Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial.

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared to intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis-when 75% of anticipated participants had completed follow up-the Data and Safety Monitoring Board recommended to terminate the trial, and upon unblinding, the Operations Committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group and in 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5%; 95% CI, -0.9 to 0.03; P = .07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3%; 95% CI, 5.2 to 11.5; P = .007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared to the intravenous group was 8.2% (95% CI, 3.4 to 12.9). CONCLUSIONS: Among patients having cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared to intravenous tranexamic acid.

The effect of perioperative benzodiazepine administration on postoperative nausea and vomiting: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Despite recent systematic reviews suggesting their benefit for postoperative nausea, vomiting, or both (PONV) prevention, benzodiazepines have not been incorporated into guidelines for PONV prophylaxis because of concerns about possible adverse effects. We conducted an updated meta-analysis to inform future practice guidelines. METHODS: We included randomised controlled trials (RCTs) of all languages comparing benzodiazepines with non-benzodiazepine comparators in adults undergoing inpatient surgery. Our outcomes were postoperative nausea, vomiting, or both. We assessed risk of bias for RCTs using the Cochrane Risk of Bias tool. We pooled data using a random-effects model and assessed the quality of evidence for each outcome using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: We screened 31 413 abstracts and 950 full texts. We included 119 RCTs; 104 were included in quantitative synthesis. Based on moderate certainty evidence, we found that perioperative benzodiazepine administration reduced the incidence of PONV (52 studies, n=5086, relative risk [RR]: 0.77, 95% confidence interval [CI] 0.66-0.89; number needed to treat [NNT] 16; moderate certainty), postoperative nausea (55 studies, n=5916, RR: 0.72, 95% CI 0.62-0.83; NNT 21; moderate certainty), and postoperative vomiting (52 studies, n=5909, RR: 0.74, 95% CI 0.60-0.91; NNT 55; moderate certainty). CONCLUSIONS: Moderate quality evidence shows that perioperative benzodiazepine administration decreases the incidence of PONV. The results of this systematic review and meta-analysis will inform future clinical practice guidelines. SYSTEMATIC REVIEW PROTOCOL: The protocol for this systematic review was pre-registered with PROSPERO International Prospective Register of Systematic Reviews (CRD42022361088) and published in BMJ Open (PMID 31831540).

Children's judgments on the acceptability of prejudice.

By middle childhood, children become aware that discriminatory behavior is unacceptable; however, the development of their anti-prejudice sentiments is largely unknown. Across two studies, 333 Australian 5- to 10-year-olds (51% female, majority White) were asked how acceptable they thought it was to have prejudicial sentiments toward 25 different targets. Children responded privately through a novel digital paradigm designed to minimize social-desirability biases. With age, children were more likely to display anti-prejudice sentiments toward targets who are prosocial, vulnerable, and of minority race and linguistic backgrounds. In contrast, they judged prejudice as "okay" for targets who are antisocial and negatively regarded in society. These findings suggest that children's perceptions of prejudice become increasingly nuanced and adult-like across the primary school years.

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.

Risk Scores for Prediction of Postoperative Atrial Fibrillation After Cardiac Surgery: A Systematic Review and Meta-Analysis.

Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and is associated with poor clinical outcomes. The objective of this systematic review and meta-analysis was to assess the performance of risk scores to predict POAF in cardiac surgery patients. We searched MEDLINE, Embase, and Cochrane CENTRAL for studies that developed/evaluated a POAF risk prediction model. Pairs of reviewers independently screened studies and extracted data. We pooled area under the receiver operating curves (AUCs), sensitivity and specificity, and adjusted odds ratios from multivariable regression analyses using the generic inverse variance method and random effects models. Forty-three studies (n = 63,847) were included in the quantitative synthesis. Most scores were originally developed for other purposes but evaluated for predicting POAF. Pooled AUC revealed moderate POAF discrimination for the EuroSCORE II (AUC 0.59, 95% confidence interval [CI] 0.54 to 0.65), Society of Thoracic Surgeons (AUC 0.60, 95% CI 0.56 to 0.63), EuroSCORE (AUC 0.63, 95% CI 0.58 to 0.68), CHADS2 (AUC 0.66, 95% CI 0.57 to 0.75), POAF Score (AUC 0.66, 95% CI 0.63 to 0.68), HATCH (AUC 0.67, 95% CI 0.57 to 0.75), CHA2DS2-VASc (AUC 0.68, 95% CI 0.60 to 0.75) and SYNTAX scores (AUC 0.74, 95% CI 0.71 to 0.78). Pooled analyses at specific cutoffs of the CHA2DS2-VASc, CHADS2, HATCH, and POAF scores demonstrated moderate-to-high sensitivity (range 46% to 87%) and low-to-moderate specificity (range 31% to 70%) for POAF prediction. In conclusion, existing clinical risk scores offer at best moderate prediction for POAF after cardiac surgery. Better models are needed to guide POAF risk stratification in cardiac surgery patients.

Landiolol for the prevention of postoperative atrial fibrillation after cardiac surgery: a systematic review and meta-analysis.

PURPOSE: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery. Although the evidence suggests that beta blockers prevent POAF, they often cause hypotension. Landiolol, an ultra-short-acting ß1 blocker, may prevent POAF, without adverse hemodynamic consequences. SOURCE: We searched MEDLINE, CENTRAL, Embase, and trial registries between January 1970 and March 2022. We included randomized controlled trials (RCTs) that evaluated the effect of landiolol for the prevention of POAF after cardiac surgery. Two reviewers independently assessed eligibility, extracted data, and assessed risk of bias using the Risk of Bias 2.0 tool. We pooled data using random-effects models. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess certainty of evidence. PRINCIPAL FINDINGS: Nine RCTs including 868 participants met the eligibility criteria. Patients randomized to landiolol (56/460) had less POAF compared with controls (133/408) with a relative risk (RR) of 0.40 (95% confidence interval [CI], 0.30 to 0.54; I2 = 0%;) and an absolute risk of 12.2% vs 32.6% (absolute risk difference, 20.4%; 95% CI, 15.0 to 25.0). Landiolol resulted in a shorter hospital length-of-stay (LOS) (268 patients; mean difference, -2.32 days; 95% CI, -4.02 to -0.57; I2 = 0%). We found no significant difference in bradycardia (RR, 1.11; 95% CI, 0.48 to 2.56; I2 = 0%). No hypotension was reported with landiolol. We judged the certainty of evidence as moderate for POAF (because of indirectness as outcomes were not clearly defined) and low for LOS (because of imprecision and concern of reporting bias). CONCLUSION: In patients undergoing cardiac surgery, landiolol likely reduces POAF and may reduce LOS. A definitive large RCT is needed to confirm these findings. STUDY REGISTRATION: PROSPERO (CRD42021262703); registered 25 July 2021.

RéSUMé: OBJECTIF: La fibrillation auriculaire postopératoire (FAPO) est une complication fréquente après une chirurgie cardiaque. Bien que les données probantes suggèrent que les bêta-bloqueurs préviennent la FAPO, ces agents provoquent souvent une hypotension. Le landiolol, un ß1-bloqueur à action ultra-courte, pourrait prévenir la FAPO sans conséquences hémodynamiques indésirables. SOURCES: Nous avons effectué des recherches dans les bases de données MEDLINE, CENTRAL et Embase, et dans les registres d'études publiées entre janvier 1970 et mars 2022. Nous avons inclus les études randomisées contrôlées (ERC) évaluant l'effet du landiolol pour la prévention de la FAPO après une chirurgie cardiaque. Deux personnes ont indépendamment révisé l'éligibilité, extrait les données et évalué le risque de biais à l'aide de l'outil Risque de biais 2.0. Nous avons regroupé les données à l'aide de modèles à effets aléatoires. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes. CONSTATATIONS PRINCIPALES: Neuf ERC incluant 868 personnes remplissaient les critères d'éligibilité. Les patient·es randomisé·es dans le groupe landiolol (56/460) présentaient moins de FAPO que les témoins (133/408), avec un risque relatif (RR) de 0,40 (intervalle de confiance [IC] à 95 %, 0,30 à 0,54; I2 = 0 %) et un risque absolu de 12,2 % vs 32,6 % (différence de risque absolue, 20,4 %; IC 95 % 95 %, 15,0 à 25,0). Le landiolol a entraîné une durée de séjour hospitalier plus courte (268 patient·es; différence moyenne, −2,32 jours; IC 95 %, −4,02 à −0,57; I2 = 0 %). Nous n'avons trouvé aucune différence significative en matière de bradycardie (RR, 1,11; IC 95 %, 0,48 à 2,56; I2 = 0 %). Aucune hypotension n'a été rapportée avec le landiolol. Nous avons jugé que la certitude des données probantes était modérée pour la FAPO (en raison du caractère indirect car les critères d'évaluation n'étaient pas clairement définis) et faible pour la durée de séjour hospitalier (en raison de l'imprécision et de questionnements concernant le biais de déclaration). CONCLUSION: Chez les patient·es bénéficiant d'une chirurgie cardiaque, le landiolol réduit probablement la FAPO et peut réduire la durée de séjour hospitalier. Une ERC définitive à grande échelle est nécessaire pour confirmer ces résultats. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021262703); enregistrée le 25 juillet 2021.

Perioperative Factors Associated With Postoperative Delirium in Patients Undergoing Noncardiac Surgery: An Individual Patient Data Meta-Analysis.

Importance: Postoperative delirium (POD) is a common and serious complication after surgery. Various predisposing factors are associated with POD, but their magnitude and importance using an individual patient data (IPD) meta-analysis have not been assessed. Objective: To identify perioperative factors associated with POD and assess their relative prognostic value among adults undergoing noncardiac surgery. Data Sources: MEDLINE, EMBASE, and CINAHL from inception to May 2020. Study Selection: Studies were included that (1) enrolled adult patients undergoing noncardiac surgery, (2) assessed perioperative risk factors for POD, and (3) measured the incidence of delirium (measured using a validated approach). Data were analyzed in 2020. Data Extraction and Synthesis: Individual patient data were pooled from 21 studies and 1-stage meta-analysis was performed using multilevel mixed-effects logistic regression after a multivariable imputation via chained equations model to impute missing data. Main Outcomes and Measures: The end point of interest was POD diagnosed up to 10 days after a procedure. A wide range of perioperative risk factors was considered as potentially associated with POD. Results: A total of 192 studies met the eligibility criteria, and IPD were acquired from 21 studies that enrolled 8382 patients. Almost 1 in 5 patients developed POD (18%), and an increased risk of POD was associated with American Society of Anesthesiologists (ASA) status 4 (odds ratio [OR], 2.43; 95% CI, 1.42-4.14), older age (OR for 65-85 years, 2.67; 95% CI, 2.16-3.29; OR for >85 years, 6.24; 95% CI, 4.65-8.37), low body mass index (OR for body mass index <18.5, 2.25; 95% CI, 1.64-3.09), history of delirium (OR, 3.9; 95% CI, 2.69-5.66), preoperative cognitive impairment (OR, 3.99; 95% CI, 2.94-5.43), and preoperative C-reactive protein levels (OR for 5-10 mg/dL, 2.35; 95% CI, 1.59-3.50; OR for >10 mg/dL, 3.56; 95% CI, 2.46-5.17). Completing a college degree or higher was associated with a decreased likelihood of developing POD (OR 0.45; 95% CI, 0.28-0.72). Conclusions and Relevance: In this systematic review and meta-analysis of individual patient data, several important factors associated with POD were found that may help identify patients at high risk and may have utility in clinical practice to inform patients and caregivers about the expected risk of developing delirium after surgery. Future studies should explore strategies to reduce delirium after surgery.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free): A Protocol for a Multi-centre Randomized Cluster Crossover Trial.

Delirium is common after cardiac surgery and is associated with adverse outcomes. Administration of benzodiazepines before and after cardiac surgery is associated with delirium; guidelines recommend minimizing their use. Benzodiazepine administration during cardiac surgery remains common because of its recognized benefits. The Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free) trial is a randomized cluster crossover trial evaluating whether an institutional policy of restricting intraoperative benzodiazepine administration (ie, ≥ 90% of patients do not receive benzodiazepines during cardiac surgery), as compared with a policy of liberal intraoperative benzodiazepine administration (ie, ≥ 90% of patients receive ≥ 0.03 mg/kg midazolam equivalent), reduces delirium. Hospitals performing ≥ 250 cardiac surgeries a year are included if their cardiac anesthesia group agrees to apply both benzodiazepine policies per their randomization, and patients are assessed for postoperative delirium every 12 hours in routine clinical care. Hospitals apply the restricted or liberal benzodiazepine policy during 12 to 18 crossover periods of 4 weeks each. Randomization for all periods takes place in advance of site startup; sites are notified of their allocated policy during the last week of each crossover period. Policies are applied to all patients undergoing cardiac surgery during the trial period. The primary outcome is the incidence of delirium at up to 72 hours after surgery. The B-Free trial will enroll ≥ 18,000 patients undergoing cardiac surgery at 20 hospitals across North America. Delirium is common after cardiac surgery, and benzodiazepines are associated with the occurrence of delirium. The B-Free trial will determine whether an institutional policy restricting the administration of benzodiazepines during cardiac surgery reduces the incidence of delirium after cardiac surgery. Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

L'état confusionnel est fréquent après une chirurgie cardiaque et il est associé à des complications. L'administration de benzodiazépines avant et après une chirurgie cardiaque est associée à l'état confusionnel; dans les lignes directrices, on recommande de réduire leur utilisation au minimum. L'administration de benzodiazépines pendant une chirurgie cardiaque demeure fréquente, en raison des leurs bienfaits reconnus. L'essai B-Free (Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium ou l'anesthésie sans benzodiazépine en contexte de chirurgie cardiaque pour la réduction de l'état confusionnel postopératoire) est un essai à répartition aléatoire par grappes et avec permutation, visant à évaluer si une politique institutionnelle de restriction de l'administration peropératoire de benzodiazépines (c.-à-d. que ≥ 90 % des patients ne reçoivent pas de benzodiazépines durant une chirurgie cardiaque) réduit l'état confusionnel, comparativement à une politique d'administration peropératoire libérale de benzodiazépines (c.-à-d. que ≥ 90 % des patients reçoivent ≥ 0,03 mg/kg d'équivalent du midazolam). Des hôpitaux effectuant au moins 250 chirurgies cardiaques par année sont inclus dans l'essai si leurs équipes d'anesthésie cardiaque acceptent d'appliquer les deux politiques relatives aux benzodiazépines en vertu de la répartition aléatoire et si les patients sont évalués toutes les 12 heures, en ce qui a trait à l'état confusionnel postopératoire, dans le cadre des soins cliniques habituels. Les hôpitaux mettent en œuvre la politique d'administration restreinte ou libérale de benzodiazépines durant 12 à 18 périodes de permutation de 4 semaines chacune. La répartition aléatoire de l'ensemble des périodes a lieu avant le début de l'essai à l'hôpital; les établissements sont avisés de la politique qui leur est attribuée au cours de la dernière semaine de chaque période de permutation. Les politiques sont appliquées à tous les patients qui subissent une chirurgie cardiaque durant la période de l'essai. Le critère d'évaluation principal est l'incidence de l'état confusionnel dans les 72 heures suivant l'intervention chirurgicale. L'étude B-Free inclura au moins 18 000 patients qui subiront une chirurgie cardiaque dans 20 hôpitaux en l'Amérique du Nord. L'état confusionnel est fréquent après une chirurgie cardiaque, et les benzodiazépines sont associées à la survenue de l'état confusionnel. L'essai B-Free permettra de déterminer si une politique institutionnelle de restriction de l'administration de benzodiazépines durant une chirurgie cardiaque réduit l'incidence de l'état confusionnel après une telle chirurgie.Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

Intraoperative use of balanced crystalloids versus 0.9% saline: a systematic review and meta-analysis of randomised controlled studies.

BACKGROUND: The evidence regarding optimal crystalloid use in the perioperative period remains unclear. As the primary aim of this study, we sought to summarise the data from RCTs examining whether use of balanced crystalloids compared with 0.9% saline (saline) leads to differences in patient-important outcomes. METHODS: We searched Ovid MEDLINE, Embase, the Cochrane library, and Clinicaltrials.gov, from inception until December 15, 2022, and included RCTs that intraoperatively randomised adult participants to receive either balanced fluids or saline. We pooled data using a random-effects model and present risk ratios (RRs) or mean differences (MDs), along with 95% confidence intervals (CIs). We assessed individual study risk of bias using the modified Cochrane tool, and certainty of evidence using GRADE. RESULTS: Of 5959 citations, we included 38 RCTs (n=3776 patients). Pooled analysis showed that intraoperative use of balanced fluids compared with saline had an uncertain effect on postoperative mortality analysed at the longest point of follow-up (RR 1.51, 95% CI: 0.42-5.36) and postoperative need for renal replacement therapy (RR 0.95, 95% CI: 0.56-1.59), both very low certainty. Furthermore, use of balanced crystalloids probably leads to a higher postoperative serum pH (MD 0.05, 95% CI: 0.04-0.06), moderate certainty. CONCLUSIONS: Use of balanced crystalloids, compared with saline, in the perioperative setting has an uncertain effect on mortality and need for renal replacement therapy but probably improves postoperative acid-base status. Further research is needed to determine whether balanced crystalloid use affects patient-important outcomes. CLINICAL TRIAL REGISTRATION: CRD42022367593.

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.

Effect of perioperative benzodiazepine use on intraoperative awareness and postoperative delirium: a systematic review and meta-analysis of randomised controlled trials and observational studies.

BACKGROUND: Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits. METHODS: We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality. RESULTS: We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I2=72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I2=13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I2=35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I2=98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality). CONCLUSIONS: In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42019128144.

Is Your Accent Right for the Job? A Meta-Analysis on Accent Bias in Hiring Decisions.

Standard-accented job candidates are perceived as more hireable than non-standard-accented candidates. Two broad perspectives have emerged as to what drives this effect: (a) that it is a pragmatic response to the perception that non-standard accents can impede job-relevant communication (processing fluency explanation) and/or (b) that non-standard accents signal "otherness" and candidates are devalued as a result (prejudice explanation). This meta-analytic integration of 139 effect sizes (N = 4,576) examined these two perspectives. Standard-accented candidates were considered more hireable than non-standard-accented candidates (d = 0.47)-a bias that was stronger for high communication jobs. Other findings, however, are difficult to explain from a processing fluency explanation: candidates' relative comprehensibility was not a significant moderator of hiring bias. Moreover, the degree of accent bias was associated with perceptions of the candidates' social status, and accent bias was particularly pronounced among female candidates and for candidates who spoke in foreign (as compared with regional) accents.

Dexmedetomidine vs other sedatives in critically ill mechanically ventilated adults: a systematic review and meta-analysis of randomized trials.

Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU). Dexmedetomidine is an alternative sedative that may achieve lighter sedation, reduce delirium, and provide analgesia. Our objective was to perform a comprehensive systematic review summarizing the large body of evidence, determining if dexmedetomidine reduces delirium compared to conventional sedatives. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and the WHO ICTRP from inception to October 2021. Independent pairs of reviewers identified randomized clinical trials comparing dexmedetomidine to other sedatives for mechanically ventilated adults in the ICU. We conducted meta-analyses using random-effects models. The results were reported as relative risks (RRs) for binary outcomes and mean differences (MDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs). In total, 77 randomized trials (n = 11,997) were included. Compared to other sedatives, dexmedetomidine reduced the risk of delirium (RR 0.67, 95% CI 0.55 to 0.81; moderate certainty), the duration of mechanical ventilation (MD - 1.8 h, 95% CI - 2.89 to - 0.71; low certainty), and ICU length of stay (MD - 0.32 days, 95% CI - 0.42 to - 0.22; low certainty). Dexmedetomidine use increased the risk of bradycardia (RR 2.39, 95% CI 1.82 to 3.13; moderate certainty) and hypotension (RR 1.32, 95% CI 1.07 to 1.63; low certainty). In mechanically ventilated adults, the use of dexmedetomidine compared to other sedatives, resulted in a lower risk of delirium, and a modest reduction in duration of mechanical ventilation and ICU stay, but increased the risks of bradycardia and hypotension.

Use of dexmedetomidine for sedation in mechanically ventilated adult ICU patients: a rapid practice guideline.

PURPOSE: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM­RPG) was to formulate evidence­based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU). METHODS: We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web­based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities. RESULTS: The ICM­RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia". CONCLUSION: This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.

Use of dexmedetomidine for sedation in mechanically ventilated adult ICU patients: a rapid practice guideline

The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM­RPG) was to formulate evidence­based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU). We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web­based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities. The ICM­RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia". This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.

High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).

Multicentre analysis of practice patterns regarding benzodiazepine use in cardiac surgery.

BACKGROUND: There is controversy regarding optimal use of benzodiazepines during cardiac surgery, and it is unknown whether and to what extent there is variation in practice. We sought to describe benzodiazepine use and sources of variation during cardiac surgeries across patients, clinicians, and institutions. METHODS: We conducted an analysis of adult cardiac surgeries across a multicentre consortium of USA academic and private hospitals from 2014 to 2019. The primary outcome was administration of a benzodiazepine from 2 h before anaesthesia start until anaesthesia end. Institutional-, clinician-, and patient-level variables were analysed via multilevel mixed-effects models. RESULTS: Of 65 508 patients cared for by 825 anaesthesiology attending clinicians (consultants) at 33 institutions, 58 004 patients (88.5%) received benzodiazepines with a median midazolam-equivalent dose of 4.0 mg (inter-quartile range [IQR], 2.0-6.0 mg). Variation in benzodiazepine dosage administration was 54.7% attributable to institution, 14.7% to primary attending anaesthesiology clinician, and 30.5% to patient factors. The adjusted median odds ratio for two similar patients receiving a benzodiazepine was 2.68 between two randomly selected clinicians and 4.19 between two randomly selected institutions. Factors strongly associated (adjusted odds ratio, <0.75, or >1.25) with significantly decreased likelihoods of benzodiazepine administration included older age (>80 vs ≤50 yr; adjusted odds ratio=0.04; 95% CI, 0.04-0.05), university affiliation (0.08, 0.02-0.35), recent year of surgery (0.42, 0.37-0.49), and low clinician case volume (0.44, 0.25-0.75). Factors strongly associated with significantly increased likelihoods of benzodiazepine administration included cardiopulmonary bypass (2.26, 1.99-2.55), and drug use history (1.29, 1.02-1.65). CONCLUSIONS: Two-thirds of the variation in benzodiazepine administration during cardiac surgery are associated with institutions and attending anaesthesiology clinicians (consultants). These data, showing wide variations in administration, suggest that rigorous research is needed to guide evidence-based and patient-centred benzodiazepine administration.