Central Nervous System Dysfunction after Noncardiac Surgery and Anesthesia in the Elderly
MORE than 50 yr ago, clinicians reported changes in mental function after anesthesia and surgery in the elderly. As these phenomena have been elucidated in subsequent years, they have been categorized into the distinct syndromes of delirium and postoperative cognitive dysfunction (POCD). These phenomena seem to be increasing in prevalence, concomitant with the increase in the number of elderly patients undergoing surgery. In this brief clinical review, we describe the presentation of, course of, risk factors for, and when applicable, management of these syndromes. Delirium and cognitive function after cardiac and neurosurgical procedures are distinct subjects beyond the scope of this review.Delirium was well described in the writings of Hippocrates 2,500 yr ago. The key diagnostic features, as described in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders are (1) that it is a change in mental status, characterized by a prominent disturbance of attention and reduced clarity of awareness of the environment; and (2) that it has an acute onset, developing within hours to days, and tends to fluctuate during the course of the day. The inability to focus, sustain, and shift attention is accompanied by other cognitive symptoms (e.g ., disorientation, episodic memory dysfunction) and/or perceptual disturbances (misinterpretations, illusions, or hallucinations). Associated features include disturbances of the sleep–wake cycle and activity level, as well as affective disturbance (mood lability, anger, sadness, euphoria) and thought disorder (disorganized thinking, delusions). The symptoms of delirium are numerous, vary from patient to patient, vary within patients over time, and are shared by a variety of other disorders such as dementia, anxiety, depression, and psychosis, all of which contribute to difficulties in diagnosis.The heterogeneous presentation of delirium has led to the identification of hyperactive, hypoactive, and mixed subtypes.1,2The hyperactive form of delirium tends to be clinically obvious. The hypoactive form, however, is often unrecognized, misdiagnosed, mistaken for depression or dementia, or simply attributed to old age, because patients may seem quiet and subdued in their disorientation. Furthermore, the relation between delirium and dementia is complex, and the syndromes may overlap.1,2Delirium can be caused by, or associated with, a wide variety of conditions,1,2and the current Diagnostic and Statistical Manual of Mental Disorders system differentiates subtypes based on the presumed etiology. These are delirium due to a general medical condition , substance-induced delirium (due to medication use or toxin exposure), substance intoxication delirium (due to intoxication), substance withdrawal delirium , delirium due to multiple etiologies , and delirium not otherwise specified (for cases in which there is insufficient evidence to establish a specific etiology).Delirium in the postoperative period can be divided into emergence delirium and postoperative delirium (PD), based on the time of onset (fig. 1). Emergence delirium is seen during or immediately after emergence from general anesthesia and usually resolves within minutes or hours. It occurs in all age groups, with some predominance in children. It seems to be directly correlated with the administration of general anesthesia, because it occurs during the emergence process, mimics stage II (excitation) of ether anesthesia as described by Guedel, and usually resolves without sequelae. Emergence delirium fits the Diagnostic and Statistical Manual of Mental Disorders , fourth edition, diagnostic criteria for a substance-induced delirium . The reader is referred to a more complete review of this subject.3After surgery, another type of delirium occurs that is not clearly related to emergence from anesthesia. Elderly patients commonly emerge from anesthesia smoothly and demonstrate coherence in the postanesthesia care unit. After a lucid interval, some patients develop a syndrome referred to as interval delirium or postoperative delirium .1,4Postoperative delirium tends to first be observed between postoperative days 1 and 3, and usually resolves within hours to days, although symptoms may persist for weeks to months. Postoperative delirium is more likely to result in complete recovery than other forms of delirium.5The term intensive care unit (ICU) delirium describes delirium that occurs in the intensive care unit, primarily in those patients requiring mechanical ventilation; it was previously referred to as ICU psychosis . ICU delirium makes no distinction between medical and surgical patients, so many cases of ICU delirium could also be classified as postoperative delirium.6There are a number of structured instruments available that can be used by a variety of personnel to diagnosis and assess delirium. Three validated methods include the Confusion Assessment Method,7the Delirium Rating Scale Revised-98,1and the Delirium Symptom Interview.1The confusion assessment method has been used for most postoperative delirium research and has been modified and validated for use in critical care patients receiving mechanical ventilation.8The reported incidence of PD is 5–15% in older adults after general anesthesia.9The reported incidence in patients undergoing surgery for hip fracture is higher, ranging from 16% to 62%, with an average rate of 35% across 12 studies of 1,823 patients.10Delirium is indeed the most common complication after hip fracture, but this patient population also has a high incidence of delirium before surgery.In elderly patients hospitalized for reasons other than surgery, the risk of developing delirium while hospitalized is predicted by an interaction between vulnerability factors present at the time of hospitalization and noxious injuries, or precipitating factors that occur during hospitalization.2Among the predisposing risk factors identified are vision impairment, severe illness, cognitive impairment, and serum urea nitrogen:creatinine ratio of 18 or greater. The precipitating factors identified are use of physical restraints, malnutrition, more than three medications added 24–48 h before the onset of delirium, use of a urinary bladder catheter, and iatrogenic events, including fluid and electrolyte abnormalities and infections.2Studies in surgical patients have identified age 70 yr or older, history of delirium, history of alcohol abuse, and preoperative use of narcotic analgesics as preoperative predisposing risk factors for PD.11Preoperative depression also seems to be a risk factor for postoperative delirium.12Perioperative risk factors include greater intraoperative blood loss, more postoperative transfusions, postoperative hematocrit less than 30%, and severe postoperative pain.13There are contradictory reports on the role of perioperative hypotension and hypoxemia in the development of PD. The role that postoperative pain plays in the development of PD is not attributable to method of analgesia, type of opioid analgesia, or cumulative opioid dose.14Drug effects are considered an important cause of delirium. In medical patients, the most important drug classes associated with delirium are the sedative–hypnotics, narcotics, and anticholinergics,1all of which are routinely used in perioperative care. The role of benzodiazepines is controversial.1Lorazepam has been specifically associated with the development of delirium in the ICU.15There is extensive literature investigating the proposition that regional anesthesia would be associated with less delirium than general anesthesia; however, the majority of these studies show no difference.16,17The underlying pathophysiology of delirium in general, and PD specifically, remains elusive. Delirium is the behavioral manifestation of diffuse cortical dysfunction and is associated with diffuse slowing of background activity in the electroencephalogram (except in cases of alcohol withdrawal, in which there is an increase in fast wave activity).1It is also associated with disturbances in a wide variety of neurotransmitter systems, and disruption of cholinergic transmission seems to be especially important.2Toxicity from anticholinergic agents mimics the electroencephalographic and behavioral aspects of delirium and is reversed by physostigmine. Serum anticholinergic activity is associated with delirium in postoperative patients.18Other potential mediators include melatonin, norepinephrine, and lymphokines.1,2Postoperative delirium is associated with increased morbidity (including risk of injury), mortality, duration of hospital stay, nursing home placement, and technical (nonphysician), consultant, and nursing costs.19In a recent study, duration of hospital stay for surgical patients was 6.0 days for those who developed delirium and 4.6 for those who did not.19The average additional in-hospital cost per surgical patient with PD was $2,947, which equates to more than $2 billion additional healthcare dollars per year in the United States.It is possible to prevent PD in some patients using safe and effective interventions for systematic detection and management of predisposing factors.1The most widely studied intervention program to prevent delirium in elderly medical patients is the Hospital Elder Life Program.20Interventions are targeted towards six risk factors for delirium: cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration. Some of the specific interventions include frequent presentation of orienting information (such as prominent display of the date, time, schedule, and names of hospital personnel), cognitive stimulation activities, physical exercise, use of visual aids and adaptations, use of auditory amplifying devices, nonpharmacologic methods to promote sleep (such as drinking warm milk before bed, relaxing music, back massage, noise-reduction strategies), and feeding and fluid assistance. Other protocols have focused on coordinated geriatric services, geriatric–psychiatric consultations, and patient and family education. A series of randomized and nonrandomized trials indicate that a substantial absolute risk reduction (in the range of 13–19%) can be achieved.1,2A trial of proactive geriatric consultation in hip fracture patients reduced delirium by more than one third and reduced cases of severe delirium by more than one half.21Treatment of agitation poses a special problem. Agitation puts the patient, visiting family, and staff at risk for physical injury and interferes with administration of normal postoperative care, but current treatment options are less than optimal. Attempts should be made to avoid the use of physical restraints, which may worsen delirium and agitation. Pharmacologic therapy is used specifically to decrease agitation.22Haloperidol, a typical antipsychotic dopaminergic antagonist, is administered to adults at a dose of 0.5–1 mg intravenously every 10–15 min until the agitated behavior is controlled.∥Intramuscular dosing is less desirable but can be employed using 2–10 mg, waiting 60–90 min between doses. By careful dosing, practitioners should limit the degree of haloperidol’s sedative side effect, because this drug has an extended half-life in the elderly (up to 72 h) and deep sedation can last for several days. It is important for the clinician to recognize that haloperidol can be useful in the immediate management of agitation but does not alter the duration of delirium. Newer antipsychotic medications, such as ziprasidone and olanzapine, are administered intramuscularly and are reportedly effective in the management of acute agitation but have not been tested in patients with either medical or surgical comorbidities.22Although most typical antipsychotics increase the corrected QT interval and may predispose to arrhythmias, haloperidol has a relatively lower propensity to do so. Cases of sudden death are rare and have not been clearly related to haloperidol.22Although it is reasonable to assume that benzodiazepines would be an effective treatment for agitation in the context of PD, anecdotal experience has shown that these medications may have a paradoxical effect in elderly patients and may worsen agitation.22If alcohol withdrawal is suspected to be the underlying cause of delirium, however, benzodiazepines are the treatment of choice.The term postoperative cognitive dysfunction (POCD) describes a deterioration of cognition that is temporally associated with surgery. As opposed to delirium, in which pathognomonic behavior must be detected, detecting, assessing the severity of, and characterizing POCD depends on valid assessments of preoperative and postoperative cognitive function. The neuropsychological examination measures the information processing abilities of the brain through a battery of tests (assessing attention, perception, verbal abilities, learning and memory, and abstract thinking) that are sensitive to the effects of brain injury and disease.23The wide variability in normal human cognitive capacities associated with aging and a possible incidence of preexisting mild cognitive impairment in the elderly make baseline (i.e ., preoperative) measures a critical component of these evaluations. In the absence of baseline data, it is impossible to associate low postoperative test scores to surgical, anesthetic, or illness variables with certainty. Subjective self-reported cognitive symptoms do not substitute for objective cognitive testing, because a poor relation between the two types of data has been demonstrated repeatedly.24There are a number of methodologic inconsistencies among studies that make the limited literature on POCD difficult to interpret. These include the selection of test instruments, timing of postoperative testing, inclusion and exclusion criteria, the inherent variability of cognitive testing, and most fundamentally, the operational definition of POCD.Mental status screening instruments such as the Mini-Mental State Examination are useful for detecting frank dementia but lack the sensitivity and specificity required to detect milder or more selective forms of cognitive impairment.23High-functioning patients who have experienced a mild decline in cognitive function and patients with “focal,” as opposed to “diffuse,” cognitive dysfunction may achieve high Mini-Mental State Examination scores. Cognition is not a unitary process, but rather is the result of activity in multiple complex, distributed, and interacting neuronal circuits that underlie specific information processing functions. There is no single measure of cognitive status; therefore, comprehensive neuropsychological assessment that a battery of tests assessing a variety of cognitive must be There however, a wide variety of tests which in their and the degree to which they are to methodologic among the studies is the timing of postoperative cognitive In general, studies cognitive function after surgery a incidence of POCD than studies cognitive function weeks to after surgery. studies have the of which does not occur but is by the postoperative status, status, and the cognitive status of the who develop POCD may be more likely to of the study, the incidence of is also important to the inclusion and exclusion criteria when the term mild cognitive impairment has to a in the of cognitive function from normal aging to such as and patients with preoperative mild cognitive impairment have not been in studies of there is no information available the of surgery and anesthesia on this of patients that may be at risk for There is no evidence that anesthesia and surgery increase the incidence of of the the of postoperative cognitive function is the absence of a the operational definition of in the methods that have used to deterioration in cognitive function in underlie the in Furthermore, studies use and effects into change method the preoperative to postoperative into a of baseline ., preoperative method data, which can be across patients for The use of however, is because a of subjects deterioration may be when other subjects over The method patients who experience a postoperative decline of some number of The of Postoperative studies required a decline to as of the method include the (1) in patients with low baseline it may not be possible to decline by more than 1 (i.e ., and (2) the absolute of change in test scores required to the between because they are from the preoperative test scores of the baseline A third patients who experience a specific (e.g ., decline from baseline of at a specific (e.g ., of the tests A of this is that patients with lower preoperative test scores a decline in to the It should be that the used by is a of the general assessment referred to as a change . has a number of related to the use of this the first of a series of studies from the that primarily from the studies is available at the tested the that insufficient to the as by the of hypotension and/or is a factor for The patients, yr or older, who or surgery during general anesthesia. tested and at 1 and with a of from the United in and in classified as cognitive dysfunction when two scores in tests by or the average greater than 1 of patients experienced a decline in cognitive with of of patients experienced a decline to preoperative of with of number of subsequent studies have described cognitive impairment within the first days after surgery and a rate of POCD of at after surgery, although in the absence of a the is to A that patients at 1 and yr that the rate of POCD to which was not it seems that elderly patients deterioration after surgery and anesthesia at 2–10 with such that the incidence at at at 1 to from subjects by 1 important are that (1) the of patients to of such the may the incidence of and (2) the clinical course of an patient be clearly from this in that there is between the In the less than of the who classified at POCD at decline at 1 (i.e ., POCD at 1 did not POCD at a of the data from the . to the of variability on the of that variability in cognitive could after surgery would be as frequent as that cognitive decline at 1 but that there was no change at months. be required to impairment is an important clinical in cognitive is an important factor that to the low between that should be in studies of all of the studies to have that age is a risk factor for of patients yr undergoing surgery a but decline in cognitive function at 1 that was no at the that POCD is primarily a of elderly surgery seems to be the for A patients undergoing general anesthesia and surgery with at a single hospital stay with patients who general anesthesia for surgery that surgery was not associated with surgery, postoperative cognitive dysfunction at 1 was associated with increased age, increased duration of anesthesia, of postoperative and age was a risk factor for POCD at postoperative pain has also been associated with postoperative cognitive function. In a of patients who surgery, greater pain on postoperative 1 was associated with on some neuropsychological degree of preoperative pain was not related to preoperative cognitive test date, the of POCD remains in neurotransmitter and system have all been but the has been general anesthesia. anesthesia is a with multiple medications, many of which are to cause delirium. The method of the potential of general anesthesia to POCD has been randomized trials of general regional anesthesia. studies that of anesthesia is not an important factor in the development of is in greater such as regional and general anesthesia have on postoperative cognitive function in clinical there are studies that general agents have effects on and of this to the clinical syndromes described additional and are potential etiologies of POCD for which potential (e.g ., that in the first the role of hypotension and hypoxemia as potential was by and blood was by the perioperative high of hypoxemia and condition was associated with may additional into this problem. research is to the role of in the of of the is associated with the development of but has not been to be an important of POCD in general for either a to POCD or a of POCD is but all such In studies of cardiac surgery patients, but not may be useful as a of research including that for aspects of (in cardiac and substantial additional research to establish clinical is that general anesthesia, which specifically the as with regional anesthesia, which primarily the or would be associated with of in a series of relatively studies that patients undergoing general anesthesia, but not anesthesia, at greater risk for an randomized of POCD that used neuropsychological the effect of general anesthesia on the incidence of POCD in patients undergoing assessment was days and 1 and scores for of the measures between the two anesthesia groups, but no observed In the of patients clinically important for test by of patients a decline in cognitive function after surgery, but no between the anesthesia As this was a there was no for a comprehensive review of studies that the of anesthesia and that it does not the incidence of the of PD and it is important to that there may be an between Postoperative delirium may be a of POCD or an who developed delirium in the not the patients who developed In ICU patients, delirium does seem to be of term cognitive majority of studies to have focused on either PD or In the studies that for PD and POCD should on this system dysfunction after anesthesia and surgery is primarily a of the elderly. The of an aging population and in anesthesia and surgery has led to in the number of elderly patients undergoing surgery. It is therefore, that postoperative dysfunction an common delirium is an diagnostic that research to as well as to effective and treatment There are available that seem to postoperative delirium. of these may be difficult limited however, assessment of patients for delirium has a of care in some and should be with the and management of to PD, the that to the or absence of POCD are The are not the of cognitive that are associated with do they the degree of dysfunction that is clinically illness requiring hospitalization may be associated with cognitive the that cognitive decline occurs as a of illness rather than it related to surgery and/or anesthesia. There are patients who after surgery and anesthesia. study, of clinical with mild cognitive impairment be for practitioners to the of cognitive dysfunction after dysfunction is a of to the risk and and underlying should the current status of postoperative delirium and cognitive dysfunction and to prevent and delirium as studies to postoperative function.