Perioperative management of patients wit

Postoperative delirium acute confusional state is a common and not unexpected problem in elderly patients in general and in neurologic patients specifically, particularly in patients who

Perioperative management of patients

with neurologic disease

a Mayo Graduate School of Medicine, Rochester, MN, USA

b Mayo Clinic, Jacksonville, FL, USA

There is little in the medical literature on perioperative management of patients who have neurologic diseases Most likely this is because perioperative management of patients who have neurologic diseases does not differ much from management of patients who do not have neurologic diseases, except in certain situations, such as patients who have neuromus-cular diseases, especially myasthenia gravis (MG) There are, however, problems that can occur in patients who harbor central nervous system disorders and also in patients who have peripheral nervous system disorders Even though age is not a neurologic disease, age must be considered at least

a neurologic risk factor in surgery of any type Many surgical procedures are performed in elderly patients, who suffer complications similar to those patients who have neurologic diseases

Exacerbations of neurologic signs and symptoms are common in the neurologic patient when there is a superimposed systemic illness or stress, as occurs in surgery In reality, these are pseudo-exacerbations but often are mistaken for progression of the underlying neurologic disease When the superimposed systemic problem or stress of surgery is alleviated, the neuro-logic patient slowly returns to his or her baseline The important issue is to treat the superimposed problem and not change treatment for the underlying neurologic disorder and not order further neurologic testing If there is an increase in signs and symptoms of the underlying neurologic disorder after surgery, the patient, family, and medical personnel need to be reassured that the patient will return to baseline after recovery from surgery

Postoperative delirium (acute confusional state) is a common and not unexpected problem in elderly patients in general and in neurologic patients specifically, particularly in patients who have dementia, Parkinson’s disease

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or related disorders, previous stroke, multiple sclerosis, or previous head trauma or brain tumors Sudden withdrawal of certain drugs, such as anti-convulsants or dopaminergics, can lead to problems, such as status epilepticus and the neuroleptic malignant syndrome Headache might be difficult to manage in the postoperative migraineur Neurologic patients who have weakness from their neurologic disease, and especially patients who have a neuropathy of any etiology, are prone to compressive neuro-pathies in the preoperative, operative, and postoperative periods Patients in general who spend any time in ICUs are subject to critical illness neuropathy/myopathy; neuromuscular dysfunction acquired in the ICU frequently is reported in patients who have sepsis, multiple organ dysfunction, or both [1] The epileptic patient might be prone to increased seizure frequency with the stress of surgery The free level of phenytoin must be assessed in the critically ill epileptic patient who has been on phenytoin and is in need of blood level monitoring, because the total level may be falsely low Phenytoin is highly protein bound and measurement of unbound phenytoin concentrations (free-level) may be more indicative of its pharmacologic effect Total phenytoin concentrations and carbamazepine levels may vary up to 20% at steady state even in compliant patients[2,3] The important concept is to treat the patient and not the blood level Because many of the perioperative problems of the neurologic patient are predictable, they should be anticipated by the neurologist so that measures can be taken to prevent as many as possible and to recognize and manage those that cannot be prevented in a timely, efficient manner

Myasthenia gravis

Neuromuscular diseases produce physiologic changes that may effect perioperative and anesthesia care MG probably is the most common requiring perioperative management by a neurologist MG is an autoim-mune disorder of neuromuscular transmission involving the production of autoantibodies directed against the nicotinic acetylcholine receptor The Lambert-Eaton myasthenic syndrome is a rare disorder of neuromuscular transmission in which muscle weakness results from a defect of presynapic acetylcholine release at the myoneural junction and involves the production

of autoantibodies directed against voltage-gated calcium channels in the nerve terminal The clinical manifestations and medical treatment of these en-tities are well described by Pascuzzi[4], and perioperative anesthesia care for patients who have neuromuscular diseases is well described by Book et al[5] Elective surgery and certainly thymectomy should be performed during

a stable phase of MG; thymectomy never should be considered an emergency procedure[6] The surgical procedure and choice of anesthesia are made by the surgeon and the anesthesiologist, but the clinical neurologist is extremely important in the management of the pre- and postoperative care of the myasthenic patient The myasthenic patient typically is sensitive to the

nondepolarizing neuromuscular blockers and shows resistance to depolariz-ing agents [5–7] Sensitivity to nondepolarizing agents, however, has been described in patients who have mild disease, in patients in remission, and in undiagnosed cases[8–10] Because it takes an average of approximately 5 years for the diagnosis of MG to be established (even in retrospect in patients with suspicious symptoms), it is not surprising for patients who have undiagnosed cases to undergo surgical procedures; the diagnosis then may be suspected in those patients who are sensitive to drugs that are well known to worsen MG The best preoperative assessment of the myasthenic patient is by

a comprehensive neurologic history and neurologic examination Bulbar signs and symptoms are primary risk factors for postoperative respiratory difficulties Although respiratory muscle strength can be quantified by pul-monary function tests, such as negative inspiratory pressure and forced ex-piratory capacity, the neurologist’s bedside assessment is an important diagnostic tool Even if the respiratory parameters are normal, one can predict that a patient who has facial weakness, dysarthria, dysphagia, and especially neck flexion weakness soon will develop respiratory difficulties For an elective procedure, the patient should be stable and either on no steroids or the lowest dose possible In an emergent situation, the unstable patient can be ‘‘tuned up’’ either with plasma exchange or intravenous immunoglobulin (IVIG) therapy Some investigators believe that improve-ment is more rapid after plasma exchange compared with IVIG but that the side effects observed with IVIG are more benign than those seen with plasma exchange[11] In addition, if pyridostigmine is needed parenterally

in the pre- or postoperative period, the dose is approximately 1/30 of the oral dose Some anesthesiologists recommend administering one half the morning dose of pyridostigmine on the day of surgery for patients who have mild disease and the full dose for patients who have more severe disease; alternatively, some anesthesiologists do not administer pyridostigmine on the morning of surgery to decrease the dose of muscle relaxant needed Cholinesterase depletion from plasma exchange or inhibition caused by pyridostigmine given preoperatively may affect the metabolism of neuro-muscular blockage agents, such as succinylcholine and mivacurium, result-ing in prolonged blockade[12]

Finally, in the preoperative period, other autoimmune diseases that can

be associated with MG, including diabetes mellitus, hyper- and hypothy-roidism, systemic lupus erythematosus, and rheumatoid arthritis, must be evaluated and controlled High cervical spine involvement with rheumatoid arthritis may severely limit neck flexion and extension during surgery, or excessive movement may cause complications after surgery

Although the anesthesiologist makes the choice of anesthetic agents and muscle relaxants, the neurologist should be acquainted at least with the effects of these drugs on the myasthenic patient Inhalation anesthetics are associated with some degree of reduced neuromuscular transmission, leading to muscle relaxation in the patient who does not have MG; this

effect may be profound in the myasthenic patient Alternatively, intravenous anesthetic agents, such as barbiturates and propofol, have been used successfully in myasthenic patients [13]

Because the myasthenic patient is sensitive to nondepolarizing (antago-nist) neuromuscular blockers, usually only one fifth of the dose required in nonmyasthenic patients is necessary; long-acting muscle relaxants are best avoided Short-acting drugs obviate the need for reversal with an anticho-linesterase, which may cause a cholinergic crisis in the postoperative period Local anesthetics may potentiate neuromuscular blocking agents by decreasing sensitivity of the muscle receptor to acetylcholine Ester anesthetics, which are metabolized by cholinesterase, may present particular problems in patients taking anticholinesterases (pyridostigmine) Therefore, regional and local anesthesia should be performed using reduced doses, to avoid high blood levels, and with amide (rather than ester) local anesthetics Epidural blockade with bupivacaine for intraoperative anesthesia and postoperative analgesia has been used successfully [14] Spinal anesthesia has the advantage of reduced drug dosage, whereas epidural techniques facilitate easier control of blockade level and may obviate the need for opioids in the postoperative pain management [7]

Adequate postoperative pain control, pulmonary toilet, and the avoidance of drugs that interfere with neuromuscular transmission facilitate tracheal extubation in the postoperative period [5,7] Lumbar epidural morphine can be successful in helping to control postoperative pain without increasing respiratory depression[15]

Several common drugs well known to neurologists can cause weakness in the myasthenic patient; these drugs include aminoglycosides, procainamide,

b-adrenergic receptor blockers, and even anticonvulsants, especially

phenyt-oin, even though phenytoin has been used successfully in treating seizures in the myasthenic patient[16]

The differential diagnosis of weakness in the postoperative period includes myasthenic crisis, residual effects of anesthetic drugs, interference

of nonanesthetic drugs with neuromuscular transmission, and cholinergic crisis[5,7] Myasthenic crisis and cholinergic crisis are neurologic emergen-cies They are defined by respiratory failure as the main symptom, and often appear together in the same patient Although some neurologists attempt to differentiate these two states by looking for cholinergic side effects of the anticholinesterase drugs or by the administration of intravenous edropho-nium, from a practical standpoint the patient’s respiratory difficulties need to

be managed in an ICU After obtaining respiratory control, usually under endotracheal intubation, there is time to decide the best therapeutic medications and the route of administration that best suits the patient’s clinical situation The pathophysiology and treatment of options for MG are reviewed by Drachman[17]

Patients who have Lambert-Eaton myasthenic syndrome are extremely sensitive to depolarizing and nondepolarizing muscle relaxants Residual

paralysis after the use of muscle relaxants may last days, and reversal with acetylcholinesterase inhibitors is poor If there is inadequate reversal, 3,4-diaminopyridine may be effective [18] 3,4-diaminopyridine blocks nerve membrane potassium efflux, prolonging the duration of the action po-tential and allowing the reduced number of calcium channels to remain open longer[19]

Delirium (acute confusional state)

Any patient who has any central nervous system (CNS) disorder is prone

to delirium, especially in the postoperative period Although delirium is common, especially in elderly patients, it often is unrecognized, perhaps because its features develop rapidly and tend to fluctuate and because there may be increased psychomotor activity (hyperactive form), decreased psychomotor activity (hypoactive form), or a combination of the two (mixed form) The etiology of delirium often is complex and multifactorial, involving the interaction of precipitating factors superimposed on a vulner-able patient who has predisposing conditions[20] Even though the causes are multiple and complex, they often are obvious and predictable after

a thorough review of the clinical chart, including special attention paid to medications and an extensive historical review with the family The famous line from the movie Casablanca applies to the causes of delirium: ‘‘round up the usual suspects.’’ The usefulness of extensive of laboratory testing, especially neuroimaging and cerebrospinal fluids analysis, has not been demonstrated[21,22] Alternatively, the electroencephalogram (EEG) often

is underused and can be a valuable diagnostic tool; for example, EEG is necessary to diagnose nonconvulsive status epilepticus, which may present

as a confusional state

It is important not only to recognize delirium but also to be able to predict it in vulnerable patients, because it is associated with higher mortality and morbidity and poor functional recovery and longer lengths of hospital stay Delirium can be divided into five major categories [23]: (1) systemic diseases, especially infections of the urinary tract and lung, and organ failure of any type, all of which secondarily affect the brain; (2) toxins and drugs, especially prescribed and over-the-counter drugs that primarily affect the brain; (3) withdrawal of drugs and substances of abuse, especially alcohol and benzodiazepines and other sedatives or hypnotic drugs; (4) pri-mary cerebral diseases, such as acute cerebral infarction (although this is an uncommon cause)[24]; ictal and postictal states and CNS infections in im-munocompromised patients; and (5) psychophysiologic states including anxiety, sensory deprivation, overstimulation, and unfamiliar environment Iatrogenic influences contributing to delirium during hospitalization include the following: (1) dehydration; (2) disorienting influences; (3) drugs, especially psychoactive medications; (4) immobilization; and (5) sleep deprivation[25]

The incidence of postoperative confusion is higher in older people than in any other age group The incidence of postoperative delirium in the elderly generally is between 10% to 60% and is broken down as follows[23,26]: (1) the incidence in general surgery is from 10% to 14%; (2) in open heart surgery from 32% to 79%; (3) in orthopedic surgery, mainly hip surgery, from 32% to 55%; and (4) after cataract surgery from 1% to 3%

The risk of delirium arises from the interplay between the patient’s baseline vulnerability and acute physiologic stress[27] The type of surgery reflects the severity of the physiologic stress and the vulnerability factors, include advanced age, alcohol abuse, cognitive impairment (even mild dementia), poor physical function, abnormal laboratory values, polypharmacy (espe-cially with psychoactive drugs and chronic narcotic use), depression and anxiety, and any type of previous cerebral disease Postoperative exposure to meperidine, which has much more anticholinergic activity than any other narcotic and benzodiazepines, also is associated with postoperative delirium [28] Pain and medications to treat pain can cause delirium, but meperidine, propoxyphene, and pentazocine should be avoided if possible in elderly patients and neurologic patients, especially because these drugs can impair renal function[29,30]

Approximately 98% of postoperative delirium occurs within 3 days of surgery[31] In the first 24 hours after surgery, patients who have undergone regional anesthesia maintain cognitive function better than patients who have had other types of anesthesia, but this difference fades quickly, and after 3 days there is no statistical difference in the effects of general, epidural, regional, or spinal anesthesia on postoperative confusion Thus, in the first

24 to 48 hours, the effects of residual anesthetics are considered important, but after that they are not[32,33]

Other intraoperative risk factors include the type of surgery: for example, cardiac surgery may lead to cerebral hypoprofusion and microemboli of air, RBC/fibrin, platelet/fibrin, or cholesterol plaques; orthopedic surgery may cause fat emboli; and cataract surgery may cause problems because of bilat-eral loss of vision and use of anticholinergic drugs Postoperative risk factors include hypoxia, hypocarbia, sepsis, hypotension, fluid and electrolyte imbalance, anemia, and medications[27,33]

It is important to solicit the help of family members, caregivers, and the nursing staff in the pre- and postoperative assessment and therapeutic programs Everyone should be aware of the patient at risk, especially the patient who has CNS disease, so that postoperative confusion is not

a complete surprise Likewise, as the patient improves, everyone should know that periods of fluctuation will continue and that return to baseline may take days or even weeks The first considerations in the management of delirium are to make sure that there is no underlying medical problem; that pain is under control; and that electrolyte balance, fluid intake, and nutritional and vitamin intake all are monitored [26,33] Next, common-sense principles should be followed, such as using the fewest number of drugs

at the lowest doses possible; reserving antipsychotic medication for the agitated, delusional, and hallucinating patient; and reserving benzodiaze-pines for restless, anxious patients, especially patients in withdrawal state, such as from alcohol, benzodiazepines, or barbiturates Other common-sense measures include the following: providing the patient a quiet reassuring environment with family members and a private duty nurse if necessary; providing reassurance and explanations as often as possible; offering reorientation and reminders of events; providing support to family members and caregivers; giving one simple instruction at a time; identifying the patient’s usual patterns of behavior for activities such as sleep, medication use, elimination, food intake, and self care; providing good lighting and orienting the patient to time of day by keeping window blinds and curtains open during daylight hours; avoiding frustrating the patient with orientation questions that cannot be answered; and having the patient use hearing aids, eyeglasses, and other devices to assist with sensory perceptions whenever possible [26,29,34] Over-stimulation and sensory deprivation can lead to confusion; therefore, television and radio broadcasts, which can precipitate delusions and hallucinations, should be monitored[34]

Finally, there are two important therapeutic principles First, sleep deprivation can cause and perpetuate confusion; therefore, confused patients should not be awakened unnecessarily and only absolutely necessary vital signs and medications should be administered during the nighttime sleep hours Second, the use of physical restraints not only is not effective in the treatment of postoperative confusion but can perpetuate confusion and lead

to medical problems No studies have shown that physical restraint use prevents patient falls, extubation, invasive line disruptions, and so forth [33,35,36]

Carotid artery disease in patients undergoing coronary artery bypass grafting

There is much controversy concerning carotid endarterectomy (CEA) in general and even more in carotid CEA in patients who undergo coronary artery bypass grafting (CABG) The literature contains conflicting opinions, compassionate arguments, and overall confusion for the practitioner, who can only individualize each case, look at the reported information objectively, make the best decision possible with the available information, and look to the future for larger controlled studies As far as consensus is concerned, there seem to be only two areas of agreement: (1) the surgery should be performed by a surgeon who is skilled in the procedure and performs the procedure on a regular basis; (2) patients who have symptomatic high-grade(>70%) stenosis usually do better with surgical treatment rather than with medical treatment for prevention of future stroke [37,38] There is more controversy regarding the benefits of CEA in moderate

(50%–69%) stenosis and in asymptomatic stenosis of 60% or higher [39] Several studies have shown that asymptomatic carotid stenosis is accompanied by a low risk of stroke [40,41] In fact, the long-term risks

of myocardial infarction and nonstroke vascular death are greater than the risk of stroke; therefore, management of patients who have asymptomatic carotid artery stenosis should concentrate as much on reduction of non-stroke vascular risks as on non-stroke risks [40] Thus, the factors associated with patients facing the highest risk of future stroke are severe (>70%) stenosis, male gender, absence of visible collaterals, hemispheric and nonretinal events, absence of intracranial stenosis, and age greater than 75 Alternatively, lesser medical risk and lesser benefit can be predicted with lesser degrees of stenosis (50%–69%), female gender, retinal symptoms only, good collaterals, and presentation with lacunar symptoms[41]

When contemplating CEA for a patient, consider the following factors, which are all cumulative and additive: (1) medical risk factors; (2) neurologic risk factors; and (3) anatomic risk factors The patient must be

in reasonable medical condition before considering surgery of any type If the patient has too many medical risk factors, especially those difficult to control, the patient is not a candidate for CEA and does not need to undergo extensive testing, although in the future such patients might be candidates for carotid angioplasty and stenting From the standpoint of neurologic risks, the best patient is one who is neurologically normal and has suffered a transient ischemic attack rather than a devastating cerebral infarction Finally, anatomic risk factors include tandem stenosis, contra-lateral stenosis, diffuse intracranial stenosis, and high cervical bifurcation of the carotid artery

Much has been written recently on the heart-brain relationship, specifi-cally coronary artery bypass surgery and the brain Four neurologic and cognitive complications have been observed after CABG: (1) embolic cerebral ischemic infarction; (2) postoperative delirium; (3) short-term cognitive changes; and (4) long-term cognitive changes [42] Diffuse encephalopathy actually is more common than stroke, with stroke risk relatively stable, between 2% and 6%[43,44] Possible mechanisms of these complications include cerebral hypoperfusion, cerebral edema, activation of inflammatory processes, and cerebral microembolism from air, atheroma-tous debris, small clots, or particulate matter from the bypass circuit (lipid particles) [45]

Although as many as 50% of patients suffer early cognitive decline after CABG, they usually recover but nevertheless are at increased risk for long-term cognitive changes[46–48]

Several investigators believe that the neurologic complications of heart surgery potentially are preventable Preoperative transesophageal echocar-diogram evaluation of the heart and the aorta allow detection of potential cardiac and aortic sources of embolization and thus can guide aortic clamping sites; in addition, placement of a filtering device in the aorta

during and after release of aortic clamps might prevent microemboli[49,50] Other investigators have suggested performing coronary bypass surgery without cardiopulmonary bypass (‘‘off-pump’’), finding that the use of the cardiopulmonary bypass (‘‘on-pump’’) is associated with significant cerebral morbidity but no difference in cardiac outcome within at least 1 year between patients who underwent ‘‘on-pump’’ surgery and those who underwent ‘‘off-pump’’ surgery[51–54] In the postoperative period, important issues are hypotension and arrhythmias, which need to be treated quickly and aggressively Fever should be controlled and excessive sedation avoided[55]

In the follow-up period, strict medical control of vascular risk factors, including hypertension, hyperlipidemia, and diabetes, may help prevent late cognitive decline[56,57]

Treatment choices for patients who have asymptomatic high-grade stenosis of the carotid arteries found during preparation for CABG is controversial The options vary from a simultaneous (same anesthetic) to

a staged procedure, whereby CEA is performed several days before (staged approach) or after (reversed staged approach) coronary revascularization [58].The incidence of cerebral infarction after CABG recently has increased, which may be the result of performing cardiac surgery on high-risk or aged patients The main cause of stroke after CABG, however, may be emboli from the heart or aorta rather than from carotid artery disease[59] Thus, there are multiple risk factors for stroke after CABG other than just carotid artery disease, including low perfusion pressure, prolonged cardiopulmo-nary bypass, low cardiac output postoperatively, and the age of the patient [60] Other investigators believe that carotid artery stenosis is a significant risk factor; the perioperative stroke risk is estimated as follows: (1) \2% in patients who have carotid stenosis that is \50%; (2) 10% with stenosis that

is 50% to 80%; (3) 11% to 19% with stenosis that is > 80%[61] The long-term risk for patients who have carotid stenosis is myocardial infarction, which is the principle cause of death in these patients Patients who have carotid artery stenosis have a higher incidence of left main coronary artery disease and decreased ejection fractions, and, of course, a perioperative complication of CEA is myocardial infarction All investigators agree that patients who have symptomatic high-grade carotid stenosis of 70% or higher should undergo CEA if they are reasonable candidates, whether or not they are undergoing CABG The controversy regards patients who are un-dergoing CABG who have significant asymptomatic carotid artery disease There are many proponents for CEA in this patient population, some advocating the staged procedures and some the combined procedures As with any other surgical procedure, the choice depends on the surgeon’s experience and skill Some investigators believe that in patients who have symptomatic coronary and carotid disease, the combined procedure should not be performed because it results in additive risks; therefore, they would treat the arterial system first that is most symptomatic Some of these same investigators believe that if the person requires CABG and has asymptomatic

carotid disease, then there is no proof that surgical or endovascular treatment of the carotid lesion is necessary [62] Alternatively, some investigators believe that in the future carotid artery stenting may be a safer and more effective alternative treatment of asymptomatic carotid stenosis that would negate the present controversy[63]

Following is a summary of recommendations from investigators who consider CEA in patients undergoing CABG: (1) an asymptomatic carotid stenosis of 70% does not by itself increase the incidence of perioperative

stroke; however, these patients should be followed because they may require CEA in the future if the stenosis increases; (2) patients who have a completed stroke from the past and no significant carotid artery stenosis do not seem to

be at perioperative risk for stroke; (3) patients who have had a previous stroke with high-grade stenosis, at least 70%, should undergo CEA; (4) most patients deemed necessary to have CEA should have it before CABG, although some investigators combine procedures; (5) patients who have asymptomatic, high-grade carotid artery stenosis > 70% should undergo CEA either as a staged or combined procedure; (6) CEA can be performed before CABG in patients who have chronic stable angina in the absence of recent myocardial infarction; and (7) in patients in whom the severity of the coronary artery disease is urgent, but in whom CEA also is deemed necessary, CEA can be performed as a combined procedure or a reversed staged procedure, although there may be an increased risk of stroke in patients who have reversed staged procedure [64,65] To complicate the situation even more, some investigators believe that the operative morbidity and mortality for the combined procedure is higher than for each procedure alone Thus, to make some sense out of all this data, the neurologist evaluating the patient who has carotid artery disease and is a candidate for CABG should evaluate the patient on an individual basis and should make the same decisions as for

a patient who has carotid artery disease but is not undergoing CABG If CEA

is deemed necessary for the symptomatic or asymptomatic patient, then the CEA probably should be done as a staged procedure if the coronary artery disease is not urgent or even as a combined procedure if that is the skill and experience of the operating surgeon If the coronary artery disease is urgent, then CABG should be done first, and the CEA as a reversed stage procedure,

or again possibly as a combined procedure, depending on the skill and experience of the operating surgeon

Miscellaneous

Migraine

There are many triggers of migraine attacks, including anxiety, stress, and hypoglycemia from fasting, any of which is likely to cause a rise in blood pressure amine levels and, of course, play a role in the perioperative care of the migraineur [66] The migraineur undergoing surgery should avoid and