Lisbeth Evered

Postoperative cognitive dysfunction is independent of type of surgery and anesthetic.

BACKGROUND: Postoperative cognitive dysfunction (POCD) has been documented after cardiac and noncardiac surgery. The type of surgery and anesthetic has been assumed to be associated with the incidence but there are few prospective data comparing the incidence after different procedures. In this study, we sought to determine the association of the type of surgical procedure and anesthesia on the incidence of POCD after procedures involving light sedation, general anesthesia for noncardiac surgery, and general anesthesia for cardiac surgery involving cardiopulmonary bypass. METHODS: Eight neuropsychological tests were administered at baseline and at 7 days and 3 months postoperatively to subjects from 3 procedure groups and a nonoperative control group. Reliable change index was used to calculate POCD. The study sample consisted of subjects involved in 3 separate trials investigating coronary angiography (CA) (percutaneous diagnostic procedure) under sedation, major noncardiac surgery (total hip joint replacement [THJR] surgery) under general anesthesia, and coronary artery bypass graft (CABG) surgery under general anesthesia. RESULTS: Data were collected from 644 patients in the patient groups and 34 subjects in the control group. Neuropsychological results were available for POCD at day 7 for THJR surgery (n = 162) and CABG surgery (n = 281). The incidence of POCD at day 7 was 17% for THJR surgery and 43% for CABG surgery (adjusted odds ratio = 0.2, 95% confidence interval [CI]: 0.1, 0.4; P < 0.01). At 3 months, the incidence of POCD for all groups combined (n = 636) was 17% (21% for CA under sedation, 16% for THJR surgery, and 16% for CABG surgery). The mean (95% CI) for the difference in proportions of POCD among groups was 0.00 (−0.07, 0.07) (P = 0.91) for CABG versus THJR; −0.05 (−0.12, 0.03) (P = 0.21) for CABG versus CA; and −0.05 (−0.13, 0.03) (P = 0.24) for THJR versus CA. There were no significant differences among groups (adjusted odds ratio = 1.21, 95% CI: 0.94, 1.55; P = 0.13). CONCLUSIONS: The incidence of POCD in old and elderly patients at day 7 was higher after CABG surgery than THJR surgery, but POCD at 3 months was independent of the nature or the type of procedure or anesthetic when comparing CA, THJR, and CABG surgery groups. Cardiovascular risk factors were not predictive of POCD after any procedure.

Preexisting cognitive impairment in patients scheduled for elective coronary artery bypass graft surgery.

BACKGROUND: An accurate assessment of the prevalence of cognitive impairment in patients scheduled for coronary artery bypass graft (CABG) surgery is necessary if valid assumptions regarding cognitive change are to be made. Such an assessment requires the use of a healthy control group free of cardiovascular disease. METHODS: In a retrospective observational study, 349 patients scheduled for CABG surgery underwent neuropsychological testing. We compared the results with those from a group of 170 healthy controls without cardiovascular disease and containing more female patients who were matched for age and IQ score. Cognitive impairment was defined as test scores ≥2 sd less than the controls on two or more of the seven tests. RESULTS: The CABG surgery patients performed significantly worse than the control group on all tests except the Grooved Pegboard test (nondominant). When analyzed by group, performance on the verbal learning test was the most impaired. Cognitive impairment was present in 122 (35%) of CABG surgery patients before their procedure. Prior myocardial infarction, age, and IQ were independent predictors of cognitive impairment. CONCLUSIONS: Cognitive impairment is prevalent in patients presenting for CABG surgery. Impaired cognition before surgery must be considered when assessing the effects of CABG surgery on cognitive performance.

A comparison of the effect of high- and low-dose fentanyl on the incidence of postoperative cognitive dysfunction after coronary artery bypass surgery in the elderly.

Background:Postoperative cognitive dysfunction (POCD) after coronary artery bypass graft surgery is a common complication for which, despite many clinical investigations, no definitive etiology has been found. The current use of both high- and low-dose fentanyl as anesthetic techniques allowed us to investigate the effect of fentanyl on the incidence of POCD. Methods:Three hundred fifty patients scheduled to undergo elective coronary artery bypass graft surgery were randomized to receive either high-dose fentanyl (50 &mgr;g/kg) or low-dose fentanyl (10 &mgr;g/kg) as the basis of the anesthetic. All patients underwent neuropsychological testing before surgery and at 1 week, 3 months, and 12 months after surgery. Results:One hundred sixty-eight patients in the low-dose group and 158 patients in the high-dose group were included in the final analysis. Neuropsychological testing was performed on 88%, 93%, and 92% of patients at 1 week, 3 months, and 12 months, respectively. There was no difference between group mean scores at any of the three testing times. Analysis of individual patients by the 20% rule did not detect any differences between groups. The one SD rule, which has fewer false-positive results, detected significantly more patients with POCD in the low-dose group than in the high-dose group at 1 week (23.6% vs. 13.7%; P = 0.03) but not at the other testing times. Patients with POCD spent an average of 1.2 days longer in the hospital than those without POCD (P = 0.021). Conclusions:High-dose fentanyl is not associated with a difference in the incidence of POCD at 3 or 12 months after surgery. Low-dose fentanyl leads to shorter postoperative ventilation times and may be associated with a greater incidence of POCD 1 week after surgery. Early POCD is associated with an increased duration of stay in the hospital.

Preexisting Cognitive Impairment and Mild Cognitive Impairment in Subjects Presenting for Total Hip Joint Replacement

Background:The prevalence of preexisting cognitive impairment (PreCI) is documented before cardiac surgery, but there is less information before noncardiac surgery. In addition, the prevalence of mild cognitive impairment, defined by different cognitive criteria and subjective complaints, and which may progress to Alzheimer disease, is unknown in these subjects. Because anesthesia and surgery have been implicated in Alzheimer disease pathology, we prospectively measured PreCI and mild cognitive impairment in subjects scheduled for total hip joint replacement surgery in an observational study. Methods:One hundred fifty-two subjects 60 y of age and older who were scheduled for total hip joint replacement surgery underwent assessment, including neuropsychologic testing, 1 week before surgery. Test results were compared with published norms. PreCI was defined as impairment in two or more of seven cognitive tests, for which impairment in an individual test was defined as ≥2 SD below norms for that test. Amnestic mild cognitive impairment (aMCI) was defined as impairment ≥1.5 SD below norms for results of the immediate and/or delayed Auditory Verbal Learning Test plus a subjective complaint. Results:Subjects performed worse compared with normative data on five of seven neuropsychologic tests. Thirty (20% [95% CI, 13–26%]) subjects were classified as having PreCI. Thirty-four (22% [95% CI, 16–29%]) were classified as having aMCI. Ten (7%) subjects were classified as having both PreCI and aMCI, representing 33% of the 30 subjects with PreCI. Conclusions:The prevalence of aMCI in subjects scheduled for total hip joint replacement surgery is similar to that in the general community. PreCI and aMCI tend to identify different subjects. Because aMCI is known to progress to Alzheimer disease, future studies that track cognition before and after anesthesia and surgery should document the presence or absence of aMCI so that the rate of conversion to Alzheimer disease after anesthesia and surgery can be compared with the rate in the nonsurgical population.

Preexisting cognitive impairment is associated with postoperative cognitive dysfunction after hip joint replacement surgery.

Background:This study investigated the prevalence of cognitive impairment in elderly noncardiac surgery patients and any association between preoperative cognitive impairment and postoperative cognitive dysfunction (POCD). Additionally, the incidence of cognitive decline at 12 months after surgery was identified. Methods:Three hundred patients for hip joint replacement and 51 nonsurgical controls aged 60 yr or older were studied in a prospective observational clinical trial. All study participants and controls completed a battery of eight neuropsychological tests before surgery and at 7 days, 3 months, and 12 months afterwards. Preoperative cognitive status was assessed using preexisting cognitive impairment (PreCI) defined as a decline of at least 2 SD on two or more of seven neuropsychological tests compared to population norms. POCD and cognitive decline were assessed using the reliable change index utilizing the results of the control group. Results:PreCI was classified in 96 of 300 (32%) patients (95% CI, 23 to 43%). After surgery, 49 of 286 (17%) patients (95% CI, 13 to 22%) and 27 of 284 (10%) patients (95% CI, 6 to 13%) demonstrated POCD at 7 days and 3 months, respectively, while 7 of 271 (3%) patients (95% CI, 1 to 4%) demonstrated cognitive decline at 12 months. Patients with PreCI had a significantly increased incidence of POCD at 7 days and 3 months and cognitive decline at 12 months. Conclusions:Patients with PreCI have an increased incidence of POCD and cognitive decline. PreCI is a good predictor of subsequent POCD and cognitive decline. The incidence of cognitive decline after 12 months in this group of patients is low.

The sensitivity and specificity of three common statistical rules for the classification of post-operative cognitive dysfunction following coronary artery bypass graft surgery

Background:  The application of statistical rules to determine post‐operative cognitive dysfunction (POCD) has varied, and partially explains the wide range of reported incidences of POCD in the literature. The current study assessed the sensitivity and specificity of three commonly used statistical rules in a sample of coronary artery bypass graft (CABG) patients and healthy non‐surgical controls.

The Apolipoprotein E ϵ4 Allele is not Associated With Cognitive Dysfunction in Cardiac Surgery

BACKGROUND The plasma protein apolipoprotein E (APOE) is a risk factor for degenerative cognitive decline manifested by mild cognitive impairment and later by Alzheimers disease. Patients undergoing coronary artery bypass grafting (CABG) are known to have a high prevalence of preexisting cognitive impairment and postoperative cognitive dysfunction. Because both mild cognitive impairment and Alzheimers disease generally occur in elderly individuals, the age group that commonly present for CABG, we investigated if the APOE epsilon4 allele was associated with patients manifesting preexisting cognitive impairment and postoperative cognitive dysfunction. METHODS The DNA of 282 patients who had undergone neuropsychologic testing before and 3 and 12 months after CABG was analyzed for APOE genotype. Patients were classified as having preexisting cognitive impairment if cognitive function was decreased in two or more tests compared with a healthy control group. Postoperative cognitive dysfunction was defined as a decrease in two or more tests compared with the group mean baseline score. RESULTS The APOE epsilon4 allele was found in 83 (29.4%) patients. Although preexisting cognitive impairment was present in 105 (37.2%) and postoperative cognitive dysfunction in 33 (12%) and 31 (11%) at 3 and 12 months postoperatively, there was no relationship with the presence of the APOE epsilon4 allele or any of the six genotypes. CONCLUSIONS Preexisting cognitive impairment and postoperative cognitive dysfunction are not associated with APOE epsilon4 genotype, suggesting that cognitive impairment both before and after CABG may not be associated with degenerative cognitive decline.

Cognitive decline in the elderly: Is anaesthesia implicated?

Postoperative cognitive dysfunction (POCD) was originally thought to be associated with cardiac surgery, but has since been associated with non-cardiac surgery and even sedation for non-invasive procedures such as coronary angiography. The focus of POCD has thus shifted from the type of surgery or anaesthetic to patient susceptibility. The realisation that cognitive impairment, such as mild cognitive impairment (MCI - the prodrome for Alzheimers disease (AD)), may already exist in many elderly patients who incidentally present for surgery beckons anaesthesia to align cognitive research with that of AD in order to draw valid parallels between the two disciplines. Long-term studies are required to understand if POCD is merely a transient phenomenon, or if it is the harbinger of long-term cognitive deterioration which may lead eventually to dementia. In this regard, the use of CSF analysis to diagnose AD many years before symptoms appear may identify susceptible individuals. Furthermore, animal studies indicate that volatile anaesthestics may augment the pathological processes of AD by affecting amyloid-beta processing. Identification of a link between surgery/anaesthesia, POCD, MCI, and AD would create a unique opportunity to fast-track the development of clinical or pharmacological preventive strategies that would benefit a significant proportion of the population.

Incidence of postoperative cognitive dysfunction after general or spinal anaesthesia for extracorporeal shock wave lithotripsy

BACKGROUND Since general anaesthesia invariably accompanies surgery, the contribution of each to the development of postoperative cognitive dysfunction (POCD) has been difficult to identify. METHODS A prospective randomized controlled trial was undertaken in elderly patients undergoing extracorporeal shock wave lithotripsy (ESWL). Between 2005 and 2011, 2706 individuals were screened to recruit 100 eligible patients. Patients were randomly assigned to receive general or spinal anaesthesia alone. A battery of eight neuropsychological tests was administered before operation and at 7 days and 3 months after operation. The reliable change index was used to calculate the incidence of POCD. Intention-to-treat analysis was used to compare rates of POCD. RESULTS Futility analysis led to stopping of the trial after recruitment of 100 patients. Fifty patients were randomly assigned to general anaesthesia, and 48 patients to spinal anaesthesia without sedation or postoperative opioids. At 3 months, POCD was detected in 6.8% [95% confidence interval (CI): 1.4-18.7%] of patients in the general anaesthesia group and 19.6% (95% CI: 9.4-33.9%) in the spinal group (P=0.07). At 7 days after operation, the incidence of POCD was 4.1% (95% CI: 0.5-14%) in the general anaesthesia group and 11.9% (95% CI: 4.0-26.6%) in the spinal group (P=0.16). CONCLUSIONS We found no significant difference in the rates of POCD when comparing general anaesthesia with spinal anaesthesia, suggesting that the surgical or procedural process itself may contribute to the development of POCD. CLINICAL TRIAL REGISTRATION Australian Clinical Trials Registry number ACTRN12605000150640.

Prevalence of Dementia 7.5 Years after Coronary Artery Bypass Graft Surgery

Background:Although postoperative cognitive dysfunction (POCD) is well described after coronary artery bypass graft (CABG) surgery, a major concern has been that a progressive decline in cognition will ultimately lead to dementia. Since dementia interferes with the ability to carry out daily functions, the impact has far greater ramifications than cognitive decline defined purely by a decreased ability to perform on a battery of neurocognitive tests. The authors hypothesized that early cognitive impairment measured as baseline cognitive impairment is associated with an increased risk of long-term dementia. Methods:The authors conducted a prospective longitudinal study on 326 patients aged 55 yr and older at the time of undergoing CABG surgery. Dementia was classified by expert opinion on review of performance on the Clinical Dementia Rating Scale and several other assessment tasks. Patients were also assessed for POCD at 3 and 12 months and at 7.5 yr using a battery of neuropsychologic tests and classified using the reliable change index. Associations were assessed using univariable analysis. Results:At 7.5 yr after CABG surgery, the prevalence of dementia was 36 of 117 patients (30.8%; 95% CI, 23 to 40). POCD was detected in 62 of 189 patients (32.8%; 95% CI, 26 to 40). Due to incomplete assessments, the majority (113 patients), but not all, were assessed for both dementia and POCD. Fourteen of 32 (44%) patients with dementia were also classified as having POCD. Preexisting cognitive impairment and peripheral vascular disease were both associated with dementia 7.5 yr after CABG surgery. POCD at both 3 (odds ratio, 3.06; 95% CI, 1.39 to 9.30) and 12 months (odds ratio, 4.74; 95% CI, 1.63 to 13.77) was associated with an increased risk of mortality by 7.5 yr. Conclusions:The prevalence of dementia at 7.5 yr after CABG surgery is greatly increased compared to population prevalence. Impaired cognition before surgery or the presence of cardiovascular disease may contribute to the high prevalence.