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.).

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.

Incidence and Risk Factors of Chronic Postoperative Pain in Same-day Surgery: A Prospective Cohort Study.

BACKGROUND: The amount of same-day surgery has increased markedly worldwide in recent decades, but there remains limited evidence on chronic postsurgical pain in this setting. METHODS: This study assessed pain 90 days after ambulatory surgery in an international, multicenter prospective cohort study of patients at least 45 yr old with comorbidities or at least 65 yr old. Pain was assessed using the Brief Pain Inventory. Chronic postsurgical pain was defined as a change of more than 1 point in self-rated average pain at the surgical site between baseline and 90 days, and moderate to severe chronic postsurgical pain was defined as a score greater than 4 in self-rated average pain at the surgical site at 90 days. Risk factors for chronic postsurgical pain were identified using multivariable logistic regression. RESULTS: Between November 2021 and January 2023, a total of 2,054 participants were included, and chronic postsurgical pain occurred in 12% of participants, of whom 93.1% had new chronic pain at the surgical site (i.e., participants without pain before surgery). Moderate to severe chronic postsurgical pain occurred in 9% of overall participants. Factors associated with chronic postsurgical pain were active smoking (odds ratio, 1.82; 95% CI, 1.20 to 2.76), orthopedic surgery (odds ratio, 4.7; 95% CI, 2.24 to 9.7), plastic surgery (odds ratio, 4.3; 95% CI, 1.97 to 9.2), breast surgery (odds ratio, 2.74; 95% CI, 1.29 to 5.8), vascular surgery (odds ratio, 2.71; 95% CI, 1.09 to 6.7), and ethnicity (i.e., for Hispanic/Latino ethnicity, odds ratio, 3.41; 95% CI, 1.68 to 6.9 and for First Nations/native persons, odds ratio, 4.0; 95% CI, 1.05 to 15.4). CONCLUSIONS: Persistent postsurgical pain after same-day surgery is common, is usually moderate to severe in nature, and occurs mostly in patients without chronic pain before surgery.

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.

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.

Preoperative Vitamin D Concentration and Cardiac, Renal, and Infectious Morbidity after Noncardiac Surgery.

BACKGROUND: Low 25-hydroxyvitamin D is associated with cardiovascular, renal, and infectious risks. Postsurgical patients are susceptible to similar complications, but whether vitamin D deficiency contributes to postoperative complications remains unclear. We tested whether low preoperative vitamin D is associated with cardiovascular events within 30 days after noncardiac surgery. METHODS: We evaluated a subset of patients enrolled in the biobank substudy of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were at least 45 yr with at least an overnight hospitalization. Blood was collected preoperatively, and 25-hydroxyvitamin D was measured in stored samples. The primary outcome was the composite of cardiovascular events (death, myocardial injury, nonfatal cardiac arrest, stroke, congestive heart failure) within 30 postoperative days. Secondary outcomes were kidney injury and infectious complications. RESULTS: A total of 3,851 participants were eligible for analysis. Preoperative 25-hydroxyvitamin D concentration was 70 ± 30 nmol/l, and 62% of patients were vitamin D deficient. Overall, 26 (0.7%) patients died, 41 (1.1%) had congestive heart failure or nonfatal cardiac arrest, 540 (14%) had myocardial injury, and 15 (0.4%) had strokes. Preoperative vitamin D concentration was not associated with the primary outcome (average relative effect odds ratio [95% CI]: 0.93 [0.85, 1.01] per 10 nmol/l increase in preoperative vitamin D, P = 0.095). However, it was associated with postoperative infection (average relative effect odds ratio [95% CI]: 0.94 [0.90, 0.98] per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.005) and kidney function (estimated mean change in postoperative estimated glomerular filtration rate [95% CI]: 0.29 [0.11, 0.48] ml min 1.73 m per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.004). CONCLUSIONS: Preoperative vitamin D was not associated with a composite of postoperative 30-day cardiac outcomes. However, there was a significant association between vitamin D deficiency and a composite of infectious complications and decreased kidney function. While renal effects were not clinically meaningful, the effect of vitamin D supplementation on infectious complications requires further study.

Breaking silence: a survey of barriers to goals of care discussions from the perspective of oncology practitioners.

BACKGROUND: Cancer is the leading cause of death in the developed world, and yet healthcare practitioners infrequently discuss goals of care (GoC) with hospitalized cancer patients. We sought to identify barriers to GoC discussions from the perspectives of staff oncologists, oncology residents, and oncology nurses. METHODS: This was a single center survey of staff oncologists, oncology residents, and inpatient oncology nurses. Barriers to GoC discussions were assessed on a 7-point Likert scale (1 = extremely unimportant; 7 = extremely important). RESULTS: Between July 2013 and May 2014, of 185 eligible oncology clinicians, 30 staff oncologists, 10 oncology residents, and 28 oncology nurses returned surveys (response rate of 37%). The most important barriers to GoC discussions were patient and family factors. They included family members' difficulty accepting poor prognoses (mean score 5.9, 95% CI [5.7, 6.2]), lack of family agreement in the goals of care (mean score 5.8, 95% CI [5.5, 6.1]), difficulty understanding the limitations of life-sustaining treatments (mean score 5.8, 95% CI [5.6, 6.1]), lack of patients' capacity to make goals of care decisions (mean score 5.7, 95% CI [5.5, 6.0]), and language barriers (mean score 5.7, 95% CI [5.4, 5.9]). Participants viewed system factors and healthcare provider factors as less important barriers. CONCLUSIONS: Oncology practitioners perceive patient and family factors as the most limiting barriers to GoC discussions. Our findings underscore the need for oncology clinicians to be equipped with strong communication skills to help patients and families navigate GoC discussions.

Association between complications and death within 30 days after noncardiac surgery.

BACKGROUND: Among adults undergoing contemporary noncardiac surgery, little is known about the frequency and timing of death and the associations between perioperative complications and mortality. We aimed to establish the frequency and timing of death and its association with perioperative complications. METHODS: We conducted a prospective cohort study of patients aged 45 years and older who underwent inpatient noncardiac surgery at 28 centres in 14 countries. We monitored patients for complications until 30 days after surgery and determined the relation between these complications and 30-day mortality using a Cox proportional hazards model. RESULTS: We included 40 004 patients. Of those, 715 patients (1.8%) died within 30 days of surgery. Five deaths (0.7%) occurred in the operating room, 500 deaths (69.9%) occurred after surgery during the index admission to hospital and 210 deaths (29.4%) occurred after discharge from the hospital. Eight complications were independently associated with 30-day mortality. The 3 complications with the largest attributable fractions (AF; i.e., potential proportion of deaths attributable to these complications) were major bleeding (6238 patients, 15.6%; adjusted hazard ratio [HR] 2.6, 95% confidence interval [CI] 2.2-3.1; AF 17.0%); myocardial injury after noncardiac surgery [MINS] (5191 patients, 13.0%; adjusted HR 2.2, 95% CI 1.9-2.6; AF 15.9%); and sepsis (1783 patients, 4.5%; adjusted HR 5.6, 95% CI 4.6-6.8; AF 12.0%). INTERPRETATION: Among adults undergoing noncardiac surgery, 99.3% of deaths occurred after the procedure and 44.9% of deaths were associated with 3 complications: major bleeding, MINS and sepsis. Given these findings, focusing on the prevention, early identification and management of these 3 complications holds promise for reducing perioperative mortality. Study registration: ClinicalTrials.gov, no. NCT00512109.

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.

Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery.

IMPORTANCE: Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). OBJECTIVE: To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. EXPOSURES: Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. MAIN OUTCOMES AND MEASURES: A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. RESULTS: Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom. CONCLUSIONS AND RELEVANCE: Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

Perioperative Aspirin for Prevention of Venous Thromboembolism: The PeriOperative ISchemia Evaluation-2 Trial and a Pooled Analysis of the Randomized Trials.

BACKGROUND: The PeriOperative ISchemia Evaluation-2 (POISE-2) trial compared aspirin with placebo after noncardiac surgery. METHODS: The authors randomly assigned 10,010 patients undergoing noncardiac surgery to receive 200 mg aspirin or placebo 2 to 4 h before surgery and then 100 mg aspirin daily or placebo daily for up to 30 days after surgery. Herein, the authors report the effect of aspirin on venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, as well as an updated pooled analysis of randomized trials of antiplatelet therapy for VTE prevention in noncardiac surgery patients. RESULTS: Six thousand five hundred forty-eight patients (65.4%) received anticoagulant prophylaxis. VTE occurred in 53 patients (1.1%) allocated to aspirin and in 60 patients (1.2%) allocated to placebo (hazard ratio, 0.89; 95% CI, 0.61 to 1.28). Major or life-threatening bleeding occurred in 312 patients (6.3%) allocated to aspirin and in 256 patients (5.1%) allocated to placebo (hazard ratio, 1.22; 95% CI, 1.04 to 1.44). Concomitant use of anticoagulant prophylaxis did not modify the effect of aspirin on VTE or bleeding. Pooled analysis of the POISE-2 and Pulmonary Embolism Prevention trials demonstrated that symptomatic VTE occurred in 173 (1.3%) of 13,724 patients allocated to aspirin and in 246 (1.8%) of 13,730 patients allocated to placebo (odds ratio, 0.71; 95% CI, 0.56 to 0.89; heterogeneity P = 0.27; I = 17%); the impact of aspirin was very similar in those who did and did not receive pharmacologic prophylaxis. Pooled estimates for symptomatic VTE were similar to the pooled estimates for any deep vein thrombosis and pulmonary embolism from the POISE-2 trial, Pulmonary Embolism Prevention trial, and the Antiplatelet Trialists' Collaboration meta-analysis. CONCLUSIONS: Aspirin in the POISE-2 trial did not reduce VTE, but two thirds of patients received anticoagulant prophylaxis, there were few VTE events, and results were consistent with a wide range of aspirin effects. A pooled analysis of the randomized trials demonstrates evidence for the efficacy of aspirin for VTE prevention in hospitalized surgical patients.

Reflecting on Diagnostic Errors: Taking a Second Look is Not Enough.

BACKGROUND: An experimenter controlled form of reflection has been shown to improve the detection and correction of diagnostic errors in some situations; however, the benefits of participant-controlled reflection have not been assessed. OBJECTIVE: The goal of the current study is to examine how experience and a self-directed decision to reflect affect the accuracy of revised diagnoses. DESIGN: Medical residents diagnosed 16 medical cases (pass 1). Participants were then given the opportunity to reflect on each case and revise their diagnoses (pass 2). PARTICIPANTS: Forty-seven medical Residents in post-graduate year (PGY) 1, 2 and 3 were recruited from Hamilton Health Care Centres. MAIN MEASURES: Diagnoses were scored as 0 (incorrect), 1 (partially correct) and 2 (correct). Accuracies and response times in pass 1 were analyzed using an ANOVA with three factors-PGY, Decision to revise yes/no, and Case 1-16, averaged across residents. The extent to which additional reflection affected accuracy was examined by analyzing only those cases that were revised, using a repeated measures ANOVA, with pass 1 or 2 as a within subject factor, and PGY and Case or Resident as a between-subject factor. KEY RESULTS: The mean score at pass 1 for each level was PGY1, 1.17 (SE 0.50); PGY2, 1.35 (SE 0.67) and PGY3, 1.27 (SE 0.94). While there was a trend for increased accuracy with level, this did not achieve significance. The number of residents at each level who revised at least one diagnosis was 12/19 PGY1 (63 %), 9/11 PGY2 (82 %) and 8/17 PGY3 (47 %). Only 8 % of diagnoses were revised resulting in a small but significant increase in scores from Pass 1 to 2, from 1.20/2 to 1.22 /2 (t = 2.15, p = 0.03). CONCLUSIONS: Participants did engage in self-directed reflection for incorrect diagnoses; however, this strategy provided minimal benefits compared to knowing the correct answer. Education strategies should be directed at improving formal and experiential knowledge.

Pathophysiology, diagnosis, and management of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a common complication of cirrhosis of the liver. It is also extremely debilitating, with an untreated 3-year survival of only 23 %. While the exact pathophysiology of HE has yet to be elucidated, a number of contributing factors have been described. Abnormal levels and altered metabolism of ammonia play a central role. Recently, inflammation has also been identified as a contributor to HE. Improved understanding of the pathophysiology of HE is crucial, as current therapy centers on reduction of the body's ammonia load. Lactulose is the first-line therapy for HE, with some antibiotics recently showing promise for improved outcomes in patients with HE. The role of anti-inflammatory therapies has yet to be evaluated.