Consider this increasingly common scenario: An older person undergoes a surgical procedure and sometime later the family reports that the patient “has not been the same since the surgery.” The patient may have had some postoperative problems that appeared to resolve over several days, or had no apparent difficulties during the immediate postoperative period. But now the patient is confused or has a change in cognitive ability that was not present at discharge. The patient may have memory problems (forgetting appointments or when to take medications), disorientation (losing track of time or not knowing the date), or problems with judgment and reasoning (mismanaging money, difficulty handling mail and bills).
Since the 1950s, healthcare providers have known that patients undergoing surgery and anesthesia experience postoperative cognitive changes. With the aging of the population, the number of older adults undergoing surgery is rising, and along with this has been an increase in postoperative cognitive complications. Older adults are four times more likely to require surgery than younger adults. Half of all surgical procedures, and one-third of all inpatient operations, are performed on patients over age 65 years, further increasing the risk for cognitive complications.1,2 In the over-65 population, cognitive problems are increasingly prevalent; about 10% of adults over age 65 years report some cognitive difficulty, and 40% to 50% of adults over age 85 years meet criteria for a dementia.3,4
Preexisting medical conditions increase the risk for postoperative complications. This is why patients of all ages benefit from preoperative clearance for cardiac, respiratory, hematologic, and kidney function. Preexisting cognitive impairment is known to increase the risk for postoperative complications involving confusion and memory, yet no requirement exists for routine preoperative cognitive assessment.
DELIRIUM OR COGNITIVE DYSFUNCTION?
Postoperative delirium, defined as acute confusion in the hours and days following surgery, is a well-documented occurrence that leads to longer hospital stays and increased costs.5 The condition can occur at any age, but is more common in young children (2 to 6 years) and in adults over age 60 years. Postoperative delirium embodies the classical clinical features of delirium—acute confusion in the first hours and days following surgery, inattention, and disorganized thinking that exhibits a fluctuating course over hours or within the course of a day. Patients frequently also have an accompanying disturbance in circadian rhythm and sleep cycles.6 Postoperative delirium can take three forms:
- hyperactive, in which the patient is agitated, may be pulling at lines, and often needs sedation and restraint
- hypoactive, in which the patient is lethargic or somnolent and runs the risk of being overlooked by medical and nursing staff
- subsyndromal, which is unrecognized during the postoperative period, and is concerning because a high percentage of patients who experience postoperative delirium later develop dementia.7
Researchers have recently identified a related syndrome, postoperative cognitive dysfunction, that occurs later than postoperative delirium and is more persistent. Postoperative cognitive dysfunction is defined as sustained (lasting several months or longer) cognitive impairment after surgery. No formal diagnostic criteria for postoperative cognitive dysfunction have been established. Affected cognitive domains that have been reported are memory, executive ability, and overall intellectual function.8 The risks for postoperative delirium and postoperative cognitive dysfunction are similar, but the relationship of these disorders to Alzheimer disease and other dementias remains unclear.
The rate of cognitive complications among older surgical patients is significant, making this a problem that demands more attention from all providers caring for patients in the preoperative, perioperative, and postoperative periods. Between 20% and 46% of older patients undergoing noncardiac surgery have been reported to exhibit postoperative delirium.9 Postoperative cognitive dysfunction has been reported in 30% to 40% of older noncardiac surgical patients within days to 1 week postoperatively, and 10% to 15% develop late postoperative cognitive dysfunction that is identified 3 to 6 months later.10,11 Postoperative delirium is known to be associated with increased 6-month mortality.12 The relationship between postoperative cognitive dysfunction and mortality is less well established.
Confusion in the immediate postoperative period occurs frequently across all age groups, but rates increase with advanced age. About 33% of young and middle-aged adults undergoing surgery experience some postoperative cognitive changes in the hours just after surgery, compared with 41% of older adults.9 Confusion decreases over time in all age groups, with 5% to 6% of young and middle-aged adults exhibiting cognitive changes days to weeks after surgery, compared with nearly 13% of older adults.
The incidence of postoperative delirium and postoperative cognitive dysfunction varies over time, and the risk differs by type of surgery and age. The association of confusion with cardiac surgery, especially in older patients, is well documented and increasingly recognized, but the long-term consequences are not well appreciated. Older age has repeatedly been found to be a risk factor associated with delirium after coronary artery bypass grafting (CABG) surgery, and delirium after CABG is a strong independent predictor of mortality.13,14 Delirium after cardiac surgery also is strongly associated with a decline in cognition that persists for 6 months or longer.15 Studies have shown no association between intraoperative factors, including length of cardiac bypass, and postoperative delirium or postoperative cognitive dysfunction.
Postoperative delirium and postoperative cognitive dysfunction also occur frequently in older adults undergoing noncardiac surgical interventions. The International Study of Postoperative Cognitive Dysfunction (ISOICD I) included more than 1,200 older patients undergoing noncardiac surgery and found that within the first week after major abdominal, noncardiac thoracic, or orthopedic surgery with general anesthesia, 25.8% of patients over age 60 years experienced confusion, compared with 19.2% ages 40 to 60 years. Three months after surgery, about 10% of patients over age 60 years who had major surgery continued to experience cognitive changes, compared with 6% of the younger group. Rates of confusion after minor surgery in older adults were about 6%, and this persisted to 3 months.16
Delirium, the sudden onset of confusion, is a true medical emergency that requires immediate attention. An estimated 40% of delirium in older hospitalized adults can be prevented. Postoperative delirium is one of the most common surgical complications in older adults, occurring in up to 50% of older adults.17 The American Geriatrics Society recently published a best practice statement outlining a plan that is easily implemented, should be standard operating procedure for older adults undergoing surgery, and could go a long way to reducing postoperative delirium (Table 1).18 A high index of suspicion for postoperative delirium is necessary among all healthcare providers involved in postoperative care, especially those who care for older patients. A minimum postoperative evaluation of the patient with acute delirium should include use of a validated instrument such as the Confusion Assessment Method, medication review, and laboratory tests including a complete blood cell count with differential, serum chemistry panel, urinanalysis, chest radiograph, and ECG if the patient is not on cardiac monitoring.18,19
Delirium is best thought of as the result of interaction between predisposing patient risk factors and a physiologic stressor. Risk factors for developing postoperative delirium are well established and include age over 65 years, cognitive decline or dementia, impaired vision or hearing, severe illness, and infection.20 For patients undergoing noncardiac surgery, additional risk factors for postoperative delirium include functional dependence, excess alcohol use, and laboratory abnormalities, specifically abnormal electrolyte levels.21 Patients with two or more risk factors are considered likely candidates for developing postoperative delirium. Note that risk is greater with emergency surgery than with elective procedures.
In the surgical setting, the type of operation and anesthesia used are the physiologic stressors that produce not only postoperative delirium, but also possibly postoperative cognitive dysfunction. One approach to minimize postoperative delirium, and likely postoperative cognitive dysfunction, is to provide a lighter depth of anesthesia.22,23 This involves smaller doses, fewer doses, or different anesthetics. In a study that compared light and deep sedation in patients undergoing surgery for hip fractures, an increased rate of postoperative delirium was found with deep sedation.24 Regional anesthesia, when appropriate, should be considered in older adults undergoing elective operations. Studies of postoperative analgesia have produced conflicting results as to whether IV or oral medications are preferable for reducing postoperative delirium and postoperative cognitive dysfunction.
CHARACTERISTICS OF COGNITIVE DECLINE
No tools exist to specifically screen for or detect postoperative cognitive dysfunction. Psychometric testing done pre- and postoperatively provides the most accurate basis for diagnosing postoperative cognitive dysfunction, yet rarely is available. A set of core psychometric tests was recommended in a consensus statement for patients undergoing cardiac surgery, but this is not generally done.25 Mental status screening tools such as the Montreal Cognitive Assessment, Mini Mental State Examination, and St. Louis Mental Status Examination often are employed postoperatively in the hospital and after discharge. Few studies have examined the scope of cognitive changes in older adults who experience postoperative cognitive dysfunction; the cognitive changes that occur postoperatively in older adults also vary in severity and type. At 3 months postoperatively, most patients have only mild impairment, with 20.8% experiencing severe, persistent cognitive changes.10 The most common area of impairment is short-term memory. Functional limitations in activities of daily living were common among the 10% of patients who had executive dysfunction or memory and executive dysfunction.
DEMENTIA DEVELOPMENT POSTOPERATIVELY
Stories of postoperative dementia exist anecdotally, but what is the association, if any, or risk for development of dementia in older adults after surgery? A 10-year longitudinal study of more than 9,000 patients age 65 years and older found that exposure to general anesthesia was associated with an increased risk for dementia several years later.26 A retrospective analysis of 15 studies found no increased risk for development of Alzheimer disease following anesthesia and surgery.27 In a large longitudinal study on the development and course of Alzheimer disease, researchers found that patients with a mild, subclinical cognitive impairment before surgery were more likely to experience postoperative cognitive dysfunction. However, as dementia progressed, the difference disappeared between those who had surgery and those who had not.28
The link between anesthesia and development of cognitive changes is not well understood. Most of the evidence is based on case reports, and no large-scale prospective studies have been conducted to address the question in a systematic manner. Observational studies have repeatedly found that postoperative cognitive dysfunction occurs more frequently after extensive surgery under general anesthesia, after a second surgery, and when patients have postoperative complications. The International Studies on Post Operative Cognitive Dysfunction (ISPOCD) found an increased risk for postoperative cognitive dysfunction with major surgery lasting more than 2 hours, and has recommended trying to limit surgery and anesthesia in older adults to less than 1 hour whenever possible.29 No evidence shows that anesthesia itself, or any one particular agent, causes postoperative cognitive dysfunction. In general, the shorter the duration of the anesthetic agent used, the shorter the duration of cognitive impairment in the postoperative period.
One theory is that surgical anesthesia may cause or contribute to neuroinflammatory response, which results in synaptic impairment in susceptible patients, such as older adults or patients with previous head injury.30 Interruption of central cholinergic neurotransmission due to surgical stress and/or direct effect of anesthesia may occur. Another possibility is that anesthesia may alter proteins in the brain in a process that contributes to cognitive dysfunction. Exposure to anesthesia has been shown alter the expression of amyloid beta and tau, two proteins associated with Alzheimer disease and other dementias.31 In mice, IV administration of propofol or sedatives has been shown to cause persistent tau hyperphosphorylation.32 Continuous administration of volatile anesthetic agents such as sevoflurane and halothane has been reported to cause tau hyperphosporylation and increased a-beta aggregation. Changes in cognition also have been demonstrated in mice exposed to inhaled anesthesia.33
Postoperative delirium and postoperative cognitive dysfunction can be thought of as the result of interaction between risk factors that involve the patient, the surgery, and the anesthesia (Table 2). Growing evidence supports an association between preoperative cognitive impairment and the development of these conditions. Patients with mild cognitive impairment have been shown to be at significantly increased risk for postoperative delirium.34 Yet, the population of older adults with mild cognitive impairment is not easily recognized and is underestimated. That makes preoperative assessment to identify this at-risk population an important step toward reducing postoperative delirium and possibly postoperative cognitive dysfunction. Use a validated mental status screening instrument that is sensitive to early cognitive changes, such as the Montreal Cognitive Assessment, to detect subtle, early cognitive changes that would put an older patient at risk for postoperative delirium and postoperative cognitive dysfunction.35
Alcohol use among older adults is underreported. Therefore, alcohol abuse in this population is frequently not recognized or noted in their charts by medical providers. Even if patients with a history of alcohol abuse stopped drinking for weeks before surgery, they have been shown to have worse cognitive impairment after surgery than patients with no history of alcohol abuse.36 Low education level, which is a risk factor for the development of dementia, also has been found to be a risk factor for the development of postoperative cognitive dysfunction.14
More rigorous and routine preoperative cognitive screening and use of alternative anesthetic regimens may reduce the incidence of postoperative delirium and postoperative cognitive dysfunction. Given what is known about risk factors for postsurgical delirium and cognitive dysfunction, screening should include identifying preexisting cognitive impairment, determining if the patient has a history of previous postoperative confusion or delirium, documenting other episodes of delirium or confusion, and assessing for low education (a known risk factor for cognitive impairment with age). At present, evidence is insufficient to recommend cognitive screening as part of routine preoperative care for all older adults undergoing surgery. However, consider a baseline evaluation of current cognitive function among patients with risk factors.28,37
A number of intraoperative factors have been studied in an attempt to better understand their effects on postoperative confusion, including general versus regional anesthesia, specific anesthetic agents, blood transfusions, systemic arterial pressure monitoring, and use of dexamethasone or statins. Avoiding centrally acting anticholinergics and meperidine are two specific recommendations that could be easily implemented to potentially reduce postoperative confusion.
Postoperative confusion, whether acute (postoperative delirium) or subacute and prolonged (postoperative cognitive dysfunction), is a common clinical occurrence that is multifactorial in origin. Recognizing patients who are at high risk is key to reducing the prevalence of these conditions as well as their long-term sequelae. Preoperative cognitive assessment to identify older patients at higher risk should be included as a routine part of clinical practice. Clinicians also should pay more attention to reducing operative risk by selecting surgical techniques and anesthetic agents that minimize complications that could contribute to postoperative delirium and postoperative cognitive dysfunction.
1. Hines RL, Marschall KE. Stoelting's Anesthesia and Co-Existing Disease
. Philadelphia, PA: W.B. Saunders Co.; 2012:648.
2. Hall MJ, DeFrances CJ, Williams SN, et al National Hospital Discharge Survey: 2007 summary. Natl Health Stat Report
3. Alzheimer's Association. 2016 Alzheimer's facts and figures. http://www.alz.org
/facts. Accessed February 1, 2017.
5. Leslie DL, Marcantonio ER, Zhang Y, et al One-year health care costs associated with delirium
in the elderly population. Arch Intern Med
6. Fitzgerald JM, Adamis D, Trzepacz PT, et al Delirium
: a disturbance of circadian integrity. Med Hypotheses
7. Rudolph JL, Marcantonio ER. Review articles: postoperative delirium
: acute change with long-term implications. Anesth Analg
8. Kalisvaart KJ, de Jonghe JF, Bogaards MJ, et al Haloperidol prophylaxis for elderly hip-surgery
patients at risk for delirium
: a randomized placebo-controlled study. J Am Geriatr Soc
9. Maldonado JR. Delirium
in the acute care setting: characteristics, diagnosis and treatment. Crit Care Clin
10. Monk TG, Weldon BC, Garvan CW, et al Predictors of cognitive dysfunction after major noncardiac surgery
11. Price CC, Garvan CW, Monk TG. Type and severity of cognitive decline in older adults
after noncardiac surgery
12. Robinson TN, Raeburn CD, Tran ZV, et al Postoperative delirium
in the elderly: risk factors and outcomes. Ann Surg
13. Loponen P, Luther M, Wistbacka JO, et al Postoperative delirium
and health related quality of life after coronary artery bypass grafting. Scand Cardiovasc J
14. Gottesman RF, Grega MA, Bailey MM, et al Delirium
after coronary artery bypass graft surgery
and late mortality. Ann Neurol
15. Saczynski JS, Marcantonio ER, Quach L, et al Cognitive trajectories after postoperative delirium
. N Engl J Med
16. Moller JT, Cluitmans P, Rasmussen LS, et al Long-term postoperative
cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet
17. Inouye SK, Westendorp RG, Saczynski JS. Delirium
in elderly people. Lancet
18. American Geriatrics Society Expert Panel on Postoperative Delirium
in Older Adults
. Postoperative delirium
in older adults
: best practice statement from the American Geriatrics Society. J Am Coll Surg
19. Robinson TN, Eiseman B. Postoperative delirium
in the elderly: diagnosis and management. Clin Interv Aging
20. United Kingdom National Institute for Health and Care Excellence. Delirium
: diagnosis, prevention and management. Clinical guideline 103. London, United Kingdom. 2010. https://http://www.nice.org.uk
/guidance/cg103/evidence/full-guideline-134653069. Accessed February 1, 2017.
21. Dasgupta M, Dumbrell AC. Preoperative risk assessment for delirium
after noncardiac surgery
: a systematic review. J Am Geriatr Soc
22. Chan MT, Cheng BC, Lee TM, et al BIS-guided anesthesia decreases postoperative delirium
and cognitive decline. J Neurosurg Anesthesiol
23. Radtke FM, Franck M, Lendner J, et al Monitoring depth of anaesthesia in a randomized trial decreases the rate of postoperative delirium
but not postoperative
cognitive dysfunction. Br J Anaesth
. 2013;110(suppl 1):i98–i105.
24. Sieber FE, Zakriya KJ, Gottschalk A, et al Sedation depth during spinal anesthesia and the development of postoperative delirium
in elderly patients undergoing hip fracture repair. Mayo Clin Proc
25. Murkin JM, Newman SP, Stump DA, Blumenthal JA. Statement of consensus on assessment of neurobehavioral outcomes after cardiac surgery
. Ann Thorac Surg
26. American Association for the Advancement of Science. Exposure to general anaesthesia could increase the risk of dementia in elderly by 35 percent. http://www.eurekalert.org
/pub_releases/2013-05/eso-etg052913.php. Accessed December 21, 2016.
27. Seitz DP, Shah PS, Herrmann N, et al Exposure to general anesthesia and risk of Alzheimer's disease: a systematic review and meta-analysis. BMC Geriatr
28. Kline RP, Pirraglia E, Cheng H, et al Surgery
and brain atrophy in cognitively normal elderly subjects and subjects diagnosed with mild cognitive impairment. Anesthesiology
29. Canet J, Raeder J, Rasmussen LS, et al Cognitive dysfunction after minor surgery
in the elderly. Acta Anaesthesiol Scand
30. Kapila AK, Watts HR, Wang T, Ma D. The impact of surgery
and anesthesia on post-operative cognitive decline and Alzheimer's disease development: biomarkers and preventive strategies. J Alzheimers Dis
31. Jevtovic-Todorovic V, Absalom AR, Blomgren K, et al Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar. Br J Anaesth
32. Bianchi SL, Tran T, Liu C, et al Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging
33. Bittner EA, Yue Y, Xie Z. Brief review: anesthetic neurotoxicity in the elderly, cognitive dysfunction and Alzheimer's disease. Can J Anaesth
34. Dasgupta M, Dumbrell AC. Preoperative risk assessment for delirium
after noncardiac surgery
: a systematic review. J Am Geriatr Soc
35. Nasreddine ZS, Phillips NA, Bédirian V, et al The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc
36. Hudetz JA, Iqbal Z, Gandhi SD, et al Postoperative
cognitive dysfunction in older patients with a history of alcohol abuse. Anesthesiology
37. Johnson T, Monk T, Rasmussen LS, et al Postoperative
cognitive dysfunction in middle-aged patients. Anesthesiology
Keywords:Copyright © 2017 American Academy of Physician Assistants
surgery; older adults; cognition; confusion; delirium; postoperative