Timing of Major Postoperative Bleeding Among Patients Undergoing Surgery.

Importance: Although major bleeding is among the most common and prognostically important perioperative complications, the relative timing of bleeding events is not well established. This information is critical for preventing bleeding complications and for informing the timing of pharmacologic thromboprophylaxis. Objective: To determine the timing of postoperative bleeding among patients undergoing surgery for up to 30 days after surgery. Design, Setting, and Participants: This is a secondary analysis of a prospective cohort study. Patients aged 45 years or older who underwent inpatient noncardiac surgery were recruited in 14 countries between 2007 and 2013, with follow-up until December 2014. Data analysis was performed from June to July 2023. Exposure: Noncardiac surgery requiring overnight hospital admission. Main Outcomes and Measures: The primary outcome (postoperative major bleeding) was a composite of the timing of the following bleeding outcomes: (1) bleeding leading to transfusion, (2) bleeding leading to a postoperative hemoglobin level less than 7 g/dL, (3) bleeding leading to death, and (4) bleeding associated with reintervention. Each of the components of the composite primary outcome (1-4) and bleeding independently associated with mortality after noncardiac surgery, which was defined as a composite of outcomes 1 to 3, were secondary outcomes. Results: Among 39 813 patients (median [IQR] age, 63.0 [54.8-72.5] years; 19 793 women [49.7%]), there were 5340 major bleeding events (primary outcome) in 4638 patients (11.6%) within the first 30 days after surgery. Of these events, 42.7% (95% CI, 40.9%-44.6%) occurred within 24 hours after surgery, 77.7% (95% CI, 75.8%-79.5%) by postoperative day 7, 88.3% (95% CI, 86.5%-90.2%) by postoperative day 14, and 94.6% (95% CI, 92.7%-96.5%) by postoperative day 21. Within 48 hours of surgery, 56.2% of major bleeding events, 56.2% of bleeding leading to transfusion, 56.1% of bleeding independently associated with mortality after noncardiac surgery, 51.8% of bleeding associated with hemoglobin less than 7 g/dL, and 51.8% of bleeding associated with reintervention had occurred. Conclusions and Relevance: In this cohort study, of the major postoperative bleeding events in the first 30 days, more than three-quarters occurred during the first postoperative week. These findings are useful for researchers for the planning future clinical research and for clinicians in prevention of bleeding-related surgical complications and in decision-making regarding starting of pharmacologic thromboprophylaxis after surgery.

Canadian Anatomic Kidney Score: Quantitative Macroscopic Assessment of Donor Kidney Quality for Transplantation.

Background: The Canadian Anatomic Kidney Score (CAKS) is a novel 6-point grading system that standardizes the gross description of a donor kidney across 3 components-vessels, anatomy, and sticky fat. We hypothesized that the CAKS predicts allograft functional outcomes and provides additional information to the Kidney Donor Profile Index (KDPI) and histologic assessment of the donor kidney. Methods: Single-center cohort of 145 patients who underwent renal transplantation with CAKS analysis between 2018 and 2021. CAKS was prospectively determined before transplantation. Preimplantation core biopsies were assessed according to the Remuzzi score (RS). The primary outcome was 1-y allograft function represented by an estimated glomerular filtration rate (eGFR). Results: Linear regression without adjustment for KDPI or RS showed a significant association between the CAKS and 1-y eGFR (-8.7 mL/min/1.73 m2 per point increase in CAKS; 95% CI, -13.0 to -4.4; P < 0.001). Most of that association was attributed to the vessel component (-12.1; -19.4 to -4.8; P = 0.002). Adjustment for KDPI and RS attenuated the relationship between 1-y function and CAKS (-4.6; -9.5 to 0.3; P = 0.065) and vessel component (-7.4; -15.2 to 0.5; P = 0.068). Conclusions: Anatomic assessment of donor kidneys at the time of transplantation associates with allograft function at 1 y. Vascular assessment appears to make the dominant contribution.

Kidney disease in trials of perioperative tranexamic acid.

STUDY OBJECTIVE: To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function. DESIGN: Systematic review and meta-analysis of randomized controlled trials. SETTING: We screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023. PATIENTS: Patients undergoing non-obstetric surgery. INTERVENTIONS: Intravenous tranexamic acid compared to placebo or usual care without tranexamic acid. MEASUREMENT: We summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function. MAIN RESULTS: We evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m2 (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m2 (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min. CONCLUSIONS: The large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown.

Desmopressin to reduce periprocedural bleeding and transfusion: a systematic review and meta-analysis.

We systematically reviewed the literature to investigate the effects of peri-procedural desmopressin in patients without known inherited bleeding disorders undergoing surgery or other invasive procedures. We included 63 randomized trials (4163 participants) published up to February 1, 2023. Seven trials were published after a 2017 Cochrane systematic review on this topic. There were 38 trials in cardiac surgery, 22 in noncardiac surgery, and 3 in non-surgical procedures. Meta-analyses demonstrated that desmopressin likely does not reduce the risk of receiving a red blood cell transfusion (25 trials, risk ratio [RR] 0.95, 95% confidence interval [CI] 0.86 to 1.05) and may not reduce the risk of reoperation due to bleeding (22 trials, RR 0.75, 95% CI 0.47 to 1.19) when compared to placebo or usual care. However, we demonstrated significant reductions in number of units of red blood cells transfused (25 trials, mean difference -0.55 units, 95% CI - 0.94 to - 0.15), total volume of blood loss (33 trials, standardized mean difference - 0.40 standard deviations; 95% CI - 0.56 to - 0.23), and the risk of bleeding events (2 trials, RR 0.45, 95% CI 0.24 to 0.84). The certainty of evidence of these findings was generally low. Desmopressin increased the risk of clinically significant hypotension that required intervention (19 trials, RR 2.15, 95% CI 1.36 to 3.41). Limited evidence suggests that tranexamic acid is more effective than desmopressin in reducing transfusion risk (3 trials, RR 2.38 favoring tranexamic acid, 95% CI 1.06 to 5.39) and total volume of blood loss (3 trials, mean difference 391.7 mL favoring tranexamic acid, 95% CI - 93.3 to 876.7 mL). No trials directly informed the safety and hemostatic efficacy of desmopressin in advanced kidney disease. In conclusion, desmopressin likely reduces periprocedural blood loss and the number of units of blood transfused in small trials with methodologic limitations. However, the risk of hypotension needs to be mitigated. Large trials should evaluate desmopressin alongside tranexamic acid and enroll patients with advanced kidney disease.

The Use of Placebo in Clinical Trials of Inflammatory Bowel Disease.

We review concerns regarding use of placebo in clinical trials of inflammatory bowel disease. We propose alternate designs to overcome ethical issues, while providing data that are clinically relevant.

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.

The Clinical Interpretation of Noninferiority Trials.

Noninferiority trials are designed to demonstrate that a new treatment is not unacceptably worse than a standard treatment, considering an allowable difference termed the noninferiority margin. We highlight that selection of noninferiority margins at the time of study design can be biased toward wider margins that favor noninferiority claims. We discuss a clinically oriented approach to interpretation of results with a focus on confidence intervals and recommend that readers base their judgments regarding noninferiority on margins reflecting patient values and preferences rather than those set by investigators. We provide examples from trials in inflammatory bowel diseases.

Risk and Timing of Major Bleeding Complications Requiring Intervention of the Percutaneous Kidney Biopsy With a Short Observation Protocol: A Retrospective Chart Review.

Background: We previously published a retrospective study of kidney biopsies performed in a tertiary care hospital in London, Ontario from 2012 to 2017. This study resulted in a change of practice in our institution to shorter postbiopsy monitoring for outpatients as well as the development of a risk calculator to predict serious bleeding complications. Objective: The primary objective of this study was to determine whether this shorter monitoring time is adequate in the outpatient setting. A secondary objective was to validate the bleeding risk calculator in both inpatients and outpatients. Design: This was a retrospective chart review. Setting: This study was performed at a tertiary academic hospital in London, Ontario, Canada. Participants: This was a retrospective study of 400 adult patients who underwent kidney biopsy between April 30, 2018 and February 25, 2022 at a tertiary academic hospital in London, Canada. Methods: We retrospectively assessed frequency and timing of major bleeding complications in patients who underwent kidney biopsy. In secondary analyses, we examined the prediction performance of the risk calculator in discrimination and calibration. Results: Major bleeding occurred in 7 patients (1.8%). Five of these patients required blood transfusions (1.3%) and 2 required embolization (0.5%). In the outpatient setting, any major bleeding events were identified immediately (1 patient) or on the routine 2-hour ultrasounds (1 patient). The risk calculator showed good discrimination (C-statistic, 0.91, 95% confidence interval [CI] = [0.84 to 0.95]) and calibration (slope, 1.10, 95% CI = [0.47 to 1.74]; intercept, 95% CI = -0.02 [-0.79 to 0.75]), but with much uncertainty in the estimates. Limitations: The occurrence of only a few major bleeding events limits the reliability of our assessment of our risk calculator. Conclusions: There appears to be little yield in extending observation beyond 2 hours after an outpatient kidney biopsy with the use of immediate and 2-hour postbiopsy ultrasounds. The bleeding risk calculator (http://perioperativerisk.com/kbrc) warrants further validation.

Contexte: Nous avons publié précédemment une étude rétrospective des biopsies rénales effectuées entre 2012 et 2017 dans un hôpital de soins tertiaires de London, en Ontario. Les résultats de cette précédente étude ont entraîné un changement de pratique dans notre établissement, soit une réduction de la durée de la surveillance post-biopsie pour les patients ambulatoires, et la mise au point d'un calculateur de risque permettant de prédire les complications hémorragiques graves. Objectifs: L'objectif principal de l'étude en cours était de vérifier si ce temps de surveillance plus court est adéquat pour les patients ambulatoires. Un deuxième objectif était de valider le calculateur de risque d'hémorragie chez les patients hospitalisés et les patients ambulatoires. Conception: Étude rétrospective des dossiers médicaux. Cadre: Étude réalisée dans un hôpital de soins tertiaires de London, en Ontario (Canada). Sujets: Cette étude rétrospective portait sur 400 patients adultes ayant subi une biopsie rénale entre le 30 avril 2018 et le 25 février 2022 dans un centre hospitalier universitaire de soins tertiaires de London, au Canada. Méthodes: Nous avons procédé à un examen rétrospectif de la fréquence des complications hémorragiques graves, et du moment où celles-ci surviennent, chez les patients ayant subi une biopsie rénale. Dans les analyses secondaires, nous avons examiné la puissance prédictive du calculateur de risque en matière de discrimination et d'étalonnage. Résultats: Sept patients (1,75 %) ont subi une hémorragie majeure; de ces patients, cinq ont eu besoin de transfusions sanguines (1,3 %) et deux, d'une embolisation (0,5 %). En contexte ambulatoire, tous les événements hémorragiques graves ont été détectés immédiatement (un patient) ou lors de l'échographie de routine à deux heures (un patient). Le calculateur de risque a montré une bonne discrimination (statistique C : 0,91 [IC 95 % : 0,84 à 0,95]) et un bon étalonnage (pente : 1,10 [0,47 à 1,74]; point d'intersection : -0,02 [-0,79 à 0,75]), mais une grande incertitude dans les estimations. Limitations: La fiabilité de l'évaluation de notre calculateur de risque est limitée par le très faible échantillon d'événements hémorragiques graves étant survenus. Conclusion: Il semble y avoir peu d'intérêt à prolonger la surveillance au-delà de deux heures après une biopsie rénale chez les patients ambulatoires lorsqu'une échographie est pratiquée immédiatement après la procédure et deux heures plus tard. Le calculateur de risque d'hémorragie (http://perioperativerisk.com/kbrc) nécessite une validation plus approfondie.

Conversion between B-type natriuretic peptide and N-terminal pro B-type natriuretic peptide in perioperative risk assessment: protocol for a prospective cohort study.

INTRODUCTION: Both B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) are used to identify patients at risk of perioperative vascular events, but prognostic thresholds have been established in a large prospective cohort for NT-pro-BNP only. We designed this study to inform perioperative risk interpretation of BNP values. Our primary objective is to validate a formula to convert BNP to NT-pro-BNP concentrations before non-cardiac surgery. The secondary objective is to determine the association between BNP categories (established based on conversion from NT-pro-BNP categories) and a composite outcome of myocardial injury after non-cardiac surgery (MINS) and vascular death. METHODS AND ANALYSIS: This is a single-centre, prospective cohort study in patients undergoing non-cardiac surgery who are >65 years old, Revised Cardiac Risk Index ≥1 or >45 years old with significant cardiovascular disease. BNP and NT-pro-BNP will be measured preoperatively, and troponin measurements will be analysed on postoperative days 1, 2 and 3. MINS and vascular death will be ascertained up to 30 days after surgery. The primary analyses will compare measured NT-pro-BNP values to those predicted by an existing formula (from a non-surgical population) based on BNP concentrations and patient characteristics, and recalibrate and update the formula with additional variables. Secondary analyses will estimate the relationship between categories of measured BNP (corresponding to established NT-pro-BNP thresholds) and the composite of MINS and vascular death. The target sample size of 431 patients is based on our primary analysis (assessing the conversion formula). ETHICS AND DISSEMINATION: Ethics approval has been obtained by the Queen's University Health Sciences Research Ethics Board, and all participants will provide informed consent for participation in the study. The results will be submitted for publication in conferences and in a peer-reviewed journal, and will inform perioperative vascular risk interpretation of preoperative BNP. TRIAL REGISTRATION NUMBER: NCT05352698.

TIPS to decide whether to prescribe aspirin for the primary prevention of cardiovascular events in chronic kidney disease.

Aspirin effectively prevents subsequent cardiovascular events. A post hoc subgroup analysis of the International Polycap Study 3 (TIPS-3) trial suggests that patients with chronic kidney disease might also benefit from aspirin for primary prevention. We consider the merits of doing so in practice.

GRADE concept paper 2: Concepts for judging certainty on the calibration of prognostic models in a body of validation studies.

BACKGROUND: Prognostic models combine several prognostic factors to provide an estimate of the likelihood (or risk) of future events in individual patients, conditional on their prognostic factor values. A fundamental part of evaluating prognostic models is undertaking studies to determine whether their predictive performance, such as calibration and discrimination, is reproduced across settings. Systematic reviews and meta-analyses of studies evaluating prognostic models' performance are a necessary step for selection of models for clinical practice and for testing the underlying assumption that their use will improve outcomes, including patient's reassurance and optimal future planning. METHODS: In this paper, we highlight key concepts in evaluating the certainty of evidence regarding the calibration of prognostic models. RESULTS AND CONCLUSION: Four concepts are key to evaluating the certainty of evidence on prognostic models' performance regarding calibration. The first concept is that the inference regarding calibration may take one of two forms: deciding whether one is rating certainty that a model's performance is satisfactory or, instead, unsatisfactory, in either case defining the threshold for satisfactory (or unsatisfactory) model performance. Second, inconsistency is the critical GRADE domain to deciding whether we are rating certainty in the model performance being satisfactory or unsatisfactory. Third, depending on whether one is rating certainty in satisfactory or unsatisfactory performance, different patterns of inconsistency of results across studies will inform ratings of certainty of evidence. Fourth, exploring the distribution of point estimates of observed to expected ratio across individual studies, and its determinants, will bear on the need for and direction of future research.

Post-discharge after surgery Virtual Care with Remote Automated Monitoring-1 (PVC-RAM-1) technology versus standard care: randomised controlled trial.

OBJECTIVE: To determine if virtual care with remote automated monitoring (RAM) technology versus standard care increases days alive at home among adults discharged after non-elective surgery during the covid-19 pandemic. DESIGN: Multicentre randomised controlled trial. SETTING: 8 acute care hospitals in Canada. PARTICIPANTS: 905 adults (≥40 years) who resided in areas with mobile phone coverage and were to be discharged from hospital after non-elective surgery were randomised either to virtual care and RAM (n=451) or to standard care (n=454). 903 participants (99.8%) completed the 31 day follow-up. INTERVENTION: Participants in the experimental group received a tablet computer and RAM technology that measured blood pressure, heart rate, respiratory rate, oxygen saturation, temperature, and body weight. For 30 days the participants took daily biophysical measurements and photographs of their wound and interacted with nurses virtually. Participants in the standard care group received post-hospital discharge management according to the centre's usual care. Patients, healthcare providers, and data collectors were aware of patients' group allocations. Outcome adjudicators were blinded to group allocation. MAIN OUTCOME MEASURES: The primary outcome was days alive at home during 31 days of follow-up. The 12 secondary outcomes included acute hospital care, detection and correction of drug errors, and pain at 7, 15, and 30 days after randomisation. RESULTS: All 905 participants (mean age 63.1 years) were analysed in the groups to which they were randomised. Days alive at home during 31 days of follow-up were 29.7 in the virtual care group and 29.5 in the standard care group: relative risk 1.01 (95% confidence interval 0.99 to 1.02); absolute difference 0.2% (95% confidence interval -0.5% to 0.9%). 99 participants (22.0%) in the virtual care group and 124 (27.3%) in the standard care group required acute hospital care: relative risk 0.80 (0.64 to 1.01); absolute difference 5.3% (-0.3% to 10.9%). More participants in the virtual care group than standard care group had a drug error detected (134 (29.7%) v 25 (5.5%); absolute difference 24.2%, 19.5% to 28.9%) and a drug error corrected (absolute difference 24.4%, 19.9% to 28.9%). Fewer participants in the virtual care group than standard care group reported pain at 7, 15, and 30 days after randomisation: absolute differences 13.9% (7.4% to 20.4%), 11.9% (5.1% to 18.7%), and 9.6% (2.9% to 16.3%), respectively. Beneficial effects proved substantially larger in centres with a higher rate of care escalation. CONCLUSION: Virtual care with RAM shows promise in improving outcomes important to patients and to optimal health system function. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344665.

Derivation and External Validation of a Risk Index for Predicting Acute Kidney Injury Requiring Kidney Replacement Therapy After Noncardiac Surgery.

Importance: Severe acute kidney injury (AKI) is a serious postoperative complication. A tool for predicting the risk of AKI requiring kidney replacement therapy (KRT) after major noncardiac surgery might assist with patient counseling and targeted use of measures to reduce this risk. Objective: To derive and validate a predictive model for AKI requiring KRT after major noncardiac surgery. Design, Setting, and Participants: In this prognostic study, 5 risk prediction models were derived and internally validated in a population-based cohort of adults without preexisting kidney failure who underwent noncardiac surgery in Alberta, Canada, between January 1, 2004, and December 31, 2013. The best performing model and corresponding risk index were externally validated in a population-based cohort of adults without preexisting kidney failure who underwent noncardiac surgery in Ontario, Canada, between January 1, 2007, and December 31, 2017. Data analysis was conducted from September 1, 2019, to May 31, 2021. Exposures: Demographic characteristics, surgery type, laboratory measures, and comorbidities before surgery. Main Outcomes and Measures: Acute kidney injury requiring KRT within 14 days after surgery. Discrimination was assessed using the C statistic; calibration was assessed using calibration intercept and slope. Logistic recalibration was used to optimize model calibration in the external validation cohort. Results: The derivation cohort included 92 114 patients (52.2% female; mean [SD] age, 62.3 [18.0] years), and the external validation cohort included 709 086 patients (50.8% female; mean [SD] age, 61.0 [16.0] years). A total of 529 patients (0.6%) developed postoperative AKI requiring KRT in the derivation cohort, and 2956 (0.4%) developed postoperative AKI requiring KRT in the external validation cohort. The following factors were consistently associated with the risk of AKI requiring KRT: younger age (40-69 years: odds ratio [OR], 2.07 [95% CI, 1.69-2.53]; <40 years: OR, 3.73 [95% CI, 2.61-5.33]), male sex (OR, 1.55; 95% CI, 1.28-1.87), surgery type (colorectal: OR, 4.86 [95% CI, 3.28-7.18]; liver or pancreatic: OR, 6.46 [95% CI, 3.85-10.83]; other abdominal: OR, 2.19 [95% CI, 1.66-2.89]; abdominal aortic aneurysm repair: OR, 19.34 [95% CI, 14.31-26.14]; other vascular: OR, 7.30 [95% CI, 5.48-9.73]; thoracic: OR, 3.41 [95% CI, 2.07-5.59]), lower estimated glomerular filtration rate (OR, 0.97; 95% CI, 0.97-0.97 per 1 mL/min/1.73 m2 increase), lower hemoglobin concentration (OR, 0.99; 95% CI, 0.98-0.99 per 0.1 g/dL increase), albuminuria (mild: OR, 1.88 [95% CI, 1.52-2.33]; heavy: OR, 3.74 [95% CI, 2.98-4.69]), history of myocardial infarction (OR, 1.63; 95% CI, 1.32-2.03), and liver disease (mild: OR, 2.32 [95% CI, 1.66-3.24]; moderate or severe: OR, 4.96 [95% CI, 3.58-6.85]). In external validation, a final model including these variables showed excellent discrimination (C statistic, 0.95; 95% CI, 0.95-0.96), with sensitivity of 21.2%, specificity of 99.9%, positive predictive value of 38.1%, and negative predictive value of 99.7% at a predicted risk threshold of 10% or greater. Conclusions and Relevance: The findings suggest that this risk model can predict AKI requiring KRT after noncardiac surgery using routine preoperative data. The model may be feasible for implementation in clinical perioperative risk stratification for severe AKI.

Association of Preeclampsia With Myocardial Injury Among Patients Undergoing Noncardiac Surgery: The PREECLAMPSIA-VISION Study.

BACKGROUND: In women, preeclampsia has a known association with increased long-term cardiovascular morbidity and mortality. However, it is unknown whether it is associated with increased postoperative cardiovascular morbidity and mortality in women. We aimed to determine if preeclampsia is an independent risk factor for myocardial injury after noncardiac surgery (MINS) and postoperative 30-day mortality. METHODS: This study was a large international multicentre cohort study of a representative sample of 40,004 patients recruited from August 2007 to November 2013. Participants were ≥ 45 years of age and underwent inpatient noncardiac surgery. Within this cohort, our study examined women with a history of pregnancy. Using multivariable models, we explored the association between a history of pregnancy affected by preeclampsia and our primary outcome of MINS and secondary outcome of postoperative mortality within 30 days. MINS was defined as prognostically relevant myocardial injury due to ischemia that occurred during or within 30 days after noncardiac surgery. RESULTS: Analyses were restricted to the 13,902 participants with a history of pregnancy. Among these women, 976 (7.0%) had a history of preeclampsia. A history of preeclampsia was associated with an increased risk of MINS, with an adjusted hazard ratio of 1.26 (95% confidence interval 1.03-1.53; P = 0.02). Preeclampsia was not significantly associated with 30-day mortality. CONCLUSIONS: Preeclampsia is a risk factor for MINS and should be considered in the preoperative cardiovascular risk assessment of women.

Predicting Myocardial Injury and Other Cardiac Complications After Elective Noncardiac Surgery with the Revised Cardiac Risk Index: The VISION Study.

BACKGROUND: The Revised Cardiac Risk Index (RCRI) is widely used to estimate risk of cardiac complications after noncardiac surgery; its estimates do not capture myocardial injury after noncardiac surgery (MINS). We evaluated the incidence of cardiac complications including MINS across RCRI risk classes and the RCRI's ability to discriminate, before surgery, between patients who will experience these complications and those who will not. METHODS: This was a secondary analysis of a prospective cohort study of 35,815 patients ≥ 45 years old who had elective inpatient noncardiac surgery from 2007 to 2013 at 28 centres in 14 countries. The primary outcome was a composite of MINS, myocardial infarction, nonfatal cardiac arrest, or cardiac death within 30 days after surgery. The secondary outcome was this composite without MINS. RESULTS: The primary outcome occurred in 4725 patients (13.2%); its incidences across RCRI classes I (no risk factors), II (1 risk factor), III (2 risk factors), and IV (≥ 3 risk factors) were, respectively, 8.2%, 15.4%, 26.6%, and 40.2% (C-statistic for discrimination 0.65 [95% confidence interval 0.62-0.68]). The secondary outcome occurred in 1174 patients (3.3%) with incidences of 1.6%, 4.0%, 7.9%, and 12.9%, respectively (C-statistic 0.69 [0.65-0.72]). Thirty-five percent of primary outcome events and 26.9% of secondary outcome events occurred in patients with no RCRI risk factors. CONCLUSION: The RCRI alone is not sufficient to guide postoperative cardiac monitoring because 1 in 12 patients ≥ 45 years of age without any RCRI risk factors have a cardiac complication after major noncardiac surgery, and most of them would be missed without systematic troponin testing.

Post Discharge after Surgery Virtual Care with Remote Automated Monitoring Technology (PVC-RAM): protocol for a randomized controlled trial.

BACKGROUND: After nonelective (i.e., semiurgent, urgent and emergent) surgeries, patients discharged from hospitals are at risk of readmissions, emergency department visits or death. During the coronavirus disease 2019 (COVID-19) pandemic, we are undertaking the Post Discharge after Surgery Virtual Care with Remote Automated Monitoring Technology (PVC-RAM) trial to determine if virtual care with remote automated monitoring (RAM) compared with standard care will increase the number of days adult patients remain alive at home after being discharged following nonelective surgery. METHODS: We are conducting a randomized controlled trial in which 900 adults who are being discharged after nonelective surgery from 8 Canadian hospitals are randomly assigned to receive virtual care with RAM or standard care. Outcome adjudicators are masked to group allocations. Patients in the experimental group learn how to use the study's tablet computer and RAM technology, which will measure their vital signs. For 30 days, patients take daily biophysical measurements and complete a recovery survey. Patients interact with nurses via the cellular modem-enabled tablet, who escalate care to preassigned and available physicians if RAM measurements exceed predetermined thresholds, patients report symptoms, a medication error is identified or the nurses have concerns they cannot resolve. The primary outcome is number of days alive at home during the 30 days after randomization. INTERPRETATION: This trial will inform management of patients after discharge following surgery in the COVID-19 pandemic and offer insights for management of patients who undergo nonelective surgery in a nonpandemic setting. Knowledge dissemination will be supported through an online multimedia resource centre, policy briefs, presentations, peer-reviewed journal publications and media engagement. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT04344665.

Bleeding Independently associated with Mortality after noncardiac Surgery (BIMS): an international prospective cohort study establishing diagnostic criteria and prognostic importance.

BACKGROUND: We aimed to establish diagnostic criteria for bleeding independently associated with mortality after noncardiac surgery (BIMS) defined as bleeding during or within 30 days after noncardiac surgery that is independently associated with mortality within 30 days of surgery, and to estimate the proportion of 30-day postoperative mortality potentially attributable to BIMS. METHODS: This was a prospective cohort study of participants ≥45 yr old having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011. Cox proportional hazards models evaluated the adjusted relationship between candidate diagnostic criteria for BIMS and all-cause mortality within 30 days of surgery. RESULTS: Of 16 079 participants, 2.0% (315) died and 36.1% (5810) met predefined screening criteria for bleeding. Based on independent association with 30-day mortality, BIMS was identified as bleeding leading to a postoperative haemoglobin <70 g L-1, transfusion of ≥1 unit of red blood cells, or that was judged to be the cause of death. Bleeding independently associated with mortality after noncardiac surgery occurred in 17.3% of patients (2782). Death occurred in 5.8% of patients with BIMS (161/2782), 1.3% (39/3028) who met bleeding screening criteria but not BIMS criteria, and 1.1% (115/10 269) without bleeding. BIMS was associated with mortality (adjusted hazard ratio: 1.87; 95% confidence interval: 1.42-2.47). We estimated the proportion of 30-day postoperative deaths potentially attributable to BIMS to be 20.1-31.9%. CONCLUSIONS: Bleeding independently associated with mortality after noncardiac surgery (BIMS), defined as bleeding that leads to a postoperative haemoglobin <70 g L-1, blood transfusion, or that is judged to be the cause of death, is common and may account for a quarter of deaths after noncardiac surgery. 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 levels of natriuretic peptides and the incidence of postoperative atrial fibrillation after noncardiac surgery: a prospective cohort study.

BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with clinically significant short- and long-term complications after noncardiac surgery. Our aim was to describe the incidence of clinically important POAF after noncardiac surgery and establish the prognostic value of N-terminal pro-brain-type natriuretic peptide (NT-proBNP) in this context. METHODS: The Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) Study was a prospective cohort study involving patients aged 45 years and older who had inpatient noncardiac surgery that was performed between August 2007 and November 2013. We determined 30-day incidence of clinically important POAF (i.e., resulting in angina, congestive heart failure, symptomatic hypotension or requiring treatment) using logistic regression models to analyze the association between preoperative NT-proBNP and POAF. RESULTS: In 37 664 patients with no history of atrial fibrillation, we found that the incidence of POAF was 1.0% (95% confidence interval [CI] 0.9%-1.1%; 369 events); 3.2% (95% CI 2.3%-4.4%) in patients undergoing major thoracic surgery, 1.3% (95% CI 1.2%-1.5%) in patients undergoing major nonthoracic surgery and 0.2% (95% CI 0.1%-0.3%) in patients undergoing low-risk surgery. In a subgroup of 9789 patients with preoperative NT-proBNP measurements, the biomarker improved the prediction of POAF risk over conventional prognostic factors (likelihood ratio test p < 0.001; fraction of new information from NT-proBNP was 16%). Compared with a reference NT-proBNP measurement set at 100 ng/L, adjusted odds ratios for the occurrence of POAF were 1.31 (95% CI 1.15-1.49) at 200 ng/L, 2.07 (95% CI 1.27-3.36) at 1500 ng/L and 2.39 (95% CI 1.26-4.51) at 3000 ng/L. INTERPRETATION: We determined that the incidence of clinically important POAF after noncardiac surgery was 1.0%. We also found that preoperative NT-proBNP levels were associated with POAF independent of established prognostic factors. Trial registration: ClinicalTrials.gov, no. NCT00512109.