The effect of goal-directed crystalloid versus colloid administration on postoperative spirometry parameters: a substudy of a randomized controlled clinical trial.

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).

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

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 0·5 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 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). 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.

Effect of Colchicine on the Risk of Perioperative Acute Kidney Injury: Clinical Protocol of a Substudy of the Colchicine for the Prevention of Perioperative Atrial Fibrillation Randomized Clinical Trial.

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 m2. 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.

Contexte: L'inflammation pendant et après une intervention chirurgicale peut causer des lésions aux organes, notamment de l'insuffisance rénale aiguë (IRA). La colchicine, un médicament anti-inflammatoire reconnu et bon marché, peut contribuer à protéger les organes contre les lésions pro-inflammatoires. Le présent protocole décrit une sous-étude rénale de l'essai Colchicine for the Prevention of Perioperative atrial fibrillation (COP-AF), qui examine l'effet de la colchicine, par rapport à un placebo, sur le risque de fibrillation auriculaire et de lésion myocardique chez les patients qui subissent une chirurgie thoracique. Objectif: Notre sous-étude rénale de l'essai COP-AF permettra de vérifier si la colchicine réduit le risque d'IRA périopératoire par rapport à un placebo. Nous tenterons également de déterminer si la colchicine présente un plus grand bénéfice absolu pour les patients atteints d'une insuffisance rénale chronique préexistante, laquelle constitue le plus important facteur de risque pour l'IRA. Cadre et type d'étude: Essai clinique à répartition aléatoire visant à démontrer une supériorité. L'étude, qui s'étend de 2018 à 2023, est menée dans 40 centers situés dans 11 pays. Sujets: Des patients (~3200) âgés de 55 ans et plus subissant une chirurgie thoracique majeure. Interventions: Les patients sont répartis 1:1 de façon aléatoire pour recevoir de la colchicine par voie orale (comprimé de 0.5 mg), ou un placebo correspondant, deux fois par jour à partir de 2 à 4 heures avant l'intervention chirurgicale, pour un total de 10 jours. Les patients, les prestataires de soins de santé, les personnes qui collectent les données et celles qui évaluent les résultats ne seront pas informés de l'attribution du traitement. Méthodologie: Les concentrations sériques de créatinine seront mesurées avant l'intervention et aux jours postopératoires 1, 2, et 3 (ou jusqu'au congé de l'hôpital). Le principal critère d'évaluation de cette sous-étude est une IRA périopératoires définie par une hausse (par rapport à la valeur mesurée avant la répartition aléatoire) d'au moins 26.5 µmol/L (≥0.3 mg/dL) de la créatinine sérique dans les 48 heures suivant l'intervention ou d'au moins 50% dans les 7 jours suivants. L'analyze primaire (intention de traiter) examinera le risque relatif d'IRA chez les patients recevant de la colchicine par rapport au placebo. L'analyze primaire sera répétée en utilisant d'autres définitions de l'IRA et nous examinerons la modification de l'effet en présence d'une insuffisance rénale préexistante, définie par un débit de filtration glomérulaire estimé (DFGe) inférieur à 60 mL/min/1.73 m2 avant la répartition aléatoire. Limites: Cette sous-étude ne sera pas assez puissante pour détecter de petits effets sur les formes plus graves d'insuffisance rénale aiguë traitées par dialyze. Résultats: Les résultats de cette sous-étude feront l'objet d'un rapport en 2024. Conclusion: Cette sous-étude permettra d'estimer l'effet de la colchicine sur le risque d'insuffisance rénale aiguë périopératoire chez les adultes âgés qui subissent une chirurgie thoracique majeure. Numéro d'enregistrement de l'essai clinique: NCT03310125.

PerIoperative iNflammatory reSponse assessment In hiGH-risk patienTs undergoing non-cardiac surgery (INSIGHT): study protocol of a prospective non-interventional observational study.

INTRODUCTION: Increased 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 ANALYSIS: In 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, DAH30 and 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 DISSEMINATION: This 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 NUMBER: NCT04753307.

Hemodynamic effects of intraoperative 30% versus 80% oxygen concentrations: an exploratory analysis.

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 FiO2 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. Clinical Trail Registration: https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.

The Performance of Opioid-Free Anesthesia for Bariatric Surgery in Clinical Practice.

PURPOSE: Opioid-free anesthesia (OFA) is an alternative to conventional opioid-based anesthesia (OBA) in patients undergoing bariatric surgery. Several small studies and a meta-analysis have suggested advantages of OFA for bariatric surgery, but current evidence is still contradictory, and a universally accepted concept has not yet been established. The purpose of this study was to determine whether patients undergoing bariatric surgery experience less postoperative pain and better postoperative recovery when anesthetized with an OFA regimen than with an OBA regimen. MATERIALS AND METHODS: This prospective observational cohort study, conducted between October 2020 and July 2021, compared patients receiving OFA with patients receiving OBA. Patients were visited 24 and 48 h after the surgical procedure and asked about their postoperative pain using the visual analogue scale (VAS). Additionally, the quality of recovery-40 questionnaire (QoR-40) and the postoperative opioid requirements were recorded. RESULTS: Ninety-nine patients were included and analyzed in this study (OFA: N = 50; OBA: N = 49). The OFA cohort exhibited less postoperative pain than the OBA cohort within 24 h (VAS median [interquartile range (IQR)]: 2.2 [1-4.4] vs. 4.1 [2-6.5]; P ≤ 0.001) and 48 h (VAS median [IQR]: 1.9 [0.4-4.1] vs. 3.1 [1.4-5.8]; P ≤ 0.001) postoperatively. Additionally, the OFA cohort had higher QoR-40 scores and required less opioid therapy postoperatively. CONCLUSION: Based on our results the use of OFA for bariatric surgery results in less pain, reduced opioid requirements, and improved postoperative recovery-adding additional evidence regarding the use of OFA in everyday clinical practice.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

Effect of Supplemental Oxygen on von Willebrand Factor Activity and Ristocetin Cofactor Activity in Patients at Risk for Cardiovascular Complications Undergoing Moderate-to High-Risk Major Noncardiac Surgery-A Secondary Analysis of a Randomized Trial.

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.

Rationale and design of the colchicine for the prevention of perioperative atrial fibrillation in patients undergoing major noncardiac thoracic surgery (COP-AF) trial.

BACKGROUND: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023. CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.

Tranexamic Acid in Patients Undergoing Noncardiac Surgery.

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).

Perioperative Supplemental Oxygen and Postoperative Copeptin Concentrations in Cardiac-Risk Patients Undergoing Major Abdominal Surgery-A Secondary Analysis of a Randomized Clinical Trial.

Noncardiac surgery is associated with hemodynamic perturbations, fluid shifts and hypoxic events, causing stress responses. Copeptin is used to assess endogenous stress and predict myocardial injury. Myocardial injury is common after noncardiac surgery, and is often caused by myocardial oxygen demand-and-supply mismatch. In this secondary analysis, we included 173 patients at risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. Patients were randomly assigned to receive 80% or 30% oxygen throughout surgery and the first two postoperative hours. We evaluated the effect of supplemental oxygen on postoperative Copeptin concentrations. Copeptin concentrations were measured preoperatively, within two hours after surgery, on the first and third postoperative days. In total, 85 patients received 0.8 FiO2, and 88 patients received 0.3 FiO2. There was no significant difference in postoperative Copeptin concentrations between both study groups (p = 0.446). Copeptin increased significantly within two hours after surgery, compared with baseline in the overall study population (estimated effect: −241.7 pmol·L−1; 95% CI −264.4, −219.1; p < 0.001). Supplemental oxygen did not significantly attenuate postoperative Copeptin release. Copeptin concentrations showed a more immediate postoperative increase compared with previously established biomarkers. Nevertheless, Copeptin concentrations did not surpass Troponin T in early determination of patients at risk for developing myocardial injury after noncardiac surgery.

Perioperative Supplemental Oxygen and Plasma Catecholamine Concentrations after Major Abdominal Surgery-Secondary Analysis of a Randomized Clinical Trial.

Perioperative stress is associated with increased sympathetic activity that leads to increases in heart rate and blood pressure, which are associated with the development of perioperative myocardial ischemia. In healthy volunteers, it was shown that the administration of supplemental oxygen attenuated sympathetic nerve activity and subsequently led to lower plasma catecholamine concentrations. We therefore tested the hypothesis that perioperative supplemental oxygen attenuates sympathetic nerve in patients at risk for cardiovascular complications undergoing major abdominal surgery. We randomly assigned 81 patients to receive either 80% or 30% inspired oxygen concentration throughout surgery and the first two postoperative hours. We assessed noradrenaline, adrenaline, and dopamine plasma concentrations before the induction of anesthesia, two hours after surgery and on the third postoperative day. There was no significant difference in postoperative noradrenaline (effect estimated: -41.5 ng·L-1, 95%CI -134.3, 51.2; p = 0.38), adrenaline (effect estimated: 11.2 ng·L-1, 95%CI -7.6, 30.1; p = 0.24), and dopamine (effect estimated: -1.61 ng·L-1, 95%CI -7.2, 3.9; p = 0.57) concentrations between both groups. Based on our results, it seems unlikely that supplemental oxygen influences endogenous catecholamine release in the perioperative setting.

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery.

BACKGROUND: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. METHODS: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. DISCUSSION: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Effect of perioperative levosimendan administration on postoperative N-terminal pro-B-type natriuretic peptide concentration in patients with increased cardiovascular risk factors undergoing non-cardiac surgery: protocol for the double-blind, randomised, placebo-controlled IMPROVE trial.

INTRODUCTION: Elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) after non-cardiac surgery is a strong predictor for cardiovascular complications and reflects increased myocardial strain. NT-pro-BNP concentrations significantly rise after non-cardiac surgery within the first 3 days. Levosimendan is a potent inotropic drug that increases calcium sensitivity to cardiac myocytes, which results in improved cardiac contractility that last for approximately 7 days. Thus, we will test the effect of a pre-emptive perioperative administration of levosimendan on postoperative NT-pro-BNP concentration as compared with the administration of a placebo in patients undergoing moderate-risk to high-risk major abdominal surgery. METHODS AND ANALYSIS: We will conduct a double-blinded prospective randomised trial at the Medical University of Vienna, Vienna, Austria (and potentially a second centre in Germany), including 230 patients at-risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. Patients will be randomly assigned to receive a single dose of 12.5 mg levosimendan versus placebo after induction of anaesthesia. The primary outcome will be the postoperative maximum NT-pro-BNP concentration between both group within the first three postoperative days. Our secondary outcomes will be the incidence of myocardial ischaemia, myocardial injury after non-cardiac surgery and a composite of myocardial infarction and death within 30 days and 1 year after surgery between both groups. Our further secondary outcome will be stratification of NT-pro-BNP values according to previously thresholds to predict mortality of myocardial infarction after surgery. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the Medical University of Vienna on 14 July 2020 (EK 2187/2019). Written informed consent will be obtained from all patients a day before surgery. Results of this study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04329624.

Effect of liver resection-induced increases in hepatic venous pressure gradient on development of postoperative acute kidney injury.

BACKGROUND: The impact of changes in portal pressure before and after liver resection (defined as ΔHVPG) on postoperative kidney function remains unknown. Therefore, we investigated the effect of ΔHVPG on (i) the incidence of postoperative AKI and (ii) the renin-angiotensin system (RAAS) and sympathetic nervous system (SNS) activity. METHODS: We included 30 patients undergoing partial liver resection. Our primary outcome was postoperative AKI according to KDIGO criteria. For our secondary outcome we assessed the plasma renin, aldosterone, noradrenaline, adrenaline, dopamine and vasopressin concentrations prior and 2 h after induction of anaesthesia, on the first and fifth postoperative day. HVPG was measured prior and immediately after liver resection. RESULTS: ΔHVPG could be measured in 21 patients with 12 patients HVPG showing increases in HVPG (∆HVPG≥1 mmHg) while 9 patients remained stable. AKI developed in 7/12 of patients with increasing HVPG, but only in 2/9 of patients with stable ΔHVPG (p = 0.302). Noradrenalin levels were significantly higher in patients with increasing ΔHVPG than in patients with stable ΔHVPG. (p = 0.009). Biomarkers reflecting RAAS and SNS activity remained similar in patients with increasing vs. stable ΔHVPG. CONCLUSIONS: Patients with increased HVPG had higher postoperative creatinine concentrations, however, the incidence of AKI was similar between patients with increased versus stable HVPG.

Effect of a Perioperative Hypotension-Avoidance Strategy Versus a Hypertension-Avoidance Strategy on the Risk of Acute Kidney Injury: A Clinical Research Protocol for a Substudy of the POISE-3 Randomized Clinical Trial.

BACKGROUND: Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery. OBJECTIVE: To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy. DESIGN: Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy). INTERVENTION: If the presurgery systolic blood pressure (SBP) is <130 mmHg, all antihypertensive medications are withheld on the morning of surgery. If the SBP is ≥130 mmHg, some medications (but not angiotensin receptor blockers [ACEIs], angiotensin receptor blockers [ARBs], or renin inhibitors) may be continued in a stepwise manner. During surgery, the patients' mean arterial pressure (MAP) is maintained at ≥80 mmHg. During the first 48 hours after surgery, some antihypertensive medications (but not ACEIs, ARBs, or renin inhibitors) may be restarted in a stepwise manner if the SBP is ≥130 mmHg. CONTROL: Patients receive their usual antihypertensive medications before and after surgery. The patients' MAP is maintained at ≥60 mmHg from anesthetic induction until the end of surgery. SETTING: Recruitment from 108 centers in 22 countries from 2018 to 2021. PATIENTS: Patients (~6800) aged ≥45 years having noncardiac surgery who have or are at risk of atherosclerotic disease and who routinely take antihypertensive medications. MEASUREMENTS: The primary outcome of the substudy is postoperative acute kidney injury, defined as an increase in serum creatinine concentration of either ≥26.5 µmol/L (≥0.3 mg/dL) within 48 hours of randomization or ≥50% within 7 days of randomization. METHODS: The primary analysis (intention-to-treat) will examine the relative risk and 95% confidence interval of acute kidney injury in the intervention versus control group. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by preexisting chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate <60 mL/min/1.73 m2. RESULTS: Substudy results will be analyzed in 2022. LIMITATIONS: It is not possible to mask patients or providers to the intervention; however, objective measures will be used to assess acute kidney injury. CONCLUSIONS: This substudy will provide generalizable estimates of the effect of a perioperative hypotension-avoidance strategy on the risk of acute kidney injury.

CONTEXTE: La plupart des patients qui prennent des médicaments antihypertenseurs continuent de les prendre le matin d'une intervention chirurgicale et pendant la période périopératoire. De plus en plus de preuves suggèrent que cette pratique pourrait entraîner l'hypotension périopératoire et augmenter le risque de complications. Ce protocole décrit une sous-étude sur l'insuffisance rénale aiguë (IRA) découlant de l'essai Perioperative Ischemic Evaluation-3 (POISE-3). Cet essai teste l'effet d'une stratégie d'évitement de l'hypotension périopératoire par rapport à une stratégie d'évitement de l'hypertension chez des patients qui subissent une chirurgie non cardiaque. OBJECTIFS: Cette sous-étude de l'essai POISE-3 vise à déterminer si une stratégie d'évitement de l'hypotension périopératoire réduit le risque d'IRA comparativement à la stratégie d'évitement de l'hypertension. TYPE D'ÉTUDE: Essai clinique randomisé à répartition 1:1 au groupe intervention (stratégie d'évitement de l'hypotension périopératoire) ou au groupe témoin (stratégie d'évitement de l'hypertension). GROUPE INTERVENTION: Si la pression artérielle systolique (PAS) avant l'opération est <130 mmHg, tous les médicaments antihypertenseurs sont suspendus le matin de la chirurgie. Si la PAS est ≥130 mmHg, certains médicaments (excluant les inhibiteurs de l'enzyme de conversion de l'angiotensine [IECA], les antagonistes du récepteur de l'angiotensine [ARA] ou les inhibiteurs de la rénine) peuvent être poursuivis de façon graduelle. Pendant la chirurgie, la pression artérielle moyenne (PAM) du patient est maintenue à ≥80 mmHg. Dans les 48 heures suivant l'intervention chirurgicale, certains médicaments antihypertenseurs (excluant les IECA, les ARA ou les inhibiteurs de la rénine) peuvent être réintroduits par étapes si la PAS est ≥130 mmHg. GROUPE TÉMOIN: Les patients reçoivent leurs médicaments antihypertenseurs habituels avant et après la chirurgie. La PAM du patient est maintenue à ≥60 mmHg de l'induction de l'anesthésie à la fin de l'intervention chirurgicale. CADRE: Recrutement à partir de 108 centres dans 22 pays entre 2018 à 2021. SUJETS: Des patients (~6 800) âgés de 45 ans et plus atteints d'athérosclérose, ou présentant un risque de l'être, devant subir une chirurgie non cardiaque et prenant des médicaments antihypertenseurs sur une base régulière. MESURES: Le principal critère d'évaluation de cette sous-étude est une IRA postopératoire définie par une hausse d'au moins 26,5 µmol/L (≥0,3 mg/dL) de la créatinine sérique dans les 48 heures suivant la randomisation ou d'au moins 50 % dans les 7 jours suivant la randomisation. MÉTHODOLOGIE: L'analyse primaire (par intention de traiter) examinera le risque relatif d'une IRA et l'intervalle de confiance à 95 % dans le groupe intervention par rapport au groupe témoin. Nous répéterons l'analyse primaire en utilisant d'autres définitions de l'IRA et nous examinerons la modification de l'effet en présence d'une insuffisance rénale préexistante (définie par un DFGe prérandomisation <60 ml/min/1,73 m2). RÉSULTATS: Les résultats de cette sous-étude seront analysés en 2022. LIMITES: Il n'est pas possible de procéder à l'insu des patients ou des prestataires de soins pour cette intervention; des mesures objectives seront toutefois utilisées pour évaluer l'IRA. CONCLUSION: Cette sous-étude fournira des estimations généralisables de l'effet d'une stratégie visant à éviter l'hypotension périopératoire sur le risque d'insuffisance rénale aiguë.

Perioperative supplemental oxygen and oxidative stress in patients undergoing moderate- to high-risk major abdominal surgery - A subanalysis of randomized clinical trial.

STUDY OBJECTIVE: Oxidative stress plays a pivotal role in the development and aggravation of cardiovascular diseases. The influence of intraoperative inspired oxygen concentrations on oxidative stress is still not entirely known. Therefore, we evaluated in this sub-study if supplemental oxygen affects the oxidation-reduction potential in patients at-risk for cardiovascular complications undergoing moderate- to high-risk major abdominal surgery. DESIGN: Sub-study of a prospective parallel-arm double-blinded single-center superiority randomized trial. SETTING: Operating room and postoperative recovery area. INTERVENTION: Administration of 0.8 FiO2 versus 0.3 FiO2 throughout surgery and for the first two postoperative hours. MEASUREMENTS: The primary outcome was the static oxidation-reduction potential (sORP) and the oxidation-reduction potential capacity (cORP) between both groups. The secondary outcome was the trend of sORP and cORP in the overall study population. We assessed sORP and cORP before induction of anesthesia, 2 h after induction of anesthesia, within 2 h after surgery and on the first and third postoperative day. MAIN RESULTS: 258 patients were analyzed. 128 patients were randomly assigned to the 80% oxygen group and 130 patients were randomly assigned to the 30% oxygen group. Postoperative sORP values did not differ significantly between the 80% and 30% oxygen group (effect estimate: -1.162 mV,95% CI: -2.584 to 0.260; p = 0.109). On average, we observed a change in sORP of 5.288 mV (95% CI:4.633 to 5.913, p < 0.001) per day. cORP values did not differ significantly between the 80% and 30% oxygen group (effect estimate: -0.015µC, (95%CI: -0.062 to 0.032; p = 0.524). On average, we observed a change in cORP values of -0.170µC (95%CI: -0.194 to -0.147, p < 0.001) per day. CONCLUSION: In contrast to previous reports, we could not find any evidence of an association between intraoperative supplemental oxygen and perioperative oxidative stress assessed by sORP and cORP. TRIAL REGISTRATION: clinicaltrials.gov: NCT03366857https://clinicaltrials.gov/ct2/show/NCT03366857?term=vienna&cond=oxygen&draw=2&rank=1.

Multiprofessional perinatal care in a pregnant patient with acute respiratory distress syndrome due to COVID-19.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has caused ongoing challenges in health services worldwide. Despite the growing body of literature on COVID-19, reports on perinatal care in COVID-19 cases are limited. CASE PRESENTATION: We describe a case of severe acute respiratory distress syndrome (ARDS) in a 36-year-old G5/P2 pregnant woman with morbid obesity, confirmed severe acute respiratory syndrome coronavirus 2 infection, and fulminant respiratory failure. At 28+ 1 gestational weeks, the patient delivered an uninfected newborn. Using ImmunoCAP ISAC® technology, we found no immunoglobulin (Ig) M antibodies, suggesting that no mother-to-child viral transmission occurred during pregnancy or delivery. The maternal respiratory state improved rapidly after delivery; both maternal and neonatal outcomes were encouraging given the early gestational age and fulminant course of respiratory failure in our patient. CONCLUSIONS: The management of ARDS in pregnant women with COVID-19 is complex and requires an individualized, multidisciplinary approach, while considering maternal and fetal outcomes.