Background: Acute kidney injury (AKI) is a common and serious complication after noncardiac surgery. While levosimendan has shown renal protective effects in cardiac surgery patients, its impact in non-cardiac surgery – especially among patients with cardiovascular risk factors – remains unknown. Therefore, in this secondary analysis, we evaluated the effect of perioperative levosimendan administration on the incidence of postoperative AKI. We further assessed its impact on perioperative maximum creatinine concentration, estimated glomerular filtration rate (eGFR), and perioperative body composition parameters. Methods: We included all 228 patients from the main trial. Among these, 115 patients were assigned to receive a single dose of levosimendan, while113 patients were allocated to the placebo group. Blood samples and body composition parameters were assessed preoperatively, within one hour after surgery, and on the first, second, third and fifth postoperative day. Results: The incidence of postoperative AKI (p=0.485) did not differ significantly; also, the logistic regression model showed no significant treatment effect between the groups (OR 1.348, 95% CI 0.466 to 4.086; p=0.584). Maximum creatinine concentrations (effect estimate: 0.04 mg.dL-1, 95% CI -0.07 to 0.15; p=0.481), eGFR (effect estimate -1.01mL.min-1.BSA, 95% CI -6.98 to 4.97; p=0.743), and postoperative overhydration were also similar between the groups. Conclusion: Unlike findings in cardiac surgery patients, perioperative levosimendan administration did not provide renal protection in high-risk cardiovascular patients undergoing major noncardiac surgery.

[This corrects the article DOI: 10.1016/j.cjco.2025.04.008.].

Volatile anesthetics modulate inflammatory responses, but it remains unclear whether desflurane and sevoflurane differ in their effects on postoperative inflammation. We evaluated in this secondary analysis of a prospective randomized trial, the effect of desflurane versus sevoflurane anesthesia on postoperative inflammatory biomarkers in older adults undergoing minor- to moderate-risk noncardiac surgery. We included all 190 patients who were enrolled in the main trial in this analysis. We administered desflurane or sevoflurane, aiming for a BIS value of 50 ± 5. C-reactive protein, Interleukin-6, and Procalcitonin concentrations were measured preoperatively, within one hour after surgery, and on the second postoperative day. We observed no significant difference in maximum postoperative Interleukin-6 (8.11 pg ml- 1 [IQR 4.77; 15.7] versus 7.84 pg ml- 1 [IQR 4.67; 12.62]) (p = 0.357), C-Reactive Protein (0.32 mg dl- 1 [IQR 0.13; 0.9] versus 0.26 mg dl- 1 [IQR 0.13; 0.83] (p = 0.433), and Procalcitonin (0.04 ng ml- 1 [IQR 0.03; 0.07] versus 0.04 ng ml- 1 [IQR 0.03; 0.06]) (p = 0.709) between desflurane and sevoflurane anesthesia. We did not find a significant difference in the concentration of postoperative inflammatory biomarkers. While prior studies indicated different effects on inflammation between different types of volatile anesthetics, we cannot observe this in our study. Our findings indicate that in this specific clinical setting, the choice between sevoflurane or desflurane for minor- to moderate-risk noncardiac surgery does not significantly affect the minor postoperative inflammatory response in older patients when volatile anesthetics at low MAC concentrations are administered.

Background: Post-induction hypotension in major non-cardiac surgery is common and a modifiable risk factor for adverse outcomes. There is an ongoing debate whether pre-operative crystalloid fluid administration can reduce the incidence or severity of post-induction hypotension. This study aims to assess whether a pre-operative intravenous crystalloid bolus reduces post-induction hypotension in high-risk patients under general anesthesia. Methods: This was a prospective, randomized, single-blind clinical trial conducted at two centers in Austria (Medical University of Graz, Medical University of Vienna). Adult patients aged 45 years and older with cardiovascular risk factors undergoing major surgery were enrolled and randomly assigned to receive a pre-operative crystalloid bolus within 60 ± 15 minutes before anesthetic induction, or to receive standard care. The primary outcome was the time-weighted average mean arterial pressure of <65 mmHg within the first 20 minutes after induction or until surgical incision. Results: Of the 504 patients analyzed (247 in the intervention group and 257 in the control group), no statistically significant difference in median time-weighted average of the mean arterial pressure <65 mmHg was observed (Intervention group: 0.0 mmHg (IQR 0.0-0.56); Standard of Care group: 0.0 mmHg (IQR 0.0-0.84, p=0.368). Conclusions: In this blinded randomized clinical trial, administering a crystalloid fluid bolus within 60 minutes before surgery did not significantly reduce the time-weighted average of a mean arterial pressure less than 65 mmHg compared to standard care in patients with cardiovascular risk factors undergoing major non-cardiac surgery. Our study suggests that administering crystalloids before surgery does not prevent post-induction hypotension.

BACKGROUND:Perioperative hemodynamic abnormalities have been associated with neurocognitive outcomes after noncardiac surgery. OBJECTIVE:To compare the effects of perioperative hypotension-avoidance versus hypertension-avoidance strategies on delirium and 1-year cognitive decline after noncardiac surgery. DESIGN:Randomized controlled trial. (ClinicalTrials.gov: NCT03505723). SETTING:54 centers, 19 countries. PARTICIPANTS:2603 high-vascular-risk patients undergoing noncardiac surgery, receiving 1 or more chronic antihypertensive medications (mean age, 70 years). INTERVENTION:In the hypotension-avoidance strategy, the intraoperative mean arterial pressure (MAP) target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld, and other chronic antihypertensive medications were administered for systolic blood pressures of 130 mm Hg or greater following an algorithm. In the hypertension-avoidance strategy, the intraoperative MAP target was 60 mm Hg or greater; all chronic antihypertensive medications were continued perioperatively. MEASUREMENTS:Delirium on postoperative day 1 to 3 (primary outcome); decline of 2 points or more at the Montreal Cognitive Assessment (MoCA) 1 year after surgery compared with baseline (secondary outcome). RESULTS:95 of 1310 patients (7.3%) in the hypotension-avoidance and 90 of 1293 patients (7.0%) in the hypertension-avoidance group had delirium (relative risk [RR], 1.04 [95% CI, 0.79 to 1.38]). Among 701 patients who completed 1-year MoCA (full or telephone version), 129 of 347 (37.2%) in the hypotension-avoidance and 117 of 354 (33.1%) in the hypertension-avoidance group had a decline of 2 or more points (RR, 1.13 [CI, 0.92 to 1.38]). Nineteen percent in the hypotension-avoidance and 27% in the hypertension-avoidance strategy had hypotension requiring an intervention (RR, 0.63 [CI, 0.52 to 0.76]), mostly intraoperatively; only 5%, in both groups, had hypotension postoperatively. LIMITATION:The COVID-19 pandemic challenged site participation in the substudy; although large, the sample size was lower than expected. CONCLUSION:There was no evidence of a difference in neurocognitive outcomes between the hypotension-avoidance and hypertension-avoidance strategies. PRIMARY FUNDING SOURCE:Canadian Institutes of Health Research, Canada; National Health and Medical Research Council, Australia; Research Grant Council, Hong Kong SAR, China.

The effect of Levosimendan on postoperative natriuretic peptides in noncardiac surgical patients remains unknown. Thus, this study evaluates the effect of a perioperative levosimendan administration on postoperative N-terminal brain pro natriuretic peptide (NT-proBNP) concentrations. In this prospective, double-blinded, parallel group, placebo-controlled, phase III trial 115 patients were assigned to perioperative single-dose of 12.5 mg of levosimendan and 115 to placebo between October 2020 through November 2023 (clinicaltrials.gov: NCT04329624). The primary outcome was postoperative maximum NT-proBNP concentration within the first 3 postoperative days. 228 patients completed the trial. Postoperative maximum NT-proBNP concentrations did not differ significantly between the groups (effect estimate: -64.51 ng.L-1; 95% CI -332.66 to 195.56; p = 0.61). Here, we show that perioperative levosimendan administration did not lead to a significantly lower release in postoperative NT-proBNP after noncardiac surgery.

Background:To determine, among patients who underwent major noncardiac thoracic surgery, the association between smoking and perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS), and whether the effect of colchicine use on these outcomes varied by smoking status. Methods:This study is a subgroup analysis of the Colchicine for the Prevention of Perioperative Atrial Fibrillation (COP-AF) randomized clinical trial. A total of 3209 participants who underwent major noncardiac thoracic surgery were randomized to receive colchicine, 0.5 mg twice daily, or identical placebo, for 10 days starting 2-4 hours before surgery. The co-primary outcomes were clinically significant perioperative AF and MINS during the 14-day follow-up. Results:A total of 687 (21.4%) were current smokers, 1577 (49.1%) were former smokers, and 945 (29.5%) were never smokers. AF occurred in 7.7%, 7.6%, and 5.3%, and MINS occurred in 21.0%, 19.7%, and 17.6% of current, former, and never smokers, respectively. Compared to never smokers, the adjusted hazard ratio for AF was 1.72 (95% confidence interval [CI] 1.07-2.77, P = 0.02) in current smokers and 1.46 (95% CI 0.99-2.16, P = 0.06) in former smokers, and the adjusted hazard ratio for MINS was 1.16 (95% CI 0.87-1.54, P = 0.32) in current smokers and 1.02 (95% CI 0.81-1.28, P = 0.88) in former smokers. No interaction occurred between smoking status and colchicine allocation for AF (interaction P, 0.82) or MINS (interaction P, 0.08). Conclusions:Current smoking was associated with a small but increased risk of perioperative AF but not MINS after thoracic surgery. The effect of colchicine use on either outcome was not modified by smoking status. Clinical Trial Registration:NCT03310125.

IntroductionThe effect of different anaesthetics on the incidence of postoperative delirium is still not entirely clear. Therefore, we will evaluate the effect of desflurane versus sevoflurane versus propofol for the maintenance of anaesthesia on the incidence of postoperative delirium in older adults undergoing moderate- to high-risk major non-cardiac surgery. We will further compare the incidences of delayed neurocognitive recovery, long-term postoperative neurocognitive disorder, postoperative nausea and vomiting between the groups.Methods and analysisIn this multicentre, prospective, observer-blinded, randomised controlled clinical trial, we will include 1332 patients ≥65 years of age undergoing moderate- to high-risk major non-cardiac surgery lasting at least 2 hours. Patients will be randomly 1:1:1 assigned to receive desflurane, sevoflurane or propofol for anaesthesia. Maintenance of anaesthesia will be performed in a goal-directed manner using processed electroencephalography with an intraoperative goal of bispectral index 40–60. Our primary outcome will be the incidence of postoperative delirium within the first five postoperative days. Postoperative delirium will be assessed using the three-dimensional-confusion assessment method (3D-CAM) or CAM-intensive care unit (ICU) in the morning and evening of the first five postoperative days by blinded study personnel. The primary outcome, the incidence of postoperative delirium, will be compared between the three study groups using a χ2test. Furthermore, a logistic regression model for the incidence of postoperative delirium will be performed, accounting for randomised groups as well as other predefined confounding factors.Ethics and disseminationThis clinical trial has been approved by the ethics committee and the Federal Office for Safety in Healthcare as the competent authority for clinical trials in Austria. The results of this trial will be published in a peer-reviewed journal.Trial registration numberClinicalTrials.govNCT05990790.

Background/Objectives: Previous preclinical studies have shown that desflurane might have the most significant cardioprotective effect of all volatile anesthetics. However, data regarding the cardioprotective effects of desflurane versus sevoflurane are lacking. Therefore, we evaluated the effect of the maintenance of anesthesia using desflurane versus sevoflurane on the postoperative maximum concentrations of cardiac biomarkers in older adults undergoing low- to moderate-risk noncardiac surgery. Methods: In this secondary analysis of a prospective randomized trial, we included all 190 older adults undergoing low- to moderate-risk noncardiac surgery. Patients were randomized to receive desflurane or sevoflurane for the maintenance of anesthesia. We administered desflurane or sevoflurane, aiming at a BIS value of 50 ± 5. The cardiac-specific biomarkers included troponin T, NT-proBNP, and copeptin, which were measured preoperatively, within one hour after surgery, and on the second postoperative day. Results: There were no significant differences between the desflurane and sevoflurane groups in the postoperative maximum concentrations of troponin T (11 ng.L−1 [8; 16] versus 13 ng.L−1 [9; 18]; p = 0.595), NT-proBNP (196 pg.mL−1 [90; 686] versus 253 pg.mL−1 [134; 499]; p = 0.288), or copeptin (19 pmol.L−1 [7; 58] versus 12 pmol.L−1 [6; 41]; p = 0.096). We also observed no significant differences in the troponin T, NT-proBNP, or copeptin concentrations between the desflurane and sevoflurane groups at any measured timepoint (all p > 0.05). Conclusions: In contrast to preclinical studies, we did not observe a significant difference in the postoperative maximum concentrations of cardiac biomarkers. It seems likely that desflurane does not exert significant clinical meaningful cardioprotective effects in older adults. Thus, our results do not support the use of desflurane in patients undergoing low- to moderate-risk noncardiac surgery.

Abstract Background Pulmonary function is impaired after major abdominal surgery and might be less impaired by restrictive fluid administration. Under the assumption of a fluid-sparing effect of colloids, we tested the hypothesis that an intraoperative colloid-based goal-directed fluid management strategy impairs postoperative pulmonary function parameters less compared to goal-directed crystalloid administration. Methods We performed a preplanned, single-center substudy within a recently published trial evaluating the effect of goal-directed crystalloids versus colloids on a composite of major complications. Sixty patients undergoing major open abdominal surgery were randomized to Doppler-guided intraoperative fluid replacement therapy with lactated Ringer’s solution (n = 31) or unbalanced 6% hydroxyethyl starch 130/0.4 (n = 29). A blinded investigator performed bedside spirometry (Spirobank-G, Medical International Research, Rome, Italy) preoperatively as well as 6, 24, and 48 h postoperatively. Results Median total intraoperative fluid requirements were significantly higher during crystalloid administration compared to patients receiving colloids (4567 ml vs. 3044 ml, p = 0.01). Six hours after surgery, pulmonary function parameters did not differ significantly between the crystalloid — and the colloid group: forced vital capacity (FVC): 1.6 l (1.2–2 l) vs. 1.9 l (1.5–2.4 l), p = 0.15; forced expiratory volume in 1 second (FEV1): 1.1 l (0.9–1.6 l) vs. 1.4 l (1.2–1.7 l), p = 0.18; and peak expiratory flow (PEF): 2 l.sec−1 (1.5 – 3.6 l.sec −1) vs. 2.3 l.sec −1 (1.8 – 3.4 l.sec −1), p = 0.23. Moreover, postoperative longitudinal time × group interactions of FVC, FEV1, and PEF between 6 and 48 postoperative hours did not differ significantly. Conclusion Postoperative pulmonary function parameters were similarly impaired in patients receiving goal-directed crystalloid administration as compared to goal-directed colloid administration during open abdominal surgery. Trial registration ClinicalTrials.gov (NCT00517127, registered on August 16, 2007) and EudraCT (2005-004602-86).

Background: Postoperative elevated NT-proBNP concentrations are independently associated with cardiovascular complications and mortality after noncardiac surgery. Levosimendan significantly decreases the release of NT-proBNP, however, the effect in noncardiac surgical patients remains unknown. Thus, this study evaluates the effect of a perioperative levosimendan administration on postoperative maximum NT-proBNP. Methods: 230 cardiovascular risk patients undergoing moderate- to high-risk major noncardiac surgery were included in this prospective, double-blinded, parallel group, placebo-controlled, phase III trial, between October 2020 through November 2023. 115 patients were assigned to perioperative single-dose of 12.5mg starting with a rate of 0.2 mcg.kg-1.min-1 of levosimendan and 115 patients were assigned to placebo. The primary outcome was postoperative maximum NT-proBNP concentration within the first three postoperative days. Secondary outcomes were MINS and maximum troponin T concentrations within the first three postoperative days. Results: Among 230 patients, 228 patients completed the trial. There was no significant difference in postoperative maximum NT-proBNP concentrations between the groups (effect estimate: -82.99ng.L-1; 95% CI -321.08 to 190.96; p=0.48). The incidence of MINS (p=0.063) and postoperative maximum troponin T (effect estimate: 0.45, 95% CI-1.66 to 3.41; p=0.728) concentrations within the first three postoperative days did not differ significantly between the groups. Conclusions: Levosimendan administration did not lead to a significantly lower release in postoperative NT-proBNP in cardiovascular risk patients undergoing major noncardiac surgery. There was no significant difference in MINS and postoperative Troponin T concentrations. The role of pre-emptive levosimendan as prophylactic treatment option in cardiovascular high-risk patients must be verified in large-scale trials.

Study objective The effect of volatile anesthetics on postoperative recovery in older adults is still not entirely clear. Thus, we evaluated the effect of desflurane versus sevoflurane anesthesia on speed of postoperative recovery in older adults eligible for same-day discharge. We further evaluated the incidence of postoperative nausea and vomiting (PONV), bispectral index (BIS) values, and S100B concentrations. Design Single-center, prospective, observer-blinded, randomized clinical trial. Setting Operating room. Patients 190 patients ≥65 years of age and scheduled for minor- to moderate-risk noncardiac surgeries. Interventions Goal-directed administration of desflurane versus sevoflurane for maintenance of anesthesia with an intraoperative goal of BIS 50 ± 5. Measurements The primary outcome was the time to anesthesia recovery, which was defined as the time between arrival at the post-anesthesia care unit (PACU) and reaching criteria for discharge from PACU, based on modified Aldrete score ≥ 12 points. Modified Aldrete scores were assessed at PACU arrival and thereafter in five-minute intervals. PONV was evaluated during PACU stay and the first three postoperative days, BIS values were recorded during PACU stay, and S100B values were measured before and after surgery, and on the second postoperative day. Main results 95 patients were randomized to receive desflurane, and 95 patients to receive sevoflurane. We did not observe a significant difference in median duration of postoperative recovery between the groups (desflurane: 0 min [0;0]; sevoflurane: 0 min [0;0]; p = 0.245). 77 patients (81.1%) in the desflurane group and 84 patients (88.4%) in the sevoflurane group already had Aldrete scores ≥12 points upon arrival at PACU (p = 0.277). There was also no significant difference in the incidences of PONV (p = 0.606), postoperative BIS values (p = 0.197), and postoperative maximum S100B concentrations (p = 0.821) between the groups. Conclusions Despite previous reports, we did not observe significant faster recovery times after desflurane anesthesia. Both volatile anesthetics may be appropriate for same-day discharge in older adults.

Background: Inflammation during and after surgery can lead to organ damage including acute kidney injury. Colchicine, an established inexpensive anti-inflammatory medication, may help to protect the organs from pro-inflammatory damage. This protocol describes a kidney substudy of the colchicine for the prevention of perioperative atrial fibrillation (COP-AF) study, which is testing the effect of colchicine versus placebo on the risk of atrial fibrillation and myocardial injury among patients undergoing thoracic surgery. Objective: Our kidney substudy of COP-AF will determine whether colchicine reduces the risk of perioperative acute kidney injury compared with a placebo. We will also examine whether colchicine has a larger absolute benefit in patients with pre-existing chronic kidney disease, the most prominent risk factor for acute kidney injury. Design and Setting: Randomized, superiority clinical trial conducted in 40 centers in 11 countries from 2018 to 2023. Patients: Patients (~3200) aged 55 years and older having major thoracic surgery. Intervention: Patients are randomized 1:1 to receive oral colchicine (0.5 mg tablet) or a matching placebo, given twice daily starting 2 to 4 hours before surgery for a total of 10 days. Patients, health care providers, data collectors, and outcome adjudicators will be blinded to the randomized treatment allocation. Methods: Serum creatinine concentrations will be measured before surgery and on postoperative days 1, 2, and 3 (or until hospital discharge). The primary outcome of the substudy is perioperative acute kidney injury, defined as an increase (from the prerandomization value) in serum creatinine concentration of either ≥26.5 μmol/L (≥0.3 mg/dL) within 48 hours of surgery or ≥50% within 7 days of surgery. The primary analysis (intention-to-treat) will examine the relative risk of acute kidney injury in patients allocated to receive colchicine versus placebo. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by pre-existing chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m 2 . Limitations: The substudy will be underpowered to detect small effects on more severe forms of acute kidney injury treated with dialysis. Results: Substudy results will be reported in 2024. Conclusions: This substudy will estimate the effect of colchicine on the risk of perioperative acute kidney injury in older adults undergoing major thoracic surgery. Clinical trial registration number: NCT03310125

BackgroundIn relatively healthy middle-aged patients, recent studies have shown that supplemental oxygen did not significantly increase one-year mortality after noncardiac surgery. If supplemental oxygen influences long-term mortality, specifically in elderly patients with cardiovascular risk-factors, remains unknown. Thus, we evaluated the effect of supplemental oxygen on two-year mortality in patients with cardiovascular risk factors undergoing moderate- to high-risk major abdominal surgery.MethodsThis is a follow-up study of a prospective, randomized, double-blinded, clinical trial. Two hundred fifty-eight patients, who were at least 45 years of age and at-risk for cardiovascular complications were randomly assigned to receive 80 vs. 30% oxygen during surgery and for the first two postoperative hours. Vital status was obtained from all patients 2 years after surgery using the national registry. Preoperative and postoperative maximum concentrations of NT-proBNP, Troponin T (TnT), Copeptin, von Willebrand Factor (vWF), static oxidation-reduction potential (sORP) and oxidation-reduction potential capacity (cORP) were tested for association with two-year mortality.ResultsThe median age of patients was 74 years (25th-75th percentile 70–78 years). 25.8% (95% CI: 17.3–32.4%) of patients in the 80% oxygen group and 22.3% (95% CI: 14.8–29.1%) in the 30% oxygen group died within 2 years after surgery. No significant difference in two-year mortality was found between patients, who received 80% oxygen concentration, versus patients, who received 30% oxygen concentration (estimated hazard ratio 1.145; 95% CI 0.693–1.893; p = 0.597). Preoperative Copeptin concentrations and postoperative maximum vWF activity were significantly associated with two-year mortality (p < 0.001).ConclusionOur results are consistent with previous studies, that showed that supplemental oxygen did not increase long-term mortality. Therefore, it is becoming more evident that supplemental oxygen may not have a significant effect on long-term outcome in patients undergoing major abdominal surgery.

IntroductionIncreased inflammatory processes after non-cardiac surgery are very common. The association between postoperative inflammation and the occurrence of cardiovascular complications after non-cardiac surgery are still not entirely clear. Therefore, we will evaluate the association between postoperative inflammation and the occurrence of major cardiovascular complications in patients at-risk for cardiovascular complications undergoing non-cardiac surgery. We will further evaluate the association of postoperative inflammation and days-at-home within 30 days after surgery (DAH30), the incidence of acute kidney injury, postoperative N-terminal probrain natriuretic peptide (NT-proBNP) concentrations and neurocognitive decline.Methods and analysisIn this multicentre study, we will include 1400 patients at-risk for cardiovascular complications undergoing non-cardiac surgery. Our primary aim is to evaluate the association of postoperative maximum C-reactive protein concentration and the occurrence of a composite of five major cardiovascular complications (myocardial infarction, myocardial injury after non-cardiac surgery, new onset of atrial fibrillation, stroke and death) within 30 days after surgery using a Mann-Whitney-U test as well as a logistic regression model. As our secondary aim, we will evaluate the association of a composite of three inflammatory biomarkers (interleukin 6, procalcitonin and copeptin) on the occurrence of our composite of five cardiovascular complications within 30 days and 1 year after surgery, acute kidney injury, DAH30and NT-proBNP concentrations using linear or logistic regression models. We will measure inflammatory biomarkers before surgery, and on the first, second, third and fifth postoperative day. We will check medical records and conduct a telephone survey 30 days and 1 year after surgery. We evaluate neurocognitive function, using a Montreal Cognitive Assessment, before and 1 year after surgery.Ethics and disseminationThis study was approved by the ethics committees at the Medical University of Vienna (2458/2020) and at the Medical University of Graz (33-274 ex 20/21).Trial registration numberNCT04753307.

Increased von Willebrand Factor (vWF) activity mediates platelet adhesion and might be a contributor to the development of thrombotic complications after surgery. Although in vitro studies have shown that hyperoxia induces endovascular damage, the effect of perioperative supplemental oxygen as a possible trigger for increased vWF activity has not been investigated yet. We tested our primary hypothesis that the perioperative administration of 80% oxygen concentration increases postoperative vWF activity as compared to 30% oxygen concentration in patients at risk of cardiovascular complications undergoing major noncardiac surgery. A total of 260 patients were randomly assigned to receive 80% versus 30% oxygen throughout surgery and for two hours postoperatively. We assessed vWF activity and Ristocetin cofactor activity in all patients shortly before the induction of anesthesia, within two hours after surgery and on the first and third postoperative day. Patient characteristics were similar in both groups. We found no significant difference in vWF activity in the overall perioperative time course between both randomization groups. We observed significantly increased vWF activity in the overall study population throughout the postoperative time course. Perioperative supplemental oxygen showed no significant effect on postoperative vWF and Ristocetin cofactor activity in cardiac risk patients undergoing major noncardiac surgery. In conclusion, we found no significant influence of supplemental oxygen in patients undergoing major non-cardiac surgery on postoperative vWF activity and Ristocetin cofactor activity.

Background Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications.Methods COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0 center dot 5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125.Findings Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51 center dot 6%] male). Clinically important atrial fibrillation occurred in 103 (6 center dot 4%) of 1608 patients assigned to colchicine, and 120 (7 center dot 5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0 center dot 85, 95% CI 0 center dot 65 to 1 center dot 10; absolute risk reduction [ARR] 1 center dot 1%, 95% CI -0 center dot 7 to 2 center dot 8; p=0 center dot 22). MINS occurred in 295 (18 center dot 3%) patients assigned to colchicine and 325 (20 center dot 3%) patients assigned to placebo (HR 0 center dot 89, 0 center dot 76 to 1 center dot 05; ARR 2 center dot 0%, -0 center dot 8 to 4 center dot 7; p=0 center dot 16). The composite outcome of sepsis or infection occurred in 103 (6 center dot 4%) patients in the colchicine group and 83 (5 center dot 2%) patients in the placebo group (HR 1 center dot 24, 0 center dot 93-1 center dot 66). Non-infectious diarrhoea was more common in the colchicine group (134 [8 center dot 3%] events) than the placebo group (38 [2 center dot 4%]; HR 3 center dot 64, 2 center dot 54-5 center dot 22).Interpretation In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea.Funding Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.Copyright (c) 2023 Elsevier Ltd. All rights reserved.

Background: Supplemental oxygen leads to an increase in peripheral vascular resistance which finally increases systemic blood pressure in healthy subjects and patients with coronary artery disease, heart failure, undergoing heart surgery, and with sepsis. However, it is unknown whether this effect can also be observed in anesthetized patients having surgery. Thus, we evaluated in this exploratory analysis of a randomized controlled trial the effect of 80% versus 30% oxygen on intraoperative blood pressure and heart rate.Methods: We present data from a previous study including 258 patients, who were randomized to a perioperative inspiratory FiO(2) of 0.8 (128 patients) versus 0.3 (130 patients) for major abdominal surgery. Continuous arterial blood pressure values were recorded every three seconds and were exported from the electronic anesthesia record system. We calculated time-weighted average (TWA) and Average Real Variability (ARV) of mean arterial blood pressure and of heart rate.Results: There was no significant difference in TWA of mean arterial pressure between the 80% (80 mmHg [76, 85]) and 30% (81 mmHg [77, 86]) oxygen group (effect estimate -0.16 mmHg, CI -1.83 to 1.51; p = 0.85). There was also no significant difference in TWA of heart rate between the 80 and 30% oxygen group (median TWA of heart rate in the 80% oxygen group: 65 beats.min(-1) [58, 72], and in the 30% oxygen group: 64 beats.min(-1) [58; 70]; effect estimate: 0.12 beats.min(-)1, CI -2.55 to 2.8, p = 0.94). Also for ARV values, no significant differences between groups could be detected.Conclusion: In contrast to previous results, we did not observe a significant increase in blood pressure or a significant decrease in heart rate in patients, who received 80% oxygen as compared to patients, who received 30% oxygen during surgery and for the first two postoperative hours. Thus, hemodynamic effects of supplemental oxygen might play a negligible role in anesthetized patients.