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.

Comparing the effect of xenon and sevoflurane anesthesia on postoperative neural injury biomarkers: a randomized controlled trial.

General anesthesia and surgery are associated with an increase in neural injury biomarkers. Elevations of these neural injury biomarkers in the perioperative period are associated with postoperative delirium. Xenon has been shown to be protective against a range of neurological insults in animal models. It remains to be seen if xenon anesthesia is neuroprotective in the perioperative setting in humans. Twenty-four participants scheduled for lithotripsy were randomized to receive either xenon or sevoflurane general anesthesia. There was no statistically significant difference in the concentrations of postoperative neural injury biomarkers between the xenon and sevoflurane group. Following the procedure there was a significant increase in the concentration from baseline of all three biomarkers at 1 hour post-induction with a return to baseline at 5 hours. General anesthesia for lithotripsy was associated with a significant increase at 1 hour post-induction in the neural injury biomarkers total tau, neurofilament light and tau phosphorylated at threonine 181, a marker of tau phosphorylation. The protocol was approved by the St. Vincent's Hospital Melbourne Ethics Committee (approval No. HREC/18/SVHM/221) on July 20, 2018 and was registered with the Australia New Zealand Clinical Trials Registry (registration No. ACTRN12618000916246) on May 31, 2018.

Digital clock drawing test metrics in older patients before and after endoscopy with sedation: An exploratory analysis.

BACKGROUND: In the postoperative period, clinically feasible instruments to monitor elderly patients' neurocognitive recovery and discharge-readiness, especially after short-stay procedures, are limited. Cognitive monitoring may be improved by a novel digital clock drawing test (dCDT). We screened for cognitive impairment with the 4 A Test (4AT) and then administered the dCDT pre and post short-stay procedure (endoscopy). The primary aim was to investigate whether the dCDT was sensitive to a change in cognitive status postendoscopy. We also investigated if preoperative cognitive status impacted postendoscopy dCDT variables. METHODS: We recruited 100 patients ≥65 years presenting for endoscopy day procedures at a single metropolitan hospital. Participants were assessed after admission and immediately before discharge from the hospital. We administered the 4AT, followed by both command and copy clock conditions of the dCDT. We analysed the total drawing time (dCDT time), as well as scored the drawn clock against the established Montreal Cognitive Assessment (MoCA) criteria both before and after endoscopy. RESULTS: Linear regression showed higher 4AT test scores (poorer performance) were associated with longer postoperative dCDT time (ß = 5.6, p = 0.012) for the command condition after adjusting for preoperative baseline dCDT metrics, sex, age, and years of education. CONCLUSION: Postoperative dCDT time-based variables slowed in those with baseline cognitive impairment detected by the 4AT, but not for those without cognitive impairment. Our results suggest the dCDT, using the command mode, may help detect cognitive impairment in patients aged >65 years after elective endoscopy.

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.

Preventing Delirium and Promoting Long-Term Brain Health: A Clinical Trial Design for the Perioperative Cognitive Enhancement (PROTECT) Trial.

BACKGROUND: Perioperative neurocognitive disorders (PND), including postoperative delirium (POD), are common in older adults and, for many, precipitate functional decline and/or dementia. OBJECTIVE: In this protocol, we describe a novel multidisciplinary, multicomponent perioperative intervention that seeks to prevent or reduce POD and associated cognitive decline. METHODS: We will conduct a prospective, single-blind, pragmatic, randomized-controlled trial to compare our tailored multi-disciplinary perioperative pathway against current standard of care practices. We will recruit a total of 692 elective surgical patients aged 65 years or more and randomize them in a 1:1 design. Our perioperative intervention targets delirium risk reduction strategies by emphasizing the importance of early mobilization, nutrition, hydration, cognitive orientation, sensory aids, and avoiding polypharmacy. To promote healthy behavior change, we will provide a tailored psychoeducation program both pre- and postoperatively, focusing on cardiovascular and psychosocial risks for cognitive and functional decline. RESULTS: Our primary outcome is the incidence of any PND (encapsulating POD and mild or major postoperative neurocognitive disorder) at three months postoperative. Secondary outcomes include any incidence of POD or neurocognitive disorder at 12 months. A specialized delirium screening instrument, the Confusion Assessment Method (3D-CAM), and a neuropsychological test battery, will inform our primary and secondary outcomes. CONCLUSION: Delirium is a common and debilitating postoperative complication that contributes to the cognitive and functional decline of older adults. By adopting a multicomponent, multidisciplinary approach to perioperative delirium prevention, we seek to reduce the burden of delirium and subsequent dementia in older adults.

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.

A novel digital clock drawing test as a screening tool for perioperative neurocognitive disorders: A feasibility study.

BACKGROUND: We developed a digital clock drawing test (dCDT), an adaptation of the original pen and paper clock test, that may be advantageous over previous dCDTs in the perioperative environment. We trialed our dCDT on a tablet device in the preoperative period to determine the feasibility of administration in this setting. To assess the clinical utility of this test, we examined the relationship between the performance on the test and compared derived digital clock measures with the 4 A's Test (4AT), a delirium and cognition screening tool. METHODS: We recruited a sample of 102 adults aged 65 years and over presenting for elective surgery in a single tertiary hospital. Participants completed the 4AT, followed by both command and copy clock conditions of the dCDT. We recorded time-based clock-drawing metrics, alongside clock replications scored using the Montreal Cognitive Assessment (MoCA) clock scoring criteria. RESULTS: The dCDT had an acceptance rate of 99%. After controlling for demographic variables and prior tablet use, regression analyses showed higher 4AT scores were associated with greater dCDT time (seconds) for both command (ß = 8.2, P = .020) and copy clocks (ß = 12, P = .005) and lower MoCA-based clock scores in both command (OR = 0.19, P = .001) and copy conditions (OR = 0.14, P = .012). CONCLUSION: The digital clock drawing test is feasible to administer and is highly acceptable to older adults in a preoperative setting. We demonstrated a significant association between both the dCDT time and clock score metrics, with the established 4AT. Our results provide convergent validity of the dCDT in the preoperative setting.

Preoperative Frailty Predicts Postoperative Neurocognitive Disorders After Total Hip Joint Replacement Surgery.

BACKGROUND: Frailty is a reduced capacity to recover from a physiologically stressful event. It is well established that preoperative frailty is associated with poor postoperative outcomes, but it is unclear if this includes cognitive decline following anesthesia and surgery. This retrospective observational study was a secondary analysis of data from a previous study (the Anaesthesia, Cognition, Evaluation [ACE] study). We aimed to identify if preoperative frailty or prefrailty is associated with preoperative and postoperative neurocognitive disorders or postoperative cognitive dysfunction. METHODS: The ACE study enrolled 300 participants aged ≥60 scheduled for elective total hip joint replacement and who underwent a full neuropsychological assessment at baseline and 3 and 12 months postoperatively. We applied patient data to 2 frailty models; both were based on an accumulation of deficits score: the reported Edmonton frail scale (REFS) and the comprehensive geriatric assessment-frailty index (CGA-FI) based on the comprehensive geriatric assessment. We calculated these 2 scores using baseline data collected from the medical history, demographic and clinical data as well as self-reported questionnaires. Some items on the REFS (3 of 18 or 17%) and the CGA-FI (37 of 51 or 27%) did not have an equivalent item in the ACE data. RESULTS: The mean age (standard deviation [SD]) was 70.1 years (6.6) with more women (197 [66%]). Using the REFS model, 40 of 300 (13.3%) patients were classified as vulnerable, mild, or moderately frail. Using the CGA-FI model, 69 of 300 (23%) were classified as intermediate or high frailty. The REFS and the CGA-FI were strongly correlated (r = 0.75; P < .01) with 34 of 300 (11%) meeting criteria for frailty by both the REFS and the CGA-FI.Frailty or prefrailty was associated with cognitive decline at 3 and 12 months using the REFS (odds ratio [OR], 1.51, 95% confidence interval [CI], 1.02-2.23 and OR, 2.00, 95% CI, 1.26-3.17, respectively) after adjusting for baseline mini-mental state examination (MMSE), smoking, hypertension, diabetes, history of acute myocardial infarction (AMI), and estimated intelligence quotient (IQ). Age did not modify this association. After adjusting for multiple comparisons, 3-month cognitive decline was no longer significantly associated with baseline frailty. CONCLUSIONS: This retrospective analysis demonstrates an association between baseline frailty and postoperative neurocognitive disorders, particularly using the more extensive REFS scoring method. This supports preoperative screening for frailty to risk-stratify patients, and identify and implement preventive strategies and to improve postoperative outcomes for older individuals.

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.

Aspirin in coronary artery surgery: 1-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery trial.

BACKGROUND: Aspirin may reduce the risk of vascular graft thrombosis after cardiovascular surgery. We previously reported the 30-day results of a trial evaluating aspirin use before coronary artery surgery. Here we report the 1-year outcomes evaluating late thrombotic events and disability-free survival. METHODS: Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score < 8. Secondary outcomes included a composite of myocardial infarction, stroke and death from any cause through to 1 year after surgery. RESULTS: Patients were randomly assigned to aspirin (1059 patients) or placebo (1068 patients). The rate of death or severe disability was 4.1% in the aspirin group and 3.5% in the placebo group (relative risk, 1.17; 95% confidence interval, 0.76-1.81; P = .48). There was no significant difference in the rates of myocardial infarction (P = .11), stroke (P = .086), or death (P = .24), or a composite of these cardiovascular end points (P = .68). With the exception of those with a low European System for Cardiac Operative Risk Evaluation score (P = .03), there were no interaction effects on these outcomes with tranexamic acid (all tests of interaction P > .10). CONCLUSIONS: In patients undergoing coronary artery surgery, preoperative aspirin did not reduce death or severe disability, or thrombotic events through to 1 year after surgery.

Tranexamic acid in coronary artery surgery: One-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial.

BACKGROUND: Tranexamic acid reduces blood loss and transfusion requirements in cardiac surgery but may increase the risk of coronary graft thrombosis. We previously reported the 30-day results of a trial evaluating tranexamic acid for coronary artery surgery. Here we report the 1-year clinical outcomes. METHODS: Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score of less than 8. Secondary outcomes included a composite of myocardial infarction, stroke, and death from any cause through to 1 year after surgery. RESULTS: The rate of death or disability at 1 year was 3.8% in the tranexamic acid group and 4.4% in the placebo group (relative risk, 0.85; 95% confidence interval, 0.64-1.13; P = .27), and this did not significantly differ according to aspirin exposure at the time of surgery (interaction P = .073). The composite rate of myocardial infarction, stroke, and death up to 1 year after surgery was 14.3% in the tranexamic acid group and 16.4% in the placebo group (relative risk, 0.87; 95% CI, 0.76-1.00; P = .053). CONCLUSIONS: In this trial of patients having coronary artery surgery, tranexamic acid did not affect death or severe disability through to 1 year after surgery. Further work should be done to explore possible beneficial effects on late cardiovascular events.

Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).

Best Practices for Postoperative Brain Health: Recommendations From the Fifth International Perioperative Neurotoxicity Working Group.

As part of the American Society of Anesthesiology Brain Health Initiative goal of improving perioperative brain health for older patients, over 30 experts met at the fifth International Perioperative Neurotoxicity Workshop in San Francisco, CA, in May 2016, to discuss best practices for optimizing perioperative brain health in older adults (ie, >65 years of age). The objective of this workshop was to discuss and develop consensus solutions to improve patient management and outcomes and to discuss what older adults should be told (and by whom) about postoperative brain health risks. Thus, the workshop was provider and patient oriented as well as solution focused rather than etiology focused. For those areas in which we determined that there were limited evidence-based recommendations, we identified knowledge gaps and the types of scientific knowledge and investigations needed to direct future best practice. Because concerns about perioperative neurocognitive injury in pediatric patients are already being addressed by the SmartTots initiative, our workshop discussion (and thus this article) focuses specifically on perioperative cognition in older adults. The 2 main perioperative cognitive disorders that have been studied to date are postoperative delirium and cognitive dysfunction. Postoperative delirium is a syndrome of fluctuating changes in attention and level of consciousness that occurs in 20%-40% of patients >60 years of age after major surgery and inpatient hospitalization. Many older surgical patients also develop postoperative cognitive deficits that typically last for weeks to months, thus referred to as postoperative cognitive dysfunction. Because of the heterogeneity of different tools and thresholds used to assess and define these disorders at varying points in time after anesthesia and surgery, a recent article has proposed a new recommended nomenclature for these perioperative neurocognitive disorders. Our discussion about this topic was organized around 4 key issues: preprocedure consent, preoperative cognitive assessment, intraoperative management, and postoperative follow-up. These 4 issues also form the structure of this document. Multiple viewpoints were presented by participants and discussed at this in-person meeting, and the overall group consensus from these discussions was then drafted by a smaller writing group (the 6 primary authors of this article) into this manuscript. Of course, further studies have appeared since the workshop, which the writing group has incorporated where appropriate. All participants from this in-person meeting then had the opportunity to review, edit, and approve this final manuscript; 1 participant did not approve the final manuscript and asked for his/her name to be removed.

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.

Association of Changes in Plasma Neurofilament Light and Tau Levels With Anesthesia and Surgery: Results From the CAPACITY and ARCADIAN Studies.

Importance: Anesthesia and surgery are believed to act on the central nervous system by a fully reversible mechanism innocuous to nerve cells. Evidence that neurological sequelae may follow would challenge this belief and would thereby suggest a need to reassess theories of the mechanism of anesthetic action or the response of the central nervous system to surgery. Objective: To measure 2 biomarkers of neurological injury (neurofilament light and tau) in plasma in a series of timed collections before and after anesthesia and surgery. Design, Setting, and Participants: These 2 related observational studies (CAPACITY and ARCADIAN) recruited patients 60 years and older who were undergoing general anesthesia for surgeries performed within a tertiary hospital. Blood samples were taken immediately before surgical anesthesia was administered and then sequentially after surgery at 30-minute, 6-hour, 24-hour, and 48-hour intervals. Sampling took place from January 2014 to August 2015. Data analysis took place from October 2016 to February 2017. Main Outcomes and Measures: Plasma neurofilament light and tau. Results: A total of 30 patients were enrolled (13 from the CAPACITY study and 17 from the ARCADIAN study). The mean (SD) age was 69.1 (7.0) years, and 18 members (59%) of the participant group were female; 22 (73%) were undergoing joint arthroplasty. Mean neurofilament light increased at each measurement from a combined baseline mean (SD) of 22.3 (20.4) pg/mL to a maximal combined mean (SD) level of 35.1 (28.7) pg/mL, a maximum increase of 67% (95% CI, 45%-89%; P < .001), at 48 hours postoperatively. The level of tau increased significantly from baseline at every measurement, from a combined baseline mean (SD) of 3.1 (1.3) pg/mL to a maximal combined mean (SD) of 10.8 (9.5) pg/mL, a peak increase of 257% (95% CI, 154%-361%; P < .001), at 6 hours postoperatively. After 6 hours, the mean level began to return to baseline but remained elevated after 48 hours. Conclusions and Relevance: Neurofilament light is a specific marker of axonal injury and has been shown to indicate neuronal damage in a number of diseases. Tau proteins are an integral component of axonal integrity, and increased tau indicates neuronal damage. The increases in both neurofilament light and tau over 48 hours after surgery suggest that general anesthesia and surgery may be associated with neuronal damage in the short term. Further investigations will be required to study any association with clinical outcomes. These preliminary findings demand that we question the prevailing assumption that anesthesia and surgery are innocuous, transient, and without injurious changes to the central nervous system.

Cognitive decline associated with anesthesia and surgery in the elderly: does this contribute to dementia prevalence?

PURPOSE OF REVIEW: To provide an update on the current state of research investigating the effects of anesthesia and surgery on cognition in the elderly, including consideration of overlap with cognitive disorders in the community. RECENT FINDINGS: The studies reviewed here identify detrimental effects of anesthesia and surgery on cognition in a proportion of elderly individuals. Animal models demonstrate an association between anesthetic agents and Alzheimer's disease pathology. Human studies demonstrate a high incidence of cognitive impairment preoperatively in the elderly and further decline postoperatively, with recent work showing that poor preoperative cognitive function is a key predictor for further postoperative decline. Results from retrospective studies into an association between Alzheimer's disease and prior anesthesia and surgery are equivocal, but there are some data to suggest an association with accelerated cognitive decline in the long term. Postoperative delirium is common and even in individuals with normal preoperative cognition is associated with long-term decline. SUMMARY: Cognitive impairment in the elderly ultimately leads to a decline in function with high personal and societal costs. Following anesthesia and surgery, decline in cognition is observed in some individuals, which may represent vulnerability for future decline or may alter their cognitive trajectory. Recent work suggests factors that impact this decline and/or impair recovery include higher risk patients and subtle cognitive impairment preoperatively. Identifying these individuals is critical to determining opportunities for intervention and preventive strategies, and ultimately reducing the impact on functional decline. It remains unclear if anesthesia and surgery play a role in the onset or progression of mild cognitive impairment and dementia across the community. Recent work showing that preoperative impairment is a significant risk factor for decline indicates that routinely assessing cognition preoperatively would allow improved management including referral pathways for patients at risk, delirium prevention, specifically optimizing care and consideration of treatment options.

Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.

BACKGROUND: Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. METHODS: In a trial with a 2-by-2 factorial design, we randomly assigned patients who were scheduled to undergo coronary-artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS: Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P=0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P=0.001), and seizures occurred in 0.7% and 0.1%, respectively (P=0.002 by Fisher's exact test). CONCLUSIONS: Among patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639 .).

Pre-existing cognitive impairment and post-operative cognitive dysfunction: should we be talking the same language?

Changes in cognition are known to follow anesthesia and surgery in older individuals (Evered et al., 2011). Although survival per se was the prime outcome in the 19th and early 20th centuries for invasive procedures, a link was none-the-less observed with adverse cognitive outcomes as far back as 1887 (Savage, 1887). Historical reports of "insanity" or "weak mindedness" after anesthesia appeared within 40 years of the first anesthetic having been administered and anecdotal and retrospective reports have implicated anesthesia ever since. However, it was not until the 1970s that these observations received any sound scientific evaluation, when clinicians became aware of cognitive changes following cardiac surgery. It was assumed that the cardiopulmonary bypass (heart lung machine) must have been the main culprit because it was this factor which so greatly distinguished cardiac surgery from non-cardiac surgery (Shaw et al., 1987). This long held belief entered surgical folklore and was the basis for many publications endeavoring to identify particular aspects of the heart lung machine responsible for this cognitive decline.

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.