Efficacy and safety of intraoperative controlled hypotension: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Intraoperative controlled hypotension improves surgical field visibility by reducing blood loss (efficacy) but poses potential risks linked to organ hypoperfusion (safety). The use of controlled hypotension persists despite increasing evidence of associations between intraoperative inadvertent hypotension and adverse outcomes. Therefore, we tested the hypothesis that the focus and results of intraoperative controlled hypertension research differ across anaesthesia and surgery investigators because of differing priorities. METHODS: We systematically reviewed randomised trials comparing controlled hypotension with usual care with trials categorised by investigators' affiliation. RESULTS: We identified 48 eligible trials, of which 37 were conducted by anaesthesia investigators and 11 by surgery investigators. For the primary outcome, 54% of the anaesthesia-led trials focused on safety, whereas all (100%) surgery-led trials focused on efficacy (P=0.004). Compared with usual care, mean arterial pressure in controlled hypotension was 23% (95% confidence interval [CI] 17-29%) lower in anaesthesia trials and 30% (95% CI 14-37%) lower in surgery trials; estimated blood loss was 44% (95% CI 30-55%) less in anaesthesia trials and 38% (95% CI 30-49%) less in surgery trials. Overall, blood loss was reduced by 43% (95% CI 32-53%), and trial sequential analysis supported an efficacy conclusion. Mean arterial pressure and estimated blood loss reductions were associated (R2=0.41, P=0.002). All trials were underpowered for safety outcomes, and none adequately evaluated myocardial or renal injury. CONCLUSIONS: Anaesthesia researchers prioritised safety outcomes, whereas surgery researchers emphasised efficacy in controlled hypotension trials. Controlled hypotension significantly reduces blood loss. In contrast, safety outcomes were poorly studied. Given increasing observational evidence linking inadvertent hypotension to myocardial and renal injury, the safety of controlled hypotension remains to be addressed. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023450397).

Perioperative Transfusion Practices in Adults Having Noncardiac Surgery.

Surgical patients are often transfused to manage bleeding and anemia. Best practices for red blood cell (RBC) transfusion administration in patient having noncardiac surgery remains controversial and a robust evaluation and description of perioperative transfusion practices is lacking. We characterized perioperative hemoglobin concentrations and transfusion practices from the prospective VISION cohort which included 39,222 patients aged ≥45 years who had inpatient noncardiac surgery. Variations in transfusion practices were analyzed using hierarchical mixed models, and associations with mortality and complications were evaluated using a nested frailty survival model. Within the cohort, 16.1% (n = 6296) were given perioperative RBC transfusions, with the fraction declining from 20% to 13% over the 6-year study period. The proportion of patients transfused varied by surgery type from 6.4% for low-risk operations (i.e., minor surgery) to 31.5% for orthopedic surgeries. Variations were largely associated with patient hemoglobin concentrations, but also with center (range: 3.7%-27.3%) and country (0.4%-25.3%). Even after adjusting for baseline hemoglobin, comorbidities and type of surgery, both center and country were significant sources of variation in transfusion practices. Among transfused participants, 60.4% (n = 3728/6170) had at least 1 hemoglobin concentration ≤80g/L and 86.0% (n = 5305/6170) had at least 1 hemoglobin concentration ≤90g/L, suggesting that relatively restrictive transfusion strategies were used in most. The proportion of patients receiving at least 1 RBC transfusion declined from 20% to 13% over 6 years. However, there was considerable unexplained variation in transfusion practices.

The relative merits of using a high-sensitivity cardiac Troponin T assay compared to a nonhigh-sensitivity troponin T assay after noncardiac surgery.

INTRODUCTION: Troponin elevation after noncardiac surgery is associated with an elevated risk of 30-day mortality. Little is known about relative merit of using a high-sensitivity Troponin T (hsTnT), the fifth-generation assay, vs the nonhigh sensitivity Troponin T (non-hsTnT), the fourth-generation assay, in the noncardiac surgery setting. We aimed to identify whether hsTnT can identify additional patients at risk that would have gone undetected with non-hsTnT measurement. METHODS: The VISION Study included 40,004 noncardiac surgery patients with postoperative troponin measurements. Among them, 1,806 patients had both fourth-generation non-hsTnT and fifth-generation hsTnT concomitant measurements (4,451 paired results). We compared the absolute concentrations, the timing, and the impact of different thresholds on predicting 30-day major cardiovascular complications (composite of death, nonfatal cardiac arrest, coronary revascularization, and congestive heart failure). RESULTS: Based on the manufacturers' threshold of 14 ng/L, 580 (32.1%) patients had postoperative hsTnT concentrations greater than the threshold, while their non-hsTnT concentrations were below the manufacturer's threshold. These 580 patients had higher risk of major cardiovascular events (OR 2.33; CI 95% 1.04-5.23; P = .049) than patients with hsTnT concentrations below the manufacturer threshold. Among patients with myocardial injury after noncardiac surgery, only 50% would be detected by the fourth-generation non-hsTnT assay at 6 to 12 hours postoperative as compared to 85% with the fifth-generation hsTnT assay (P-value < .001). CONCLUSIONS: Within the first 3 postoperative days, fifth-generation hsTnT identified at least 1 in 3 patients with troponin elevation that would have gone undetected by fourth-generation non-hsTnT using published thresholds in this setting. Furthermore, fifth-generation hsTnT identified patients with an elevation earlier than fourth-generation non-hsTnT, indicating potential to improve postoperative risk stratification.

Risk Factors for Hospital Readmission Following Noncardiac Surgery: International Cohort Study.

Objective: To determine timing and risk factors associated with readmission within 30 days of discharge following noncardiac surgery. Background: Hospital readmission after noncardiac surgery is costly. Data on the drivers of readmission have largely been derived from single-center studies focused on a single surgical procedure with uncertainty regarding generalizability. Methods: We undertook an international (28 centers, 14 countries) prospective cohort study of a representative sample of adults ≥45 years of age who underwent noncardiac surgery. Risk factors for readmission were assessed using Cox regression (ClinicalTrials.gov, NCT00512109). Results: Of 36,657 eligible participants, 2744 (7.5%; 95% confidence interval [CI], 7.2-7.8) were readmitted within 30 days of discharge. Rates of readmission were highest in the first 7 days after discharge and declined over the follow-up period. Multivariable analyses demonstrated that 9 baseline characteristics (eg, cancer treatment in past 6 months; adjusted hazard ratio [HR], 1.44; 95% CI, 1.30-1.59), 5 baseline laboratory and physical measures (eg, estimated glomerular filtration rate or on dialysis; HR, 1.47; 95% CI, 1.24-1.75), 7 surgery types (eg, general surgery; HR, 1.86; 95% CI, 1.61-2.16), 5 index hospitalization events (eg, stroke; HR, 2.21; 95% CI, 1.24-3.94), and 3 other factors (eg, discharge to nursing home; HR, 1.61; 95% CI, 1.33-1.95) were associated with readmission. Conclusions: Readmission following noncardiac surgery is common (1 in 13 patients). We identified perioperative risk factors associated with 30-day readmission that can help frontline clinicians identify which patients are at the highest risk of readmission and target them for preventive measures.

PeriOperative Quality Initiative (POQI) international consensus statement on perioperative arterial pressure management.

Arterial pressure monitoring and management are mainstays of haemodynamic therapy in patients having surgery. This article presents updated consensus statements and recommendations on perioperative arterial pressure management developed during the 11th POQI PeriOperative Quality Initiative (POQI) consensus conference held in London, UK, on June 4-6, 2023, which included a diverse group of international experts. Based on a modified Delphi approach, we recommend keeping intraoperative mean arterial pressure ≥60 mm Hg in at-risk patients. We further recommend increasing mean arterial pressure targets when venous or compartment pressures are elevated and treating hypotension based on presumed underlying causes. When intraoperative hypertension is treated, we recommend doing so carefully to avoid hypotension. Clinicians should consider continuous intraoperative arterial pressure monitoring as it can help reduce the severity and duration of hypotension compared to intermittent arterial pressure monitoring. Postoperative hypotension is often unrecognised and might be more important than intraoperative hypotension because it is often prolonged and untreated. Future research should focus on identifying patient-specific and organ-specific hypotension harm thresholds and optimal treatment strategies for intraoperative hypotension including choice of vasopressors. Research is also needed to guide monitoring and management strategies for recognising, preventing, and treating postoperative hypotension.

Association between hydroxyethyl starch 130/0.4 administration during noncardiac surgery and postoperative acute kidney injury: A propensity score-matched analysis of a large cohort in China.

STUDY OBJECTIVE: The use of hydroxyethyl starch 130/0.4 has been linked to renal injury in critically ill patients, but its impact on surgical patients remains uncertain. DESIGN: A retrospective cohort study. SETTING: This study was conducted at one tertiary care hospital in China. PATIENTS: We evaluated the records of 51,926 Chinese adults who underwent noncardiac surgery from 2013 to 2022. Patients given a combination of hydroxyethyl starch 130/0.4 and crystalloids were propensity-matched at a 1: 1 ratio of baseline characteristics to patients given only crystalloids (11,725 pairs). INTERVENTIONS: Eligible patients were divided into those given a combination of hydroxyethyl starch 130/0.4 and crystalloid during surgery and a reference crystalloid group consisting of patients who were not given any colloid. MEASUREMENTS: The primary outcome was the incidence of acute kidney injury. Secondarily, acute kidney injury stage, need for renal replacement therapy, intensive care unit transfer rate, and duration of postoperative hospitalization were considered. MAIN RESULTS: After matching, hydroxyethyl starch use [8.5 (IQR: 7.5-10.0) mL/kg] did not increase the incidence of acute kidney injury compared with that in the crystalloid group [2.0 vs. 2.2%, OR: 0.90 (0.74-1.08), P = 0.25]. Nor did hydroxyethyl starch use worsen acute kidney injury stage [OR 0.90 (0.75-1.08), P = 0.26]. No significant differences between the fluid groups were observed in renal replacement therapy [OR 0.60 (0.41-0.90), P = 0.02)] or intensive care unit transfers [OR 1.02 (0.95-1.09), P = 0.53] after Bonferroni correction. Even in a subset of patients at high risk of renal injury, hydroxyethyl starch use was not associated with worse outcomes. CONCLUSIONS: Hydroxyethyl starch 130/0.4 use was not significantly associated with a greater incidence of postoperative acute kidney injury compared to receiving crystalloid solutions only.

How three linked clinical observations led to an understanding of perioperative heat balance: A personal reflection on the scientific process.

Three linked clinical observations prompted our current understanding of perioperative heat balance. The first was the extraordinarily rapid decrease in core temperature after induction of general anesthesia which led to an understanding of redistribution hypothermia. The second was the linear reduction in core temperature during the subsequent 2-3 h which led to an understanding of anesthetic effects on metabolic heat production and factors that influence cutaneous heat loss. And the third was the observation that core temperature reaches a plateau at about 34.5 °C which led to the understanding that thermoregulatory vasoconstriction re-emerges when patients become sufficiently hypothermic, and that arteri-venous shunt constriction constrains metabolic heat to the core thermal compartment.

Pressure injury treatment by intermittent electrical stimulation (PROTECT-2): protocol for a multicenter randomized clinical trial.

BACKGROUND: Pressure ulcers account for a substantial fraction of hospital-acquired pathology, with consequent morbidity and economic cost. Treatments are largely focused on preventing further injury, whereas interventions that facilitate healing remain limited. Intermittent electrical stimulation (IES) increases local blood flow and redistributes pressure from muscle-bone interfaces, thus potentially reducing ulcer progression and facilitating healing. METHODS: The Pressure Injury Treatment by Intermittent Electrical Stimulation (PROTECT-2) trial will be a parallel-arm multicenter randomized trial to test the hypothesis that IES combined with routine care reduces sacral and ischial pressure injury over time compared to routine care alone. We plan to enroll 548 patients across various centers. Hospitalized patients with stage 1 or stage 2 sacral or ischial pressure injuries will be randomized to IES and routine care or routine care alone. Wound stage will be followed until death, discharge, or the development of an exclusion criteria for up to 3 months. The primary endpoint will be pressure injury score measured over time. DISCUSSION: Sacral and ischial pressure injuries present a burden to hospitalized patients with both clinical and economic consequences. The PROTECT-2 trial will evaluate whether IES is an effective intervention and thus reduces progression of stage 1 and stage 2 sacral and ischial pressure injuries. TRIAL REGISTRATION: ClinicalTrials.gov NCT05085288 Registered October 20, 2021.

Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial.

BACKGROUND: It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. METHODS: In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery. RESULTS: We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis. CONCLUSIONS: Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications. CLINICAL TRIAL REGISTRATION: NCT03021525.

Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial.

OBJECTIVE: To determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression. DESIGN: Randomised, double blind, placebo controlled trial with two parallel arms. SETTING: Five tertiary care hospitals in China, 19 June 2020 to 3 August 2022. PARTICIPANTS: 364 mothers aged ≥18 years who had at least mild prenatal depression as indicated by Edinburgh postnatal depression scale scores of ≥10 (range 0-30, with higher scores indicating worse depression) and who were admitted to hospital for delivery. INTERVENTIONS: Participants were randomly assigned 1:1 to receive either 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth once the umbilical cord had been clamped. MAIN OUTCOME MEASURES: The primary outcome was prevalence of a major depressive episode at 42 days post partum, diagnosed using the mini-international neuropsychiatric interview. Secondary outcomes included the Edinburgh postnatal depression scale score at seven and 42 days post partum and the 17 item Hamilton depression rating scale score at 42 days post partum (range 0-52, with higher scores indicating worse depression). Adverse events were monitored until 24 hours after childbirth. RESULTS: A total of 364 mothers (mean age 31.8 (standard deviation 4.1) years) were enrolled and randomised. At 42 days post partum, a major depressive episode was observed in 6.7% (12/180) of participants in the esketamine group compared with 25.4% (46/181) in the placebo group (relative risk 0.26, 95% confidence interval (CI) 0.14 to 0.48; P<0.001). Edinburgh postnatal depression scale scores were lower in the esketamine group at seven days (median difference -3, 95% CI -4 to -2; P<0.001) and 42 days (-3, -4 to -2; P<0.001). Hamilton depression rating scale scores at 42 days post partum were also lower in the esketamine group (-4, -6 to -3; P<0.001). The overall incidence of neuropsychiatric adverse events was higher in the esketamine group (45.1% (82/182) v 22.0% (40/182); P<0.001); however, symptoms lasted less than a day and none required drug treatment. CONCLUSIONS: For mothers with prenatal depression, a single low dose of esketamine after childbirth decreases major depressive episodes at 42 days post partum by about three quarters. Neuropsychiatric symptoms were more frequent but transient and did not require drug intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04414943.

One-lung ventilation with fixed and variable tidal volumes on oxygenation and pulmonary outcomes: A randomized trial.

OBJECTIVE: Test the hypothesis that one-lung ventilation with variable tidal volume improves intraoperative oxygenation and reduces postoperative pulmonary complications after lung resection. BACKGROUND: Constant tidal volume and respiratory rate ventilation can lead to atelectasis. Animal and human ARDS studies indicate that oxygenation improves with variable tidal volumes. Since one-lung ventilation shares characteristics with ARDS, we tested the hypothesis that one-lung ventilation with variable tidal volume improves intraoperative oxygenation and reduces postoperative pulmonary complications after lung resection. DESIGN: Randomized trial. SETTING: Operating rooms and a post-anesthesia care unit. PATIENTS: Adults having elective open or video-assisted thoracoscopic lung resection surgery with general anesthesia were randomly assigned to intraoperative ventilation with fixed (n = 70) or with variable (n = 70) tidal volumes. INTERVENTIONS: Patients assigned to fixed ventilation had a tidal volume of 6 ml/kgPBW, whereas those assigned to variable ventilation had tidal volumes ranging from 6 ml/kg PBW ± 33% which varied randomly at 5-min intervals. MEASUREMENTS: The primary outcome was intraoperative oxygenation; secondary outcomes were postoperative pulmonary complications, mortality within 90 days of surgery, heart rate, and SpO2/FiO2 ratio. RESULTS: Data from 128 patients were analyzed with 65 assigned to fixed-tidal volume ventilation and 63 to variable-tidal volume ventilation. The time-weighted average PaO2 during one-lung ventilation was 176 (86) mmHg in patients ventilated with fixed-tidal volume and 147 (72) mmHg in the patients ventilated with variable-tidal volume, a difference that was statistically significant (p < 0.01) but less than our pre-defined clinically meaningful threshold of 50 mmHg. At least one composite complication occurred in 11 (17%) of patients ventilated with variable-tidal volume and in 17 (26%) of patients assigned to fixed-tidal volume ventilation, with a relative risk of 0.67 (95% CI 0.34-1.31, p = 0.24). Atelectasis in the ventilated lung was less common with variable-tidal volumes (4.7%) than fixed-tidal volumes (20%) in the initial three postoperative days, with a relative risk of 0.24 (95% CI 0.01-0.8, p = 0.02), but there were no significant late postoperative differences. No other secondary outcomes were both statistically significant and clinically meaningful. CONCLUSION: One-lung ventilation with variable tidal volume does not meaningfully improve intraoperative oxygenation, and does not reduce postoperative pulmonary complications.

Blood bupivacaine concentrations after pecto-serratus and serratus anterior plane injections of plain and liposomal bupivacaine in robotically-assisted mitral valve surgery: Sub-study of a randomized trial.

STUDY OBJECTIVE: To investigate the timing of peak blood concentrations and potential toxicity when using a combination of plain and liposomal bupivacaine for thoracic fascial plane blocks. DESIGN: Pharmacokinetic analysis. SETTING: Operating room. PATIENTS: Eighteen adult patients undergoing robotically-assisted mitral valve surgery. INTERVENTIONS: Ultrasound-guided pecto-serratus and serratus anterior plane blocks using a mixture of 0.5% bupivacaine HCl up to 2.5 mg/kg and liposomal bupivacaine up to 266 mg. MEASUREMENTS: Arterial plasma bupivacaine concentration. MAIN RESULTS: Samples from 13 participants were analyzed. There was substantial inter-patient variability in plasma concentrations. A geometric mean maximum bupivacaine concentration was 1492 ng/ml (range 660 to 4650 ng/ml) at median time of 30 min after injection. In 4/13 (31%) patients, plasma bupivacaine concentrations exceeded our predefined 2000 ng/ml toxic threshold. A second much smaller peak was observed about 32 h after the injection. No obvious signs of local anesthetic toxicity were observed. CONCLUSIONS: Combined injection of plain and liposomal bupivacaine for pecto-serratus/serratus anterior plane blocks produced a biphasic pattern, with the highest arterial plasma concentrations observed within 30 min. Maximum concentrations exceeded the potential toxic threshold in nearly a third of patients, but without clinical evidence of toxicity. Clinicians should not assume that routine combinations of plain and liposomal bupivacaine for thoracic fascial plane blocks are inherently safe.

Comparison of differences in cohort (forwards) and case control (backwards) methodological approaches for validation of the Hypotension Prediction Index.

BACKGROUND: The Hypotension Prediction Index (the index) software is a machine learning algorithm that detects physiological changes that may lead to hypotension. The original validation used a case control (backwards) analysis that has been suggested to be biased. We therefore conducted a cohort (forwards) analysis and compared this to the original validation technique. METHODS: We conducted a retrospective analysis of data from previously reported studies. All data were analysed identically with 2 different methodologies and receiver operating characteristic curves (ROC) constructed. Both backwards and forwards analyses were performed to examine differences in area under the ROC for HPI and other haemodynamic variables to predict a MAP < 65mmHg for at least 1 minute 5, 10 and 15 minutes in advance. RESULTS: Two thousand and twenty-two patients were included in the analysis, yielding 4,152,124 measurements taken at 20 second intervals. The area-under-the-curve for the index predicting hypotension analysed by backward and forward methodologies respectively was 0.957 (95% CI, 0.947-0.964) vs 0.923 (95% CI, 0.912-0.933) 5 minutes in advance, 0.933 (95% CI, 0.924-0.942) vs 0.923 (95% CI, 0.911-0.933) 10 minutes in advance , and 0.929 (95% CI, 0.918-0.938) vs. 0.926 (95% CI, 0.914-0.937) 15 minutes in advance. No other variable had an area-under-the-curve > 0.7 except for MAP. Area-under-the-curve using forward analysis for MAP predicting hypotension 5, 10, and 15 minutes in advance was 0.932 (95% CI, 0.920-0.940), 0.929 (95% CI, 0.918-0.938), and 0.932 (95% CI, 0.921-0.940). The R 2 for the variation in the index due to MAP was 0.77. CONCLUSION: Using an updated methodology, we found the utility of the HPI index to predict future hypotensive events is high, with an area under the receiver-operating-characteristics curve similar to that of the original validation method.

Incidence and Risk Factors of Chronic Postoperative Pain in Same-day Surgery: A Prospective Cohort Study.

BACKGROUND: The amount of same-day surgery has increased markedly worldwide in recent decades, but there remains limited evidence on chronic postsurgical pain in this setting. METHODS: This study assessed pain 90 days after ambulatory surgery in an international, multicenter prospective cohort study of patients at least 45 yr old with comorbidities or at least 65 yr old. Pain was assessed using the Brief Pain Inventory. Chronic postsurgical pain was defined as a change of more than 1 point in self-rated average pain at the surgical site between baseline and 90 days, and moderate to severe chronic postsurgical pain was defined as a score greater than 4 in self-rated average pain at the surgical site at 90 days. Risk factors for chronic postsurgical pain were identified using multivariable logistic regression. RESULTS: Between November 2021 and January 2023, a total of 2,054 participants were included, and chronic postsurgical pain occurred in 12% of participants, of whom 93.1% had new chronic pain at the surgical site (i.e., participants without pain before surgery). Moderate to severe chronic postsurgical pain occurred in 9% of overall participants. Factors associated with chronic postsurgical pain were active smoking (odds ratio, 1.82; 95% CI, 1.20 to 2.76), orthopedic surgery (odds ratio, 4.7; 95% CI, 2.24 to 9.7), plastic surgery (odds ratio, 4.3; 95% CI, 1.97 to 9.2), breast surgery (odds ratio, 2.74; 95% CI, 1.29 to 5.8), vascular surgery (odds ratio, 2.71; 95% CI, 1.09 to 6.7), and ethnicity (i.e., for Hispanic/Latino ethnicity, odds ratio, 3.41; 95% CI, 1.68 to 6.9 and for First Nations/native persons, odds ratio, 4.0; 95% CI, 1.05 to 15.4). CONCLUSIONS: Persistent postsurgical pain after same-day surgery is common, is usually moderate to severe in nature, and occurs mostly in patients without chronic pain before surgery.

Cognitive Training for Reduction of Delirium in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial.

IMPORTANCE: Postoperative delirium is a common and impactful neuropsychiatric complication in patients undergoing coronary artery bypass grafting surgery. Cognitive training may enhance cognitive reserve, thereby reducing postoperative delirium. OBJECTIVE: To determine whether preoperative cognitive training reduces the incidence of delirium in patients undergoing coronary artery bypass grafting. DESIGN, SETTING, and PARTICIPANTS: This prospective, single-blind, randomized clinical trial was conducted at 3 university teaching hospitals in southeastern China with enrollment between April 2022 and May 2023. Eligible participants included those scheduled for elective coronary artery bypass grafting who consented and enrolled at least 10 days before surgery. INTERVENTIONS: Participating patients were randomly assigned 1:1, stratified by site, to either routine care or cognitive training, which included substantial practice with online tasks designed to enhance cognitive functions including memory, imagination, reasoning, reaction time, attention, and processing speed. MAIN OUTCOMES AND MEASURES: The primary outcome was occurrence of delirium during postoperative days 1 to 7 or until hospital discharge, diagnosed using the Confusion Assessment Method or the Confusion Assessment Method for Intensive Care Units. Secondary outcomes were postoperative cognitive dysfunction, delirium characteristics, and all-cause mortality within 30 days following the operation. RESULTS: A total of 218 patients were randomized and 208 (median [IQR] age, 66 [58-70] years; 64 female [30.8%] and 144 male [69.2%]) were included in final analysis, with 102 randomized to cognitive training and 106 randomized to routine care. Of all participants, 95 (45.7%) had only a primary school education and 54 (26.0%) had finished high school. In the cognitive training group, 28 participants (27.5%) developed delirium compared with 46 participants (43.4%) randomized to routine care. Those receiving cognitive training were 57% less likely to develop delirium compared with those receiving routine care (adjusted odds ratio [aOR] 0.43; 95% CI, 0.23-0.77; P = .007). Significant differences were observed in the incidence of severe delirium (aOR, 0.46; 95% CI, 0.25-0.82; P = .01), median (IQR) duration of delirium (0 [0-1] days for cognitive training vs 0 [0-2] days for routine care; P = .008), and median (IQR) number of delirium-positive days (0 [0-1] days for cognitive training vs 0 [0-2] days for routine care; P = .007). No other secondary outcomes differed significantly. CONCLUSIONS AND RELEVANCE: In this randomized trial of 208 patients undergoing coronary artery bypass grafting, preoperative cognitive training reduced the incidence of postoperative delirium. However, our primary analysis was based on fewer than 75 events and should therefore be considered exploratory and a basis for future larger trials. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200058243.

Processed electroencephalography-guided general anesthesia and norepinephrine requirements: A randomized trial in patients having vascular surgery.

STUDY OBJECTIVE: Processed electroencephalography (pEEG) may help clinicians optimize depth of general anesthesia. Avoiding excessive depth of anesthesia may reduce intraoperative hypotension and the need for vasopressors. We tested the hypothesis that pEEG-guided - compared to non-pEEG-guided - general anesthesia reduces the amount of norepinephrine needed to keep intraoperative mean arterial pressure above 65 mmHg in patients having vascular surgery. DESIGN: Randomized controlled clinical trial. SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany. PATIENTS: 110 patients having vascular surgery. INTERVENTIONS: pEEG-guided general anesthesia. MEASUREMENTS: Our primary endpoint was the average norepinephrine infusion rate from the beginning of induction of anesthesia until the end of surgery. MAIN RESULT: 96 patients were analyzed. The mean ± standard deviation average norepinephrine infusion rate was 0.08 ± 0.04 µg kg-1 min-1 in patients assigned to pEEG-guided and 0.12 ± 0.09 µg kg-1 min-1 in patients assigned to non-pEEG-guided general anesthesia (mean difference 0.04 µg kg-1 min-1, 95% confidence interval 0.01 to 0.07 µg kg-1 min-1, p = 0.004). Patients assigned to pEEG-guided versus non-pEEG-guided general anesthesia, had a median time-weighted minimum alveolar concentration of 0.7 (0.6, 0.8) versus 0.8 (0.7, 0.8) (p = 0.006) and a median percentage of time Patient State Index was <25 of 12 (1, 41) % versus 23 (3, 49) % (p = 0.279). CONCLUSION: pEEG-guided - compared to non-pEEG-guided - general anesthesia reduced the amount of norepinephrine needed to keep mean arterial pressure above 65 mmHg by about a third in patients having vascular surgery. Whether reduced intraoperative norepinephrine requirements resulting from pEEG-guided general anesthesia translate into improved patient-centered outcomes remains to be determined in larger trials.