS. Immunomodulation with a variety of drugs has been used in an attempt to halt disease progression, and ocrelizumab has received regulatory approval for this indication. The systemic effects of these therapies on coagulation, immunological, hepatic, and cardiac function should be reviewed preoperatively.

Anesthetic Considerations

The effect of stress, anesthesia, and surgery on the course of MS is controversial. Overall, the effect of anesthesia is unpredictable. Elective surgery should be avoided during relapse, regardless of the anesthetic technique employed. The preoperative consent record should document counseling of the patient to the effect that the stress of surgery and anesthesia might worsen symptoms. Spinal anesthesia has been associated with exacerbation of the disease; however, the entire surgery/delivery/anesthetic process may likewise lead to exacerbations. Peripheral nerve blocks are less of a concern because MS is a disease of the central nervous system; however, patients may have preexisting peripheral neuropathies. Epidural and other regional techniques seem to have no adverse effect on the course of the disease. No specific interactions with general anesthetics are recognized. Patients with advanced disease may have a labile cardiovascular system due to autonomic dysfunction. In the setting of paresis or paralysis, succinylcholine should be avoided because of possible hyperkalemia. Increases in body temperature should be avoided. Irrespective of anesthetic technique, patients may experience a worsening of symptoms perioperatively and should be counseled accordingly.

AMYOTROPHIC LATERAL SCLEROSIS

Motor neuron disease is another common neurodegenerative disease, with amyotrophic lateral sclerosis (ALS) being the most prevalent. The cause of ALS is unknown, although small numbers of patients with the familial form of the disease have a defect in the superoxide dismutase-1 gene. ALS is a rapidly progressive disorder of both upper and lower motor neurons. Patients often present in the fifth or sixth decade of life with muscular weakness, atrophy, fasciculation, and spasticity. The disease may initially be asymmetric, but over the course of 2 to 3 years becomes generalized, involving all skeletal and bulbar muscles. Progressive respiratory muscle weakness makes the patient susceptible to aspiration and eventually leads to death from ventilatory failure. Although the heart is unaffected, autonomic dysfunction can be seen. There is no specific treatment for ALS.

The primary emphasis in management is judicious respiratory care. As with other patients with lower motor neuron disease, succinylcholine is contraindicated because of the risk of hyperkalemia. Adequacy of ventilation should be carefully assessed both intraoperatively and postoperatively; an awake extubation is desirable. Difficulty in weaning patients from mechanical ventilation postoperatively may be anticipated in patients with advanced disease.

GUILLAIN–BARRÉ SYNDROME

Guillain–Barré syndrome (GBS), a relatively common disorder affecting 1 to 4 individuals per 100,000 population, is characterized by a sudden onset of ascending motor paralysis, areflexia, and variable paresthesias. Subtypes of GBS include acute inflammatory demyelinating polyneuropathy (about 75% of cases), acute motor axonal neuropathy (with antibodies against gangliosides), and acute motor sensory axonal neuropathy. Bulbar involvement, including respiratory muscle paralysis, is a frequent complication. Pathologically, the disease seems to be an immunological reaction against the myelin sheath of peripheral nerves, particularly lower motor neurons. In most instances, the syndrome seems to follow an infection; the disorder can also present as a paraneoplastic syndrome associated with Hodgkin disease or as a complication of human immunodeficiency virus infection. Some patients respond to plasmapheresis. The prognosis is relatively good, with most patients recovering completely; however, approximately 10% of patients die of complications, and another 10% are left with long-term neurological sequelae.

Anesthetic management is complicated by lability of the autonomic nervous system in addition to concerns about respiratory insufficiency. Exaggerated hypotensive and hypertensive responses during anesthesia may be seen. As with other lower motor neuron disorders, succinylcholine should not be used because of the risk of hyperkalemia. The use of regional anesthesia in these patients remains controversial, as it might worsen symptoms. As with all decisions, the risks and benefits of regional versus general anesthesia must be weighed on an individual basis. As damaged nerves are more susceptible to a second injury (the “double crush” effect), performance of regional techniques in patients with preexistent neurological dysfunction should be carefully considered.

AUTONOMIC DYSFUNCTIONS

Preoperative Considerations

Autonomic dysfunction, or dysautonomia, may be due to generalized or segmental disorders of the central or peripheral nervous system. Symptoms can be generalized, segmental, or focal. These disorders may be congenital, familial, or acquired. Common manifestations include impotence; bladder and gastrointestinal dysfunction; abnormal regulation of body fluids; decreased sweating, lacrimation, and salivation; and orthostatic hypotension. The latter can be the most serious manifestation of the disorder.

Acquired autonomic dysfunction can be isolated (pure autonomic failure), part of a more generalized degenerative process (Shy–Drager syndrome, PD, olivopontocerebellar atrophy), part of a segmental neurological process (MS, syringomyelia, reflex sympathetic dystrophy, or spinal cord injury), or a manifestation of disorders affecting peripheral nerves (GBS, diabetes, chronic alcoholism, amyloidosis, or porphyria).

There are at least three forms of hereditary sensory and autonomic neuropathies, each with its own underlying genetic mutation(s). Autonomic dysfunction is prominent and is associated with generalized diminished sensation and emotional lability. Moreover, patients are predisposed to dysautonomic crises triggered by stress and characterized by marked hypertension, tachycardia, abdominal pain, diaphoresis, vomiting, and the risk of dehydration.

Anesthetic Considerations

The major risk of anesthesia in patients with autonomic dysfunction is severe hypotension, compromising cerebral and coronary blood flow. Marked hypertension can be equally deleterious. Most patients are chronically hypovolemic, and if volume deficits are not corrected the vasodilatory effects of spinal and epidural anesthesia are poorly tolerated. The vasodilatory and cardiac depressant effects of most general anesthetic agents combined with positive airway pressure can be equally problematic. Continuous intraarterial blood pressure monitoring is useful. Hypotension should be treated with fluids and direct-acting vasopressors (in preference to indirect-acting agents). The dose–response relationship for vasopressors may be abnormal due to denervation. Blood loss also is usually poorly tolerated. Body temperature should be monitored closely. Patients with anhidrosis are particularly susceptible to hyperpyrexia.

SYRINGOMYELIA

Syringomyelia results in progressive cavitation of the spinal cord. In many cases, obstruction of cerebrospinal fluid outflow from the fourth ventricle seems to be contributory. Many patients have craniovertebral abnormalities, particularly the Arnold–Chiari malformation. Increased pressure in the central canal of the spinal cord produces enlargement or diverticulation to the point of cavitation. Syringomyelia typically affects the cervical spine, producing sensory and motor deficits in the upper extremities, and, frequently, thoracic scoliosis. Extension upward into the medulla (syringobulbia) leads to cranial nerve deficits. Syringo-peritoneal shunting and other decompressive procedures have variable success in arresting the disease.

Anesthetic evaluation should focus on defining existing neurological deficits and any pulmonary impairment due to scoliosis. Autonomic instability should be expected in patients with extensive lesions. Succinylcholine should be avoided when muscle wasting is present because of the risk of hyperkalemia. As always, adequacy of ventilation and reversal of nondepolarizing NMBs should be achieved prior to extubation. Spinal puncture is contraindicated with intracranial hypertension. Epidural anesthetics have been used successfully for labor analgesia in patients with Arnold–Chiari malformations, with and without syringomyelia. Risks of cerebral herniation, worsening nerve injury, and infection must be weighed against potential benefits.

Preoperative Considerations

Spinal cord injuries are most often traumatic and may arise from partial or complete transection. The majority of injuries are due to fracture and dislocation of the vertebral column. The mechanism is usually either compression and flexion at the thoracic spine or extension at the cervical spine. Clinical manifestations depend on the level of the injury. Injuries above C3–5 (diaphragmatic innervation) require patients to receive ventilatory support to stay alive. Transections above T1 result in quadriplegia, whereas those above L4 result in paraplegia. The most common sites of injury are C5–6 and T12–L1. Acute spinal cord transection produces loss of sensation, flaccid paralysis, and loss of spinal reflexes below the level of injury. These findings characterize a period of spinal shock that typically lasts 1 to 3 weeks.

Over the course of the next few weeks, spinal reflexes gradually return, together with muscle spasms and signs of sympathetic overactivity. Injury in the low thoracic or lumbar spine may result in cauda equina (conus medullaris) syndrome. The latter usually consists of incomplete injury to nerve roots rather than the spinal cord.

Overactivity of the sympathetic nervous system is common with transections at T5 or above, but is unusual with injuries below T10. Interruption of normal descending inhibitory impulses in the cord results in autonomic hyperreflexia. Cutaneous or visceral stimulation below the level of injury can induce intense autonomic reflexes: sympathetic discharge produces hypertension and vasoconstriction below the transection and a baroreceptor-mediated reflex bradycardia and vasodilation above the transection. Cardiac arrhythmias are common.

Emergent surgical management is undertaken whenever there is reversible compression of the spinal cord due to dislocation of a vertebral body or bony fragment. Operative treatment is also indicated for spinal instability to prevent further injury.

Anesthetic Considerations

A. Acute Transection

Anesthetic management depends on the age of the injury. In the early care of acute injuries, the emphasis should be on preventing further spinal cord damage during patient movement, airway manipulation, and positioning. High-dose corticosteroid therapy (methylprednisolone) has been traditionally given for the first 24 h following injury to possibly improve neurological outcome. Airway management of the patient with an unstable cervical spine is discussed in Chapter 19. Patients with high transections often have impaired airway reflexes and are further predisposed to hypoxemia because of a decrease in functional residual capacity and atelectasis. Spinal shock can lead to hypotension and bradycardia prior to any anesthetic administration. Direct arterial pressure monitoring is helpful. An intravenous fluid bolus and the use of ketamine for anesthesia may help to prevent further decreases in blood pressure; vasopressors may also be required. Succinylcholine can be used safely in the first 24 h but should not be used thereafter because of the risk of hyperkalemia. The latter can occur within the first week following injury and is due to excessive release of potassium secondary to the proliferation of acetylcholine receptors beyond the neuromuscular synaptic cleft.

B. Chronic Transection

Anesthetic management of patients with nonacute transections is complicated by the possibility of autonomic hyperreflexia and the risk of hyperkalemia. Autonomic hyperreflexia should be expected in patients with spinal cord lesions above T6 and can be precipitated by surgical manipulations. Regional anesthesia and deep general anesthesia are effective in preventing hyperreflexia. Many clinicians, however, are reluctant to administer spinal and epidural anesthesia in these patients because of the difficulties encountered in determining anesthetic level, exaggerated hypotension, and technical problems resulting from deformities. Severe hypertension can result in pulmonary edema, myocardial ischemia, or cerebral hemorrhage and should be treated promptly. Direct arterial vasodilators should be readily available. Nondepolarizing muscle relaxants may be used. Body temperature should be monitored carefully, particularly in patients with transections above T1, because chronic vasodilation and loss of normal reflex cutaneous vasoconstriction predispose to hypothermia. Many patients with a long-standing spinal cord injury have a long history of undergoing surgery without hyperreflexia. These patients can often be managed with monitoring and sedation.

Various forms of encephalitis can present secondary to infectious or autoimmune mechanisms. Patients with encephalitis are managed with the normal care given any patient with potentially increased intracranial pressure at risk of cerebral hypoperfusion.

DEPRESSION

Depression is a very common mood disorder characterized by sadness and pessimism. Its cause is multifactorial, but pharmacological treatment is based on the presumption that its manifestations are due to a brain deficiency of dopamine, norepinephrine, and serotonin or altered receptor activities. Up to 50% of patients with major depression hypersecrete cortisol and have abnormal circadian secretion. Current pharmacological therapy utilizes drugs that increase brain levels of these neurotransmitters: tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), MAO inhibitors, and atypical antidepressants. The mechanisms of action of these drugs result in some potentially serious anesthetic interactions. Electroconvulsive therapy (ECT) is increasingly used for refractory severe cases and may be continued prophylactically after the patient’s mood recovers. The use of general anesthesia for ECT is largely responsible for its safety and widespread acceptance.

Selective Serotonin Reuptake Inhibitors

SSRIs include fluoxetine, sertraline, and paroxetine, which some clinicians consider first-line agents of choice for depression. A surprisingly large fraction of patients undergoing elective surgery will be receiving one of these agents. These agents have little or no anticholinergic activity and do not generally affect cardiac conduction. Their principal side effects are headache, agitation, and insomnia. Other agents include the norepinephrine–dopamine reuptake inhibitors and the serotonin–norepinephrine reuptake inhibitors.

Tricyclic Antidepressants

Tricyclic antidepressants are used for the treatment of depression and chronic pain syndromes. All tricyclic antidepressants work at nerve synapses by blocking neuronal reuptake of catecholamines, serotonin, or both. Desipramine and nortriptyline are used because they are less sedating and tend to have fewer side effects. Other agents are generally more sedating and include amitriptyline, imipramine, protriptyline, amoxapine, doxepin, and trimipramine. Clomipramine is used in the treatment of obsessive–compulsive disorders. Most tricyclic antidepressants also have significant anticholinergic (antimuscarinic) actions: dry mouth, blurred vision, prolonged gastric emptying, and urinary retention. Quinidine-like cardiac effects include tachycardia, T-wave flattening or inversion, and prolongation of the PR, QRS, and QT intervals. Amitriptyline has the most marked anticholinergic effects, whereas doxepin has the fewest cardiac effects.

Herbal Approaches

St. John’s wort is being used with increased frequency as an over-the-counter therapy for depression. Because it induces hepatic enzymes, blood levels of other drugs may decrease, sometimes with serious complications. During the preoperative evaluation, the use of all over-the-counter medications should be reviewed.

Perioperative Management

Antidepressant drugs are generally continued perioperatively. Increased anesthetic requirements, presumably from enhanced brain catecholamine activity, have been reported with these agents. Potentiation of centrally acting anticholinergic agents (atropine and scopolamine) may increase the likelihood of postoperative sedation, confusion, delirium, blurred vision, and urinary retention. The most important interaction between anesthetic agents and tricyclic antidepressants is an exaggerated response to both indirect-acting vasopressors and sympathetic stimulation. Chronic therapy with tricyclic antidepressants is reported to deplete cardiac catecholamines, theoretically potentiating the cardiac depressant effects of anesthetics. If hypotension occurs, small doses of a direct-acting vasopressor should be used instead of an indirect-acting agent. Amitriptyline’s anticholinergic action may occasionally contribute to postoperative delirium.

Monoamine Oxidase Inhibitors

MAO inhibitors were the first medications shown to be effective for depression. They are no longer considered first- or second-line agents due to their side effects. MAO inhibitors block the oxidative deamination of naturally occurring amines. At least two MAO isoenzymes (types A and B) with differential substrate selectivities have been identified. MAO-A is selective for serotonin, dopamine, and norepinephrine, whereas MAO-B is selective for dopamine and phenylethylamine. Nonselective MAO inhibitors include phenelzine, isocarboxazid, and tranylcypromine. Selective MAO-B inhibitors are useful in the treatment of PD. Additionally, unlike older nonreversible MAO inhibitors, reversible MAO-A inhibitors have been developed. Side effects include orthostatic hypotension, agitation, tremor, seizures, muscle spasms, urinary retention, paresthesias, and jaundice. The most serious sequela is a hypertensive crisis that occurs following ingestion of tyramine-containing foods (cheeses and red wines), because tyramine is used to generate norepinephrine.

Phenelzine can decrease plasma cholinesterase activity and prolong the duration of succinylcholine. Opioids should generally be used with caution in patients receiving MAO inhibitors, as rare but serious reactions to opioids have been reported. Most serious reactions are associated with meperidine, resulting in hyperthermia, seizures, and coma. Meperidine should not be administered to patients receiving MAO inhibitors. As with tricyclic antidepressants, exaggerated responses to vasopressors and sympathetic stimulation should be expected. If a vasopressor is necessary, a direct-acting agent in small doses should be employed. MAO inhibitors are used today infrequently.

Patients taking St. John’s wort are at increased risk of serotonin syndrome, as are those taking drugs with similar effects (eg, MAO inhibitors, meperidine). Serotonin syndrome manifestations include agitation, hypertension, hyperthermia, tremor, acidosis, and autonomic instability. Treatment is supportive, along with the administration of a 5-HT antagonist (eg, cyproheptadine).

BIPOLAR DISEASE

Mania is a mood disorder characterized by elation, hyperactivity, and flight of ideas. Manic episodes may alternate with depression in patients with a bipolar (formerly manic–depressive) disorder. Mania is thought to be related to excessive norepinephrine activity in the brain. The most common agents used for maintenance therapy for this condition are lithium, valproate, quetiapine, and lamotrigine. Aripiprazole, olanzapine, and risperidone are used if the first group fails.

The mechanism of action of lithium is poorly understood. It has a narrow therapeutic range, with a desirable blood concentration between 0.8 and 1.0 mEq/L. Side effects include reversible T-wave changes, mild leukocytosis, and, on rare occasions, hypothyroidism or a vasopressin-resistant diabetes insipidus-like syndrome. Toxic blood concentrations produce confusion, sedation, muscle weakness, tremor, and slurred speech. Still higher concentrations result in widening of the QRS complex, atrioventricular block, hypotension, and seizures.

Although lithium is reported to decrease minimum alveolar concentration and prolong the duration of some NMBs, clinically these effects seem to be minor. Blood levels should be checked perioperatively. Sodium depletion (secondary to loop or thiazide diuretics) decreases renal excretion of lithium and can lead to lithium toxicity. Fluid restriction and overdiuresis should be avoided. Lithium dilution cardiac output measurements are contraindicated in patients on lithium therapy.

SCHIZOPHRENIA

Patients with schizophrenia display delusions, hallucinations, disorganized or withdrawn behavior, disorganized speech, and severe emotional withdrawal. The diagnoses of schizoaffective disorder, bipolar disorder, and severe depression will need to be excluded. Schizophrenia is thought to result from an excess of dopaminergic activity in the brain.

The most commonly used antipsychotics include phenothiazines, thioxanthenes, phenylbutylpiperidines, dihydroindolones, dibenzapines, benzisoxazoles, and butyrophenones. There are numerous trade names for these drugs. First-generation antipsychotic medications had strong dopamine antagonistic effects, leading to extrapyramidal side effects (eg, muscle rigidity and progression to tardive dyskinesia). Second-generation agents have less dopamine antagonism and reduced extrapyramidal effects. The antipsychotic effect of these agents seems to be due to dopamine antagonist activity. Most cause weight gain and sedation and are mildly anxiolytic. Mild α-adrenergic blockade and anticholinergic activity are also observed. Side effects include orthostatic hypotension, acute dystonic reactions, and parkinsonism-like manifestations. Risperidone and clozapine have little extrapyramidal activity, but the latter is associated with a significant incidence of granulocytopenia. T-wave flattening, ST segment depression, and prolongation of the PR and QT intervals may be seen, increasing the risk of les torsades des pointes.

Continuing antipsychotic medication perioperatively is desirable. Reduced anesthetic requirements may be observed in some patients, and some patients may experience perioperative hypotension.

NEUROLEPTIC MALIGNANT SYNDROME

Neuroleptic malignant syndrome is a rare and life-threatening complication of antipsychotic therapy that may occur hours or weeks after drug administration. It has also accompanied abrupt withdrawal of medication for PD. Meperidine and metoclopramide can also precipitate the disorder. The mechanism is related to dopamine blockade in the basal ganglia and hypothalamus and impairment of thermoregulation. In its most severe form, the presentation is similar to that of malignant hyperthermia. Muscle rigidity, hyperthermia, rhabdomyolysis, autonomic instability, and altered consciousness are seen. Creatine kinase levels are often high. The mortality rate approaches 20% to 30%, with deaths occurring primarily as a result of kidney failure or arrhythmias. Treatment begins with stopping the offending agent and initiating supportive care. Dantrolene and bromocriptine have been used, but there is no strong evidence for consistent efficacy. Differential diagnoses include serotonin syndrome, malignant hyperthermia, malignant catatonia, and some other acute intoxications (eg, cocaine).

SUBSTANCE ABUSE

Behavioral disorders from abuse of psychotropic (mind-altering) substances may involve a socially acceptable drug (alcohol), a medically prescribed drug (eg, an opioid or diazepam), or an illegal substance (eg, cocaine or “ecstasy”). With chronic abuse, patients develop tolerance to the drug and varying degrees of psychological and physical dependence. Physical dependence is most often seen with opioids, barbiturates, alcohol, and benzodiazepines. Life-threatening complications primarily due to sympathetic overactivity can develop during abstention.

Knowledge of a patient’s substance abuse preoperatively may prevent adverse drug interactions, predict tolerance to anesthetic agents, and facilitate the recognition of drug withdrawal. The history of substance abuse may be volunteered by the patient (usually only on direct questioning) or deliberately hidden.

Anesthetic requirements for substance abusers vary, depending on whether the drug exposure is acute or chronic (Table 28–4). Elective procedures should be postponed for acutely intoxicated patients and those with signs of withdrawal. When surgery is deemed necessary in patients with physical dependence, perioperative doses of the abused substance should be provided, or specific agents should be given to prevent withdrawal. In the case of opioid dependence, any opioid can be used, whereas for alcohol, a benzodiazepine is usually substituted due to the reluctance of hospital pharmacies to dispense alcohol-containing beverages to patients. Alcoholic patients should receive B vitamin/folate supplementation to prevent Korsakoff syndrome. Tolerance to most anesthetic agents is often seen but is not always predictable. For general anesthesia, a technique primarily relying on a volatile inhalation agent may be preferable so that anesthetic depth can be readily adjusted according to individual need. Awareness monitoring should be likewise considered. Opioids with mixed agonist–antagonist activity can precipitate acute withdrawal. Nevertheless, buprenorphine is often used to manage substance disorders. Clonidine is a useful adjuvant in the treatment of postoperative withdrawal syndromes.

Patients routinely present acutely intoxicated for emergency surgery following trauma related to substance abuse. Patients may have consumed more than one intoxicating agent. Acute cocaine intoxication may produce hypertension secondary to the increase in central neurotransmitters, such as norepinephrine and dopamine. Hypertension and arrhythmias can occur perioperatively. Chronic abusers deplete their sympathomimetic neurotransmitters, potentially developing hypotension. Amphetamine abusers have similar anesthetic concerns, as amphetamines also affect the sympathetic nervous system.

Patients on chronic, prescribed opioid therapy, or those taking medications illicitly, have substantially increased postoperative opioid requirements. We strongly advocate for multimodal approaches to pain control perioperatively. Whenever possible patients should remain on their maintenance methadone or buprenorphine.

Consultation with pain management and addiction specialists is often indicated.