Emilie P. Belley-Côté

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.

Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery

BACKGROUND The effect of a restrictive versus liberal red‐cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. METHODS In this multicenter, open‐label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red‐cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red‐cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non‐ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new‐onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red‐cell transfusion and other clinical outcomes. RESULTS The primary outcome occurred in 11.4% of the patients in the restrictive‐threshold group, as compared with 12.5% of those in the liberal‐threshold group (absolute risk difference, ‐1.11 percentage points; 95% confidence interval [CI], ‐2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive‐threshold group and 3.6% in the liberal‐threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red‐cell transfusion occurred in 52.3% of the patients in the restrictive‐threshold group, as compared with 72.6% of those in the liberal‐threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between‐group differences with regard to the other secondary outcomes. CONCLUSIONS In patients undergoing cardiac surgery who were at moderate‐to‐high risk for death, a restrictive strategy regarding red‐cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new‐onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898.)

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.

Methylprednisolone for the Treatment of Patients with Acute Spinal Cord Injuries: A Systematic Review and Meta-Analysis

Abstract Previous meta-analyses of methylprednisolone (MPS) for patients with acute traumatic spinal cord injuries (TSCIs) have not addressed confidence in the quality of evidence used for pooled effect estimates, and new primary studies have been recently published. We aimed to determine whether MPS improves motor recovery and is associated with increased risks for adverse events. We searched MEDLINE, EMBASE, and The Cochrane Library, and two reviewers independently screened articles, extracted data, and evaluated risk of bias. We pooled outcomes from randomized, controlled trials (RCTs) and controlled observational studies separately and used the Grades of Recommendation, Assessment, Development, and Evaluation approach to evaluate confidence. We included four RCTs and 17 observational studies. MPS was not associated with an increase in long-term motor score recovery (two RCTs: 335 participants; mean difference [MD], −1.11; 95% confidence interval [CI], −4.75 to 2.53; p = 0.55, low confidence; two observational studies: 528 participants; MD, 1.37; 95% CI, −3.08 to 5.83; p = 0.55, very low confidence) or improvement by at least one motor grade (three observational studies: 383 participants; risk ratio [RR], 0.84; 95% CI, 0.53–1.33; p = 0.46, very low confidence). Evidence from two RCTs demonstrated superior short-term motor score improvement if MPS was administered within 8 h of injury (two RCTs: 250 participants; MD, 4.46; 95% CI, 0.97–7.94; p = 0.01, low confidence), but risk of bias and imprecision limit confidence in these findings. Observational studies demonstrated a significantly increased risk for gastrointestinal bleeding (nine studies: 2857 participants; RR, 2.18; 95% CI, 1.13–4.19; p = 0.02, very low confidence), but RCTs did not. Pooled evidence does not demonstrate a significant long-term benefit for MPS in patients with acute TSCIs and suggests it may be associated with increased gastrointestinal bleeding. These findings support current guidelines against routine use, but strong recommendations are not warranted because confidence in the effect estimates is limited.

Heart Failure in Africa, Asia, the Middle East and South America: The INTER-CHF study

BACKGROUND There are few data on heart failure (HF) patients from Africa, Asia, the Middle East and South America. METHODS INTER-CHF is a prospective study that enrolled HF patients in 108 centers in 16 countries from 2012 to 2014. Consecutive ambulatory or hospitalized adult patients with HF were enrolled. Baseline data were recorded on sociodemographics, clinical characteristics, HF etiology and treatments. Age- and sex-adjusted results are reported. RESULTS We recruited 5813 HF patients: mean(SE) age=59(0.2)years, 39% female, 65% outpatients, 31% from rural areas, 26% with HF with preserved ejection fraction, with 1294 from Africa, 2661 from Asia, 1000 from the Middle-East, and 858 from South America. Participants from Africa-closely followed by Asians-were younger, had lower literacy levels, and were less likely to have health or medication insurance or be on beta-blockers compared with participants from other regions, but were most likely to be in NYHA class IV. Participants from South America were older, had higher insurance and literacy levels, and, along with Middle Eastern participants, were more likely to be on beta-blockers, but had the lowest proportion in NYHA IV. Ischemic heart disease was the most common HF etiology in all regions except Africa where hypertensive heart disease was most common. CONCLUSIONS INTER-CHF describes significant regional variability in socioeconomic and clinical factors, etiologies and treatments in HF patients from Africa, Asia, the Middle East and South America. Opportunities exist for improvement in health/medication insurance rates and proportions of patients on beta blockers, particularly in Africa and Asia.

Blood pressure targets for vasopressor therapy: a systematic review.

ABSTRACT Physicians often prescribe vasopressors to correct pathological vasodilation and improve tissue perfusion in patients with septic shock, but the evidence to inform practice on vasopressor dosing is weak. We undertook a systematic review of clinical studies evaluating different blood pressure targets for the dosing of vasopressors in septic shock. We searched MEDLINE, EMBASE, CENTRAL (to November 2013), reference lists from included articles, and trial registries for randomized controlled trials (RCTs) and observational and crossover intervention studies comparing different blood pressure targets for vasopressor therapy in septic shock. Two reviewers independently selected eligible studies and extracted data on standardized forms. We identified 2 RCTs and 10 crossover trials but no observational studies meeting our criteria. Only one RCT measured clinical outcomes after comparing mean arterial pressure targets of 80 to 85 mmHg versus 65 to 70 mmHg. There was no effect on 28-day mortality, but confidence intervals were wide (hazard ratio, 95% confidence interval [95% CI] 0.84 – 1.38). In contrast, this intervention was associated with a greater risk of atrial fibrillation (relative risk, 2.36; 95% CI, 1.18 – 4.72) and a lower risk of renal replacement therapy in hypertensive patients (relative risk, 0.75; 95% CI, 0.57 – 1.0). Crossover trials suggest that achieving higher blood pressure targets by increasing vasopressor doses increases heart rate and cardiac index with no effect on serum lactate. Our findings underscore the paucity of clinical evidence to guide the administration of vasopressors in critically ill patients with septic shock. Further rigorous research is needed to establish an evidence base for vasopressor administration in this population.

Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation. A systematic review and meta-analysis.

Variability in vitamin K antagonist (VKA) dosing is partially explained by genetic polymorphisms. We performed a meta-analysis to determine whether genotype-guided VKA dosing algorithms decrease a composite of death, thromboembolic events and major bleeding (primary outcome) and improve time in therapeutic range (TTR). We searched MEDLINE, EMBASE, CENTRAL, trial registries and conference proceedings for randomised trials comparing genotype-guided and standard (non genotype-guided) VKA dosing algorithms in adults initiating anticoagulation. Data were pooled using a random effects model. Of the 12 included studies (3,217 patients), six reported all components of the primary outcome of mortality, thromboembolic events and major bleeding (2,223 patients, 87 events). Our meta-analysis found no significant difference between groups for the primary outcome (relative risk 0.85, 95% confidence interval [CI] 0.54-1.34; heterogeneity Χ(²)=4.46, p=0.35, I(²)=10%). Based on 10 studies (2,767 patients), TTR was significantly higher in the genotype-guided group (mean difference (MD) 4.31%; 95% CI 0.35, 8.26; heterogeneity Χ(²)=43.31, p<0.001, I(²)=79%). Pre-specified exploratory analyses demonstrated that TTR was significantly higher when genotype-guided dosing was compared with fixed VKA dosing (6 trials, 997 patients: MD 8.41%; 95% CI 3.50,13.31; heterogeneity Χ(²)=15.18, p=0.01, I(²)=67%) but not when compared with clinical algorithm-guided dosing (4 trials, 1,770 patients: MD -0.29%; 95% CI -2.48,1.90; heterogeneity Χ(²)=1.53, p=0.68, I(²)=0%; p for interaction=0.002). In conclusion, genotype-guided compared with standard VKA dosing algorithms were not found to decrease a composite of death, thromboembolism and major bleeding, but did result in improved TTR. An improvement in TTR was observed in comparison with fixed VKA dosing algorithms, but not with clinical algorithms.

Methylprednisolone does not reduce persistent pain after cardiac surgery

Background:Persistent incisional pain is common after cardiac surgery and is believed to be in part related to inflammation and poorly controlled acute pain. Methylprednisolone is a corticosteroid with substantial antiinflammatory and analgesic properties and is thus likely to ameliorate persistent surgical pain. Therefore, the authors tested the primary hypothesis that patients randomized to methylprednisolone have less persistent incisional pain than those given placebo. Methods:One thousand forty-three patients having cardiopulmonary bypass for cardiac surgery via a median sternotomy were included in this substudy of Steroids in Cardiac Surgery (SIRS) trial. Patients were randomized to 500 mg intraoperative methylprednisolone or placebo. Incisional pain was assessed at 30 days and 6 months after surgery, and the potential risk factors were also evaluated. Results:Methylprednisolone administration did not reduce pain at 30 days or persistent incisional pain at 6 months, which occurred in 78 of 520 patients (15.7%) in the methylprednisolone group and in 88 of 523 patients (17.8%) in the placebo group. The odds ratio for methylprednisolone was 0.93 (95% CI, 0.79 to 1.09, P = 0.37). Furthermore, there was no difference in worst pain and average pain in the last 24 h, pain interference with daily life, or use of pain medicine at 6 months. Younger age, female sex, and surgical infections were associated with the development of persistent incisional pain. Conclusions:Intraoperative methylprednisolone administration does not reduce persistent incisional pain at 6 months in patients recovering from cardiac surgery.

Heart failure in low- and middle-income countries: Background, rationale, and design of the INTERnational Congestive Heart Failure Study (INTER-CHF)

BACKGROUND Although heart failure (HF) has been referred to as a global epidemic, most HF information comes from high-income countries, with little information about low-income countries (LIC) and middle-income countries (MIC) in Africa, Asia, the Middle East, and South America, which make up the majority of the worlds population. METHODS The INTERnational Congestive Heart Failure Study is a cohort study of 5,813 HF patients enrolled in 108 centers in 16 LIC and MIC. At baseline, data were recorded on sociodemographic and clinical risk factors, HF etiology, laboratory variables, management, and barriers to evidence-based HF care at the patient, physician, and system levels. We sought to enroll consecutive and consenting patients ≥18 years of age with a clinical diagnosis of HF seen in outpatient clinics (2/3 of patients) or inpatient hospital wards (1/3 of patients). Patients were followed up at 6 and 12 months post-enrollment to record clinical status, treatments, and clinical outcomes such as death and hospitalizations. In the 5,813 enrolled HF patients, the mean age was 59 ± 15 years, 40% were female, 62% had a history of hypertension, 30% had diabetes, 21% had prior myocardial infarction, 64% were recruited from outpatient clinics, 36% lived in rural areas, and 29% had HF with preserved left ventricular ejection fraction. CONCLUSIONS This unique HF registry aims to systematically gather information on sociodemographic and clinical risk factors, etiologies, treatments, barriers to evidence-based care, and outcomes of HF in LIC and MIC. This information will help improve the management of HF globally.

β-Blockers in sepsis: protocol for a systematic review and meta-analysis of randomised control trials

Introduction Sepsis is a common and deadly complication of infection. As part of the host response, sympathetic stimulation can result in septic myocardial depression, and metabolic, haematological and immunological dysfunction. Administration of β-blockers may attenuate this pathophysiological response to infection, but the effects on clinical outcomes are unknown. The objective of this systematic review is to determine the efficacy and safety of β-blockers in adults with sepsis using data from randomised control trials. Methods and analysis We will identify randomised control trials comparing treatment with β-blockers, versus placebo or standard care in adults with sepsis. Data sources will include MEDLINE, EMBASE, CENTRAL, clinical trial registries and conference proceedings. Two reviewers will independently determine trial eligibility. For each included trial, we will conduct duplicate independent data extraction, risk of bias assessment and evaluation of the quality of the evidence using the GRADE approach. Ethics and dissemination Our systematic review will evaluate the effects of β-blockers in adults with sepsis, comprehensively summarising and appraising the available evidence from randomised control trials. The results of this systematic review will help clinicians treating patients with sepsis to understand the potential role of β-blockade, and inform future research on this topic. Our findings will be disseminated through conference presentation and publication in a peer-reviewed journal. Trial registration number CRD42016036933.