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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.

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.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.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).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.

ObjectiveTo characterize the clinical course of delirium for COVID-19 patients in the intensive care unit, including post-discharge cognitive outcomes.Patients and MethodsA retrospective chart review was conducted for patients diagnosed with COVID-19 (n=148) admitted to an intensive care unit at Michigan Medicine between March 1, 2020 and May 31, 2020. A validated chart review method was used to identify presence of delirium, and various measures (e.g., Family Confusion Assessment Method, Short Blessed Test, Patient-Health Questionnaire-9) were used to determine neuropsychological outcomes between 1-2 months after hospital discharge.ResultsDelirium was identified in 108/148 (73%) patients in the study cohort, with median (interquartile range) 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 standardized differences >.30). Sedation regimens, inflammation, deviation from delirium prevention protocols, and hypoxic-ischemic 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 hospitalization, 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 two months after discharge.ConclusionPatients 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.

BACKGROUND: The objective of this study was to test whether postoperative electroencephalographic 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 electroencephalographic 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 via 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 electroencephalographic patterns were characterized by a predominance of alpha parietal power and frontal-parietal connectivity. Neither relative parietal alpha power (% alpha, −0.25, 95% 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.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New 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.