Electroencephalographic Biomarkers, Cerebral Oximetry, and Postoperative Cognitive Function in Adult Noncardiac Surgical Patients: A Prospective Cohort Study.

BACKGROUND: Perioperative neurocognitive disorders are a major public health issue, although there are no validated neurophysiologic biomarkers that predict cognitive function after surgery. This study tested the hypothesis that preoperative posterior electroencephalographic alpha power, alpha frontal-parietal connectivity, and cerebral oximetry would each correlate with postoperative neurocognitive function. METHODS: This was a single-center, prospective, observational study of adult (older than 18 yr) male and female noncardiac surgery patients. Whole-scalp, 16-channel electroencephalography and cerebral oximetry were recorded in the preoperative, intraoperative, and immediate postoperative settings. The primary outcome was the mean postoperative T-score of three National Institutes of Health Toolbox Cognition tests-Flanker Inhibitory Control and Attention, List Sorting Working Memory, and Pattern Comparison Processing Speed. These tests were obtained at preoperative baseline and on the first two postoperative mornings. The lowest average score from the first two postoperative days was used for the primary analysis. Delirium was a secondary outcome (via 3-min Confusion Assessment Method) measured in the postanesthesia care unit and twice daily for the first 3 postoperative days. Last, patient-reported outcomes related to cognition and overall well-being were collected 3 months postdischarge. RESULTS: Sixty-four participants were recruited with a median (interquartile range) age of 59 (48 to 66) yr. After adjustment for baseline cognitive function scores, no significant partial correlation (ρ) was detected between postoperative cognition scores and preoperative relative posterior alpha power (%; ρ = -0.03, P = 0.854), alpha frontal-parietal connectivity (via weight phase lag index; ρ = -0.10, P = 0.570, respectively), or preoperative cerebral oximetry (%; ρ = 0.21, P = 0.246). Only intraoperative frontal-parietal theta connectivity was associated with postoperative delirium (F[1,6,291] = 4.53, P = 0.034). No electroencephalographic or oximetry biomarkers were associated with cognitive or functional outcomes 3 months postdischarge. CONCLUSIONS: Preoperative posterior alpha power, frontal-parietal connectivity, and cerebral oximetry were not associated with cognitive function after noncardiac surgery.

Delirium and neuropsychological outcomes in critically Ill patients with COVID-19: a cohort study.

OBJECTIVE: To characterise the clinical course of delirium for patients with COVID-19 in the intensive care unit, including postdischarge neuropsychological outcomes. DESIGN: Retrospective chart review and prospective survey study. SETTING: Intensive care units, large academic tertiary-care centre (USA). PARTICIPANTS: Patients (n=148) with COVID-19 admitted to an intensive care unit at Michigan Medicine between 1 March 2020 and 31 May 2020 were eligible for inclusion. PRIMARY AND SECONDARY OUTCOME MEASURES: Delirium was the primary outcome, assessed via validated chart review method. Secondary outcomes included measures related to delirium, such as delirium duration, antipsychotic use, length of hospital and intensive care unit stay, inflammatory markers and final disposition. Neuroimaging data were also collected. Finally, a telephone survey was conducted between 1 and 2 months after discharge to determine neuropsychological function via the following tests: Family Confusion Assessment Method, Short Blessed Test, Patient-Reported Outcomes Measurement Information System Cognitive Abilities 4a and Patient-Health Questionnaire-9. RESULTS: Delirium was identified in 108/148 (73%) patients, with median (IQR) duration lasting 10 (4-17) days. In the delirium cohort, 50% (54/108) of patients were African American and delirious patients were more likely to be female (76/108, 70%) (absolute standardised differences >0.30). Sedation regimens, inflammation, delirium prevention protocol deviations and hypoxic-ischaemic injury were likely contributing factors, and the most common disposition for delirious patients was a skilled care facility (41/108, 38%). Among patients who were delirious during hospitalisation, 4/17 (24%) later screened positive for delirium at home based on caretaker assessment, 5/22 (23%) demonstrated signs of questionable cognitive impairment or cognitive impairment consistent with dementia and 3/25 (12%) screened positive for depression within 2 months after discharge. CONCLUSION: Patients with COVID-19 commonly experience a prolonged course of delirium in the intensive care unit, likely with multiple contributing factors. Furthermore, neuropsychological impairment may persist after discharge.

The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial.

BACKGROUND: Surgical patients are vulnerable to opioid dependency and related risks. Clinical-translational data suggest that caffeine may enhance postoperative analgesia. This trial tested the hypothesis that intraoperative caffeine would reduce postoperative opioid consumption. The secondary objective was to assess whether caffeine improves neuropsychological recovery postoperatively. METHODS: This was a single-center, randomized, placebo-controlled trial. Participants, clinicians, research teams, and data analysts were all blinded to the intervention. Adult (≥18 years old) surgical patients (n = 65) presenting for laparoscopic colorectal and gastrointestinal surgery were randomized to an intravenous caffeine citrate infusion (200 mg) or dextrose 5% in water (40 mL) during surgical closure. The primary outcome was cumulative opioid consumption through postoperative day 3. Secondary outcomes included subjective pain reporting, observer-reported pain, delirium, Trail Making Test performance, depression and anxiety screens, and affect scores. Adverse events were reported, and hemodynamic profiles were also compared between the groups. RESULTS: Sixty patients were included in the final analysis, with 30 randomized to each group. The median (interquartile range) cumulative opioid consumption (oral morphine equivalents, milligrams) was 77 mg (33-182 mg) for caffeine and 51 mg (15-117 mg) for placebo (estimated difference, 55 mg; 95% confidence interval [CI], -9 to 118; P = .092). After post hoc adjustment for baseline imbalances, caffeine was associated with increased opioid consumption (87 mg; 95% CI, 26-148; P = .005). There were otherwise no differences in prespecified pain or neuropsychological outcomes between the groups. No major adverse events were reported in relation to caffeine, and no major hemodynamic perturbations were observed with caffeine administration. CONCLUSIONS: Caffeine appears unlikely to reduce early postoperative opioid consumption. Caffeine otherwise appears well tolerated during anesthetic emergence.

Cortical Oscillations and Connectivity During Postoperative Recovery.

BACKGROUND: The objective of this study was to test whether postoperative electroencephalographic (EEG) biomarkers, parietal alpha power and frontal-parietal connectivity, were associated with measures of clinical recovery in adult surgical patients. METHODS: This is a secondary analysis of a prospective cohort study that analyzed intraoperative connectivity patterns in adult surgical patients (N=53). Wireless, whole-scalp EEG data were collected in the postanesthesia care unit and assessed for relevance to clinical and neurocognitive recovery. Parietal alpha power and frontal-parietal connectivity (estimated by weighted phase lag index) were tested for associations with postanesthesia care unit discharge readiness and University of Michigan Sedation Scale scores upon postoperative admission. Bivariable correlation and regression models were constructed to test for unadjusted associations, then multivariable regression models were constructed to adjust for confounding. RESULTS: Postoperative EEG patterns were characterized by a predominance of alpha parietal power and frontal-parietal connectivity. Neither relative parietal alpha power (% alpha, -0.25; 95% confidence interval [CI], -1.41 to 0.90; P=0.657) nor alpha frontal-parietal connectivity (weighted phase lag index, -82; 95% CI, -237 to 73; P=0.287) were associated with time until postanesthesia discharge criteria were met. Furthermore, neither alpha power (-0.03; 95% CI, -0.07 to 0.01; P=0.206) nor alpha frontal-parietal connectivity (-4.2; 95% CI, -11 to 2.6; P=0.226) were associated with sedation scores upon initial assessment. CONCLUSIONS: In a pragmatic study investigating clinically relevant endpoints of postoperative recovery, we found no correlation with surrogate measures of brain neurodynamics. These data contribute to the overall impetus of developing anesthetic-invariant and generalizable markers of brain recovery.

Cerebrovascular Disease and Perioperative Neurologic Vulnerability: A Prospective Cohort Study.

Background: Stroke is a devastating perioperative complication without effective methods for prevention or diagnosis. The objective of this study was to analyze evidence-based strategies for detecting cerebrovascular vulnerability and injury in a high-risk cohort of non-cardiac surgery patients. Methods: This was a single-center, prospective cohort study. Fifty patients undergoing non-cardiac surgery were recruited -25 with known cerebrovascular disease and 25 matched controls. Neurologic vulnerability was measured with intraoperative cerebral oximetry as the primary outcome. Perioperative neurocognitive testing and serum biomarker analysis (S-100ß, neuron specific enolase, glial fibrillary acid protein, and matrix metalloproteinase-9) were measured as secondary outcomes. Results: Cerebral desaturation events (an oximetry decrease ≥20% from baseline or <50% absolute value for ≥3 min) occurred in 7/24 (29%) cerebrovascular disease patients and 2/24 (8.3%) controls (relative risk 3.5, 95% CI 0.81-15.2; P = 0.094). Cognitive function trends were similar in both groups, though overall scores (range: 1,500-7,197) were ~1 standard deviation lower in cerebrovascular patients across the entire perioperative period (-1,049 [95% CI -1,662, -436], P < 0.001). No significant serum biomarker differences were found between groups over time. One control patient experienced intraoperative hypoxic-ischemic injury, but no robust biomarker or oximetry changes were observed. Conclusions: Cerebrovascular disease patients did not demonstrate dramatic differences in cerebral oximetry, cognitive trajectory, or molecular biomarkers compared to controls. Moreover, a catastrophic hypoxic-ischemic event was neither predicted nor detected by any strategy tested. These findings support the need for novel research into cerebrovascular risk and vulnerability.

Dynamic Cortical Connectivity during General Anesthesia in Surgical Patients.

BACKGROUND: Functional connectivity across the cortex has been posited to be important for consciousness and anesthesia, but functional connectivity patterns during the course of surgery and general anesthesia are unknown. The authors tested the hypothesis that disrupted cortical connectivity patterns would correlate with surgical anesthesia. METHODS: Surgical patients (n = 53) were recruited for study participation. Whole-scalp (16-channel) wireless electroencephalographic data were prospectively collected throughout the perioperative period. Functional connectivity was assessed using weighted phase lag index. During anesthetic maintenance, the temporal dynamics of connectivity states were characterized via Markov chain analysis, and state transition probabilities were quantified. RESULTS: Compared to baseline (weighted phase lag index, 0.163, ± 0.091), alpha frontal-parietal connectivity was not significantly different across the remaining anesthetic and perioperative epochs, ranging from 0.100 (± 0.041) to 0.218 (± 0.136) (P > 0.05 for all time periods). In contrast, there were significant increases in alpha prefrontal-frontal connectivity (peak = 0.201 [0.154, 0.248]; P < 0.001), theta prefrontal-frontal connectivity (peak = 0.137 [0.091, 0.182]; P < 0.001), and theta frontal-parietal connectivity (peak = 0.128 [0.084, 0.173]; P < 0.001) during anesthetic maintenance. Additionally, shifts occurred between states of high prefrontal-frontal connectivity (alpha, beta) with suppressed frontal-parietal connectivity, and high frontal-parietal connectivity (alpha, theta) with reduced prefrontal-frontal connectivity. These shifts occurred in a nonrandom manner (P < 0.05 compared to random transitions), suggesting structured transitions of connectivity during general anesthesia. CONCLUSIONS: Functional connectivity patterns dynamically shift during surgery and general anesthesia but do so in a structured way. Thus, a single measure of functional connectivity will likely not be a reliable correlate of surgical anesthesia.

Recommendations and Alerting for Delirium Alleviation in Real-Time (RADAR): Protocol for a pilot randomized controlled trial.

Background: Delirium is a common and serious complication of major surgery for older adults. Postoperative social and behavioral support (e.g., early mobilization, mealtime assistance) may reduce the incidence and impact of delirium, and these efforts are possible with proactive patient-care programs. This pilot trial tests the hypothesis that a multicomponent decision support system, which sends automated alerts and recommendations to patient-care programs and family members for high-risk patients, will improve the postoperative environment for neurocognitive and clinical recovery. Methods: This will be a randomized, controlled, factorial pilot trial at a large academic medical center. High-risk, non-cardiac surgery patients (≥70 years old) will be recruited. Patients will be allocated to a usual care group (n=15), Hospital Elder Life Program (HELP)-based paging system (n=15), family-based paging system (n=15), or combined HELP- and family-based system (n=15). The primary outcome will be the presence of delirium, defined by positive long-form Confusion Assessment Method screening. Secondary outcomes will include additional HELP- and family-based performance metrics along with various neurocognitive and clinical recovery measures. Exploratory outcomes include the incidence of positive family-based delirium assessments post-discharge, 36-item Short Form Survey, PROMIS Cognitive Function Abilities Subset 4a, and 30-day readmission rates. Ethics and dissemination: This trial has received approval by the University of Michigan Medical Institutional Review Board (IRBMED). Dissemination plans include presentation at scientific conferences, publication in medical journals, and distribution via educational and news media. Registration: ClinicalTrials.gov Identifier NCT04007523, registered on 7/3/2019.

Home-based Cognitive Prehabilitation in Older Surgical Patients: A Feasibility Study.

BACKGROUND: Cognitive training is beneficial in various clinical settings, although its perioperative feasibility and impact remain unknown. The objective of this pilot study was to determine the feasibility of home-based cognitive prehabilitation before major surgery in older adults. MATERIALS AND METHODS: Sixty-one patients were enrolled, randomized, and allocated to either a home-based preoperative cognitive training regimen or no training before surgery. Outcomes included postoperative delirium incidence (primary outcome; assessed with the 3D-Confusion Assessment Method), perioperative cognitive function based on NIH Toolbox measures, hospital length of stay, and physical therapy session participation. Reasons for declining enrollment were reported, as were reasons for opting out of the training program. RESULTS: Postoperative delirium incidence was 6 of 23 (26%) in the prehabilitation group compared with 5 of 29 (17%) in the control group (P=0.507). There were no significant differences between groups in NIH Toolbox cognitive function scoring, hospital length of stay, or physical therapy participation rates. Study feasibility data were also collected and reported. The most common reasons for declining enrollment were lack of computer access (n=19), time commitment (n=9), and feeling overwhelmed (n=9). In the training group, only 5 of 29 (17%) included patients were able to complete the prescribed 7 days of training, and 14 of 29 (48%) opted out of training once home. Most common reasons were feeling overwhelmed (n=4) and computer difficulties (n=3). CONCLUSIONS: Short-term, home-based cognitive training before surgery is unlikely to be feasible for many older patients. Barriers to training include feeling overwhelmed, technical issues with training, and preoperative time commitment.

Age-Related Changes in Cortical Connectivity During Surgical Anesthesia.

An advanced understanding of the neurophysiologic changes that occur with aging may help improve care for older, vulnerable surgical patients. The objective of this study was to determine age-related changes in cortical connectivity patterns during surgical anesthesia. This was a substudy analysis of a prospective, observational study characterizing cortical connectivity during surgical anesthesia in adult patients (n = 45) via whole-scalp (16-channel) electroencephalography. Functional connectivity was estimated using a weighted phase lag index (wPLI), which was classified into a discrete set of states through k-means analysis. Temporal dynamics were quantified by occurrence rate and state transition probabilities. The mean global connectivity state transition probability [13.4% (±8.1)] was not correlated with age (ρ = 0.100, p = 0.513). Increasing age was inversely correlated with prefrontal-frontal alpha-beta connectivity (ρ = -0.446, p = 0.002) and positively correlated with frontal-parietal theta connectivity (ρ = 0.414, p = 0.005). After adjusting for anesthetic-related confounders, prefrontal-frontal alpha-beta connectivity remained significantly associated with age (ß = -0.625, 95% CI -0.99 to -0.26; p = 0.001), while frontal-parietal theta connectivity was no longer significant (ß = 0.436, 95% CI -0.03 to 0.90; p = 0.066). Specific transition states were also examined. Between frontal-parietal connectivity states, transitioning from theta-alpha to theta-dominated connectivity positively correlated with age (ρ = 0.545, p = 0.001). Dynamic connectivity states during surgical anesthesia, particularly involving alpha and theta bandwidths, maybe an informative measure to assess neurophysiologic changes that occur with aging.