Background: Postoperative delirium (POD) might be associated with anesthetic management, but research has focused on choice or dosage of anesthetic drugs. We examined potential contributions of intraoperative ventilatory and hemodynamic management to POD.Methods: This was a sub-study of the ENGAGES-Canada trial (NCT02692300) involving non-cardiac surgery patients enrolled in Winnipeg, Canada. Patients received preoperative psychiatric and cognitive assessments, and intraoperatively underwent high-fidelity data collection of blood pressure, end-tidal respiratory gases and anesthetic agent concentration. POD was assessed by peak and mean POD scores using the Confusion Assessment Method-Severity (CAM-S) tool. Bivariate and multiple linear regression models were constructed controlling for age, psychiatric illness, and cognitive dysfunction in the examination of deviations in intraoperative end-tidal carbon dioxide (areas over (AOC) and under the curve (AUC)) on POD severity scores.Results: A total of 101 subjects [69 (6) years of age] were studied; 89 had comprehensive intraoperative hemodynamic and end-tidal gas measurements (data recorded at 1 Hz). The incidence of POD was 11.9% (12/101). Age, cognitive dysfunction, anxiety, depression, and intraoperative end-tidal CO2 (AUC) were significant correlates of POD severity. In the multiple regression model, cognitive dysfunction and AUC end-tidal CO2 (0.67 kPa below median intra-operative value) were the only independent significant predictors across both POD severity (mean and peak) scores. There was no association between cumulative anesthetic agent exposure and POD.Conclusions: POD was associated with intraoperative ventilatory management, reflected by low end-tidal CO2 concentrations, but not with cumulative anesthetic drug exposure. These findings suggest that maintenance of intraoperative normocapnia might benefit patients at risk of POD.

Introduction: Risk assessment for post-operative delirium (POD) is poorly developed. Improved metrics could greatly facilitate peri-operative care as costs associated with POD are staggering. In this preliminary study, we develop a novel stress-diathesis model based on comprehensive pre-operative psychiatric and neuropsychological testing, a blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) carbon dioxide (CO2) stress test, and high fidelity measures of intra-operative parameters that may interact facilitating POD.Methods: The study was approved by the ethics board at the University of Manitoba and registered at clinicaltrials.gov as NCT02126215. Twelve patients were studied. Pre-operative psychiatric symptom measures and neuropsychological testing preceded MRI featuring a BOLD MRI CO2 stress test whereby BOLD scans were conducted while exposing participants to a rigorously controlled CO2 stimulus. During surgery the patient had hemodynamics and end-tidal gases downloaded at 0.5 hz. Post-operatively, the presence of POD and POD severity was comprehensively assessed using the Confusion Assessment Measure –Severity (CAM-S) scoring instrument on days 0 (surgery) through post-operative day 5, and patients were followed up at least 1 month post-operatively.Results: Six of 12 patients had no evidence of POD (non-POD). Three patients had POD and 3 had clinically significant confusional states (referred as subthreshold POD; ST-POD) (score ≥ 5/19 on the CAM-S). Average severity for delirium was 1.3 in the non-POD group, 3.2 in ST-POD, and 6.1 in POD (F-statistic = 15.4, p < 0.001). Depressive symptoms, and cognitive measures of semantic fluency and executive functioning/processing speed were significantly associated with POD. Second level analysis revealed an increased inverse BOLD responsiveness to CO2 pre-operatively in ST-POD and marked increase in the POD groups when compared to the non-POD group. An association was also noted for the patient population to manifest leucoaraiosis as assessed with advanced neuroimaging techniques. Results provide preliminary support for the interacting of diatheses (vulnerabilities) and intra-operative stressors on the POD phenotype.Conclusions: The stress-diathesis model has the potential to aid in risk assessment for POD. Based on these initial findings, we make some recommendations for intra-operative management for patients at risk of POD.

Background: Mechanical ventilation to alter and improve respiratory gases is a fundamental feature of critical care and intraoperative anesthesia management. The range of inspired O 2 and expired CO 2 during patient management can significantly deviate from values in the healthy awake state. It has long been appreciated that hyperoxia can have deleterious effects on organs, especially the lung and retina. Recent work shows intraoperative end-tidal (ET) CO 2 management influences the incidence of perioperative neurocognitive disorder (POND). The interaction of O 2 and CO 2 on cerebral blood flow (CBF) and oxygenation with alterations common in the critical care and operating room environments has not been well studied. Methods: We examine the effects of controlled alterations in both ET O 2 and CO 2 on cerebral blood flow (CBF) in awake adults using blood oxygenation level-dependent (BOLD) and pseudo-continuous arterial spin labeling (pCASL) MRI. Twelve healthy adults had BOLD and CBF responses measured to alterations in ET CO 2 and O 2 in various combinations commonly observed during anesthesia. Results: Dynamic alterations in regional BOLD and CBF were seen in all subjects with expected and inverse brain voxel responses to both stimuli. These effects were incremental and rapid (within seconds). The most dramatic effects were seen with combined hyperoxia and hypocapnia. Inverse responses increased with age suggesting greater risk. Conclusions: Human CBF responds dramatically to alterations in ET gas tensions commonly seen during anesthesia and in critical care. Such alterations may contribute to delirium following surgery and under certain circumstances in the critical care environment. Trial registration: ClincialTrials.gov NCT02126215 for some components of the study. First registered April 29, 2014.

Dissociative symptoms and suicidality are transdiagnostic features of posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). The primary objective of this study was to examine associations between dissociation (i.e., depersonalization and derealization) and suicidality (i.e., self‐harm and suicide attempts) among individuals with PTSD and BPD. We analyzed data from the 2012–2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC‐III; N = 36,309). The Alcohol Use Disorder and Associated Disabilities Interview Schedule for DSM‐5 was used to assess lifetime PTSD and BPD. Estimated rates of self‐harm among individuals who endorsed dissociation were 15.5%–26.2% for those with PTSD and 13.7%–23.5% for those with BPD, and estimates of suicide attempts among individuals who endorsed dissociation were 34.5%–38.1% for those with PTSD and 28.3%–33.1% for those with BPD. Multiple logistic regressions were conducted to examine the associations between dissociation (derealization, depersonalization, and both) and both self‐harm and suicide attempts among respondents with PTSD and BPD. The results indicated that dissociation was associated with self‐harm and suicide attempts, especially among individuals with BPD, aORs = 1.39–2.66; however, this association may be driven in part by a third variable, such as other symptoms of PTSD or BPD (e.g., mood disturbance, PTSD or BPD symptom severity). These results may inform risk assessments and targeted interventions for vulnerable individuals with PTSD, BPD, or both aimed at mitigating the risk of self‐harm and suicide.

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