METHODS: We included patients from the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were ≥45 years of age, scheduled for overnight hospital admission, and had intraoperative F io2 recorded. The primary outcome was myocardial injury after noncardiac surgery (MINS), and secondary outcomes included mortality and pneumonia, all within 30 postoperative days. Data were analyzed with logistic regression, adjusted for many baseline cardiovascular risk factors, and illustrated in relation to findings from 2 recent controlled trials.
RESULTS: We included 6588 patients with mean age of 62 years of whom 49% had hypertension. The median intraoperative F io2 was 0.46 (5%-95% range, 0.32-0.94). There were 808 patients (12%) with MINS. Each 0.10 increase in median F io2 was associated with a confounder-adjusted increase in odds for MINS: odds ratio (OR), 1.17 (95% confidence interval [CI], 1.12-1.23; P < .0001). MINS occurred in contrast with similar frequencies and no significant difference in controlled trials (2240 patients, 194 events), in which patients were given 80% vs 30% oxygen. Mortality was 2.4% and was not significantly associated with a median F io2 (OR, 1.07; 95% CI, 0.97-1.19 per 0.10 increase; P = .18), and 2.9% of patients had pneumonia (OR, 1.05; 95% CI, 0.95-1.15 per 0.10 increase; P = .34).
CONCLUSIONS: We observed an association between intraoperative F io2 and risk of myocardial injury within 30 days after noncardiac surgery, which contrasts with recent controlled clinical trials. F io2 was not significantly associated with mortality or pneumonia. Unobserved confounding presumably contributed to the observed association between F io2 and myocardial injury that is not supported by trials.
DATA SOURCES: MEDLINE, EMBASE, PubMed and CENTRAL were searched systematically from their inception until June 2018.
REVIEW METHODS: All the randomised clinical trials (RCTs) were included.
RESULTS: Twelve trials were eligible (n = 1867) for inclusion in the data synthesis. In comparison to the placebo cohort, the levosimendan cohort showed a significant reduction in mortality (TSA = inconclusive; ρ = 0.002; I2 = 0%; FEM: OR 0.56; 95% CI 0.39, 0.80), especially in the subgroups of preoperative severe low LVEF ≤ 30% (ρ = 0.003; OR 0.33; 95% CI 0.16, 0.69), preoperative administering of levosimendan (ρ = 0.001; OR 0.46; 95% CI 0.29, 0.74) and patients who had bolus followed by infusion of levosimendan (ρ = 0.005; OR 0.50; 95% CI 0.30, 0.81). However, the effect on mortality was not significant in the subgroup analysis of high quality trials (ρ = 0.14; OR 0.73; 95% CI 0.47, 1.12). The levosimendan cohort showed a significantly lower incidence of low-cardiac-output-syndrome (ρ
DESIGN: Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio.
SETTING: Tertiary and University hospitals.
INTERVENTIONS: Patients (n=10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia.
MEASUREMENTS AND MAIN RESULTS: The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-day death or non-fatal myocardial infarction (composite endpoint); cardiac mortality at 30day and at one year; incidence of hospital re-admission during the one year follow-up period and duration of intensive care unit, and hospital stay. The sample size is based on the hypothesis that volatile anesthetics will reduce 1-year unadjusted mortality from 3% to 2%, using a two-sided alpha error of 0.05, and a power of 0.9.
CONCLUSIONS: The trial will determine whether the simple intervention of adding a volatile anesthetic, an intervention that can be implemented by all anesthesiologists, can improve one-year survival in patients undergoing coronary artery bypass graft surgery.
BACKGROUND: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in vascular surgery patients are poorly described.
METHODS: This was an international prospective cohort study of 15,102 noncardiac surgery patients 45 years or older, of whom 502 patients underwent vascular surgery. All patients had fourth-generation plasma troponin T (TnT) concentrations measured during the first 3 postoperative days. MINS was defined as a TnT of 0.03 ng/mL of higher secondary to ischemia. The objectives of the present study were to determine (i) if MINS is prognostically important in vascular surgical patients, (ii) the clinical characteristics of vascular surgery patients with and without MINS, (iii) the 30-day outcomes for vascular surgery patients with and without MINS, and (iv) the proportion of MINS that probably would have gone undetected without routine troponin monitoring.
RESULTS: The incidence of MINS in the vascular surgery patients was 19.1% (95% confidence interval (CI), 15.7%-22.6%). 30-day all-cause mortality in the vascular cohort was 12.5% (95% CI 7.3%-20.6%) in patients with MINS compared with 1.5% (95% CI 0.7%-3.2%) in patients without MINS (P < 0.001). MINS was independently associated with 30-day mortality in vascular patients (odds ratio, 9.48; 95% CI, 3.46-25.96). The 30-day mortality was similar in MINS patients with (15.0%; 95% CI, 7.1-29.1) and without an ischemic feature (12.2%; 95% CI, 5.3-25.5, P = 0.76). The proportion of vascular surgery patients who suffered MINS without overt evidence of myocardial ischemia was 74.1% (95% CI, 63.6-82.4).
CONCLUSIONS: Approximately 1 in 5 patients experienced MINS after vascular surgery. MINS was independently associated with 30-day mortality. The majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.
METHODS: In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated "abnormal" laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria.
RESULTS: An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors' diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96-5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6-41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom.
CONCLUSION: Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.
METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h.
RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1).
CONCLUSIONS: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.
METHODS: Analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007-2013 of patients aged ≥45 years followed to one year after surgery. We estimated 1) the cumulative post-discharge incidence of death and other outcomes up to a year after surgery and 2) the adjusted time-varying associations between post-discharge death and pre-discharge 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 one-year incidence was 5.8% (95% CI, 5.5-6.0%) for all-cause death and 24.7% (24.2-25.1%) for all-cause hospital readmission. Pre-discharge complications were associated with 33.7% (27.2-40.2%) of deaths up to 30 days after discharge and 15.0% (12.0-17.9%) up to one year. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [9.3-21.9%) of deaths within 30 days, 6.4% [4.1-8.7%] within one year), major bleeding (15.0% [8.3-21.7%] within 30 days, 4.7% [2.2-7.2%] within one year), and sepsis (5.4% [2.2-8.6%] within 30 days, 2.1% [1.0-3.1%] within one year).
CONCLUSIONS: One in 18 patients ≥45 years old discharged after inpatient noncardiac surgery died within one year and one quarter were readmitted to hospital. The risk of death associated with pre-discharge perioperative complications persists for weeks to months after discharge.
METHODS: This was a secondary analysis of an international prospective cohort study from 2012 to 2014. This study included patients who were 45 yr of age or older who underwent major inpatient noncardiac surgery. Data were collected perioperatively and at 1 yr after surgery to assess for the development of persistent incisional pain (pain present around incision at 1 yr after surgery).
RESULTS: Among 14,831 patients, 495 (3.3%; 95% CI, 3.1 to 3.6) reported persistent incisional pain at 1 yr, with an average pain intensity of 3.6 ± 2.5 (0 to 10 numeric rating scale), with 35% and 14% reporting moderate and severe pain intensities, respectively. More than half of patients with persistent pain reported needing analgesic medications, and 85% reported interference with daily activities (denominator = 495 in the above proportions). Risk factors for persistent pain included female sex (P = 0.007), Asian ethnicity (P < 0.001), surgery for fracture (P < 0.001), history of chronic pain (P < 0.001), coronary artery disease (P < 0.001), history of tobacco use (P = 0.048), postoperative patient-controlled analgesia (P < 0.001), postoperative continuous nerve block (P = 0.010), insulin initiation within 24 h of surgery (P < 0.001), and withholding nonsteroidal anti-inflammatory medication or cyclooxygenase-2 inhibitors on the day of surgery (P = 0.029 and P < 0.001, respectively). Older age (P < 0.001), endoscopic surgery (P = 0.005), and South Asian (P < 0.001), Native American/Australian (P = 0.004), and Latin/Hispanic ethnicities (P < 0.001) were associated with a lower risk of persistent pain.
CONCLUSIONS: Persistent incisional pain is a common complication of inpatient noncardiac surgery, occurring in approximately 1 in 30 adults. It results in significant morbidity, interferes with daily living, and is associated with persistent analgesic consumption. Certain demographics, ethnicities, and perioperative practices are associated with increased risk of persistent pain.
EDITOR’S PERSPECTIVE:
METHODS: This was a planned post-hoc analysis of multicenter prospective cohort study involving 1,218 at-risk surgical patients without prior diagnosis of sleep apnea. All patients underwent home sleep apnea testing (ApneaLink Plus, ResMed) simultaneously with pulse oximetry (PULSOX-300i, Konica Minolta Sensing, Inc). The predictive performance of the 4% oxygen desaturation index (ODI) versus apnea-hypopnea index (AHI) were determined.
RESULTS: Of 1,218 patients, the mean age was 67.2 ± 9.2 years and body mass index (BMI) was 27.0 ± 5.3 kg/m2. The optimal cut-off for predicting moderate-to-severe and severe OSA was ODI ≥15 events/hour. For predicting moderate-to-severe OSA (AHI ≥15), the sensitivity and specificity of ODI ≥ 15 events per hour were 88.4% (95% confidence interval [CI], 85.7-90.6) and 95.4% (95% CI, 94.2-96.4). For severe OSA (AHI ≥30), the sensitivity and specificity were 97.2% (95% CI, 92.7-99.1) and 78.8% (95% CI, 78.2-79.0). The area under the curve (AUC) for moderate-to-severe and severe OSA was 0.983 (95% CI, 0.977-0.988) and 0.979 (95% CI, 0.97-0.909) respectively.
DISCUSSION: ODI from oximetry is sensitive and specific in predicting moderate-to-severe or severe OSA in at-risk surgical population. It provides an easy, accurate, and accessible tool for at-risk surgical patients with suspected OSA.
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.
DESIGN AND SETTING: The study was a planned post hoc analyses of a multicenter prospective cohort study.
PATIENTS: The inclusion criteria were patients ≥45 years old undergoing major non-cardiac surgery with cardiovascular risk factors.
INTERVENTIONS AND MEASUREMENTS: All patients underwent pre-operative pulse oximetry (PULSOX-300i, Konica-Minolta Sensing, Inc). The severity of OSA was classified based on oxygen desaturation index (ODI) (mild: ≥5 to <15, moderate: ≥15 to <30, and severe OSA: ≥30 events/h). The 30 days cardiovascular events were a composite of myocardial injury, cardiac death, congestive heart failure, thromboembolism, atrial fibrillation, and stroke.
MAIN RESULTS: For 1218 patients with mild, moderate, or severe OSA (mean age: 67.2 ± 9.3 years; body mass index: 27.0 ± 5.3 kg/m2), the rate of postoperative cardiovascular events was 16.4%, 25.2%, and 29.8% respectively. The multivariable analysis showed that preoperative oxygen desaturation index (ODI) ≥30 events per hour {adjusted hazard ratio (aHR) 1.63 [95% confidence interval (CI): 1.05-2.53]}, and cumulative time spent during sleep with oxygen saturation below 80% (CT80) ≥10 min {aHR 1.79 [95% CI: 1.28-2.50]} were independent predictors of 30-day postoperative cardiovascular events.
CONCLUSIONS: Preoperative ODI ≥30 events per hour and CT80 ≥ 10 min are associated with increased risk of postoperative cardiovascular events. Preoperative screening using oximetry helps in risk stratification for unrecognized sleep apnea.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01494181.