The Influence of Preoperative Physical Activity on Intraoperative Brain Function in Cardiac Surgical patients.

Background Preoperative physical activity and intraoperative brain health are recognized to influence postoperative delirium (POD). Electroencephalogram (EEG) burst suppression and cerebral desaturation are indicators of abnormal intraoperative brain health. Our study aimed to investigate the associations between preoperative physical activity and intraoperative EEG burst suppression and cerebral desaturation. Methods We retrospectively analyzed data from 67 patients from one of the institutions participating in a multisite randomized controlled trial, PANDORA, involving patients undergoing cardiac surgery. The preoperative PCS12 score calculated using the SF12 questionnaire was used as an indicator of preoperative physical activity. Intraoperative EEG and cerebral oximetry data (not the current standard of care in this facility) were collected, and the anesthesiologists were blinded to the information. We analyzed the following associations between the PCS12 score and i) burst suppression duration, ii) the number of cerebral desaturations, and iii) the number of observations with concurrent cerebral desaturation and burst suppression using a generalized linear model. The results are presented as percentage changes in outcomes, and a 95% C.I. p value < 0.05 was considered to indicate statistical significance. Results Each unit increase in the PCS12 score was associated with a 3.3% decrease in the duration of burst suppression (-3.3 [-5.3, -1.2], p value = 0.002). The duration of burst suppression decreased by 29.2% with each successive quartile increase in the PCS-12 score, indicating a dose‒response relationship (-29.2 [-41.6, -16], p < 0.001). Specifically, the patients in the last three quartiles exhibited a 55.4% reduction in BSD compared to those in the first quartile (-55.4 [-74.4, -24.6], p = 0.002) (Fig. 2). We did not observe any significant association between the PCS12 score and cerebral desaturation. Conclusion Decreased preoperative physical activity, as measured by the SF-12 questionnaire, is significantly associated with increased EEG burst suppression duration. Preoperative physical activity did not show any association with cerebral desaturations and concurrent cerebral desaturation and burst suppression. Clinical Trial information ClinicalTrials.gov Identifier- NCT04093219 https://clinicaltrials.gov/ct2/show/NCT04093219 Principal Investigator - Balachundhar Subramaniam Date of registration - September 13, 2019.

Blood pressure fragmentation as a new measure of blood pressure variability: association with predictors of cardiac surgery outcomes.

Background: Fluctuations in beat-to-beat blood pressure variability (BPV) encode untapped information of clinical utility. A need exists for developing new methods to quantify the dynamical properties of these fluctuations beyond their mean and variance. Objectives: Introduction of a new beat-to-beat BPV measure, termed blood pressure fragmentation (BPF), and testing of whether increased preoperative BPF is associated with (i) older age; (ii) higher cardiac surgical risk, assessed using the Society of Thoracic Surgeons' (STS) Risk of Morbidity and Mortality index and the European System for Cardiac Operative Risk Evaluation Score (EuroSCORE II); and (iii) longer ICU length of stay (LOS) following cardiac surgery. The secondary objective was to use standard BPV measures, specifically, mean, SD, coefficient of variation (CV), average real variability (ARV), as well a short-term scaling index, the detrended fluctuation analysis (DFA) ⍺1 exponent, in the same type of analyses to compare the results with those obtained using BPF. Methods: Consecutive sample of 497 adult patients (72% male; age, median [inter-quartile range]: 67 [59-75] years) undergoing cardiac surgery with cardiopulmonary bypass. Fragmentation, standard BPV and DFA ⍺1 measures were derived from preoperative systolic blood pressure (SBP) time series obtained from radial artery recordings. Results: Increased preoperative systolic BPF was associated with older age, higher STS Risk of Morbidity and Mortality and EuroSCORE II values, and longer ICU LOS in all models. Specifically, a one-SD increase in systolic BPF (9%) was associated with a 26% (13%-40%) higher likelihood of longer ICU LOS (>2 days). Among the other measures, only ARV and DFA ⍺1 tended to be associated with longer ICU LOS. However, the associations did not reach significance in the most adjusted models. Conclusion: Preoperative BPF was significantly associated with preoperative predictors of cardiac surgical outcomes as well as with ICU LOS. Our findings encourage future studies of preoperative BPF for assessment of health status and risk stratification of surgical and non-surgical patients.

Intraoperative Use of Phenylephrine versus Ephedrine and Postoperative Delirium: A Multicenter Retrospective Cohort Study.

BACKGROUND: The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium. METHODS: A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied. RESULTS: Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each µg/kg increase in the cumulative phenylephrine dose). CONCLUSIONS: The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.

Pro: Individualized Optimal Perfusion Pressure-Maximizing Patient Care During Cardiopulmonary Bypass.

Cardiopulmonary bypass (CPB) has revolutionized cardiac surgery but poses challenges such as hemodynamic instability and adverse clinical outcomes. Achieving optimal perfusion during CPB ensures adequate oxygen delivery to vital organs. Although mean arterial pressure is a key determinant of perfusion pressure, clear guidelines for optimal perfusion have yet to be established. Autoregulation, the organ's ability to maintain consistent blood flow, plays a vital role in perfusion. Individual variability in autoregulation responses and intraoperative factors necessitate an individualized approach to determining the autoregulation range. Continuous assessment of autoregulation during surgery allows for personalized perfusion targets, optimizing organ perfusion. Exploring techniques like multimodal intravenous anesthesia guided by electroencephalogram can enhance perfusion maintenance within the auto-regulatory range. By adopting an individualized approach to perfusion targets on CPB, we can improve outcomes and enhance patient care.

Dose-dependent relationship between intra-procedural hypoxaemia or hypocapnia and postoperative delirium in older patients.

BACKGROUND: Previous studies indicated an association between impaired cerebral perfusion and post-procedural neurological disorders. We investigated whether intra-procedural hypoxaemia or hypocapnia are associated with delirium after surgery. METHODS: Inpatients ≥60 yr of age undergoing anaesthesia for surgical or interventional procedures between 2009 and 2020 at an academic healthcare network in the USA (Massachusetts) were included in this hospital registry study. The primary exposure was intra-procedural hypoxaemia, defined as peripheral oxygen saturation <90% for >2 cohering min. The co-primary exposure was hypocapnia during general anaesthesia, defined as end-tidal carbon dioxide pressure ≤25 mm Hg for >5 cohering min. The primary outcome was delirium within 7 days after surgery. RESULTS: Of 71 717 included patients, 1702 (2.4%) developed postoperative delirium, and hypoxaemia was detected in 2532 (3.5%). Of 42 894 patients undergoing general anaesthesia, 532 (1.2%) experienced hypocapnia. The occurrence of either hypoxaemia (adjusted odds ratio [ORadj]=1.71; 95% confidence interval [CI], 1.40-2.07; P<0.001) or hypocapnia (ORadj=1.77; 95% CI, 1.30-2.41; P<0.001) was associated with a higher risk of delirium within 7 days. Both associations were dependent on the magnitude, and increased with event duration (ORadj=1.03; 95% CI, 1.02-1.04; P<0.001 and ORadj=1.01; 95% CI, 1.00-1.01; P=0.005, for each minute increase in the longest continuous episode, respectively). There was no association between occurrence of hypercapnia and postoperative delirium (ORadj=1.24; 95% CI, 0.90-1.71; P=0.181). CONCLUSIONS: Intra-procedural hypoxaemia and hypocapnia were dose-dependently associated with a higher risk of postoperative delirium. These findings support maintaining normal gas exchange to avoid postoperative neurological disorders.

Sedative polypharmacy mediates the effect of mechanical ventilation on delirium in critically ill COVID-19 patients: A retrospective cohort study.

BACKGROUND: Polypharmacy of sedatives (PP) is a potentially modifiable, iatrogenic risk factor for ICU delirium. The extent to which sedative PP influenced development of high rates of delirium among critically ill COVID-19 patients is unknown. We tested the hypothesis that PP, defined as the use of four or more classes of intravenous agents, is a mediator in the causal pathway of mechanical ventilation and delirium. METHODS: Retrospective cohort study of adults admitted with a primary diagnosis of RT-PCR+ for SARS-CoV2 to ICUs of a tertiary-level academic medical center between February 2020 and April 2021. Mediation analysis was conducted with bootstrap estimation to assess whether an association between mechanical ventilation and delirium was mediated by PP. Analyses were adjusted for potential confounders related to mechanical ventilation, mediator, and outcome, including age, gender, vasopressor use, median RASS scores, SOFA score within 24 h of admission, and maximum CRP levels. RESULTS: A total of 212 patients were included in the analysis. Of total patients, 72.6%(154/212) of patients had delirium (CAM-ICU+) during ICU stay. 54.7%(116/212) patients received PP. Mechanical ventilation (OR 3.81 [1.16-12.52]) and PP (OR 7.38 [2.4-22.68]) were identified as risk factors for development of ICU delirium after adjusting for prespecified confounders. PP acts as a mediator in the causal pathway between mechanical ventilation and delirium. 39% (95% CI: 17%-94%) of the effect of mechanical ventilation on delirium was mediated through PP. CONCLUSION: PP mediates approximately 39% of the effect of mechanical ventilation on delirium, which is clinically and statistically significant. Studies should assess whether mitigating PP could lead to reduction in ICU delirium. IMPLICATION STATEMENT: PP of sedatives (defined as use of four or more intravenous agents) mediates approximately 39% of the effect of mechanical ventilation on development of ICU delirium. Avoidance of sedative PP may represent a viable strategy for reduction of ICU delirium.

Anesthetics to Prevent Lung Injury in Cardiac Surgery: A Randomized Controlled Trial.

OBJECTIVES: To investigate if sevoflurane based anesthesia is superior to propofol in preventing lung inflammation and preventing postoperative pulmonary complications. DESIGN: Randomized controlled trial. SETTING: Single tertiary care university hospital. PARTICIPANTS: Forty adults undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Patients were randomized in a 1:1 ratio to anesthetic maintenance with sevoflurane or propofol. MEASUREMENTS AND MAIN RESULTS: Blood and bronchoalveolar lavage fluid was sampled before and after bypass to measure pulmonary inflammation using a biomarker panel. The change in bronchoalveolar lavage concentration of tumor necrosis factor alpha (TNFα) was the primary outcome. Secondary outcomes included lung inflammation defined as changes in other biomarkers and postoperative pulmonary complications. There were no significant differences between groups in the change in bronchoalveolar lavage TNFα concentration (median [IQR] change, 17.24 [1.11-536.77] v 101.51 [1.47-402.84] pg/mL, sevoflurane v propofol, p = 0.31). There was a significantly lower postbypass concentration of plasma interleukin 8 (median [IQR], 53.92 [34.5-55.91] v 66.92 [53.03-94.44] pg/mL, p = 0.04) and a significantly smaller postbypass increase in the plasma receptor for advanced glycosylation end products (median [IQR], 174.59 [73.59-446.06] v 548.22 [193.15-852.39] pg/mL, p = 0.03) in the sevoflurane group compared with propofol. The incidence of postoperative pulmonary complications was 100% in both groups, with high rates of pleural effusion (17/18 [94.44%] v 19/22 [86.36%], p = 0.39) and hypoxemia (16/18 [88.88%] v 22/22 [100%], p = 0.11). CONCLUSIONS: Sevoflurane anesthesia during cardiac surgery did not consistently prevent lung inflammation or prevent postoperative pulmonary complications compared to propofol. There were significantly lower levels of 2 plasma biomarkers specific for lung injury and inflammation in the sevoflurane group.

Preoperative Treatment of Severe Diabetes Mellitus and Hypertension Mitigates Healthcare Disparities and Prevents Adverse Postoperative Discharge to a Nursing Home.

OBJECTIVE: To evaluate whether patients of Black race are at higher risk of adverse postoperative discharge to a nursing home, and if a higher prevalence of severe diabetes mellitus and hypertension are contributing. BACKGROUND: It is unclear whether a patient's race predicts adverse discharge to a nursing home after surgery, and if preexisting diseases are contributing. METHODS: A total of 368,360 adults undergoing surgery between 2007 and 2020 across 2 academic healthcare networks in New England were included. Patients of self-identified Black or White race were compared. The primary outcome was postoperative discharge to a nursing facility. Mediation analysis was used to examine the impact of preexisting severe diabetes mellitus and hypertension on the primary association. RESULTS: In all, 10.3% (38,010/368,360) of patients were Black and 26,434 (7.2%) patients were discharged to a nursing home. Black patients were at increased risk of postoperative discharge to a nursing facility (adjusted absolute risk difference: 1.9%; 95% confidence interval: 1.6%-2.2%; P <0.001). A higher prevalence of preexisting severe diabetes mellitus and hypertension in Black patients mediated 30.2% and 15.6% of this association. Preoperative medication-based treatment adherent to guidelines in patients with severe diabetes mellitus or hypertension mitigated the primary association ( P -for-interaction <0.001). The same pattern of effect mitigation by pharmacotherapy was observed for the endpoint 30-day readmission. CONCLUSIONS: Black race was associated with postoperative discharge to a nursing facility compared to White race. Optimized preoperative assessment and treatment of diabetes mellitus and hypertension improves surgical outcomes and provides an opportunity to the surgeon to help eliminate healthcare disparities.

Postoperative pulmonary complications with adjuvant regional anesthesia versus general anesthesia alone: a sub-analysis of the Perioperative Research Network study.

BACKGROUND: Adjuvant regional anesthesia is often selected for patients or procedures with high risk of pulmonary complications after general anesthesia. The benefit of adjuvant regional anesthesia to reduce postoperative pulmonary complications remains uncertain. In a prospective observational multicenter study, patients scheduled for non-cardiothoracic surgery with at least one postoperative pulmonary complication surprisingly received adjuvant regional anesthesia more frequently than those with no complications. We hypothesized that, after adjusting for surgical and patient complexity variables, the incidence of postoperative pulmonary complications would not be associated with adjuvant regional anesthesia. METHODS: We performed a secondary analysis of a prospective observational multicenter study including 1202 American Society of Anesthesiologists physical status 3 patients undergoing non-cardiothoracic surgery. Patients were classified as receiving either adjuvant regional anesthesia or general anesthesia alone. Predefined pulmonary complications within the first seven postoperative days were prospectively identified. Groups were compared using bivariable and multivariable hierarchical logistic regression analyses for the outcome of at least one postoperative pulmonary complication. RESULTS: Adjuvant regional anesthesia was performed in 266 (22.1%) patients and not performed in 936 (77.9%). The incidence of postoperative pulmonary complications was greater in patients receiving adjuvant regional anesthesia (42.1%) than in patients without it (30.9%) (site adjusted p = 0.007), but this association was not confirmed after adjusting for covariates (adjusted OR 1.37; 95% CI, 0.83-2.25; p = 0.165). CONCLUSION: After adjusting for surgical and patient complexity, adjuvant regional anesthesia versus general anesthesia alone was not associated with a greater incidence of postoperative pulmonary complications in this multicenter cohort of non-cardiothoracic surgery patients.

Twelve-Month Cognitive and Functional Outcomes Following Cardiac Surgery: The DEXACET Trial of Intravenous Acetaminophen Versus Placebo.

Background: Delirium, an acute decline in attention and global cognitive dysfunction, occurs frequently following cardiac surgery and has been demonstrated to be significantly associated with cognitive dysfunction and reduced functional ability. In the DEXACET trial, we demonstrated a significant reduction in postoperative in-hospital delirium with intravenous (IV) acetaminophen when compared with placebo. In this analysis we examined whether this protective association also extended to 12 month cognitive and functional outcomes. Methods: This study was a prospective, randomized, placebo-controlled, triple-blinded, factorial design trial conducted at Beth Israel Deaconess Medical Center, approved by the IRB. In this trial, 120 older cardiac surgical patients were randomly assigned to receive either intravenous (IV) acetaminophen or placebo in addition to propofol or dexmedetomidine. Those receiving IV acetaminophen displayed a significant reduction in in-hospital delirium. We collected cognitive, mood and functional outcome data using the Montreal Cognitive Assessment, telephone version (T-MoCA), Geriatric Depression Scale (GDS) and the Basic and Instrumental Activities of Daily Living (ADLs, IADLs) at 1 month and 12 months after surgery. Results: Of the 120 enrolled patients in the primary trial, 93 (77.5%) and 83 (69.2%) patients responded to assessments at 1 month and 12 months, respectively. No statistically significant differences in median T-MoCA scores were observed between acetaminophen and placebo groups at 1 month (18.0 vs.18.0, p = 0.52) or 12 months (19.0 vs.18.0, p = 0.62) following surgery. There were similarly no differences in GDS, ADLs or IADLs between treatment groups. Losses to follow-up limited the sample sizes and 10 of the 23 (45%) original study participants who had postoperative delirium were lost to follow up. Conclusion: Administration of intravenous acetaminophen was not associated with a difference in long term cognitive or functional status following cardiac surgery. Additional research on long-term outcomes following postoperative delirium with a larger sample size and improved cohort retention strategies will be needed to address this important area.

Intraoperative Hypotension and Acute Kidney Injury, Stroke, and Mortality during and outside Cardiopulmonary Bypass: A Retrospective Observational Cohort Study.

BACKGROUND: In cardiac surgery, the association between hypotension during specific intraoperative phases or vasopressor-inotropes with adverse outcomes remains unclear. This study's hypothesis was that intraoperative hypotension duration throughout the surgery or when separated into hypotension during and outside cardiopulmonary bypass may be associated with postoperative major adverse events. METHODS: This retrospective observational cohort study included data for adults who had cardiac surgery between 2008 and 2016 in a tertiary hospital. Intraoperative hypotension was defined as mean arterial pressure of less than 65 mmHg. The total duration of hypotension was divided into three categories based on the fraction of overall hypotension duration that occurred during cardiopulmonary bypass (more than 80%, 80 to 60%, and less than 60%). The primary outcome was a composite of stroke, acute kidney injury, or mortality during the index hospitalization. The association with the composite outcome was evaluated for duration of hypotension during the entire surgery, outside cardiopulmonary bypass, and during cardiopulmonary bypass and the fraction of hypotension during cardiopulmonary bypass adjusting for vasopressor-inotrope dose, milrinone dose, patient, and surgical factors. RESULTS: The composite outcome occurred in 256 (5.1%) of 4,984 included patient records; 66 (1.3%) patients suffered stroke, 125 (2.5%) had acute kidney injury, and 109 (2.2%) died. The primary outcome was associated with total duration of hypotension (adjusted odds ratio, 1.05; 95% CI, 1.02 to 1.08; P = 0.032), hypotension outside cardiopulmonary bypass (adjusted odds ratio, 1.06; 95% CI, 1.03 to 1.10; P = 0.001) per 10-min exposure to mean arterial pressure of less than 65 mmHg, and fraction of hypotension duration during cardiopulmonary bypass of less than 60% (reference greater than 80%; adjusted odds ratio, 1.67; 95% CI, 1.10 to 2.60; P = 0.019) but not with each 10-min period hypotension during cardiopulmonary bypass (adjusted odds ratio, 1.04; 95% CI, 0.99 to 1.09; P = 0.118), fraction of hypotension during cardiopulmonary bypass of 60 to 80% (adjusted odds ratio, 1.45; 95% CI, 0.97 to 2.23; P = 0.082), or total vasopressor-inotrope dose (adjusted odds ratio, 1.00; 95% CI, 1.00 to 1.00; P = 0.247). CONCLUSIONS: This study confirms previous single-center findings that intraoperative hypotension throughout cardiac surgery is associated with an increased risk of acute kidney injury, mortality, or stroke.

Association Between Intraoperative Arterial Hypotension and Postoperative Delirium After Noncardiac Surgery: A Retrospective Multicenter Cohort Study.

BACKGROUND: It is unclear whether intraoperative arterial hypotension is associated with postoperative delirium. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with increased odds of delirium after surgery. METHODS: Adult noncardiac surgical patients undergoing general anesthesia at 2 academic medical centers between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as the cumulative duration of an intraoperative mean arterial pressure (MAP) <55 mm Hg, categorized into and short (<15 minutes; median [interquartile range {IQR}], 2 [1-4] minutes) and prolonged (≥15 minutes; median [IQR], 21 [17-31] minutes) durations of intraoperative hypotension. The primary outcome was a new diagnosis of delirium within 30 days after surgery. In secondary analyses, we assessed the association between a MAP decrease of >30% from baseline and postoperative delirium. Multivariable logistic regression adjusted for patient- and procedure-related factors, including demographics, comorbidities, and markers of procedural severity, was used. RESULTS: Among 316,717 included surgical patients, 2183 (0.7%) were diagnosed with delirium within 30 days after surgery; 41.7% and 2.6% of patients had a MAP <55 mm Hg for a short and a prolonged duration, respectively. A MAP <55 mm Hg was associated with postoperative delirium compared to no hypotension (short duration of MAP <55 mm Hg: adjusted odds ratio [ORadj], 1.22; 95% confidence interval [CI], 1.11-1.33; P < .001 and prolonged duration of MAP <55 mm Hg: ORadj, 1.57; 95% CI, 1.27-1.94; P < .001). Compared to a short duration of a MAP <55 mm Hg, a prolonged duration of a MAP <55 mm Hg was associated with greater odds of postoperative delirium (ORadj, 1.29; 95% CI, 1.05-1.58; P = .016). The association between intraoperative hypotension and postoperative delirium was duration-dependent (ORadj for every 10 cumulative minutes of MAP <55 mm Hg: 1.06; 95% CI, 1.02-1.09; P =.001) and magnified in patients who underwent surgeries of longer duration (P for interaction = .046; MAP <55 mm Hg versus no MAP <55 mm Hg in patients undergoing surgery of >3 hours: ORadj, 1.40; 95% CI, 1.23-1.61; P < .001). A MAP decrease of >30% from baseline was not associated with postoperative delirium compared to no hypotension, also when additionally adjusted for the cumulative duration of a MAP <55 mm Hg (short duration of MAP decrease >30%: ORadj, 1.13; 95% CI, 0.91-1.40; P = .262 and prolonged duration of MAP decrease >30%: ORadj, 1.19; 95% CI, 0.95-1.49; P = .141). CONCLUSIONS: In patients undergoing noncardiac surgery, a MAP <55 mm Hg was associated with a duration-dependent increase in odds of postoperative delirium. This association was magnified in patients who underwent surgery of long duration.

Perioperative Multimodal General Anesthesia Focusing on Specific CNS Targets in Patients Undergoing Cardiac Surgeries: The Pathfinder Feasibility Trial.

Multimodal general anesthesia (MMGA) is a strategy that utilizes the well-known neuroanatomy and neurophysiology of nociception and arousal control in designing a rational and clinical practical paradigm to regulate the levels of unconsciousness and antinociception during general anesthesia while mitigating side effects of any individual anesthetic. We sought to test the feasibility of implementing MMGA for seniors undergoing cardiac surgery, a high-risk cohort for hemodynamic instability, delirium, and post-operative cognitive dysfunction. Twenty patients aged 60 or older undergoing on-pump coronary artery bypass graft (CABG) surgery or combined CABG/valve surgeries were enrolled in this non-randomized prospective observational feasibility trial, wherein we developed MMGA specifically for cardiac surgeries. Antinociception was achieved by a combination of intravenous remifentanil, ketamine, dexmedetomidine, and magnesium together with bupivacaine administered as a pecto-intercostal fascial block. Unconsciousness was achieved by using electroencephalogram (EEG)-guided administration of propofol along with the sedative effects of the antinociceptive agents. EEG-guided MMGA anesthesia was safe and feasible for cardiac surgeries, and exploratory analyses found hemodynamic stability and vasopressor usage comparable to a previously collected cohort. Intraoperative EEG suppression events and postoperative delirium were found to be rare. We report successful use of a total intravenous anesthesia (TIVA)-based MMGA strategy for cardiac surgery and establish safety and feasibility for studying MMGA in a full clinical trial. Clinical Trial Number: www.clinicaltrials.gov; identifier NCT04016740 (https://clinicaltrials.gov/ct2/show/NCT04016740).

Neurofilament light: a narrative review on biomarker utility.

Neurofilament light (NfL) is a scaffolding protein that is located primarily within myelinated axons and that provides increased conduction speed and structural support. In recent years, NfL has been used as a disease biomarker on the basis of the observation that axonal injury results in elevated levels of NfL in cerebrospinal fluid or blood. This review focuses on how cerebrospinal fluid and plasma NfL have been studied in various disorders such as Alzheimer's disease (AD) and multiple sclerosis (MS) in relation to neuroinflammation and cognitive dysfunction. Focusing on the role of NfL as a biomarker for AD and MS, this review aims to further explore the potential of NfL as a promising biomarker with regard to surgery- and anesthesia-based incidents for postoperative cognitive decline and delirium. A search of the PubMed database yielded 36 articles, 31 of which are from within the last 3 years, that show how NfL has been observed and studied under various types of trials and disease cohorts and potential future directions. Higher levels of NfL have frequently been correlated with disease progression and prognosis of AD and MS, and delirium has been found to share a neuroinflammatory pathophysiology that NfL could help to measure. Focusing on NfL as a biomarker for neurodegenerative decline, these studies indicate that the protein could be further tested and related to postoperative aspects that result in cognitive dysfunction, and it has the potential to be an established delirium biomarker, particularly in the realm of the perioperative course.

Impact of frailty in cardiac surgical patients-Assessment, burden, and recommendations.

Elderly patients undergoing cardiac surgery are at an increased risk of adverse postoperative outcomes. Frailty, a state of decreased physiological reserve, is highly prevalent among elderly patients. Despite being associated with adverse surgical outcomes, no universally accepted definition or measurement tool for frailty exists. Moreover, regardless of all the recommendations, a routine perioperative frailty assessment is often ignored. In addition to complications, frailty increases the burden to the healthcare system, which is of particular concern in Southeast Asia due to its socioeconomically disadvantaged and resource limited settings. This narrative review focuses to develop clinical practice plans for perioperative frailty assessment in the context of a cardiac surgical setting.

Scheduled Prophylactic 6-Hourly IV AcetaminopheN to Prevent Postoperative Delirium in Older CaRdiac SurgicAl Patients (PANDORA): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Postoperative delirium is common among older cardiac surgery patients. Often difficult to predict and address prophylactically, delirium complicates the postoperative course by increasing morbidity and mortality as well as prolonging both hospital and intensive care unit (ICU) lengths of stay. Based on our pilot trial, we intend to study the effect of scheduled 6-hourly acetaminophen administration for 48 hours post-cardiac surgery with cardiopulmonary bypass (CPB) on the incidence of in-hospital delirium and long-term neurocognitive outcomes. Additionally, effect on duration and severity of delirium, rescue analgesic consumption, acute and chronic pain scores and lengths of hospital and ICU stay will also be explored. METHODS AND ANALYSIS: This multicentre, randomised, placebo-controlled, quadruple-blinded trial will include 900 older (>60 years) cardiac surgical patients requiring CPB. Patients meeting the inclusion criteria and not meeting any exclusion criteria will be enrolled at seven centres across the USA with Beth Israel Deaconess Medical Center (BIDMC), Boston, as the central coordinating centre. Additional sites may be included to broaden or speed accrual. The primary outcome measure is the incidence of in-hospital delirium till day 30. Secondary outcomes include the duration and severity of in-hospital delirium, hospital and ICU lengths of stay, postoperative pain scores, postoperative rescue analgesic consumption, postoperative cognitive function and chronic sternal pain. Creation of a biorepository and the use of intraoperative-blinded electroencephalogram (EEG) and cerebral oximetry data will support exploratory endpoints to determine mechanistic predictors of postoperative delirium. ETHICS AND DISSEMINATION: This trial is approved and centrally facilitated by the Institutional Review Board at BIDMC. An independent Data Safety and Monitoring Board is responsible for maintaining safety oversight. Protocol # 2019 P00075, V.1.4 (dated 20 October 2020). TRIAL REGISTRATION NUMBER: NCT04093219.

Ultrasound-Guided Pecto-Intercostal Fascial Block for Postoperative Pain Management in Cardiac Surgery: A Prospective, Randomized, Placebo-Controlled Trial.

OBJECTIVE: To explore the effect of pecto-intercostal fascial plane block (PIFB) on postoperative opioid requirements, pain scores, lengths of intensive care unit and hospital stays and incidence of postoperative delirium in cardiac surgical patients. DESIGN: Single- center, prospective, randomized (1:1), quadruple- blinded, placebo-controlled trial. SETTING: Single center, tertiary- care center. PARTICIPANTS: The study comprised 80 adult cardiac surgical patients (age >18 y) requiring median sternotomy. INTERVENTION: Patients were randomly assigned to receive ultrasound-guided PIFB, with either 0.25% bupivacaine or placebo, on postoperative days 0 and 1. MEASUREMENTS AND MAIN RESULTS: Of the 80 patients randomized, the mean age was 65.78 ± 8.73 in the bupivacaine group and 65.70 ± 9.86 in the placebo group (p = 0.573). Patients receiving PIFB with 0.25% bupivacaine showed a statistically significant reduction in visual analog scale scores (4.8 ± 2.7 v 5.1 ± 2.6; p < 0.001), but the 48-hour cumulative opioid requirement computed as morphine milligram equivalents was similar (40.8 ± 22.4 mg v 49.1 ± 26.9 mg; p = 0.14). There was no difference in the incidence of postoperative delirium between the groups evaluated using the 3-minute diagnostic Confusion Assessment Method (3/40 [7.5%] v 5/40 [12.5%] placebo; p = 0.45). CONCLUSION: Patients who received PIFB with bupivacaine showed a decline in cumulative opioid consumption postoperatively, but this difference between the groups was not statistically significant. Low incidence of complications and improvement in visual analog scale pain scores suggested that the PIFB can be performed safely in this population and warrants additional studies with a larger sample size.

Machine Learning Models with Preoperative Risk Factors and Intraoperative Hypotension Parameters Predict Mortality After Cardiac Surgery.

OBJECTIVES: Machine learning models used to predict postoperative mortality rarely include intraoperative factors. Several intraoperative factors like hypotension (IOH), vasopressor-inotropes, and cardiopulmonary bypass (CPB) time are significantly associated with postoperative outcomes. The authors explored the ability of machine learning models incorporating intraoperative risk factors to predict mortality after cardiac surgery. DESIGN: Retrospective study. SETTING: Tertiary hospital. PARTICIPANTS: A total of 5,015 adults who underwent cardiac surgery from 2008 to 2016. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The intraoperative phase was divided into the following: (1) CPB, (2) outside CPB, and (3) total surgery for quantifying IOH only. Phase-specific IOH parameters (area under the curve for mean arterial pressure <65 mmHg), vasopressor-inotropes (norepinephrine equivalents), duration, and cross-clamp time, along with preoperative risk factors ,were incorporated into the models. The primary outcome was mortality. The following 5 models were applied to 3 intraoperative phases separately: (1) logistic regression, (2) random forests, (3) neural networks, (4) support vector machines, and (5) extreme gradient boosting (XGB). Mortality was predicted using area under the receiver operating characteristic curve. Of 5,015 patients included, 112 (2.2%) died. XGB model from the outside-CPB phase predicted mortality better with area under the receiver operating characteristic curve, 95% confidence interval (CI): 0.88(0.83-0.94); positive predictive value, 0.10(0.06-0.15); specificity 0.85 (0.83-0.87) and sensitivity 0.75 (0.57-0.90). CONCLUSION: XGB machine learning model from IOH outside the CPB phase seemed to offer a better discrimination, sensitivity, specificity, and positive predictive value compared with other models. Machine learning models incorporating intraoperative adverse factors might offer better predictive ability for risk stratification and triaging of patients after cardiac surgery.

Intraoperative Oxygen Concentration and Neurocognition after Cardiac Surgery.

BACKGROUND: Despite evidence suggesting detrimental effects of perioperative hyperoxia, hyperoxygenation remains commonplace in cardiac surgery. Hyperoxygenation may increase oxidative damage and neuronal injury leading to potential differences in postoperative neurocognition. Therefore, this study tested the primary hypothesis that intraoperative normoxia, as compared to hyperoxia, reduces postoperative cognitive dysfunction in older patients having cardiac surgery. METHODS: A randomized double-blind trial was conducted in patients aged 65 yr or older having coronary artery bypass graft surgery with cardiopulmonary bypass. A total of 100 patients were randomized to one of two intraoperative oxygen delivery strategies. Normoxic patients (n = 50) received a minimum fraction of inspired oxygen of 0.35 to maintain a Pao2 above 70 mmHg before and after cardiopulmonary bypass and between 100 and 150 mmHg during cardiopulmonary bypass. Hyperoxic patients (n = 50) received a fraction of inspired oxygen of 1.0 throughout surgery, irrespective of Pao2 levels. The primary outcome was neurocognitive function measured on postoperative day 2 using the Telephonic Montreal Cognitive Assessment. Secondary outcomes included neurocognitive function at 1, 3, and 6 months, as well as postoperative delirium, mortality, and durations of mechanical ventilation, intensive care unit stay, and hospital stay. RESULTS: The median age was 71 yr (interquartile range, 68 to 75), and the median baseline neurocognitive score was 17 (16 to 19). The median intraoperative Pao2 was 309 (285 to 352) mmHg in the hyperoxia group and 153 (133 to 168) mmHg in the normoxia group (P < 0.001). The median Telephonic Montreal Cognitive Assessment score on postoperative day 2 was 18 (16 to 20) in the hyperoxia group and 18 (14 to 20) in the normoxia group (P = 0.42). Neurocognitive function at 1, 3, and 6 months, as well as secondary outcomes, were not statistically different between groups. CONCLUSIONS: In this randomized controlled trial, intraoperative normoxia did not reduce postoperative cognitive dysfunction when compared to intraoperative hyperoxia in older patients having cardiac surgery. Although the optimal intraoperative oxygenation strategy remains uncertain, the results indicate that intraoperative hyperoxia does not worsen postoperative cognition after cardiac surgery.

Association Between Intraoperative Hypotension and Postoperative Adverse Outcomes in Patients Undergoing Vascular Surgery - A Retrospective Observational Study.

OBJECTIVE: Intraoperative hypotension (IOH) is associated with adverse outcomes. It could be challenging to define IOH in vascular surgical patients with increased baseline blood pressure (BP). The authors studied the relationship between (1) absolute and relative BP thresholds of IOH, (2) preoperative pulse pressure (PP) and isolated systolic hypertension, and (3) endovascular versus open surgical approach with adverse outcomes in vascular surgical patients. DESIGN: Retrospective observational study. SETTING: Teaching hospital. PATIENTS: A total of 566 vascular surgical patients from 2011 to 2018. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: BP thresholds were as follows: IOH - absolute mean arterial pressure (MAP) <65 mmHg, relative MAP >20% decrease from baseline, preoperative PP hypertension - PP >40 mmHg, isolated systolic hypertension - baseline systolic BP ≥140 mmHg with diastolic BP <90 mmHg. Thresholds were characterized by (1) total duration and (2) area under the curve. Primary outcome was a composite of postoperative in-hospital complications (acute kidney injury, stroke, myocardial infarction, congestive heart failure, and mortality). Forty-six (8.1%) patients had in-hospital complications. Only IOH duration-MAP <65 mmHg (odds ratio 1.01; 95% confidence interval 1.00-1.02; p = 0.004) was significantly associated with outcome. No associations were found with MAP >20% decrease from baseline and preoperative BP. Significant interaction was observed with the surgical approach and outcome (p = 0.031), which was stronger after 60 minutes of IOH in endovascular approach. CONCLUSION: Longer periods of IOH (MAP <65 mmHg for >60 minutes) during endovascular surgery were associated with adverse outcomes. Relative fall in BP from baseline, preoperative isolated systolic, and PP hypertension were not associated with postoperative complications.