Examining Subjective Psychological Experiences of Postoperative Delirium in Older Cardiac Surgery Patients.

BACKGROUND: Postoperative delirium (POD) is an acute syndrome including inattention and impaired cognition that affects approximately 42% of older cardiac surgical patients. POD is linked to adverse outcomes including morbidity, mortality, and further cognitive decline. Less is known about the subjective psychological experience of POD and its ongoing impact on well-being. METHODS: We performed a qualitative analysis of the long-term psychological sequelae of older adults who experience POD after cardiac surgery. We sampled 30 patients aged 60 years and older who experienced at least 2 episodes of POD during a prior hospital admission. We administered semistructured interviews with participants via telephone 3 to 5 years postoperatively. Interviews were transcribed and thematically analyzed. Data were interpreted in accordance with the naturalist paradigm. RESULTS: Three overarching themes emerged in our qualitative analysis. The first reflected the multifaceted presentation of POD, including distortion of time and reality; feelings of isolation; and a loss of self, identity, and control. The second theme reflected the psychological challenges associated with functional decline after surgery. Common examples of functional decline included cognitive difficulties, excessive fatigue, and a perceived loss of independence. The final theme captured the emotional sequelae of acute illness, which included low mood, reduced motivation, and social comparisons. CONCLUSIONS: Our findings emphasize the multidimensional experience of POD and long-term effects on psychological wellbeing. Our research highlights the beneficial role multidisciplinary clinicians play in managing POD including strategies that may be embedded into clinical practice and helps anesthesiologists understand why patients who have experienced POD in the past may present with specific concerns should they require subsequent surgery.

Inflammatory Biomarker Levels After Propofol or Sevoflurane Anesthesia: A Meta-analysis.

BACKGROUND: The perioperative inflammatory response may be implicated in adverse outcomes including neurocognitive dysfunction and cancer recurrence after oncological surgery. The immunomodulatory role of anesthetic agents has been demonstrated in vitro; however, its clinical relevance is unclear. The purpose of this meta-analysis was to compare propofol and sevoflurane with respect to biomarkers of perioperative inflammation. The secondary aim was to correlate markers of inflammation with clinical measures of perioperative cognition. METHODS: Databases were searched for randomized controlled trials examining perioperative inflammation after general anesthesia using propofol compared to sevoflurane. Inflammatory biomarkers investigated were interleukin (IL)-6, IL-10, tissue necrosis factor alpha (TNF-α), and C-reactive protein (CRP). The secondary outcome was incidence of perioperative neurocognitive disorders. Meta-analysis with metaregression was performed to determine the difference between propofol and sevoflurane. RESULTS: Twenty-three studies were included with 1611 participants. Studies varied by surgery type, duration, and participant age. There was an increase in the mean inflammatory biomarker levels following surgery, with meta-analysis revealing no difference in effect between propofol and sevoflurane. Heterogeneity between studies was high, with surgery type, duration, and patient age contributing to the variance across studies. Only 5 studies examined postoperative cognitive outcomes; thus, a meta-analysis could not be performed. Nonetheless, of these 5 studies, 4 reported a reduced incidence of cognitive decline associated with propofol use. CONCLUSIONS: Surgery induces an inflammatory response; however, the inflammatory response did not differ as a function of anesthetic technique. This absence of an effect suggests that patient and surgical variables may have a far more significant impact on the postoperative inflammatory responses than anesthetic technique. The majority of studies assessing perioperative cognition in older patients reported a benefit associated with the use of propofol; however, larger trials using homogenous outcomes are needed to demonstrate such an effect.

Impaired cognitive performance on MoCA testing at discharge in elderly patients following day endoscopy and its relationship to preoperative mild cognitive impairment.

In patients admitted to hospital, preoperative mild cognitive impairment predicts postoperative complications. The effect of mild cognitive impairment on discharge readiness among the day stay surgery population is unknown. Our aims were to determine the incidence of impaired cognitive performance at discharge after day stay endoscopy and whether pre-existing mild cognitive impairment was associated with its development. A single-centre cohort study of elective day stay endoscopy patients was undertaken. Over a three-month period, data were collected from 69 patients aged 65 years and over. Patients were cognitively assessed on admission and discharge using the Montreal cognitive assessment tool and the three-minute diagnostic confusion assessment method. At baseline, patients who scored 1.5 or more standard deviations below age-adjusted levels on the Montreal cognitive assessment tool in conjunction with a subjective memory complaint were classified as having mild cognitive impairment. At discharge, patients were classified as having impaired cognitive performance if there was a reduction in the Montreal cognitive assessment tool score by at least two points. We also assessed delirium and subsyndromal delirium at discharge using the three-minute diagnostic confusion assessment method. We identified mild cognitive impairment in 23 patients (33.3%) on admission, and impaired performance on the Montreal cognitive assessment tool test at discharge in 35 (50.7%) patients. There was no association between mild cognitive impairment on admission and impaired cognitive performance at discharge (50.0% versus 51.1%, P = 0.94). This study demonstrates that evidence of impaired cognitive performance on the Montreal cognitive assessment tool testing is present after day stay endoscopy in over 50% of elderly patients, but this is not associated with preoperative cognitive status.

Informed Consent in Patients With Frailty Syndrome.

Frailty is present in more than 30% of individuals older than 65 years of age presenting for anesthesia and surgery, and poses a number of unique issues in the informed consent process. Much attention has been directed at the increased incidence of poor outcomes in these individuals, including postoperative mortality, complications, and prolonged length of stay. These material risks are not generally factored into conventional risk predictors, so it is likely that individuals with frailty are never fully informed of the true risk for procedures undertaken in the hospital setting. While the term "frailty" has the advantage of alerting to risk and allowing appropriate care and interventions, the term has the social disadvantage of encouraging objectivity to ageism. This may encourage paternalistic behavior from carers and family encroaching on self-determination and, in extreme cases, manifesting as coercion and compromising autonomy. There is a high prevalence of neurocognitive disorder in frail elderly patients, and care must be taken to identify those without capacity to provide informed consent; equally important is to not exclude those with capacity from providing consent. Obtaining consent for research adds an extra onus to that of clinical consent. The informed consent process in the frail elderly poses unique challenges to the busy clinical anesthesiologist. At the very least, an increased time commitment should be recognized. The gap between theoretical goals and actual practice of informed consent should be acknowledged.

Postoperative Cognitive Dysfunction and Noncardiac Surgery.

Postoperative cognitive dysfunction (POCD) is an objectively measured decline in cognition postoperatively compared with preoperative function. POCD has been considered in the anesthetic and surgical literature in isolation of cognitive decline which is common in the elderly within the community and where it is labeled as mild cognitive impairment, neurocognitive disorder, or dementia. This narrative review seeks to place POCD in the broad context of cognitive decline in the general population. Cognitive change after anesthesia and surgery was described over 100 years ago, initially as delirium and dementia. The term POCD was applied in the 1980s to refer to cognitive decline assessed purely on the basis of a change in neuropsychological test results, but the construct has been the subject of great heterogeneity. The cause of POCD remains unknown. Increasing age, baseline cognitive impairment, and fewer years of education are consistently associated with POCD.In geriatric medicine, cognitive disorders defined and classified as mild cognitive impairment, neurocognitive disorder, and dementia have definitive clinical features. To identify the clinical impact of cognitive impairment associated with the perioperative period, POCD has recently been redefined in terms of these geriatric medicine constructs so that the short-, medium-, and long-term clinical and functional impact can be elucidated. As the aging population present in ever increasing numbers for surgery, many individuals with overt or subclinical dementia require anesthesia. Anesthesiologists must be equipped to understand and manage these patients.

Cognitive Function Before and After Left Heart Catheterization.

BACKGROUND: Hospital procedures have been associated with cognitive change in older patients. This study aimed to document the prevalence of mild cognitive impairment in individuals undergoing left heart catheterization (LHC) before the procedure and the incidence of cognitive decline to 3 months afterwards. METHODS AND RESULTS: We conducted a prospective, observational, clinical investigation of elderly participants undergoing elective LHC. Cognition was assessed using a battery of written tests and a computerized cognitive battery before the LHC and then at 3 months afterwards. The computerized tests were also administered at 24 hours (or discharge) and 7 days after LHC. A control group of 51 community participants was recruited to calculate cognitive decline using the Reliable Change Index. Of 437 participants, mild cognitive impairment was identified in 226 (51.7%) before the procedure. Computerized tests detected an incidence of cognitive decline of 10.0% at 24 hours and 7.5% at 7 days. At 3 months, written tests detected an incidence of cognitive decline of 13.1% and computerized tests detected an incidence of 8.5%. Cognitive decline at 3 months using written tests was associated with increasing age, whereas computerized tests showed cognitive decline was associated with baseline amnestic mild cognitive impairment, diabetes mellitus, and prior coronary stenting. CONCLUSIONS: More than half the patients aged >60 years presenting for LHC have mild cognitive impairment. LHC is followed by cognitive decline in 8% to 13% of individuals at 3 months after the procedure. Subtle cognitive decline both before and after LHC is common and may have important clinical implications. CLINICAL TRIAL REGISTRATION INFORMATION: URL: www.anzctr.org.au. Unique identifier: ACTRN12607000051448.

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.

Cognitive dysfunction follows left heart catheterisation but is not related to microembolic count.

BACKGROUND: Left heart catheterisation with coronary angiography (CA) may lead to cognitive dysfunction, as a result of neurological injury. The aim was to assess the incidence of cognitive dysfunction in elderly patients three months after CA and investigate any association between cognitive dysfunction and microembolic count during CA. METHODS: This was a prospective observational study with a control cohort. Cognitive testing was undertaken at baseline and at 3 months using a battery of 8 neuropsychological tests. Subjects comprised 51 CA patients, aged ≥ 50 years, with normal baseline cognition, and 31 community control participants. Microemboli were measured by Transcranial Doppler throughout the procedure. All patients underwent trans-femoral CA with aortography and ventriculography. Cognitive dysfunction was defined in an individual when their reliable change index score was less than -1.96 on 2 or more tests and/or their combined z score was less than -1.96. Microembolic count was assessed by off-line manual counting and automatic software was also used to count and differentiate gaseous from solid microemboli. RESULTS: Cognitive dysfunction was identified in 15.7% of patients at 3 months. Microemboli were detected in all patients, predominantly during aortography and ventriculography. The median total embolic count was 365 (IQR 192, 574), the majority being gaseous (84%). There was no multivariable association between cognitive dysfunction at 3 months and microembolic count. CONCLUSIONS: This study demonstrated that cognitive dysfunction following CA is not associated with microembolic load. Cognitive dysfunction occurs in 15.7% of patients at 3 months. This is reassuring for the proceduralist and suggests that other perioperative elements are involved.

Cardiac surgery, the brain, and inflammation.

Cognitive deterioration can reliably be measured after procedures requiring anesthesia and surgery. Cardiac surgery has had the spotlight because of the high reported incidence of postoperative cognitive dysfunction in early studies, but such effects occur after other surgical procedures as well. "Early" postoperative cognitive dysfunction should be considered as a different phenomenon, relating to acute pharmacological, physiological, and stress-related recovery. The focus should be on what is affecting patients at 3 months, 12 months, and 5 years later. Like with many other aspects of perioperative risk, a significant element is the patient's preoperative cognitive status. We now know that up to one-third of overtly "normal" elective cardiac surgical patients enter surgery with some degree of pre-existing cognitive impairment or, when applying psychogeriatric measures, mild cognitive impairment. The latter is a known prodrome or early stage of the amyloid associated Alzheimer's disease dementia. Inflammatory responses during cardiac surgery have been recognized for years, but our understanding of the complexity of systemic inflammatory response has grown significantly with the ability to assay neurohumoral markers such as interleukins. The blood-brain barrier is made vulnerable by both pre-existing disorders (mild cognitive impairment/amyloid; vascular disease) and by the inflammatory response to surgery and cardiopulmonary bypass. Inflammation affecting the brain at this time may set in motion accelerated neurological and hence cognitive decline that, despite an initial recovery and even functional improvement, may proceed to further long-term decline at an accelerated rate in susceptible individuals. Clinical data are emerging from longer-term studies to support this concern, but evidence for effective preventive or therapeutic strategies is limited.

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.

Nitrous oxide and long-term morbidity and mortality in the ENIGMA trial.

BACKGROUND: There is a plausible pathophysiologic rationale for increased long-term cardiovascular morbidity and mortality in patients receiving significant exposure to nitrous oxide. However, this relationship has not been established clinically. The ENIGMA trial randomized 2050 patients having noncardiac surgery lasting more than 2 hours to nitrous oxide-based or nitrous oxide-free anesthesia. We conducted a follow-up study of the ENIGMA patients to evaluate the risk of cardiovascular events in the longer term. METHODS: The trial case report forms and medical records of all study patients were reviewed. The date and cause of death and occurrence of myocardial infarction or stroke were recorded. A telephone interview was then conducted with all surviving patients. The primary endpoint of the study was survival. RESULTS: The median follow-up time was 3.5 (range: 0 to 5.7) years. Three hundred eighty patients (19%) had died since the index surgery, 91 (4.5%) were recorded as having myocardial infarction, and 44 (2.2%) had a stroke during the entire follow-up period. Nitrous oxide did not significantly increase the risk of death [hazard ratio = 0.98 (95% confidence interval, CI: 0.80 to 1.20; P = 0.82)]. The adjusted odds ratio for myocardial infarction in patients administered nitrous oxide was 1.59 (95% CI: 1.01 to 2.51; P = 0.04) and for stroke was 1.01 (95% CI: 0.55 to 1.87; P = 0.97). CONCLUSIONS: The administration of nitrous oxide was associated with increased long-term risk of myocardial infarction, but not of death or stroke in patients enrolled in the ENIGMA trial. The exact relationship between nitrous oxide administration and serious long-term adverse outcomes will require confirmation by an appropriately designed large randomized controlled trial.

Postoperative cognitive dysfunction and aortic atheroma.

BACKGROUND: The relationship of aortic atheroma to postoperative cognitive dysfunction (POCD), a common complication of coronary artery bypass graft surgery, has not been resolved. We undertook assessment of aortic atheroma using intraoperative ultrasonography and related the degree of aortic atheroma to POCD. METHODS: Aortic atheroma was assessed using intraoperative transesophageal and epiaortic echocardiography in 311 patients who underwent coronary artery bypass graft surgery. Atheroma was graded from 0 (normal or minimal) to 3 (mobile or rough) in each of four quadrants of the proximal ascending to proximal descending thoracic aorta. Atheroma burden was defined as the atheroma score divided by the total possible score for that patient. Patients also completed a neuropsychological battery consisting of eight tests taken the week before surgery and at 1 week and 3 and 12 months afterward. Decreased cognitive function for each test was defined as an individual decrease of at least 1 standard deviation of the group baseline mean for that test, and POCD was defined as a decrease in two or more tests. RESULTS: The atheroma burden (%) was greater in the patients with POCD. The difference was greatest at 1 week (10.4+/-14.7 versus 4.4+/-9.0, p=0.0002) and diminished progressively at 3 months (8.9+/-14.1 versus 5.4+/-10.1, p=0.06) and 12 months (6.6+/-12.0 versus 5.6+/-10.2, p=0.56). Multivariable analysis showed that atheroma burden strongly predicted POCD at 1 week. CONCLUSIONS: Aortic atheroma burden predicts POCD at 1 week but has less impact on POCD as time progresses. Atheroma burden is highly correlated with age and may be a good predictor of early POCD.

Plasma amyloid beta42 and amyloid beta40 levels are associated with early cognitive dysfunction after cardiac surgery.

BACKGROUND: Decreased cognitive function associated with coronary artery bypass graft surgery is common. These deficits may be similar to the cognitive dysfunction seen in the spectrum of mild cognitive impairment to Alzheimer's disease, which are believed to result from the accumulation of amyloid beta (Abeta) peptide in the brain. We measured cognition both before and after coronary artery bypass graft surgery and assayed Abeta levels to investigate whether the cognitive dysfunction of cardiac surgery was associated with Abeta levels. METHODS: The plasma of 332 patients, who had undergone neuropsychological testing before and 3 and 12 months after coronary artery bypass graft surgery, was analyzed for Abeta(42) and Abeta(40). Patients were classified as having preexisting cognitive impairment if cognitive function was decreased in two or more tests compared with a healthy control group, and postoperative cognitive dysfunction was defined as a decline in two or more tests compared with the group mean baseline score. RESULTS: Preexisting cognitive impairment was present in 117 patients (35.2%), and postoperative cognitive dysfunction was present in 40 (12%) at 3 months and 41 (13%) at 12 months after surgery. Both plasma Abeta(42) and Abeta(40) levels assessed before the surgery were significantly lower in patients who later had postoperative cognitive dysfunction at 3 months. CONCLUSIONS: Decreased preoperative plasma levels of Abeta(42) and Abeta(40) in patients who exhibit postoperative cognitive dysfunction at 3 months suggest that postoperative cognitive dysfunction at this time may share a common mechanism with mild cognitive impairment and Alzheimer's disease. This process may be exacerbated by anesthesia.

Early cognitive impairment after sedation for colonoscopy: the effect of adding midazolam and/or fentanyl to propofol.

BACKGROUND: The sedative drug combination that produces minimal cognitive impairment and optimal operating conditions during colonoscopy has not been determined. We sought to determine if the use of propofol alone results in less cognitive impairment at discharge than the use of propofol plus midazolam and/or fentanyl in patients presenting for elective outpatient colonoscopy. METHODS: Two hundred adult patients presenting for elective outpatient colonoscopy were randomized to receive propofol alone or propofol plus midazolam, and/or fentanyl for IV sedation. Baseline cognitive function was measured using the computerized CogState test battery (Cogstate, Melbourne, Australia) before sedation. During the procedure, sedative drug doses, depth of sedation (via the bispectral index and observer's assessment of alertness/sedation score), complications, and treatability were recorded. Patients were interviewed about recall immediately after emerging from sedation, and cognitive testing was repeated at hospital discharge. Recovery times, quality of recovery, and satisfaction with care were also recorded. RESULTS: In the propofol plus adjuvants group, 84 patients received fentanyl 50 microg (25-100) (median [range]) and 57 patients received midazolam 2 mg (0.5-10). Patients' cognitive function at discharge was worse than their performance at baseline. However, the changes in cognitive function between discharge and baseline were not significantly different between the two groups. At discharge, 18.5% of patients were cognitively impaired to an extent equivalent to a blood-alcohol concentration of 0.05%. Sedation with propofol plus midazolam and/or fentanyl produced better operating conditions than sedation with propofol alone and was associated with shorter procedure times. Recovery times, recall, dreaming, quality of recovery, and patient satisfaction with care were similar between the groups. Administration of >2 mg of midazolam was a predictor of impaired cognitive function at discharge. CONCLUSIONS: Significant cognitive impairment was common at discharge from elective outpatient colonoscopy. However, the addition of midazolam and/or fentanyl to propofol sedation did not result in more cognitive impairment than the use of propofol alone. Furthermore, the use of adjuvants improved the ease of colonoscopy without increasing the rate of complications or prolonging early recovery times..

Nitrous oxide and perioperative cardiac morbidity (ENIGMA-II) Trial: rationale and design.

BACKGROUND: Globally there are >200 million major surgical procedures undertaken annually, and about 20% of these involve patients who have coronary artery disease. Many receive nitrous oxide, which impairs methionine synthase, thus inhibiting folate synthesis and increasing postoperative homocysteine levels. Nitrous oxide anesthesia leads to postoperative endothelial dysfunction, and there is some evidence that it increases myocardial ischemia and, possibly, myocardial infarction. We have initiated the Nitrous oxide and perioperative cardiac morbidity (ENIGMA-II) Trial to test the hypothesis that in inpatients undergoing anesthesia for major noncardiac surgery, avoidance of nitrous oxide will reduce the incidence of death and major cardiovascular events. METHODS: ENIGMA-II is a 7,000-patient, international randomized trial involving patients at risk of coronary artery disease undergoing noncardiac surgery. The patients, health care providers (except for the anesthesiologists), data collectors, and outcome adjudicators are blinded to whether patients receive nitrous oxide-containing or nitrous oxide-free anesthetic. The primary outcome is a composite of death and major nonfatal events (ie, myocardial infarction, cardiac arrest, pulmonary embolism, and stroke) at 30 days after surgery. RESULTS: At present, ENIGMA-II has randomized >1,000 patients in 22 hospitals in 5 countries. To date, patients' mean age is 70 years, 66% are men, 38% have a history of coronary artery disease, 19% have a history of cerebrovascular disease, and 84% have a history of hypertension. Most patients have undergone intra-abdominal 28%, vascular 32%, and orthopedic 16% surgery. CONCLUSIONS: The ENIGMA-II Trial will be the largest study yet conducted to ascertain the benefits and risks of removing nitrous oxide from the gas mixture in anesthesia. The results of this large international trial will guide the clinical care of the hundreds of millions of adults undergoing noncardiac surgery annually.