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.).

High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).

Association between Complications and Death within 30 days after General Surgery: A Vascular Events in Noncardiac Surgery Patients Cohort Evaluation (VISION) substudy.

OBJECTIVE: To determine the epidemiology of post-operative complications among general surgery patients, inform their relationships with 30-day mortality, and determine the attributable fraction of death of each postoperative complication. BACKGROUND: The contemporary causes of post-operative mortality among general surgery patients are not well characterized. METHODS: VISION is a prospective cohort study of adult non-cardiac surgery patients across 28 centres in 14 countries, who were followed for 30 days after surgery. For the subset of general surgery patients, a cox proportional hazards model was used to determine associations between various surgical complications and post-operative mortality. The analyses were adjusted for preoperative and surgical variables. Results were reported in adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 7950 patients included in the study, 240 (3.0%) patients died within 30 days of surgery. Five post-operative complications (myocardial injury after non-cardiac surgery [MINS], major bleeding, sepsis, stroke, and acute kidney injury resulting in dialysis) were independently associated with death. Complications associated with the largest attributable fraction (AF) of post-operative mortality (i.e., percentage of deaths in the cohort that can be attributed to each complication, if causality were established) were major bleeding (n=1454, 18.3%, HR 2.49 95%CI 1.87-3.33, P<0.001, AF 21.2%), sepsis (n=783, 9.9%, HR 6.52, 95%CI 4.72-9.01, P<0.001, AF 15.6%), and MINS (n=980, 12.3%, HR 2.00, 95%CI 1.50-2.67, P<0.001, AF 14.4%). CONCLUSION: The complications most associated with 30-day mortality following general surgery are major bleeding, sepsis, and MINS. These findings may guide the development of mitigating strategies, including prophylaxis for perioperative bleeding.

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

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

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.

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.

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.

Effect of perioperative benzodiazepine use on intraoperative awareness and postoperative delirium: a systematic review and meta-analysis of randomised controlled trials and observational studies.

BACKGROUND: Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits. METHODS: We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality. RESULTS: We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I2=72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I2=13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I2=35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I2=98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality). CONCLUSIONS: In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42019128144.

Landiolol for the prevention of postoperative atrial fibrillation after cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery. Although the evidence suggests that beta blockers prevent POAF, they often cause hypotension. Landiolol, an ultra-short-acting ß1 blocker, may prevent POAF, without adverse hemodynamic consequences. SOURCE: We searched MEDLINE, CENTRAL, Embase, and trial registries between January 1970 and March 2022. We included randomized controlled trials (RCTs) that evaluated the effect of landiolol for the prevention of POAF after cardiac surgery. Two reviewers independently assessed eligibility, extracted data, and assessed risk of bias using the Risk of Bias 2.0 tool. We pooled data using random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess certainty of evidence. PRINCIPAL FINDINGS: Nine RCTs including 868 participants met the eligibility criteria. Patients randomized to landiolol (56/460) had less POAF compared with controls (133/408) with a relative risk (RR) of 0.40 (95% confidence interval [CI], 0.30 to 0.54; I2 = 0%;) and an absolute risk of 12.2% vs 32.6% (absolute risk difference, 20.4%; 95% CI, 15.0 to 25.0). Landiolol resulted in a shorter hospital length-of-stay (LOS) (268 patients; mean difference, -2.32 days; 95% CI, -4.02 to -0.57; I2 = 0%). We found no significant difference in bradycardia (RR, 1.11; 95% CI, 0.48 to 2.56; I2 = 0%). No hypotension was reported with landiolol. We judged the certainty of evidence as moderate for POAF (because of indirectness as outcomes were not clearly defined) and low for LOS (because of imprecision and concern of reporting bias). CONCLUSION: In patients undergoing cardiac surgery, landiolol likely reduces POAF and may reduce LOS. A definitive large RCT is needed to confirm these findings. STUDY REGISTRATION: PROSPERO (CRD42021262703); registered 25 July 2021.

RéSUMé: OBJECTIF: La fibrillation auriculaire postopératoire (FAPO) est une complication fréquente après une chirurgie cardiaque. Bien que les données probantes suggèrent que les bêta-bloqueurs préviennent la FAPO, ces agents provoquent souvent une hypotension. Le landiolol, un ß1-bloqueur à action ultra-courte, pourrait prévenir la FAPO sans conséquences hémodynamiques indésirables. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, CENTRAL et Embase, et dans les registres d'études publiées entre janvier 1970 et mars 2022. Nous avons inclus les études randomisées contrôlées (ERC) évaluant l'effet du landiolol pour la prévention de la FAPO après une chirurgie cardiaque. Deux personnes ont indépendamment révisé l'éligibilité, extrait les données et évalué le risque de biais à l'aide de l'outil Risque de biais 2.0. Nous avons regroupé les données à l'aide de modèles à effets aléatoires. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes. CONSTATATIONS PRINCIPALES: Neuf ERC incluant 868 personnes remplissaient les critères d'éligibilité. Les patient·es randomisé·es dans le groupe landiolol (56/460) présentaient moins de FAPO que les témoins (133/408), avec un risque relatif (RR) de 0,40 (intervalle de confiance [IC] à 95 %, 0,30 à 0,54; I2 = 0 %) et un risque absolu de 12,2 % vs 32,6 % (différence de risque absolue, 20,4 %; IC 95 % 95 %, 15,0 à 25,0). Le landiolol a entraîné une durée de séjour hospitalier plus courte (268 patient·es; différence moyenne, −2,32 jours; IC 95 %, −4,02 à −0,57; I2 = 0 %). Nous n'avons trouvé aucune différence significative en matière de bradycardie (RR, 1,11; IC 95 %, 0,48 à 2,56; I2 = 0 %). Aucune hypotension n'a été rapportée avec le landiolol. Nous avons jugé que la certitude des données probantes était modérée pour la FAPO (en raison du caractère indirect car les critères d'évaluation n'étaient pas clairement définis) et faible pour la durée de séjour hospitalier (en raison de l'imprécision et de questionnements concernant le biais de déclaration). CONCLUSION: Chez les patient·es bénéficiant d'une chirurgie cardiaque, le landiolol réduit probablement la FAPO et peut réduire la durée de séjour hospitalier. Une ERC définitive à grande échelle est nécessaire pour confirmer ces résultats. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021262703); enregistrée le 25 juillet 2021.

Determinants of tobacco smoking abstinence one year after major noncardiac surgery: a secondary analysis of the VISION study.

BACKGROUND: Tobacco smoking is a leading preventable cause of death and increases perioperative risk. Determinants of smoking abstinence after noncardiac surgery and the association between smoking and 1-yr vascular outcomes are not fully elucidated. METHODS: We did a prospective cohort study of 40 004 patients, aged ≥45 yr, enrolled between August 2007 and November 2013, and followed for 1 yr after surgery. Patients were categorised as never smokers, ex-smokers (quit >4 weeks preoperatively), and current smokers (smoking ≤4 weeks preoperatively). Primary outcome was abstinence at 1 yr. Secondary outcome was a composite of all-cause death, non-fatal myocardial infarction, and non-fatal stroke at 1 yr. RESULTS: Of 4658 current smokers, 1838 (39.5%) were abstinent 1 yr after surgery. Median (inter-quartile range) time to resumption was 7 (3-23) days post-surgery. Perioperatively, 7.2% of current smokers obtained smoking cessation pharmacotherapy. Older age (adjusted risk ratio [aRR] 1.21; 95% confidence interval [CI]: 1.12-1.32); having recent coronary artery disease (aRR 1.41; 95% CI: 1.29-1.55); cancer (aRR 1.37; 95% CI: 1.18-1.59); and undergoing major vascular (aRR 1.20; 95% CI: 1.02-1.41), urgent/emergent (aRR 1.14; 95% CI: 1.05-1.23), or thoracic (aRR 1.41; 95% CI: 1.26-1.56) surgeries increased abstinence. One-year abstinence was less likely when patients stopped smoking 0-1 day (aRR 0.53; 95% CI: 0.43-0.66) and 2-14 days (aRR 0.76; 95% CI: 0.71-0.82) before surgery compared with >14 days before surgery. Current smokers (adjusted hazard ratio [aHR] 1.14; 95% CI: 1.01-1.29) and ex-smokers (aHR 1.11; 95% CI: 1.03-1.21) had higher risk of the 1-yr vascular outcome compared with never smokers. CONCLUSIONS: Long-term tobacco abstinence is more likely after major surgery in those with serious medical comorbidities. Interventions to prevent smoking resumption after surgery remain a priority. Clinical trial registration NCT00512109.

Preoperative prediction of Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study.

BACKGROUND: Diagnostic criteria for Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS) have been defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, leads to blood transfusion, or is judged to be the direct cause of death. Preoperative prediction guides for BIMS can facilitate informed consent and planning of perioperative care. METHODS: In a prospective cohort study of 16 079 participants aged ≥45 yr having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011, 17.3% (2782) experienced BIMS. An electronic risk calculator for BIMS was developed and internally validated by logistic regression with bootstrapping, and further simplified to a risk index. Decision curve analysis assessed the potential utility of each prediction guide compared with a strategy of identifying risk of BIMS based on preoperative haemoglobin <120 g L-1. RESULTS: With information about the type of surgery, preoperative haemoglobin, age, sex, functional status, kidney function, history of high-risk coronary artery disease, and active cancer, the risk calculator accurately predicted BIMS (bias-corrected C-statistic, 0.84; 95% confidence interval, 0.837-0.852). A simplified index based on preoperative haemoglobin <120 g L-1, open surgery, and high-risk surgery also predicted BIMS, but less accurately (C-statistic, 0.787; 95% confidence interval, 0.779-0.796). Both prediction guides could improve decision making compared with knowledge of haemoglobin <120 g L-1 alone. CONCLUSIONS: BIMS, defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, leads to blood transfusion, or that is judged to be the direct cause of death, can be predicted by a simple risk index before surgery. CLINICAL TRIAL REGISTRATION: NCT00512109.

Preoperative N-Terminal Pro-B-Type Natriuretic Peptide and Cardiovascular Events After Noncardiac Surgery: A Cohort Study.

Background: Preliminary data suggest that preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) may improve risk prediction in patients undergoing noncardiac surgery. Objective: To determine whether preoperative NT-proBNP has additional predictive value beyond a clinical risk score for the composite of vascular death and myocardial injury after noncardiac surgery (MINS) within 30 days after surgery. Design: Prospective cohort study. Setting: 16 hospitals in 9 countries. Patients: 10 402 patients aged 45 years or older having inpatient noncardiac surgery. Measurements: All patients had NT-proBNP levels measured before surgery and troponin T levels measured daily for up to 3 days after surgery. Results: In multivariable analyses, compared with preoperative NT-proBNP values less than 100 pg/mL (the reference group), those of 100 to less than 200 pg/mL, 200 to less than 1500 pg/mL, and 1500 pg/mL or greater were associated with adjusted hazard ratios of 2.27 (95% CI, 1.90 to 2.70), 3.63 (CI, 3.13 to 4.21), and 5.82 (CI, 4.81 to 7.05) and corresponding incidences of the primary outcome of 12.3% (226 of 1843), 20.8% (542 of 2608), and 37.5% (223 of 595), respectively. Adding NT-proBNP thresholds to clinical stratification (that is, the Revised Cardiac Risk Index [RCRI]) resulted in a net absolute reclassification improvement of 258 per 1000 patients. Preoperative NT-proBNP values were also statistically significantly associated with 30-day all-cause mortality (less than 100 pg/mL [incidence, 0.3%], 100 to less than 200 pg/mL [incidence, 0.7%], 200 to less than 1500 pg/mL [incidence, 1.4%], and 1500 pg/mL or greater [incidence, 4.0%]). Limitation: External validation of the identified NT-proBNP thresholds in other cohorts would reinforce our findings. Conclusion: Preoperative NT-proBNP is strongly associated with vascular death and MINS within 30 days after noncardiac surgery and improves cardiac risk prediction in addition to the RCRI. Primary Funding Source: Canadian Institutes of Health Research.

Withholding versus Continuing Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers before Noncardiac Surgery: An Analysis of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN Prospective Cohort.

BACKGROUND: The effect on cardiovascular outcomes of withholding angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in chronic users before noncardiac surgery is unknown. METHODS: In this international prospective cohort study, the authors analyzed data from 14,687 patients (including 4,802 angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users) at least 45 yr old who had in-patient noncardiac surgery from 2007 to 2011. Using multivariable regression models, the authors studied the relationship between withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and a primary composite outcome of all-cause death, stroke, or myocardial injury after noncardiac surgery at 30 days, with intraoperative and postoperative clinically important hypotension as secondary outcomes. RESULTS: Compared to patients who continued their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, the 1,245 (26%) angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users who withheld their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the 24 h before surgery were less likely to suffer the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1,245 [12.0%] vs. 459/3,557 [12.9%]; adjusted relative risk, 0.82; 95% CI, 0.70 to 0.96; P = 0.01) and intraoperative hypotension (adjusted relative risk, 0.80; 95% CI, 0.72 to 0.93; P < 0.001). The risk of postoperative hypotension was similar between the two groups (adjusted relative risk, 0.92; 95% CI, 0.77 to 1.10; P = 0.36). Results were consistent across the range of preoperative blood pressures. The practice of withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was only modestly correlated with patient characteristics and the type and timing of surgery. CONCLUSIONS: Withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers before major noncardiac surgery was associated with a lower risk of death and postoperative vascular events. A large randomized trial is needed to confirm this finding. In the interim, clinicians should consider recommending that patients withhold angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 24 h before surgery.

Barriers and facilitators to perioperative smoking cessation: A scoping review.

OBJECTIVE: Smoking cessation interventions are underutilized in the surgical setting. We aimed to systematically identify the barriers and facilitators to smoking cessation in the surgical setting. METHODS: Following the Joanna Briggs Institute (JBI) framework for scoping reviews, we searched 5 databases (MEDLINE, Embase, Cochrane CENTRAL, CINAHL, and PsycINFO) for quantitative or qualitative studies published in English (since 2000) evaluating barriers and facilitators to perioperative smoking cessation interventions. Data were analyzed using thematic analysis and mapped to the theoretical domains framework (TDF). RESULTS: From 31 studies, we identified 23 unique barriers and 13 facilitators mapped to 11 of the 14 TDF domains. The barriers were within the domains of knowledge (e.g., inadequate knowledge of smoking cessation interventions) in 23 (74.2%) studies; environmental context and resources (e.g., lack of time to deliver smoking cessation interventions) in 19 (61.3%) studies; beliefs about capabilities (e.g., belief that patients are nervous about surgery/diagnosis) in 14 (45.2%) studies; and social/professional role and identity (e.g., surgeons do not believe it is their role to provide smoking cessation interventions) in 8 (25.8%) studies. Facilitators were mainly within the domains of environmental context and resources (e.g., provision of quit smoking advice as routine surgical care) in 15 (48.4%) studies, reinforcement (e.g., surgery itself as a motivator to kickstart quit attempts) in 8 (25.8%) studies, and skills (e.g., smoking cessation training and awareness of guidelines) in 5 (16.2%) studies. CONCLUSION: The identified barriers and facilitators are actionable targets for future studies aimed at translating evidence informed smoking cessation interventions into practice in perioperative settings. More research is needed to evaluate how targeting these barriers and facilitators will impact smoking outcomes.