Mortality and major postoperative complications within 1 year after vascular surgery: a prospective cohort study.

INTRODUCTION: Patients undergoing vascular procedures are prone to developing postoperative complications affecting their short­term mortality. Prospective reports describing the incidence of long­term complications after vascular surgery are lacking. OBJECTIVES: We aimed to describe the incidence of complications 1 year after vascular surgery and to evaluate an association between myocardial injury after noncardiac surgery (MINS) and 1­year mortality. PATIENTS AND METHODS: This is a substudy of a large prospective cohort study Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION). Recruitment took place in 28 centers across 14 countries from August 2007 to November 2013. We enrolled patients aged 45 years or older undergoing vascular surgery, receiving general or regional anesthesia, and hospitalized for at least 1 night postoperatively. Plasma cardiac troponin T concentration was measured before the surgery and on the first, second, and third postoperative day. The patients or their relatives were contacted 1 year after the procedure to assess the incidence of major postoperative complications. RESULTS: We enrolled 2641 patients who underwent vascular surgery, 2534 (95.9%) of whom completed 1­year follow­up. Their mean (SD) age was 68.2 (9.8) years, and the cohort was predominantly male (77.5%). The most frequent 1­year complications were myocardial infarction (224/2534, 8.8%), amputation (187/2534, 7.4%), and congestive heart failure (67/2534, 2.6%). The 1­year mortality rate was 8.8% (223/2534). MINS occurred in 633 patients (24%) and was associated with an increased 1­year mortality (hazard ratio, 2.82; 95% CI, 2.14-3.72; P <0.001). CONCLUSIONS: The incidence of major postoperative complications after vascular surgery is high. The occurrence of MINS is associated with a nearly 3­fold increase in 1­year mortality.

One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study.

BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.

Predictors of acute kidney injury after lung resection surgery: a retrospective case-control study.

PURPOSE: Patients undergoing lung resection are at increased risk for acute kidney injury (AKI) in the immediate postoperative period, with important consequences for longer term morbidity and mortality. Lung resection surgery has unique considerations that could increase the risk of AKI, including lung resection volume, duration of one-lung ventilation (OLV), and intraoperative fluid restriction. Yet, specific risk factor data are lacking. The objective of this study was to identify independent risk factors for early AKI after lung resection surgery. METHODS: We conducted a retrospective case-control study of all patients presenting for elective lung resection surgery at an academic medical centre over a four-year period. Cases were patients who experienced an AKI and control patients were those who did not experience an AKI, based on KDIGO criteria. Baseline demographics and comorbidities along with duration of OLV and amount of lung resected were collected by retrospective chart review. The data were analyzed using multivariable logistic regression to identify independent predictors of AKI. RESULTS: Acute kidney injury occurred within 48 hr in 57/1,045 (5.5%; 95% confidence interval, 4.2 to 7.0) of patients. On multivariable analysis, our model of best fit included preoperative serum creatinine, male sex, use of angiotensin II receptor blockers, and duration of OLV. The rate of complications, intensive care unit admission, and risk of death were all higher in the group of patients who experienced AKI. CONCLUSIONS: Acute kidney injury occurs frequently after lung resection surgery and is associated with increased risk of postoperative complications. Increased duration of OLV may be a risk factor for AKI in this population.

RéSUMé: OBJECTIF: Les patient·es bénéficiant d'une résection pulmonaire courent un risque accru d'insuffisance rénale aiguë (IRA) en période postopératoire immédiate, avec des conséquences importantes pour la morbidité et la mortalité à long terme. La chirurgie de résection pulmonaire entraîne des considérations uniques qui pourraient augmenter le risque d'IRA, notamment le volume de la résection pulmonaire, la durée de la ventilation unipulmonaire (VUP) et la restriction liquidienne peropératoire. Pourtant, les données spécifiques sur les facteurs de risque font défaut. L'objectif de cette étude était d'identifier les facteurs de risque indépendants d'IRA précoce après une chirurgie de résection pulmonaire. MéTHODE: Nous avons mené une étude cas témoins rétrospective de toute la patientèle se présentant pour une chirurgie de résection pulmonaire non urgente dans un centre médical universitaire sur une période de quatre ans. Les cas étaient des patient·es qui ont présenté une IRA et des patient·es témoins qui n'ont pas eu d'IRA, selon les critères KDIGO. Les données démographiques et les comorbidités de base ainsi que la durée de la VUP et le volume de poumon réséqué ont été recueillis par examen rétrospectif des dossiers. Les données ont été analysées à l'aide d'une régression logistique multivariée afin d'identifier des prédicteurs indépendants d'IRA. RéSULTATS: Une insuffisance rénale aiguë est survenue dans les premières 48 heures postopératoires chez 57/1045 (5,5 %; intervalle de confiance à 95 %, 4,2 à 7,0) des patient·es. Sur l'analyse multivariée, notre modèle de meilleur ajustement incluait la créatininémie préopératoire, le sexe masculin, l'utilisation d'antagonistes des récepteurs de l'angiotensine II et la durée de la VUP. Le taux de complications, l'admission en unité de soins intensifs et le risque de décès étaient tous plus élevés dans le groupe de patient·es ayant présenté une IRA. CONCLUSION: L'insuffisance rénale aiguë survient fréquemment après une chirurgie de résection pulmonaire et est associée à un risque accru de complications postopératoires. Une durée prolongée de VUP pourrait constituer un facteur de risque d'IRA dans cette population.

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.

Temporal and Spatial Patterns of Inflammation and Tissue Injury in Patients with Postoperative Respiratory Failure after Lung Resection Surgery: A Nested Case-Control Study.

Thoracic surgeries involving resection of lung tissue pose a risk of severe postoperative pulmonary complications, including acute respiratory distress syndrome (ARDS) and respiratory failure. Lung resections require one-lung ventilation (OLV) and, thus, are at higher risk of ventilator-induced lung injury (VILI) attributable to barotrauma and volutrauma in the one ventilated lung, as well as hypoxemia and reperfusion injury on the operated lung. Further, we also aimed to assess the differences in localized and systemic markers of tissue injury/inflammation in those who developed respiratory failure after lung surgery versus matched controls who did not develop respiratory failure. We aimed to assess the different inflammatory/injury marker patterns induced in the operated and ventilated lung and how this compared to the systemic circulating inflammatory/injury marker pattern. A case-control study nested within a prospective cohort study was performed. Patients with postoperative respiratory failure after lung surgery (n = 5) were matched with control patients (n = 6) who did not develop postoperative respiratory failure. Biospecimens (arterial plasma, bronchoalveolar lavage separately from ventilated and operated lungs) were obtained from patients undergoing lung surgery at two timepoints: (1) just prior to initiation of OLV and (2) after lung resection was completed and OLV stopped. Multiplex electrochemiluminescent immunoassays were performed for these biospecimen. We quantified 50 protein biomarkers of inflammation and tissue injury and identified significant differences between those who did and did not develop postoperative respiratory failure. The three biospecimen types also display unique biomarker patterns.

Association of Preoperative Growth Differentiation Factor-15 Concentrations and Postoperative Cardiovascular Events after Major Noncardiac Surgery.

BACKGROUND: The association between growth differentiation factor-15 concentrations and cardiovascular disease has been well described. The study hypothesis was that growth differentiation factor-15 may help cardiac risk stratification in noncardiac surgical patients, in addition to clinical evaluation. METHODS: The objective of the study was to determine whether preoperative serum growth differentiation factor-15 is associated with the composite primary outcome of myocardial injury after noncardiac surgery and vascular death at 30 days and can improve cardiac risk prediction in noncardiac surgery. This is a prospective cohort study of patients 45 yr or older having major noncardiac surgery. The association between preoperative growth differentiation factor-15 and the primary outcome was determined after adjusting for the Revised Cardiac Risk Index. Preoperative N-terminal-pro hormone brain natriuretic peptide was also added to compare predictive performance with growth differentiation factor-15. RESULTS: Between October 27, 2008, and October 30, 2013, a total of 5,238 patients were included who had preoperative growth differentiation factor-15 measured (median, 1,325; interquartile range, 880 to 2,132 pg/ml). The risk of myocardial injury after noncardiac surgery and vascular death was 99 of 1,705 (5.8%) for growth differentiation factor-15 less than 1,000 pg/ml, 161 of 1,332 (12.1%) for growth differentiation factor-15 1,000 to less than 1,500 pg/ml, 302 of 1476 (20.5%) for growth differentiation factor-15 1,500 to less than 3,000 pg/ml, and 247 of 725 (34.1%) for growth differentiation factor-15 concentrations 3,000 pg/ml or greater. Compared to patients who had growth differentiation factor-15 concentrations less than 1,000 pg/ml, the corresponding adjusted hazard ratio for each growth differentiation factor-15 category was 1.93 (95% CI, 1.50 to 2.48), 3.04 (95% CI, 2.41 to 3.84), and 4.8 (95% CI, 3.76 to 6.14), respectively. The addition of growth differentiation factor-15 improved cardiac risk classification by 30.1% (301 per 1,000 patients) compared to Revised Cardiac Risk Index alone. It also provided additional risk classification beyond the combination of preoperative N-terminal-pro hormone brain natriuretic peptide and Revised Cardiac Risk Index (16.1%; 161 per 1,000 patients). CONCLUSIONS: Growth differentiation factor-15 is strongly associated with 30-day risk of major cardiovascular events and significantly improved cardiac risk prediction in patients undergoing noncardiac surgery.

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.

High-sensitivity Troponin I Predicts Major Cardiovascular Events after Non-Cardiac Surgery: A Vascular Events in Non-Cardiac Surgery Patients Cohort Evaluation (VISION) Substudy.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS), based on measurement of troponin T, is associated with perioperative major adverse cardiovascular events (MACE). We therefore determined the high-sensitivity troponin I (hsTnI) thresholds associated with 30 day MACE after non-cardiac surgery. METHODS: We performed a nested biobank cohort study of 4553 patients from the Vascular Events in Non-Cardiac Surgery Patients Cohort Evaluation (VISION) Study. We measured hsTnI (ADVIA Centaur® hsTnI assay) on postoperative days 1 to 3 in patients ≥45 years undergoing non-cardiac surgery. An iterative Cox proportional hazard model determined peak postoperative hsTnI thresholds independently associated with MACE (i.e., death, myocardial infarction occurring on postoperative day 4 or after, non-fatal cardiac arrest, or congestive heart failure) within 30 days after surgery. RESULTS: MACE occurred in 89/4545 (2.0%) patients. Peak hsTnI values of <75 ng/L, 75 ng/L to <1000 ng/L, and ≥1000 ng/L were associated with 1.2% (95% CI, 0.9-1.6), 7.1% (95% CI, 4.8-10.5), and 25.9% (95% CI, 16.3-38.4) MACE, respectively. Compared to peak hsTnI <75 ng/L, values 75 ng/L to <1000 ng/L and ≥1000 ng/L were associated with adjusted hazard ratios (aHR) of 4.53 (95% CI, 2.75-7.48) and 16.17 (95% CI, 8.70-30.07), respectively. MACE was observed in 9% of patients with peak hsTnI ≥75 ng/L vs 1% in patients with peak hsTnI <75 ng/L (aHR 5.76; 95% CI, 3.64-9.11). A peak hsTnI ≥75 ng/L was associated with MACE in the presence (aHR 9.35; 95% CI, 5.28-16.55) or absence (aHR 3.99; 95% CI, 2.19-7.25) of ischemic features of myocardial injury. CONCLUSION: A peak postoperative hsTnI ≥75 ng/L was associated with >5-fold increase in the risk of 30 days MACE compared to levels <75 ng/L. This threshold could be used for MINS diagnosis when the ADVIA Centaur hsTnI assay is used.Clinicaltrials.gov Registration Number: NCT00512109.

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.

High-Sensitivity Cardiac Troponin I Thresholds to Identify Myocardial Injury After Noncardiac Surgery: A Cohort Study.

BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is common and associated with short- and long-term major cardiovascular events. Diagnostic criteria for MINS using Abbott high-sensitivity cardiac troponin I (hs-cTnI) are unknown. METHODS: We performed a prospective cohort study of adults who had in-patient noncardiac surgery and measured hs-cTnI (Abbott Laboratories) on postoperative serum samples collected up to postoperative day 3. The objective was to determine prognostically important hs-cTnI thresholds associated with major cardiac events and death at 30 days after noncardiac surgery. Using Cox proportional iterative analyses, we determined peak postoperative hs-cTnI thresholds associated with the occurrence of the 30-day composite of major cardiac events (ie, nonfatal myocardial infarction after 3 postoperative days, cardiac arrest, and congestive heart failure) and death. RESULTS: Of 3953 included patients, 66 (1.7%) experienced the primary outcome at 30 days. Peak hs-cTnI values and associated incidence of major cardiac events and death were as follows: < 60 ng/L: 1.0% (95% CI 0.7-1.3); 60 to < 700 ng/L: 8.6% (5.6-13.0); and ≥ 700 ng/L: 27.3% (16.4-41.9). Compared with peak hs-cTnI < 60 ng/L, adjusted hazard ratios were 7.54 (95% CI% 4.27-13.32) for hs-cTnI values of 60 to < 700 ng/L and 26.87 (13.27-54.41) for values ≥ 700 ng/L. CONCLUSIONS: Hs-cTnI elevation within the first 3 days after noncardiac surgery independently predicts major cardiac events and death at 30 days. A postoperative hs-cTnI ≥ 60 ng/L was associated with a > 7-fold increase in the risk of subsequent major cardiac events and mortality at 30 days.

Impact of cost-awareness education and surgeon-led positive deviance on intraoperative costs of thoracoscopic lobectomy.

OBJECTIVE: Disposable instrument use during video-assisted thoracoscopic lobectomy is a significant driver of cost. The purpose of the study was to measure the effect of increasing surgeon cost awareness via successive "value improvement initiatives" on instrument costs. METHODS: We prospectively collected disposable instrument use data for all video-assisted thoracoscopic lobectomies performed by 5 Board-certified thoracic surgeons over 4 successive time periods: Period 1: control group of consecutive video-assisted thoracoscopic lobectomies before interventions; Period 2: video-assisted thoracoscopic lobectomies after displaying disposables price list in operating room; Period 3: video-assisted thoracoscopic lobectomies after educational presentation outlining disposable instrument price differences; Period 4: video-assisted thoracoscopic lobectomies after surgeon self-assessment with peer comparison of cost data from Period 3 and positive deviance seminar identifying the lowest-cost surgeon to lead discussion of optimal cost-reduction strategies. Instrument use and costs were compared among the 4 groups using the Kruskal-Wallis test. RESULTS: A total of 373 lobectomy cases were analyzed. Compared with Period 1, median stapler-related and total disposable costs for video-assisted thoracoscopic lobectomy cases decreased after successive value improvement initiatives, with lowest costs in Period 4 (P < .0001). Multiple linear regression analysis demonstrated per lobectomy disposables cost reduction of $397.53 in Period 4, after controlling for surgeon and lobe (P < .0001). Operating room time was reduced after successive value improvement initiatives (P < .0001). CONCLUSIONS: Cost awareness and surgeon engagement activities were associated with sustained cost reduction for video-assisted thoracoscopic lobectomies. Surgeon self-assessment, peer comparison, and positive deviance seminar were associated with the largest cost reduction. Significant hospital cost-savings may be realized with surgeon-led value improvement initiatives.

Identifying biomarkers of ventilator induced lung injury during one-lung ventilation surgery: a scoping review.

Background: Ventilator-induced lung injury (VILI) can occur as a result of mechanical ventilation to two lungs. Thoracic surgery often requires one-lung ventilation (OLV). The potential for VILI is likely higher in OLV. The impact of OLV on development of post-operative pulmonary complications is not well understood. We aimed to perform a scoping review to determine reliable biomarkers of VILI after OLV. Methods: A scoping review was performed using Cochrane Collaboration methodology. We searched Medline, EMBASE and SCOPUS. Gray literature was searched. Studies of adult human or animal models without pre-existing lung damage exposed to OLV, with biomarker responses analyzed were included. Results: After screening 5,613 eligible papers, 89 papers were chosen for full text review, with 29 meeting inclusion. Approximately half (52%, n=15) of studies were conducted in humans in an intra-operative setting. Bronchoalveolar lavage (BAL) & serum analyses with enzyme-linked immunosorbent assay (ELISA)-based assays were most commonly used. The majority of analytes were investigated by a single study. Of the analytes that were investigated by two or more studies (n=31), only 16 were concordant in their findings. Across all sample types and studies 84% (n=66) of the 79 inflammatory markers and 75% (n=6) of the 8 anti-inflammatory markers tested were found to increase. Half (48%) of all studies showed an increase in TNF-α or IL-6. Conclusions: A scoping review of the state of the evidence demonstrated that candidate biomarkers with the most evidence and greatest reliability are general markers of inflammation, such as IL-6 and TNF-α assessed using ELISA assays. Studies were limited in the number of biomarkers measured concurrently, sample size, and studies using human participants. In conclusion these identified markers can potentially serve as outcome measures for studies on OLV.

Data-driven identification of plasma metabolite clusters and metabolites of interest for potential detection of early-stage non-small cell lung cancer cases versus cancer-free controls.

BACKGROUND: Metabolomics is a potential means for biofluid-based lung cancer detection. We conducted a non-targeted, data-driven assessment of plasma from early-stage non-small cell lung cancer (ES-NSCLC) cases versus cancer-free controls (CFC) to explore and identify the classes of metabolites for further targeted metabolomics biomarker development. METHODS: Plasma from 250 ES-NSCLC cases and 250 CFCs underwent ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) in positive and negative electrospray ionization (ESI) modes. Molecular feature extraction, formula generation, and find-by-ion tools annotated metabolic entities. Analysis was restricted to endogenous metabolites present in ≥ 80% of samples. Unsupervised hierarchical cluster analysis identified clusters of metabolites. The metabolites with the strongest correlation with the principal component of each cluster were included in logistic regression modeling to assess discriminatory performance with and without adjustment for clinical covariates. RESULTS: A total of 1900 UHPLC-QTOF-MS assessments identified 1667 and 2032 endogenous metabolites in the ESI-positive and ESI-negative modes, respectively. After data filtration, 676 metabolites remained, and 12 clusters of metabolites were identified from each ESI mode. Multivariable logistic regression using the representative metabolite from each cluster revealed effective classification of cases from controls with overall diagnostic accuracy of 91% (ESI positive) and 94% (ESI negative). Metabolites of interest identified for further targeted analysis include the following: 1b, 3a, 12a-trihydroxy-5b-cholanoic acid, pyridoxamine 5'-phosphate, sphinganine 1-phosphate, gamma-CEHC, 20-carboxy-leukotriene B4, isodesmosine, and 18-hydroxycortisol. CONCLUSIONS: Plasma-based metabolomic detection of early-stage NSCLC appears feasible. Further metabolomics studies targeting phospholipid, steroid, and fatty acid metabolism are warranted to further develop noninvasive metabolomics-based detection of early-stage NSCLC.

Healthcare-related correlates of preoperative psychological distress among a mixed surgical and cancer-specific sample.

OBJECTIVE: Preoperative distress is commonly experienced by surgical patients and is associated with adverse health-related outcomes. Research suggests preoperative distress may be elevated among cancer surgery patients relative to other surgical groups and there appears to be greater recognition of the adverse impacts of distress for these patients. This study examined associations between preoperative distress and postoperative healthcare-related correlates (e.g., length of stay, re-hospitalization) among a large, mixed surgical sample, and separately among cancer surgery patients with active cancer. METHODS: We analyzed secondary data from the Vascular Events In Non-cardiac Surgery Patients Cohort Evaluation (VISION) study - Mental Health Supplement (N = 997; n = 370 active cancer/cancer surgery). The Kessler 6-item Psychological Distress Scale assessed preoperative distress on the day of surgery. Multivariable regressions examined associations between distress and healthcare-related correlates. For significant relationships, we examined associations between anxiety and depressive subscales of distress with the correlates of interest. RESULTS: Among the full surgical sample, after adjustment, preoperative distress was associated with a greater length of stay (b = 0.01, 95% CI [0.00-0.02], R2 = 0.15, f2 = 0.18) and increased odds of re-hospitalization (AOR = 1.07, 95%CI [1.01-1.13]). Results were comparable among cancer surgery patients (length of stay: b = 0.02, re-hospitalization: AOR = 1.11). Post-hoc analyses revealed associations between anxiety symptoms and re-hospitalization (AOR range: 1.13-1.26) and between depressive symptoms and length of hospital stay (b range: 0.02-0.04, R2 range: 0.07-0.15, f2 range: 0.07-0.18). CONCLUSIONS: Findings suggest preoperative distress may be associated with greater postoperative healthcare needs. Results support the importance of screening for distress in the perioperative period.

Metabolic Alterations in Sputum and Exhaled Breath Condensate of Early Stage Non-Small Cell Lung Cancer Patients After Surgical Resection: A Pilot Study.

Every year, close to two million people world-wide are diagnosed with and die of lung cancer. Most patients present with advanced-stage cancer with limited curative options and poor prognosis. Diagnosis of lung cancer at an early stage provides the best chance for a cure. Low- dose CT screening of the chest in the high-risk population is the current standard of care for early detection of lung cancer. However, CT screening is invasive due to radiation exposure and carries the risk of unnecessary biopsies in non-cancerous tumors. In this pilot study, we present metabolic alterations observed in sputum and breath condensate of the same population of early- stage non-small cell lung cancer (NSCLC) patients cancer before and after surgical resection (SR), which could serve as noninvasive diagnostic tool. Exhaled breath condensate (EBC) (n=35) and sputum (n=15) were collected from early-stage non-small cell lung cancer (NSCLC) patients before and after SR. Median number of days for EBC and sputum collection before and after SR were 7 and 42; and 7 and 36 respectively Nuclear magnetic resonance (NMR) and liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) were used to analyze the metabolic profile of the collected samples. A total of 26 metabolites with significant alteration post SR were identified, of which 14 (54%) were lipids and 12 constituted nine different chemical metabolite classes. Eighteen metabolites (69%) were significantly upregulated and 8 (31%) were downregulated. Median fold change for all the up- and downregulated metabolites (LC-QTOF-MS) were 10 and 8, respectively. Median fold change (MFC) in concentration of all the up- and downregulated metabolites (NMR) were 0.04 and 0.27, respectively. Furthermore, glucose (median fold change, 0.01, p=0.037), adenosine monophosphate (13 log fold, p=0.0037) and N1, N12- diacetylspermine (8 log fold p=0.011) sputum levels were significantly increased post-SR. These identified sputa and EBC indices of altered metabolism could serve as basis for further exploration of biomarkers for early detection of lung cancer, treatment response, and targets for drug discovery. Validation of these promising results by larger clinical studies is warranted.

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.

Tidal volume during 1-lung ventilation: A systematic review and meta-analysis.

BACKGROUND: The selection of tidal volumes for 1-lung ventilation remains unclear, because there exists a trade-off between oxygenation and risk of lung injury. We conducted a systematic review and meta-analysis to determine how oxygenation, compliance, and clinical outcomes are affected by tidal volume during 1-lung ventilation. METHODS: A systematic search of MEDLINE and EMBASE was performed. A systematic review and random-effects meta-analysis was conducted. Pooled mean difference estimated arterial oxygen tension, compliance, and length of stay; pooled odds ratio was calculated for composite postoperative pulmonary complications. Risk of bias was determined using the Cochrane risk of bias and Newcastle-Ottawa tools. RESULTS: Eighteen studies were identified, comprising 3693 total patients. Low tidal volumes (5.6 [±0.9] mL/kg) were not associated with significant differences in partial pressure of oxygen (-15.64 [-88.53-57.26] mm Hg; P = .67), arterial oxygen tension to fractional intake of oxygen ratio (14.71 [-7.83-37.24]; P = .20), or compliance (2.03 [-5.22-9.27] mL/cmH2O; P = .58) versus conventional tidal volume ventilation (8.1 [±3.1] mL/kg). Low versus conventional tidal volume ventilation had no significant impact on hospital length of stay (-0.42 [-1.60-0.77] days; P = .49). Low tidal volumes are associated with significantly decreased odds of pulmonary complications (pooled odds ratio, 0.40 [0.29-0.57]; P < .0001). CONCLUSIONS: Low tidal volumes during 1-lung ventilation do not worsen oxygenation or compliance. A low tidal volume ventilation strategy during 1-lung ventilation was associated with a significant reduction in postoperative pulmonary complications.

The Cost Implications of Dabigatran in Patients with Myocardial Injury After Non-Cardiac Surgery.

BACKGROUND: The Management of Myocardial Injury after Non-Cardiac Surgery (MANAGE) trial demonstrated that dabigatran 110 mg twice daily was more effective than placebo in preventing the primary composite outcome of vascular mortality, non-fatal myocardial infarction, non-hemorrhagic stroke, peripheral arterial thrombosis, amputation and symptomatic venous thromboembolism in patients with myocardial injury after non-cardiac surgery (MINS). The cost implications of dabigatran for this population are unknown but are important given the significant clinical implications. METHODS: Hospitalized events, procedures, and study and non-study medications were documented. We applied Canadian unit costs to healthcare resources consumed for all patients in the trial, and calculated the average cost per patient in Canadian dollars for the duration of the study (median follow-up of 16 months). A sensitivity analysis was performed using only Canadian patients, and subgroup analyses were also conducted. RESULTS: The total study cost for the dabigatran group was $9985 per patient, compared with $10,082 for placebo, a difference of - $97 (95% confidence interval [CI] - $2128 to $3672). Savings arising from fewer clinical events and procedures in the dabigatran 110 mg twice-daily group were enough to offset the cost of the study drug. In Canadian patients, the difference was $250 (95% CI -$2848 to $4840). Both differences were considered cost neutral. Dabigatran 110 mg twice daily was cost saving or cost neutral in many subgroups that were considered. CONCLUSION: Dabigatran 110 mg twice daily was cost neutral for patients in the MANAGE trial. Our cost findings support the use of dabigatran 110 mg twice daily in patients with MINS. TRIAL REGISTRATION: ClinicalTrials.gov identifier number NCT01661101.