Postoperative Cognitive Dysfunction

In conclusion, postoperative cognitive dysfunction includes a wide variety of conditions—POD, POCD, POCNCD—associated with specific time frame and pre, intra, and postoperative risk factors that also include anesthesia.

From: Complications in Neuroanesthesia, 2016

Chapters and Articles

Postoperative Cognitive Dysfunction

Giuseppina Magni, Federico Bilotta, in Complications in Neuroanesthesia, 2016

Conclusions

In conclusion, postoperative cognitive dysfunction includes a wide variety of conditions—POD, POCD, and POCNCD—associated with specific time frame and pre, intra, and postoperative risk factors that also include anesthesia. Current evidence is limited and rapidly evolving, and includes adequate clinical surveillance, right from the preoperative period, with accurate screening of individual risk factors and assessment of cognitive status, systematic use of dedicated and structured tests and a dedicated path for high risk patients that can effectively reduce the incidence and related complication. Long-term prospective studies or randomized controlled trials are necessary to clarify the possible associations between anesthesia, surgery, and the various forms of perioperative cognitive impairment and how to prevent and minimize the related impact.

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Postoperative Cognitive Dysfunction and Delirium

Mark F. Newman, ... Joseph P. Mathew, in Perioperative Medicine (Second Edition), 2022

POCD Associated with Noncardiac Surgery

POCD, an accepted complication of cardiac surgery, has been, until the last 20 years, less appreciated or defined after noncardiac surgery. In 1998, the International Study of Postoperative Cognitive Dysfunction (ISPOCD-1) evaluated cognitive decline in 1218 elderly patients who underwent major noncardiac surgery and found that cognitive dysfunction was present in 25% of patients 1 week after surgery and in 10% of patients 3 months after surgery.39

To investigate further POCD after noncardiac surgery, Monk et al. completed a prospective assessment of 1064 patients undergoing elective noncardiac surgery.40 This assessment was divided among young (18–39 years of age), middle-aged (40–59 years of age), and elderly (60 years and older) patients. A group of 210 primary family members were used as controls to provide a change score similar to that used in the ISPOCD. The patients completed a battery of cognitive tests at baseline (preoperatively) and at both 1 week and 3 months postoperatively.40 Fig. 42.2 shows the incidence of POCD at the hospital discharge and 3-month postoperatively based on neuropsychological evaluations. At hospital discharge, the incidence of POCD was 36% in the young, 30.4% in the middle-aged, and 41.4% in the elderly patients. The incidence of cognitive decline was significantly lower in middle-aged patients compared with elderly patients (P = 0.01), but was not different for young versus elderly or young versus middle-aged patients. The incidence of cognitive decline was similar for control subjects of all age groups at the first postoperative testing session: 4.1% in young, 2.8% in middle-aged, and 5.1% in elderly patients. However, the differences in cognitive decline between age-matched controls and patients were significant for all age groups (P < 0.001).39 At 3 months after surgery, POCD was identified in 5.7% of young, 5.6% of middle-aged, and 12.7% of elderly patients. POCD was significantly higher in elderly compared to young or middle-aged patients (P = 0.001). There was no difference in the incidence of POCD between age-matched control subjects and patients in the young and middle-aged groups. However, elderly patients exhibited a significantly greater incidence of cognitive decline at 3 months after surgery compared with elderly control subjects (P < 0.001). Of the significant univariate predictive factors for POCD at 3 months after surgery, only increasing age, lower educational level, and POCD at hospital discharge remained significant in the multiple logistic regression analysis. The results of this trial indicate that postoperative cognitive dysfunction is common in all age groups at 1 week. However, at 3 months after surgery it is more common in the elderly with lower educational achievement. Monk et al. not only reported on the incidence of POCD, but also reevaluated patients at 1 year to collect mortality data. They found an increase in 3-month mortality associated with POCD at discharge compared with those without POCD at discharge (P = 0.02). They also found that patients with POCD at both discharge and 3 months have a significantly higher 1-year mortality rate than any other group39,40 (Fig. 42.3).

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Central Nervous System Risk Assessment: Preventing Postoperative Brain Injury

Megan Maxwell, ... David L. McDonagh, in Perioperative Medicine (Second Edition), 2022

Definition

Postoperative cognitive dysfunction (POCD) describes a syndrome of prolonged impairment or deterioration of cognitive function with onset usually occurring weeks to months after surgery.39,40 Assessment of decline is made with preoperative and postoperative testing. Features include limitations in memory, intellectual ability, and executive function.39,40 A standardized approach to the identification and study of POCD has been limited by the lack of consensus diagnostic criteria.39,40 In general, the diagnosis involves identifying a worsening in postoperative formal neurocognitive testing relative to preoperative levels and is hence difficult outside of a research protocol.41 The International Study of Postoperative Cognitive Dysfunction (ISPOCD) made the diagnosis of POCD based on a combined Z-score > 2 (i.e., 2 standard deviations from the mean) across a multitude of individual cognitive tests or at least two Z-scores > 2 for single test parameters.40,42 Other investigators have looked at changes in cognitive domains such as memory and executive function, based on similar individual neurocognitive tests, relative to the patient’s baseline or to a control group.43

Although a consensus definition remains elusive, most investigators agree the morbidity of cognitive decline is significant. POCD is associated with longer hospital stays and cost, premature withdrawal from the workforce, and greater 1-year mortality, and it may possibly cause a change in the trajectory toward dementia.40,44–46

Attention to preoperative recognition of patients at risk for POCD has increased in recent years in the hope that identification, preoperative counseling, risk factor modification, and possible interventional strategies can help mitigate the untoward effects of POCD on individual patients and health-care systems as a whole.40,44

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Neurologic Disorders and Anesthesia

Alejandro A. Rabinstein, in Aminoff's Neurology and General Medicine (Sixth Edition), 2021

Cognitive Dysfunction

Postoperative cognitive dysfunction after exposure to general anesthesia occurs more often in older patients and in those with postoperative delirium.3,4 Mild global cognitive decline is typically observed, although short-term memory and executive function are predominantly affected. Its incidence is greatest after major cardiovascular surgery, ranging from 30 to 80 percent during the first few weeks after surgery and 10 to 60 percent after 3 to 6 months.3 Patients undergoing noncardiac surgery may also develop postoperative cognitive dysfunction, which has been shown to be associated with the occurrence of perioperative infarctions detectable by MRI.5 Additional risk factors include alcohol abuse, lower educational level, and previous stroke. Patients affected by this complication, even when transient, may have worse long-term cognitive outcomes, greater disability (particularly in the elderly), and a higher mortality.3 The impact of anesthesia exposure in early life (i.e., neonates and infants) on subsequent intellectual development has been quite extensively investigated but remains a matter of persistent debate due to inconsistent results across studies.6

There is no definitive evidence that the choice of anesthetic regimen (such as general or regional anesthesia) or the depth of anesthesia alters the risk of postoperative cognitive dysfunction. Activation of neuroinflammatory responses has been proposed as a key mechanism underlying the development of cognitive changes after exposure to anesthesia and surgery.7 Maintenance of physiologic homeostasis during and after surgery may minimize the risk of this complication.

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FUTURE ADVANCES IN NEUROANESTHESIA

W. Andrew Kofke, in Cottrell and Young's Neuroanesthesia (Fifth Edition), 2010

Nonneurotoxic Agents

Postoperative cognitive dysfunction is an object of increasing scrutiny, because it has a fairly robust incidence in elderly patients after noncardiac surgery, ranging from 10% to 15%.214-216 Although the precise mechanism of this phenomenon remains to be elucidated, there are ample data to suggest that specific neurotoxic effects of anesthetics could be important factors. Eckenhoff and coworkers217 reported the amyloidogenic properties of halothane and isoflurane, and Bianchi and colleagues218 have described behavioral changes after isoflurane but not sevoflurane anesthesia. Moreover, Wei and associates219 have reported that intracellular calcium homeostasis may be an important factor: Sevoflurane does not induce an increase in intracellular calcium and there is no apoptosis, whereas isoflurane induces release of calcium from intracellular stores with associated apoptosis. In immature brains, some anesthetics appear to induce unplanned apoptosis with delayed cognitive deficits (see earlier discussion in this chapter for possible impact on stem cell function).79 Nitrous oxide has dose-dependent and paradoxical protective and neurotoxic effects.220 Finally, opioids used in moderate to high doses produce hypermetabolism and histologically verifiable brain damage.221-225

All of these observations and others strongly implicate at least a partial role for many anesthetics in the pathogenesis of postoperative cognitive dysfunction. Moreover, a provocative set of studies by Bohnen and colleagues226,227 suggest a possible role of cumulative lifetime anesthetic (and surgical) experience in the genesis of Alzheimer’s disease, with a relevant study by Kofke and associates12 suggesting a differential pattern of brain blood flow with remifentanil as a function of a subject’s ApoE4 status. The ApoE4 allele of the ApoE SNP relates to a person’s likelihood to later experience Alzheimer’s disease.228,229

As answers begin to accumulate as to factors that contribute to anesthetic neurotoxicity and postoperative cognitive dysfunction, it is to be expected that anesthetic paradigms will be developed that will not have such deleterious side effects.

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How Can We Prevent Postoperative Cognitive Dysfunction?

Terri G. Monk MD, MS, Catherine C. Price PhD, in Evidence-Based Practice of Anesthesiology (Second Edition), 2009

AREAS OF UNCERTAINTY

It is now accepted that POCD occurs in a significant number of elderly patients, but the mechanisms responsible for this problem are unknown. Likewise, there are no known interventions to minimize or prevent this complication.

Because advancing age, lower educational level, and previous CVA with no residual deficit have been found to be independent predictors of POCD, it is likely that a patient's preoperative cognition may be the most important determinant of postoperative cognitive problems.2,3,6 The brain reserve hypothesis argues that individuals with larger cognitive reserve have greater capacity to replace compromised brain areas and maintain high functioning.43 This theory suggests that elders who are cognitively impaired before surgery might be at higher risk for postoperative cognitive problems. Thus, even mild perioperative neurologic trauma may be a sufficient proximal cause to move people over that functional cliff and into the range of cognitive functioning that might be classified as impaired.44 It is, therefore, possible that patients with borderline cognition before surgery may be predisposed to POCD when exposed to anesthetic agents, surgical trauma, the perioperative inflammatory response, or other perioperative events. One reason that the RCTs (see Tables 41-1, 41-2, and 41-3) evaluating interventions to improve cognitive outcome have had limited success may be that the subject groups may not include enough high-risk patients to detect differences in treatments.

Extensive data support the use of cholinesterase inhibitors, including tacrine, donepezil, rivastigmine, and galantamine, for the treatment of mild to moderate Alzheimer's disease. A small pilot study evaluated the efficacy of donepezil in treating patients with cognitive decline at 1 year after CABG and found cognitive improvement on delayed and immediate recall tests at 12 weeks after surgery but no changes on tests of executive function or word association.45 Although the findings in this study are preliminary, they provide hope that pharmacologic interventions to treat POCD will be developed in the future.

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Postoperative Management of Acute Pain

Jeffrey J. Mojica, ... Eugene R. Viscusi, in Cohen's Comprehensive Thoracic Anesthesia, 2022

Clinical Advantages

Following thoracic surgery, TEA reduces overall opioid consumption while improving analgesia.32,62 Reduced opioid consumption may allow for patients to ambulate earlier and could help in reducing sedation and postoperative cognitive dysfunction, especially in the elderly.

Inadequate analgesia and oversedation in the postoperative period may compromise pulmonary function and increase pulmonary complications. TEA has been shown to improve pulmonary function when compared with systemic analgesia. TEA decreases the degree of postoperative diaphragmatic dysfunction after thoracic surgery by minimizing the impact of surgical injury on phrenic motor nerve activity.72 A metaanalysis of the protective effects of TEA showed that from 1971 to 2006 the incidence of pneumonia with TEA remained about 8% but decreased from 34% to 12% with systemic analgesia.73 This difference reached statistical significance and suggests that the relative benefit of TEA has lessened over time. Finally, a metaanalysis of 65 RCTs comparing TEA using opioids and local anesthetics versus systemic opioids demonstrated a significant decrease in the incidence of atelectasis, pulmonary infections, hypoxemia, and overall pulmonary complications.74

Postoperative ileus is a common concern related to systemic opioids. TEA with local anesthetics results in faster return of bowel function compared with systemic opioids.75 In fact, TEA infusions of local anesthetic, with or without opioids, have been shown to enhance gastrointestinal recovery from surgery.76 The prevailing understanding is that TEA can selectively block nociceptive afferent fibers and the sympathetic nervous system but spares the parasympathetic nervous system. Specifically, the preservation of vagal tone may increase gastrointestinal motility postoperatively and limit the duration of ileus after thoracic surgery.

The partial blockade of the sympathetic nervous system with TEA may reduce some specific cardiac complications. Injury to cardiac parasympathetic nerves during thoracic surgery may be the source of tachyarrhythmias in the postoperative period because of the relatively unopposed innervation of the sympathetic nervous system. Investigators have found that postoperative thoracic sympathetic blockade with continuous thoracic epidural bupivacaine infusion after pulmonary resection reduced supraventricular tachyarrhythmias compared with epidural morphine infusion.77

Another clinical advantage of TEA is decreased postoperative catabolism and decreased muscle protein synthesis. TEA has been observed to reduce amino acid oxidation and nitrogen excretion to preserve lean body mass in the postoperative period.78,79

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Volume 3

Zuzana Kovacsova, ... Ilias Tachtsidis, in Encyclopedia of Biomedical Engineering, 2019

Cardiac surgery

The application of NIRS in cardiac surgery is of great interest as poor neurological outcome is a major concern. 1 to 3% of patients undergoing cardiopulmonary bypass suffer from stroke, and more than 50% of patients develop long-standing postoperative cognitive dysfunction. NIRS is used as a guiding tool during cardiac surgery as the likely cause of these issues includes emboli and cerebral hypoperfusion. NIRS is also used for monitoring during valve replacement or transplants. Several studies have been conducted supporting the positive impact of NIRS during cardiac surgery; they have shown correlation between cerebral desaturation and adverse outcome after cardiopulmonary bypass and outcome improvement, including a reduction in stroke occurrence. TOI can also be an alternative marker for poor outcome and it is likely that the duration and degree of cerebral desaturation determine the severity of ischemia.

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Special Characteristics of Pediatric Anesthesia

Peter J. Davis, ... Franklyn P. Cladis, in Smith's Anesthesia for Infants and Children (Eighth Edition), 2011

Intraoperative and postoperative analgesia in neonates

It has long been thought that newborn infants do not feel pain the way older children and adults do and therefore do not require anesthetic or analgesic agents (Lippman et al., 1976). Thus, in the past, neonates undergoing surgery were often not afforded the benefits of anesthesia. Later studies, however, indicated that pain experienced by neonates can affect behavioral development (Dixon et al., 1984; Taddio et al., 1995, 2005). Rats exposed to chronic pain without the benefit of anesthesia or analgesia showed varying degrees of neuroapoptosis (Anand et al., 2007). However, to add further controversy to the issue of adequate anesthesia for infants, concerns regarding the neurotoxic effects of both intravenous and inhalational anesthetic agents (GABAminergic and NMDA antagonists) have been raised. Postoperative cognitive dysfunction (POCD) has been noted in adult surgical patients (Johnson et al., 2002; Monk et al., 2008). In adults, POCD may also be a marker for 1-year survival after surgery. Although POCD is an adult phenomenon, animal studies by multiple investigators have raised concerns about anesthetic agents being toxic to the developing brains of infants and small children (Jevtovic-Todorovic et al., 2003, 2008; Mellon et al., 2007; Wang and Slikker, 2008). Early work by Uemura and others (1985) noted that synaptic density was decreased in rats exposed to halothane in utero. Further work with rodents, by multiple investigators, has shown evidence of apoptosis in multiple areas of the central nervous system during the rapid synaptogenesis period. This window of vulnerability appears to be a function of time, dose, and duration of anesthetic exposure. In addition to the histochemical changes of apoptosis, the exposed animals also demonstrated learning and behavioral deficits later in life.

In addition to apoptotic changes that occurred in rodents, Slikker and colleagues have demonstrated neuroapoptotic changes in nonhuman primates (rhesus monkeys) exposed to ketamine (an NMDA antagonist). As with the rodents, ketamine exposure in monkeys resulted in long-lasting deficits in brain function (Dr. Merle Poule, personal communication on the Safety of Key Inhaled and Intravenous Drugs in Pediatric Anesthesia [SAFEKIDS] Scientific Workshop, November 2009, White Oaks Campus Symposium). How these animal studies relate to human findings is unclear to date. However, three clinical studies have been reported, and all three studies are retrospective. Wilder et al. (2009) studied a cohort group of children from Rochester, Minnesota, and noted that children exposed to two or more anesthetics in the first 4 years of life were more likely to have learning disabilities, compared with children exposed to one anesthetic or none at all. Kalkman and others (2009) studied a group of children undergoing urologic surgery before age 6 years and reported that there was a tendency for parents to report more behavioral disturbances than those operated on at a later age. However, in a twin cohort study from the Netherlands, Bartels and coworkers (2009) reported no causal relationship between anesthesia and learning deficits in 1,143 monozygotic twin pairs.

In an effort to determine the impact of anesthetic agents or neurocognitive development, a collaborative partnership between the U.S. Food and Drug Administration (FDA) and the International Anesthesia Research Society has formed Safety of Key Inhaled and Intravenous Drugs in Pediatric Anesthesia (SAFEKIDS), a program designed to fund and promote research in this area.

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Regional and Peripheral Techniques

BRIAN KINIRONS, DOMINIC HARMON, in Postoperative Pain Management, 2006

Study-Design Issues

Study-design concerns may contribute to ambiguity in the interpretation of currently available studies. Almost all of the trials comparing the effects of intraoperative neuraxial anesthesia and general anesthesia have allowed the routine use of benzodiazepines in the perioperative period, which is significantly associated with development of POCD.43

Another area of potential concern is the general lack of control of postoperative analgesia in currently available trials. The effect of postoperative analgesia on mental function has not been rigorously investigated, and it is recognized that higher levels of postoperative pain are associated with a higher rate of POCD (especially delirium).60 Thus, control of postoperative pain may theoretically influence the incidence of POCD, which typically peaks within the first 3 postoperative days.39 Furthermore, different analgesic regimens may potentially have different effects on postoperative cognitive function; certain types of analgesic regimens (e.g., epidural analgesia with a local anesthetic–based solution) not only provide better pain control than systemic opioids56 but also avoid the systemic side effects of opioids, which may be associated with development of POCD.43 Finally, like almost all “regional versus general” anesthesia trials, none of the randomized controlled trials was blinded, leading to the possibility of bias.57

Future studies in this area will allow correlation of the level of cognitive impairment (as assessed by appropriate neuropsychological testing) with a clinically relevant drop in cognitive function.61 Peripheral nerve blockade is a component of regional anesthesia practice. Its role in diminishing postoperative cognitive dysfunction in those at risk must also be examined in future studies.

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