METHODS: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization.
DISCUSSION: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.
DESIGN: A post hoc analysis of a randomized trial.
SETTING: Cardiac surgical operating rooms.
PARTICIPANTS: Patients undergoing elective, isolated CABG.
INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes.
MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03).
CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.
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.
METHODS: From June 2015 to Jan 2018, a total of 4,603 adults were enrolled from 628 communities in 18 countries and 7 regions of the world. Each participant performed concurrent measurements from the MicroGP and EasyOne spirometer. Measurements were compared by the intra-class correlation coefficient (ICC) and Bland-Altman method.
RESULTS: Approximately 65% of the participants achieved clinically acceptable quality measurements. Overall correlations between paired FEV1 (ICC 0.88 [95% CI 0.87, 0.88]) and FVC (ICC 0.84 [0.83, 0.85]) were high. Mean differences between paired FEV1 (-0.038 L [-0.053, -0.023]) and FVC (0.033 L [0.012, 0.054]) were small. The 95% limits of agreement were wide but unbiased (FEV1 984, -1060; FVC 1460, -1394). Similar findings were observed across regions. The source of variation between spirometers was mainly at the participant level. Older age, higher body mass index, tobacco smoking and known COPD/asthma did not adversely impact on the inter-device variability. Furthermore, there were small and acceptable mean differences between paired FEV1 and FVC z-scores using the Global Lung Initiative normative values, suggesting minimal impact on lung function interpretation.
CONCLUSIONS: In this multicenter, diverse community-based cohort study, measurements from two portable spirometers provided good correlation, small and unbiased differences between measurements. These data support their interchangeable use across diverse populations to provide accurate trends in serial lung function measurements in epidemiological studies.
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:
Objective: To assess whether sleep timing and napping behavior are associated with increased obesity, independent of nocturnal sleep length.
Design, Setting, and Participants: This large, multinational, population-based cross-sectional study used data of participants from 60 study centers in 26 countries with varying income levels as part of the Prospective Urban Rural Epidemiology study. Participants were aged 35 to 70 years and were mainly recruited during 2005 and 2009. Data analysis occurred from October 2020 through March 2021.
Exposures: Sleep timing (ie, bedtime and wake-up time), nocturnal sleep duration, daytime napping.
Main Outcomes and Measures: The primary outcomes were prevalence of obesity, specified as general obesity, defined as body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or greater, and abdominal obesity, defined as waist circumference greater than 102 cm for men or greater than 88 cm for women. Multilevel logistic regression models with random effects for study centers were performed to calculate adjusted odds ratios (AORs) and 95% CIs.
Results: Overall, 136 652 participants (81 652 [59.8%] women; mean [SD] age, 51.0 [9.8] years) were included in analysis. A total of 27 195 participants (19.9%) had general obesity, and 37 024 participants (27.1%) had abdominal obesity. The mean (SD) nocturnal sleep duration was 7.8 (1.4) hours, and the median (interquartile range) midsleep time was 2:15 am (1:30 am-3:00 am). A total of 19 660 participants (14.4%) had late bedtime behavior (ie, midnight or later). Compared with bedtime between 8 pm and 10 pm, late bedtime was associated with general obesity (AOR, 1.20; 95% CI, 1.12-1.29) and abdominal obesity (AOR, 1.20; 95% CI, 1.12-1.28), particularly among participants who went to bed between 2 am and 6 am (general obesity: AOR, 1.35; 95% CI, 1.18-1.54; abdominal obesity: AOR, 1.38; 95% CI, 1.21-1.58). Short nocturnal sleep of less than 6 hours was associated with general obesity (eg, <5 hours: AOR, 1.27; 95% CI, 1.13-1.43), but longer napping was associated with higher abdominal obesity prevalence (eg, ≥1 hours: AOR, 1.39; 95% CI, 1.31-1.47). Neither going to bed during the day (ie, before 8pm) nor wake-up time was associated with obesity.
Conclusions and Relevance: This cross-sectional study found that late nocturnal bedtime and short nocturnal sleep were associated with increased risk of obesity prevalence, while longer daytime napping did not reduce the risk but was associated with higher risk of abdominal obesity. Strategic weight control programs should also encourage earlier bedtime and avoid short nocturnal sleep to mitigate obesity epidemic.