A Systematic Review and Meta-analysis Examining the Impact of Age on Perioperative Inflammatory Biomarkers.

BACKGROUND: Dysregulation of immune responses to surgical stress in older patients and those with frailty may manifest as differences in inflammatory biomarkers. We conducted a systematic review and meta-analysis to examine differences in perioperative inflammatory biomarkers between older and younger patients, and between patients with and without frailty. METHODS: MEDLINE, Embase, Cochrane, and CINAHL databases were searched (Inception to June 23, 2020). Observational or experimental studies reporting the perioperative level or activity of biomarkers in surgical patients stratified by age or frailty status were included. The primary outcome was inflammatory biomarkers (grouped by window of ascertainment: pre-op; post-op: <12 hours, 12-24 hours, 1-3 days, 3 days to 1 week, and >1 week). Quality assessment was conducted using the Newcastle-Ottawa Scale. Inverse-variance, random-effects meta-analysis was conducted. RESULTS: Forty-five studies (4263 patients) were included in the review, of which 36 were pooled for meta-analysis (28 noncardiac and 8 cardiac studies). Two studies investigated frailty as the exposure, while the remaining investigated age. In noncardiac studies, older patients had higher preoperative levels of interleukin (IL)-6 and C-reactive protein (CRP), lower preoperative levels of lymphocytes, and higher postoperative levels of IL-6 (<12 hours) and CRP (12-24 hours) than younger patients. In cardiac studies, older patients had higher preoperative levels of IL-6 and CRP and higher postoperative levels of IL-6 (<12 hours and >1 week). CONCLUSIONS: Our findings demonstrate a paucity of frailty-specific studies; however, the presence of age-associated differences in the perioperative inflammatory response is consistent with age-associated states of chronic systemic inflammation and immunosenescence. Additional studies assessing frailty-specific changes in the systemic biologic response to surgery may inform the development of targeted interventions.

Prophylaxis for patients at Risk to Eliminate Post-operative Atrial Fibrillation (PREP-AF trial): a protocol for a feasibility randomized controlled study.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent adverse event after thoracic surgery with associated morbidity, mortality, and healthcare costs. It has been shown to be preventable with prophylactic amiodarone, which is only recommended in high-risk individuals due to the potential associated side effects. Risk factors for POAF have been identified and incorporated into a prediction model to identify high-risk patients. Further evaluation in the form of a multicenter clinical trial is required to assess the effectiveness of prophylaxis specifically in this high-risk population. The feasibility of such a trial first needs to be assessed. METHODS: The PREP-AF trial is a double-blind randomized controlled feasibility trial. Individuals undergoing major thoracic surgery who are identified to be high-risk by the POAF prediction model will be randomized 1:1 to receive a short course of amiodarone vs. placebo in the immediate postoperative period. The primary outcome is feasibility, which will be measured by the number of eligible patients identified, consented, and randomized; intervention adherence; and measurement of future outcomes of a full trial. DISCUSSION: This study will determine the feasibility of a randomized controlled trial to assess the effectiveness of prophylactic amiodarone, in high-risk patients undergoing major thoracic surgery. This will inform the development of a multi-center trial to establish if prophylactic amiodarone is safe and effective at reducing the incidence of POAF. Preventing this adverse event will not only improve outcomes for patients but also reduce the associated health resource utilization and costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04392921 . Registered on 19 May 2020.

External Validation and Updating of the Cardiac Surgery Score for Prediction of Mortality in a Cardiac Surgery Intensive Care Unit.

OBJECTIVE: To externally validate the predictive performance of the logistic and additive Cardiac Surgery Score (CASUS), a postoperative severity of illness score designed specifically for prediction of mortality in the cardiac surgery intensive care unit. DESIGN: A retrospective analysis of prospectively collected data between July 1, 2012, and September 30, 2015. SETTING: Single university cardiac surgery intensive care unit in Canada. PARTICIPANTS: Consecutive adult patients (n = 4,519) admitted to the intensive care unit after cardiac surgery. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The mortality predicted by logistic CASUS was calculated for each patient on admission day 0 and postoperative days 2, 4, 7, and 10 using the original model equation. The mortality predicted by additive CASUS was determined on each day with separate logistic regression models, using the total score as a single variable. The observed mortality was 1.8%. Logistic CASUS overestimated mortality by 78%, 59%, 51%, 52%, and 29% on days 0, 2, 4, 7, and 10, respectively. After model updating with logistic calibration, logistic CASUS consistently provided estimates of death comparable with the observed mortality, as determined with the Hosmer-Lemeshow goodness-of-fit test. The stability of those estimates was confirmed by bootstrapping. Similar calibration results were obtained with additive CASUS. Logistic and additive CASUS had good discrimination with areas under the receiver operating characteristic curve greater than 0.7 on each study day. CONCLUSIONS: Recalibrated logistic CASUS reliably predicts mortality in the intensive care unit after cardiac surgery. Logistic regression models derived from additive CASUS perform as well as logistic CASUS.

Association of Frailty and Long-Term Survival in Patients Undergoing Coronary Artery Bypass Grafting.

BACKGROUND: Frailty is increasing in prevalence and poses a formidable challenge for clinicians. The cardiac surgery literature consists primarily of small single-center studies with limited follow-up, and the epidemiological features of frailty remain to be elucidated in long-term follow-up. METHODS AND RESULTS: We conducted a population-based, retrospective, cohort study in Ontario, Canada, between 2008 and 2015. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups frailty indicator (a multidimensional instrument validated for research using administrative data). The primary outcome was mortality. Mortality rates were calculated using the Kaplan-Meier method. The hazard of death was assessed using a multivariable Cox proportional hazard model. Of 40 083 patients, 8803 (22%) were frail. At 4±2 years of follow-up, age- and sex-standardized mortality rate per 1000 person-years was higher in frail (33; 95% confidence interval, 29-36) compared with nonfrail (22; 95% confidence interval, 19-24) patients. Frailty was associated with an increased risk of long-term mortality (adjusted hazard ratio, 1.20; 95% confidence interval, 1.12-1.28) and greater differences in the survival of patients between 40 and 74 years of age than in those who were ≥85 years old. CONCLUSIONS: Frailty was present in a large proportion of patients undergoing coronary artery bypass grafting and was independently associated with long-term mortality. The adjusted risk of frailty-related death was inversely proportional to age. Our findings highlight the need for more comprehensive preoperative risk stratification models to assist with optimal selection of operative candidates. In addition, we identified the <75 years age group as a potential target for comprehensive preoperative optimization programs, such as cardiac prehabilitation, nutritional augmentation, and psychosocial support.

Practice meta-environment of the cardiovascular perfusionist.

Though historically the development of cardiovascular perfusion grew out of the need for cardiopulmonary bypass, the application of technologies of extracorporeal support has more recently expanded beyond the traditional domain of the cardiac surgical operative and peri-operative environment. As a result, perfusionists are sometimes required to work in novel clinical settings. As part of our recent national survey to evaluate the effects of changes in entry-to-practice criteria introduced in Canada in 2006, we asked perfusionists if their current position as a perfusionist involves work outside the OR. We found that, in addition to regularly working in the Intensive Care Unit and Cardiac Catheterization Lab, 55.3% of respondents reported working "occasionally" in the Emergency Room and 74.7% reported working "occasionally" or "often" in other clinical areas. However, while 96% of respondents believed their training adequately prepared them for their job as a perfusionist, only 68% felt their training adequately prepared them for their duties outside the operating room. We also noted a trend that admission under experience-based entry-to-practice criteria was associated with a higher likelihood of perceived adequacy of training in preparation for duties outside the OR than education-based admission criteria (72% vs 59.4%, p=0.065). These findings raise important questions pertaining to the sufficiency of perfusion education in Canada and the influence of soft skills in preparing perfusionists for their duties, and indicate that a systematic study of the practice environment of cardiovascular perfusionists is timely.

Prospective External Validation of Three Preoperative Risk Scores for Prediction of New Onset Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is associated with early and late morbidity and mortality of cardiac surgical patients. Prophylactic treatment of atrial fibrillation (AF) has been recommended to improve outcome in cardiac surgical patients at high risk of developing POAF. Reliable models for prediction of POAF are needed to achieve that goal. This study attempted to externally validate 3 risk models proposed for preoperative prediction of POAF in cardiac surgical patients: the POAF score, the CHA2DS2-VASc score, and the Atrial Fibrillation Risk Index. METHODS: This was a prospective cohort study of 1416 adult patients who underwent nonemergent coronary artery bypass graft and/or valve surgery in a single cardiac surgical center between February 2014 and September 2015. A risk score for each of the 3 prediction models was calculated in each patient. All patients were followed for up to 2 weeks, or until hospital discharge, to observe the primary outcome of new onset AF requiring treatment. Discrimination was assessed using receiver operating characteristic curves. Calibration was assessed using the Pearson χ goodness-of-fit test and calibration plots. Utility of the score to implement AF prophylaxis based on the risk of POAF, in comparison to strategies of treating all patients, or not treating any patients, was assessed via a net benefit analysis. RESULTS: Of the 1416 patients included in this study, 478 had the primary outcome (33.8%). The areas under the receiver operating characteristic curve for prediction of POAF in the population subsets for which the scores were validated were as follows: 0.651 (95% confidence interval [CI], 0.621-0.681) for the POAF score, 0.593 (95% CI, 0.557-0.629) for the CHA2DS2-VASc score (P < .001 versus POAF score, P < .222 versus Atrial Fibrillation Risk Index), and 0.563 (95% CI, 0.522-0.604) for the Atrial Fibrillation Risk Index (P < .001 versus POAF score). The calibration analysis showed that the predictive models had a poor fit between the observed and expected rates of POAF. Net benefit analysis showed that AF preventive strategies based on these scores, and targeting patients with moderate or high risk of POAF, improve decision-making in comparison to preventive strategies of treating all patients. CONCLUSIONS: The 3 prediction scores evaluated in this study have limited ability to predict POAF in cardiac surgical patients. Despite this, they may be useful in preventive strategies targeting patients with moderate or high risk of PAOF in comparison with preventive strategies applied to all patients.

Effects of a change in entry-to-practice criteria for cardiovascular perfusion in Canada: results of a national survey.

INTRODUCTION: Years of experience and level of education are two important determinants of a clinician's expertise. While entry-to-practice criteria for admission to perfusion training in Canada changed from clinical experience-based criteria to education-based criteria in 2006, the effects of these changes have not been studied. OBJECTIVE: To determine the academic and clinical backgrounds of perfusionists in Canada, ascertain perceptions about the adequacy of training and evaluate the effects of the changes on the composition of the perfusion community of Canada. METHODS: An electronic questionnaire was distributed to all practicing perfusionists in Canada, addressing details regarding clinical experience, academic education and perceptions about the adequacy of training. RESULTS: Two hundred and twenty-eight questionnaires were completed, representing a 72% response rate. Perfusionists admitted under academic-based criteria have significantly higher levels of education (100% degree holders vs 69.1%, p<0.001), but less antecedent clinical training and experience (median, IQR: 0, 0 - 4.5 years vs 2, 2 - 8 years, p<0.0001), are younger (median age range 31-35 years vs 51-55 years, p<0.0001), more likely to be female (58.7% vs 41.3%, p=0.006) and are significantly more likely to enter perfusion because of attraction to the type of work (p=0.045). Many perfusionists (70, 32%) in Canada believe themselves inadequately trained for their clinical assignments outside the OR. In addition, 19% of perfusionists plan to retire over the next 10 years. CONCLUSIONS: The introduction of education-based entry criteria has changed the academic and clinical experience levels of perfusionists in Canada. Strategies designed to better prepare perfusionists for their clinical assignments outside the OR are merited.

Rocuronium versus succinylcholine for rapid sequence induction intubation.

BACKGROUND: Patients often require a rapid sequence induction (RSI) endotracheal intubation technique during emergencies or electively to protect against aspiration, increased intracranial pressure, or to facilitate intubation. Traditionally succinylcholine has been the most commonly used muscle relaxant for this purpose because of its fast onset and short duration; unfortunately, it can have serious side effects. Rocuronium has been suggested as an alternative to succinylcholine for intubation. This is an update of our Cochrane review published first in 2003 and then updated in 2008 and now in 2015. OBJECTIVES: To determine whether rocuronium creates intubating conditions comparable to those of succinylcholine during RSI intubation. SEARCH METHODS: In our initial review we searched all databases until March 2000, followed by an update to June 2007. This latest update included searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 2), MEDLINE (1966 to February Week 2 2015), and EMBASE (1988 to February 14 2015 ) for randomized controlled trials (RCTs) or controlled clinical trials (CCTs) relating to the use of rocuronium and succinylcholine. We included foreign language journals and handsearched the references of identified studies for additional citations. SELECTION CRITERIA: We included any RCT or CCT that reported intubating conditions in comparing the use of rocuronium and succinylcholine for RSI or modified RSI in any age group or clinical setting. The dose of rocuronium was at least 0.6 mg/kg and succinylcholine was at least 1 mg/kg. DATA COLLECTION AND ANALYSIS: Two authors (EN and DT) independently extracted data and assessed methodological quality for the 'Risk of bias' tables. We combined the outcomes in Review Manager 5 using a risk ratio (RR) with a random-effects model. MAIN RESULTS: The previous update (2008) had identified 53 potential studies and included 37 combined for meta-analysis. In this latest update we identified a further 13 studies and included 11, summarizing the results of 50 trials including 4151 participants. Overall, succinylcholine was superior to rocuronium for achieving excellent intubating conditions: RR 0.86 (95% confidence interval (CI) 0.81 to 0.92; n = 4151) and clinically acceptable intubation conditions (RR 0.97, 95% CI 0.95 to 0.99; n = 3992, 48 trials). A high incidence of detection bias amongst the trials coupled with significant heterogeneity provides moderate-quality evidence for these conclusions, which are unchanged from the previous update. Succinylcholine was more likely to produce excellent intubating conditions when using thiopental as the induction agent: RR 0.81 (95% CI: 0.73 to 0.88; n = 2302, 28 trials). In the previous update, we had concluded that propofol was the superior induction agent with succinylcholine. There were no reported incidences of severe adverse outcomes. We found no statistical difference in intubation conditions when succinylcholine was compared to 1.2 mg/kg rocuronium; however, succinylcholine was clinically superior as it has a shorter duration of action. AUTHORS' CONCLUSIONS: Succinylcholine created superior intubation conditions to rocuronium in achieving excellent and clinically acceptable intubating conditions.

Predicting New-Onset Postoperative Atrial Fibrillation in Cardiac Surgery Patients.

OBJECTIVE: To derive a simple clinical prediction rule identifying patients at high risk of developing new-onset postoperative atrial fibrillation (POAF) after cardiac surgery. DESIGN: Retrospective analysis on prospectively collected observational data. SETTING: A university-affiliated cardiac hospital. PARTICIPANTS: Adult patients undergoing coronary artery bypass grafting and/or valve surgery. INTERVENTIONS: Observation for the occurrence of new-onset postoperative atrial fibrillation. MEASUREMENTS AND MAIN RESULTS: Details on 28 preoperative variables from 999 patients were collected and significant predictors (p<0.2) were inserted into multivariable logistic regression and reconfirmed with recursive partitioning. A total of 305 (30.5%) patients developed new-onset POAF. Eleven variables were associated significantly with atrial fibrillation. A multivariable logistic regression model included left atrial dilatation, mitral valve disease, and age. Coefficients from the model were converted into a simple 7-point predictive score. The risk of POAF per score is: 15.0%, if 0; 20%, if 1; 27%, if 2; 35%, if 3; 44%, if 4; 53%, if 5; 62%, if 6; and 70%, if 7. A score of 4 has a sensitivity of 44% and a specificity of 82% for POAF. A score of 6 has a sensitivity of 11% and a specificity of 97%. Bootstrapping with 5,000 samples confirmed the final model provided consistent predictions. CONCLUSIONS: This study proposed a simple predictive score incorporating three risk variables to identify cardiac surgical patients at high risk of developing new-onset POAF. Preventive treatment should target patients ≥ 65 years with left atrial dilatation and mitral valve disease.

Comparison of the EuroSCORE and Cardiac Anesthesia Risk Evaluation (CARE) score for risk-adjusted mortality analysis in cardiac surgery.

OBJECTIVE: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) and the Cardiac Anesthesia Risk Evaluation (CARE) score are risk indices designed in the mid-1990 s to predict mortality after cardiac surgery. This study assesses their ability to provide risk-adjusted mortality in a contemporary cardiac surgical population. METHODS: The mortality probability was estimated with the additive and logistic EuroSCORE, and CARE score, for 3818 patients undergoing cardiac surgery at one institution between 1 April 2006 and 31 March 2009. Model discrimination was obtained using the area under the receiver operating characteristics (ROC) curve and calibration using the appropriate chi-square goodness-of-fit test. Recalibration of risk models was obtained by logistic calibration, when needed. Calculation of risk-adjusted mortality was performed for the institution and eight surgeons, using each model before and when needed, after recalibration. RESULTS: The area under the ROC curve is 0.72 (95% confidence interval (CI): 0.71-0.74) with the additive EuroSCORE, 0.84 (95% CI: 0.83-0.85) with the logistic EuroSCORE, and 0.79 (95% CI: 0.78-0.81) with the CARE score. The additive and logistic EuroSCORE have poor calibration, predicting a hospital mortality of 6.24% and 7.72%, respectively, versus an observed mortality of 3.25% (P < 0.001). Consequently, the risk-adjusted mortality obtained with those models is significantly underestimated for the institution and all surgeons. The CARE score has good calibration, predicting a mortality of 3.38% (P = 0.50). The hospital risk-adjusted mortality with the recalibrated additive and logistic EuroSCORE and CARE score is 3.24% (95% CI: 3.05-3.43%), 3.25% (95% CI: 3.05-3.44%), and 3.12% (95% CI: 2.94-3.34%), respectively. The individual surgeons' risk-adjusted mortality is similar with the recalibrated EuroSCORE models and CARE score, identifying two surgeons with higher rates than the hospital average mortality. CONCLUSIONS: The original additive and logistic EuroSCORE models significantly overestimate the risk of mortality after cardiac surgery. However, after recalibration both models provide reliable risk-adjusted mortality results. Despite its lower discrimination as compared with the logistic EuroSCORE, the CARE score remains calibrated a decade after its development. It is as robust as the recalibrated additive and logistic EuroSCORE to perform risk-adjusted mortality analysis.

Ternary nanoclusters of CuHgS, CuHgSe, and CuInS.

Two copper-mercury-chalcogenide clusters [Hg(15)Cu(20)E(25)(PPr(3))(18)] (1, E = S; 2, E = Se) are synthesized in good yield from the reaction of (Pr(3)P)(3)Cu-ESiMe(3) and (Pr(3)P)(2).Hg(OAc)(2) at low temperatures. Single-crystal X-ray analyses illustrate that the two ternary clusters are isomorphous and consist of a phosphine-stabilized core of mixed Hg, Cu, and E centers. Thermolysis of 1 leads to the formation of mercury metal and various forms of copper-sulfide. The copper-indium-sulfide cluster [Cu(6)In(8)S(13)Cl(4)(PEt(3))(12)] (3) is similarly prepared in 50% yield from (Et(3)P)(3)Cu-SSiMe(3), InCl(3), and S(SiMe(3))(2).