Postoperative Delirium and Neurocognitive Disorders: Updates for Providers Caring for Cancer Patients.

PURPOSE OF REVIEW: To provide up to date information on postoperative delirium and neurocognitive disorders in surgical cancer patients. RECENT FINDINGS: Established risk factors such as age, psychosocial factors, comorbidities, frailty and preexisting cognitive decline continue to exhibit associations with perioperative neurocognitive disorders (PND); novel risk factors identified recently include microbiome composition and vitamin D deficiency. Prevention measures include cognitive prehabilitation, perioperative geriatric assessment and multidisciplinary care, dexmedetomidine and multimodal analgesic techniques. Studies investigating ciprofol, remimazolam, esketamine, ramelteon and suvorexant have shown encouraging results. Controversy remains regarding the use of inhalational versus intravenous general anesthesia. Innovative approaches to address PND are a rapidly developing area of research, but more studies are needed to identify effective prevention and management interventions. Despite challenges and controversy in the field, implementation of best practice can reduce the detrimental impact of PND on patients, caregivers, and society at large.

Perioperative Primary Care Utilization and Postoperative Readmission, Emergency Department Use, and Mortality in Older Surgical Patients.

BACKGROUND: Postdischarge primary care follow-up is associated with lower readmission rates after medical hospitalizations. However, the effect of primary care utilization on readmission has not been studied in surgical patients. METHODS: Retrospective cohort study of Medicare beneficiaries aged 65 and older undergoing major inpatient diagnostic or therapeutic procedures (n = 3,552,906) from 2017 through 2018, examining the association between postdischarge primary care visits within 14 days of discharge (primary exposure), and Annual Wellness Visits in the year prior (secondary exposure), with 30-day unplanned readmission (primary outcome), emergency department visits, and mortality (secondary outcomes). RESULTS: Overall, 9.5% (n = 336,837) had postdischarge visits within 14 days, 2.9% (n = 104,571) had Annual Wellness Visits in the year preceding the procedure, 9.5% (n = 336,401) were readmitted, 9% (n = 319,054) had emergency department visits, and 0.6% (n = 22,103) of the cohort died within 30 days. Our fully adjusted propensity-matched proportional hazards Cox regression analysis showed that postdischarge visits were associated with a 5% lower risk of readmission (hazard ratio [HR], 0.95, 95% confidence interval [CI], 0.93-0.97), 43% higher risk of emergency department use (HR, 1.43, 95% CI, 1.40-1.46) and no difference in mortality risk (HR, 0.98, 95% CI, 0.90-1.06), compared with not having a visit within 14 days of discharge. In a separate set of regression models, Annual Wellness Visits were associated with a 9% lower risk of readmission (HR, 0.91, 95% CI, 0.88-0.95), 45% higher risk of emergency department utilization (HR, 1.45, 95% CI, 1.40-1.49) and an 18% lower mortality risk (HR, 0.82, 95% CI, 0.75-0.89) compared with no Annual Wellness Visit in the year before the procedure. CONCLUSIONS: Both postdischarge visits and the Medicare Annual Wellness Visit appear to be extremely underutilized among the older surgical population. In those patients who do utilize primary care, compared with propensity-matched patients who do not, our study suggests primary care use is associated with modestly lower readmission rates. Prospective studies are needed to determine whether targeted primary care involvement can reduce readmission.

Implementation of a Multidisciplinary Team to Improve the Quality of Care for Older Surgical Patients at a Rural Academic Medical Center.

For the first time in history, people age older than 65 years make up >20% of the non-metro population, compared with 16% of the metro population. From 2010 to 2020 the nonmetro population age older than 65 years grew by 22%, while the working-age population declined by 4.9%, and the population aged under 18 years declined by 5.7%.1,2 Multidisciplinary geriatric surgical programs are an increasingly recognized approach to the care of older surgical patients and preliminary data suggest they can reduce length of stay. Although rural areas have the greatest proportion of patients age older than 65 years, implementation of such programs faces special challenges in rural settings with limited resources. Dartmouth-Hitchcock Medical Center is one of the most rural academic centers in the United States. Challenges include a shortage of geriatric-trained providers, long distances to access primary care and subspecialists, and extremely limited postacute care options and skilled nursing facility beds. To address the unique needs of our provider and patient population we began with a development period where we conducted stakeholder interviews. Using these data, we mapped out a workflow and developed pilot projects to address different portions of the workflow, such as preoperative screening for frailty and cognitive impairment, interdisciplinary weekly case conferences, proactive case management, delirium and geriatric surgery postoperative pathway order sets, and a variety of tools for reorientation and delirium management. Herein we describe the process of development and pragmatic clinical implementation of geriatric-focused care for older surgical patients in our rural tertiary center, including some of the main challenges we faced and the strategies we undertook to overcome them, and some of our early patient centered and clinical outcomes. This information may assist other institutions as they design geriatric-focused surgical programs to address the growing population of older adults and the need for compliance with state legislation. The clinical program described is not a research study, and the outcome data we report is for the purpose of description, and should not be interpreted as a rigorous research investigation of the effect of our intervention.

Administration of the American Board of Anesthesiology's virtual APPLIED Examination: successes, challenges, and lessons learned.

In response to the COVID-19 pandemic, the American Board of Anesthesiology transitioned from in-person to virtual administration of its APPLIED Examination, assessing more than 3000 candidates for certification purposes remotely in 2021. Four hundred examiners were involved in delivering and scoring Standardized Oral Examinations (SOEs) and Objective Structured Clinical Examinations (OSCEs). More than 80% of candidates started their exams on time and stayed connected throughout the exam without any problems. Only 74 (2.5%) SOE and 45 (1.5%) OSCE candidates required rescheduling due to technical difficulties. Of those who experienced "significant issues", concerns with OSCE technical stations (interpretation of monitors and interpretation of echocardiograms) were reported most frequently (6% of candidates). In contrast, 23% of examiners "sometimes" lost connectivity during their multiple exam sessions, on a continuum from minor inconvenience to inability to continue. 84% of SOE candidates and 89% of OSCE candidates described "smooth" interactions with examiners and standardized patients/standardized clinicians, respectively. However, only 71% of SOE candidates and 75% of OSCE candidates considered themselves to be able to demonstrate their knowledge and skills without obstacles. When compared with their in-person experiences, approximately 40% of SOE examiners considered virtual evaluation to be more difficult than in-person evaluation and believed the remote format negatively affected their development as an examiner. The virtual format was considered to be less secure by 56% and 40% of SOE and OSCE examiners, respectively. The retirement of exam materials used virtually due to concern for compromise had implications for subsequent exam development. The return to in-person exams in 2022 was prompted by multiple factors, especially concerns regarding standardization and security. The technology is not yet perfect, especially for testing in-person communication skills and displaying dynamic exam materials. Nevertheless, the American Board of Anesthesiology's experience demonstrated the feasibility of conducting large-scale, high-stakes oral and performance exams in a virtual format and highlighted the adaptability and dedication of candidates, examiners, and administering board staff.

Pro-Con Debate: Judicious Benzodiazepine Administration for Preoperative Anxiolysis in Older Patients.

In this Pro-Con commentary article, we discuss the risks and benefits of administering preoperative benzodiazepines to older patients to decrease preoperative anxiety. The Pro side first focuses on the critical importance of treating preoperative anxiety and that benzodiazepines are the best tool to achieve that goal. The competing argument presented by the Con side is that myriad options exist to treat preoperative anxiety without simultaneously increasing the risk for devastating complications such as postoperative delirium. Both sides call for more high-quality investigations to determine the most effective strategies for decreasing preoperative anxiety in older adults while improving outcomes and reducing morbidity.

Comparing characteristics and perspectives of U.S. anesthesiology fellows in training and anesthesiologists in their first year of practice.

BACKGROUND: The purpose of this study was to evaluate relationships between demographics, professional characteristics, and perceived challenges facing the specialty of anesthesiology among physicians who entered a fellowship and those who started independent practice immediately after finishing a U.S. anesthesiology residency. METHODS: Anesthesiologists in the year after their residency graduation were invited to take an online survey during the academic years of 2016-2017, 2017-2018, and 2018-2019, with questions about their personal characteristics, the nature of their professional lives, and their perceptions of the greatest challenge facing the profession of anesthesiology. RESULTS: A total of 884 fellows-in-training and 735 anesthesiologists starting independent practice right after the completion of their residency responded. Fellows were slightly younger (mean = 33.2 vs. 34.0 years old, p < 0.001), were more likely to have a spouse who works outside the home (63.9% vs. 57.0%, p = 0.002), had fewer children (mean = 0.69 vs. 0.88, p < 0.001), worked more hours per week (mean = 56.2 vs. 52.4, p < 0.001), and were less likely to report a personal and professional life balance (66.4% vs. 72.3% positive, p = 0.005) than direct-entry anesthesiologists. Fellows and direct-entry anesthesiologists identified similar challenges in three broad themes - workforce competition (80.3% and 71.8%), healthcare system changes (30.0% and 37.9%), and personal challenges (6.4% and 8.8%). Employment security issues posed by non-physician anesthesia providers and perceived lack of appreciation of anesthesiologists' value were commonly cited. Relative weighting of challenge concerns varied between fellows and direct-entry physicians, as well as within these groups based on gender, fellowship subspecialty, location or size of practice, and frequency of supervisory roles. CONCLUSIONS: Anesthesiology fellows and direct-entry anesthesiologists had largely similar demographics and perspectives on the challenges facing anesthesiology in the United States. Group differences found in some demographics and perspectives may reflect different motivations for choosing their professional paths and their diverse professional experiences.

Lateralisation of subcortical functional connectivity during and after general anaesthesia.

BACKGROUND: Arousal and awareness are two important components of consciousness states. Functional neuroimaging has furthered our understanding of cortical and thalamocortical mechanisms of awareness. Investigating the relationship between subcortical functional connectivity and arousal has been challenging owing to the relatively small size of brainstem structures and thalamic nuclei, and their depth in the brain. METHODS: Resting state functional MRI scans of 72 healthy volunteers were acquired before, during, 1 h after, and 1 day after sevoflurane general anaesthesia. Functional connectivity of subcortical regions of interest vs whole brain and homotopic functional connectivity for assessment of left-right symmetry analyses of both cortical and subcortical regions of interest were performed. Both analyses used high resolution atlases generated from deep brain stimulation applications. RESULTS: Functional connectivity in subcortical loci within the thalamus and of the ascending reticular activating system was sharply restricted under anaesthesia, featuring a general lateralisation of connectivity. Similarly, left-right homology was sharply reduced under anaesthesia. Subcortical bilateral functional connectivity was not fully restored after emergence from anaesthesia, although greater restoration was seen between ascending reticular activating system loci and specific thalamic nuclei thought to be involved in promoting and maintaining arousal. Functional connectivity was fully restored to baseline by the following day. CONCLUSIONS: Functional connectivity in the subcortex is sharply restricted and lateralised under general anaesthesia. This restriction may play a part in loss and return of consciousness. CLINICAL TRIAL REGISTRATION: NCT02275026.

Perioperative Brain Health in the Older Adult: A Patient Safety Imperative.

While people 65 years of age and older represent 16% of the population in the United States, they account for >40% of surgical procedures performed each year. Maintaining brain health after anesthesia and surgery is not only important to our patients, but it is also an increasingly important patient safety imperative for the specialty of anesthesiology. Aging is a complex process that diminishes the reserve of every organ system and often results in a patient who is vulnerable to the stress of surgery. The brain is no exception, and many older patients present with preoperative cognitive impairment that is undiagnosed. As we age, a number of changes occur in the human brain, resulting in a patient who is less resilient to perioperative stress, making older adults more susceptible to the phenotypic expression of perioperative neurocognitive disorders. This review summarizes the current scientific and clinical understanding of perioperative neurocognitive disorders and recommends patient-centered, age-focused interventions that can better mitigate risk, prevent harm, and improve outcomes for our patients. Finally, it discusses the emerging topic of sleep and cognitive health and other future frontiers of scientific inquiry that might inform clinical best practices.

Cognitive Recovery by Decade in Healthy 40- to 80-Year-Old Volunteers After Anesthesia Without Surgery.

BACKGROUND: Postoperative delirium and postoperative cognitive dysfunction are the most common complications for older surgical patients. General anesthesia may contribute to the development of these conditions, but there are little data on the association of age with cognitive recovery from anesthesia in the absence of surgery or underlying medical condition. METHODS: We performed a single-center cohort study of healthy adult volunteers 40 to 80 years old (N = 71, mean age 58.5 years, and 44% women) with no underlying cognitive dysfunction. Volunteers underwent cognitive testing before and at multiple time points after 2 hours of general anesthesia consisting of propofol induction and sevoflurane maintenance, akin to a general anesthetic for a surgical procedure, although no procedure was performed. The primary outcome was time to recovery to cognitive baseline on the Postoperative Quality of Recovery Scale (PQRS) within 30 days of anesthesia. Secondary cognitive outcomes were time to recovery on in-depth neuropsychological batteries, including the National Institutes of Health Toolbox and well-validated paper-and-pencil tests. The primary hypothesis is that time to recovery of cognitive function after general anesthesia increases across decades from 40 to 80 years of age. We examined this with discrete-time logit regression (for the primary outcome) and linear mixed models for interactions of age decade with time postanesthesia (for secondary outcomes). RESULTS: There was no association between age group and recovery to baseline on the PQRS; 36 of 69 (52%) recovered within 60-minute postanesthesia and 63 of 69 (91%) by day 1. Hazard ratios (95% confidence interval) for each decade compared to 40- to 49-year olds were: 50 to 59 years, 1.41 (0.50-4.03); 60 to 69 years, 1.03 (0.35-3.00); and 70 to 80 years, 0.69 (0.25-1.88). There were no significant differences between older decades relative to the 40- to 49-year reference decade in recovery to baseline on secondary cognitive measures. CONCLUSIONS: Recovery of cognitive function to baseline was rapid and did not differ between age decades of participants, although the number in each decade was small. These results suggest that anesthesia alone may not be associated with cognitive recovery in healthy adults of any age decade.

A Processed Electroencephalogram-Based Brain Anesthetic Resistance Index Is Associated With Postoperative Delirium in Older Adults: A Dual Center Study.

BACKGROUND: Some older adults show exaggerated responses to drugs that act on the brain. The brain's response to anesthetic drugs is often measured clinically by processed electroencephalogram (EEG) indices. Thus, we developed a processed EEG-based measure of the brain's resistance to volatile anesthetics and hypothesized that low scores on it would be associated with postoperative delirium risk. METHODS: We defined the Duke Anesthesia Resistance Scale (DARS) as the average bispectral index (BIS) divided by the quantity (2.5 minus the average age-adjusted end-tidal minimum alveolar concentration [aaMAC] inhaled anesthetic fraction). The relationship between DARS and postoperative delirium was analyzed in 139 older surgical patients (age ≥65) from Duke University Medical Center (n = 69) and Mt Sinai Medical Center (n = 70). Delirium was assessed by geriatrician interview at Duke, and by research staff utilizing the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) instrument at Mt Sinai. We examined the relationship between DARS and delirium and used the Youden index to identify an optimal low DARS threshold (for delirium risk), and its associated 95% bootstrap confidence bounds. We used multivariable logistic regression to examine the relationship between low DARS and delirium risk. RESULTS: The relationship between DARS and delirium risk was nonlinear, with higher delirium risk at low DARS scores. A DARS threshold of 28.755 maximized the Youden index for the association between low DARS and delirium, with bootstrap 95% confidence bounds of 26.18 and 29.80. A low DARS (<28.755) was associated with increased delirium risk in multivariable models adjusting for site (odds ratio [OR] [95% confidence interval {CI}] = 4.30 [1.89-10.01]; P = .001), or site-plus-patient risk factors (OR [95% CI] = 3.79 [1.63-9.10]; P = .003). These associations with postoperative delirium risk remained significant when using the 95% bootstrap confidence bounds for the low DARS threshold (P < .05 for all). Further, a low DARS (<28.755) was associated with delirium risk after accounting for opioid, midazolam, propofol, phenylephrine, and ketamine dosage as well as site (OR [95% CI] = 4.21 [1.80-10.16]; P = .002). This association between low DARS and postoperative delirium risk after controlling for these other medications remained significant (P < .05) when using either the lower or the upper 95% bootstrap confidence bounds for the low DARS threshold. CONCLUSIONS: These results demonstrate that an intraoperative processed EEG-based measure of lower brain anesthetic resistance (ie, low DARS) is independently associated with increased postoperative delirium risk in older surgical patients.

Multi-domain analysis of non-surgical risk factors amenable to pre-operative optimization in microvascular head and neck surgery.

PURPOSE: The goal of this study was to conduct a multi-domain, organ system-based analysis of non-surgical comorbidities amenable to pre-operative optimization in patients undergoing free tissue transfer, in order to better understand factors that influence patient outcomes. STUDY DESIGN: Retrospective review. SETTINGS: Tertiary academic center. MATERIALS AND METHODS: A retrospective analysis of 546 patients in a prospectively maintained database who underwent free tissue transfer reconstruction between 2007 and 2016 was performed. Analysis of the relationship between binary-coded system-based domains and log-transformed length of stay (LOS), rehabilitation requirement, 30-day readmission, and post-operative complications was conducted with multiple linear regression or logistic regression models. RESULTS: Poor nutritional status and the presence of anxiety/depression independently increased median hospital LOS. Endocrine and metabolic deficits, poor nutrition status, and psychiatric comorbidities were significant predictors for rehabilitation facility requirement upon discharge. CONCLUSION: Interventions targeted to patient psychiatric and nutritional health may yield substantially improved outcomes in the head and neck cancer population receiving free tissue transfer surgery.

Processed intraoperative burst suppression and postoperative cognitive dysfunction in a cohort of older noncardiac surgery patients.

Postoperative cognitive dysfunction (POCD) is a decline in cognitive test performance which persists months after surgery. There has been great interest in the anesthesia community regarding whether variables generated by commercially available processed EEG monitors originally marketed to prevent awareness under anesthesia can be used to guide intraoperative anesthetic management to prevent POCD. Processed EEG monitors represent an opportunity for anesthesiologists to directly monitor the brain even if they have not been trained to interpret EEG waveforms. There is continued equipoise regarding whether any of the variables generated by the machines' interpretation of raw data are associated with POCD. Most literature has focused on the depth of anesthesia number, however recent studies have shown that processed depth may not be accurate in older age groups due to reduced alpha band power. Burst suppression is an encephalographic pattern of high voltage activity alternating with periods of electrical silence and is another marker of depth which can be obtained from commercial processed EEG monitors. We performed a prospective cohort study to determine whether burst suppression and burst suppression ratio as measured by the BIS Monitor (Bispectral Index, BIS Medtronic, Boulder CO), is associated with cognitive dysfunction 3 months after surgery. We recruited 167 elective surgery patients, 65 years of age and older, anticipated to require at least 2 day inpatient admission. Our main outcome measure was cognitive decline in composite z-score on the Alzheimer's Disease Research Center UDS Battery of at least 1 standard deviation 3 months after surgery relative to preoperative baseline. 14% experienced POCD, this group was older (72 [70, 74] versus 70 [67, 75] years), and had frailty scores as measured by the FRAIL Scale (2 [0, 3] versus 1 [0, 2]) and lower baseline z-scores (- 0.2 [- 0.6, 0.5] versus 0.1 [- 0.3, 0.5]). There was a univariable association between suppression ratio > 10 (SR > 10) and POCD (4.8 [0, 37.3] versus 15.4 [4.0-142.4] min), p = .038. However, after adjustment this relationship did not persist, only anesthetic technique, age, and pain remained in the model. In our cohort of older elective noncardiac surgery patients we found a marginal association between processed burst suppression (total burst suppression p = .067, SR > 5 p = .052, SR > 10.038) which did not persist in a multivariable model. Patients with POCD had almost twice the number of minutes of burst suppression, and three times the amount of time for SR > 5 and > 10. Our finding may be a limitation of the monitor's ability to detect burst suppression. The consistent trend towards more intraoperative burst suppression in patients who developed POCD suggests that future studies are needed to investigate the relationship of raw intraoperative burst suppression and POCD.Trial registry Clinical trial number and registry URL: Optimizing Postoperative Cognitive Dysfunction in the Elderly-PRESERVE, Clinical Trials Gov# NCT02650687; https://clinicaltrials.gov/ct2/show/NCT02650687 .

Does Postoperative Cognitive Decline Result in New Disability After Surgery?

OBJECTIVE: Establish whether POCD is associated with new disability after surgery, which would inform whether POCD impacts patient-centered outcomes. BACKGROUND: POCD is a decline in neuropsychiatric tests scores from presurgical baseline which occurs in approximately 15% of older patients 3 months after surgery. POCD is a research construct meant to investigate patient and family reports of older adults who were "never the same after surgery." However, many patients with POCD do not perceive difficulty with thinking and memory, and the question remains whether POCD impacts patient function. METHODS: We performed a prospective cohort study of 167 older adults undergoing major noncardiac surgery (requiring at least a 2-day hospital stay). Exclusion criteria were: history of dementia, cardiac or intracranial procedure, inability to consent for themselves, or emergency surgery. We administered formal neuropsychiatric testing (Alzheimer Disease Research Center UDS battery), basic and instrumental activities of daily living (Alzheimer Disease Research Center IADLs), pain (geriatric pain measure), and depression screening (hospital depression and anxiety scale) before and 3 months after surgery. We recorded all patient refined diagnostic related groups codes, blood pressure, anesthetics and narcotics administered, surgical and anesthesia duration, and measured complications and severity, length of stay, and readmissions. RESULTS: Patients with POCD (21/167, 14.1%) had twice the proportion of new impairment in IADL as compared to those without POCD (57% vs 27%, P = .01). The most common areas of decline were social activities, ability to find items around the house, remember appointments, shop and pay for items, do laundry, drive a car/use public transport, and do housework. Predictors of IADL change after surgery included POCD, presurgical cognition, presurgical function, postoperative depression, and the development of postoperative complications. CONCLUSIONS: Patients with POCD experience a much higher incidence of new disability after surgery. Baseline cognitive or functional limitations are also risk factors for new disability. Many patients are not aware of their limitations before surgery. Future study is needed to identify practical ways to routinely screen patients and reduce risk. Patients need to be informed of their risk for new disability after surgery to inform their medical decision making.

Improving perioperative brain health: an expert consensus review of key actions for the perioperative care team.

Delirium and postoperative neurocognitive disorder are the commonest perioperative complications in patients more than 65 yr of age. However, data suggest that we often fail to screen patients for preoperative cognitive impairment, to warn patients and families of risk, and to take preventive measures to reduce the incidence of perioperative neurocognitive disorders. As part of the American Society of Anesthesiologists (ASA) Perioperative Brain Health Initiative, an international group of experts was invited to review published best practice statements and guidelines. The expert group aimed to achieve consensus on a small number of practical recommendations that could be implemented by anaesthetists and their partners to reduce the incidence of perioperative neurocognitive disorders. Six statements were selected based not only on the strength of the evidence, but also on the potential for impact and the feasibility of widespread implementation. The actions focus on education, cognitive and delirium screening, non-pharmacologic interventions, pain control, and avoidance of antipsychotics. Strategies for effective implementation are discussed. Anaesthetists should be key members of multidisciplinary perioperative care teams to implement these recommendations.

Human plasma biomarker responses to inhalational general anaesthesia without surgery.

BACKGROUND: Postoperative neurocognitive disorders may arise in part from adverse effects of general anaesthetics on the CNS, especially in older patients or individuals otherwise vulnerable to neurotoxicity because of systemic disease or the presence of pre-existing neuropathology. Previous studies have documented cytokine and injury biomarker responses to surgical procedures that included general anaesthesia, but it is not clear to what degree anaesthetics contribute to these responses. METHODS: We performed a prospective cohort study of 59 healthy volunteers aged 40-80 yr who did not undergo surgery. Plasma markers of neurological injury and inflammation were measured immediately before and 5 h after induction of general anaesthesia with 1 minimum alveolar concentration of sevoflurane. Biomarkers included interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), C-reactive protein (CRP), and neural injury (tau, neurofilament light [NF-L], and glial fibrillary acidic protein [GFAP]). RESULTS: Baseline biomarkers were in the normal range, although NF-L and GFAP were elevated as a function of age. At 5 h after induction of anaesthesia, plasma tau, NF-L, and GFAP were significantly decreased relative to baseline. Plasma IL-6 was significantly increased after anaesthesia, but by a biologically insignificant degree (<1 pg ml-1); plasma TNF-α and CRP were unchanged. CONCLUSIONS: Sevoflurane general anaesthesia without surgery, even in older adults, did not provoke an inflammatory state or neuronal injury at a concentration that is detectable by an acute elevation of measured plasma biomarkers in the early hours after exposure. CLINICAL TRIAL REGISTRATION: NCT02275026.

Resting-state functional connectivity in early postanaesthesia recovery is characterised by globally reduced anticorrelations.

BACKGROUND: A growing body of literature addresses the possible long-term cognitive effects of anaesthetics, but no study has delineated the normal trajectory of neural recovery attributable to anaesthesia alone in adults. We obtained resting-state functional MRI scans on 72 healthy human volunteers between ages 40 and 80 (median: 59) yr before, during, and after general anaesthesia with sevoflurane, in the absence of surgery, as part of a larger study on cognitive function postanaesthesia. METHODS: Region-of-interest analysis, independent component analysis, and seed-to-voxel analysis were used to characterise resting-state functional connectivity and to differentiate between correlated and anticorrelated connectivity before, during, and after general anaesthesia. RESULTS: Whilst positively correlated functional connectivity remained essentially unchanged across these perianaesthetic states, anticorrelated functional connectivity decreased globally by 35% 1 h after emergence from general anaesthesia compared with baseline, as seen by the region-of-interest analysis. This decrease corresponded to a consistent reduction in expression of canonical resting-state networks, as seen by independent component analysis. All measures returned to baseline 1 day later. CONCLUSIONS: The normal perianaesthesia trajectory of resting-state connectivity in healthy adults is characterised by a transient global reduction in anticorrelated activity shortly after emergence from anaesthesia that returns to baseline by the following day. CLINICAL TRIAL REGISTRATION: NCT02275026.

Frailty Is Associated With Postoperative Delirium But Not With Postoperative Cognitive Decline in Older Noncardiac Surgery Patients.

BACKGROUND: Postoperative cognitive dysfunction (POCD) and delirium are the most common perioperative cognitive complications in older adults undergoing surgery. A recent study of cardiac surgery patients suggests that physical frailty is a risk factor for both complications. We sought to examine the relationship between preoperative frailty and postoperative delirium and preoperative frailty and POCD after major noncardiac surgery. METHODS: We performed a prospective cohort study of patients >65 years old having major elective noncardiac surgery with general anesthesia. Exclusion criteria were preexisting dementia, inability to consent, cardiac, intracranial, or emergency surgery. Preoperative frailty was determined using the FRAIL scale, a simple questionnaire that categorizes patients as robust, prefrail, or frail. Delirium was assessed with the Confusion Assessment Method for the intensive care unit (CAM-ICU) twice daily, starting in the recovery room until hospital discharge. All patients were assessed with neuropsychological tests (California Verbal Learning Test II, Trail Making Test, subtests from the Wechsler Adult Intelligence Scale, Logical Memory Story A, Immediate and Delayed Recall, Animal and Vegetable verbal fluency, Boston Naming Test, and the Mini-Mental Status Examination) before surgery and at 3 months afterward. RESULTS: A total of 178 patients met inclusion criteria; 167 underwent major surgery and 150 were available for follow-up 3 months after surgery. The median age was 70 years old. Thirty-one patients (18.6%) tested as frail, and 72 (43.1%) prefrail before surgery. After adjustment for baseline cognitive score, age, education, surgery duration, American Society of Anesthesiologists (ASA) physical status, type of surgery, and sex, patients who tested frail or prefrail had an estimated 2.7 times the odds of delirium (97.5% confidence interval, 1.0-7.3) when compared to patients who were robust. There was no significant difference between the proportion of POCD between patients who tested as frail, prefrail, or robust. CONCLUSIONS: After adjustment for baseline cognition, testing as frail or prefrail with the FRAIL scale is associated with increased odds of postoperative delirium, but not POCD after noncardiac surgery.

Modifiable factors associated with postoperative delirium after hip fracture repair: An age-stratified retrospective cohort study.

BACKGROUND: Postoperative delirium in hip fracture patients is common and is associated with substantial morbidity and consumption of resources. OBJECTIVE: Using data from the USA, we aimed to examine the relationship between postoperative delirium and (modifiable) peri-operative factors mentioned in the American Geriatrics Society Best Practice Statement on Postoperative Delirium in Older Adults, stratified by 'young old' (<80 years) and 'old-old' (≥80 years) categories. DESIGN: Retrospective cohort study from 2006 to 2016. SETTING: Population-based claims data from the USA. PARTICIPANTS: Patients undergoing 505 152 hip fracture repairs between 2006 and 2016 as recorded in the Premier Healthcare Database. MAIN OUTCOMES AND MEASURES: The main outcome was postoperative delirium; modifiable factors of interest were peri-operative opioid use (high, medium or low; <25th, 25 to 75th or >75th percentile of oral morphine equivalents), anaesthesia type (general, neuraxial, both), use of benzodiazepines (long acting, short acting, both), pethidine, nonbenzodiazepine hypnotics, ketamine, corticosteroids and gabapentinoids. Multilevel models assessed associations between these factors and postoperative delirium, in the full cohort, and separately in those aged less than 80 and at least 80 years. Odds ratios (ORs) and Bonferroni-adjusted 95% confidence intervals (95% CIs) are reported. RESULTS: Overall, postoperative delirium incidence was 15.7% (n = 79 547). After adjustment for relevant covariates, the use of long-acting (OR 1.82, CI 1.74 to 1.89) and combined short and long-acting benzodiazepines (OR 1.56, CI 1.48 to 1.63) and ketamine (OR 1.09, CI 1.03 to 1.15), in particular, was associated with increased odds for postoperative delirium, while neuraxial anaesthesia (OR 0.91 CI 0.85 to 0.98) and opioid use (OR 0.95, CI 0.92 to 0.98 and OR 0.88, CI 0.84 to 0.92 for medium and high dose compared with low dose) were associated with lower odds; all P < 0.05. When analysing data separately by age group, effects of benzodiazepines persisted, while opioid use was only relevant in those aged less than 80 years. CONCLUSION: We identified modifiable factors associated with postoperative delirium incidence among patients undergoing hip fracture repair surgery.

Subjective cognitive complaints in patients undergoing major non-cardiac surgery: a prospective single centre cohort trial.

BACKGROUND: Few perioperative studies have assessed subjective cognitive complaint (SCC) in combination with neuropsychological testing. New nomenclature guidelines require both SCC and objective decline on cognitive testing. The objective of our study was to compare SCC and neuropsychological testing in an elderly surgical cohort. METHODS: This was a secondary analysis of a prospective cohort trial at a single urban medical centre. We included patients older than 65 yr, undergoing major non-cardiac surgery with general anaesthesia. Those with dementia or inability to consent were excluded, as were those undergoing emergency, cardiac, or intracranial procedures. Patients completed a neuropsychiatry battery before and 3 months after surgery. SCC was defined utilising the single question: 'do you feel that surgery and anaesthesia have impacted your clarity of thought?' Objective cognitive decline was defined as 1 standard deviation decline from the baseline of the cohort. RESULTS: Of the 120 patients who completed assessments, 16/120 (13%) had SCC after surgery, and 41/120 (34%) had objective decline. The sensitivity of SCC in relation to objective decline was 24% and specificity was 92%. Of the patients with SCC, 43.8% were screened positive for depression after surgery compared with 4.9% without SCC; P=0.001. CONCLUSIONS: Many patients with objective cognitive decline did not report SCC. There appears to be a relationship between SCC and depression. The use of SCC in surgical patients to define postoperative neurocognitive disorders needs to be better delineated. CLINICAL TRIAL REGISTRATION: NCT02650687.

State of the clinical science of perioperative brain health: report from the American Society of Anesthesiologists Brain Health Initiative Summit 2018.

Cognitive recovery after anaesthesia and surgery is a concern for older adults, their families, and caregivers. Reports of patients who were 'never the same' prompted a scientific inquiry into the nature of what patients have experienced. In June 2018, the ASA Brain Health Initiative held a summit to discuss the state of the science on perioperative cognition, and to create an implementation plan for patients and providers leveraging the current evidence. This group included representatives from the AARP (formerly the American Association of Retired Persons), American College of Surgeons, American Heart Association, and Alzheimer's Association Perioperative Cognition and Delirium Professional Interest Area. This paper summarises the state of the relevant clinical science, including risk factors, identification and diagnosis, prognosis, disparities, outcomes, and treatment of perioperative neurocognitive disorders. Finally, we discuss gaps in current knowledge with suggestions for future directions and opportunities for clinical and translational projects.