Jessica Spence

Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery

Importance Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). Objective To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). Design, Setting, and Participants Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. Exposures Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. Main Outcomes and Measures A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. Results Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT <5 ng/L), peak postoperative hsTnT levels of 20 to less than 65 ng/L, 65 to less than 1000 ng/L, and 1000 ng/L or higher had 30-day mortality rates of 3.0% (123/4049; 95% CI, 2.6%-3.6%), 9.1% (102/1118; 95% CI, 7.6%-11.0%), and 29.6% (16/54; 95% CI, 19.1%-42.8%), with corresponding adjusted HRs of 23.63 (95% CI, 10.32-54.09), 70.34 (95% CI, 30.60-161.71), and 227.01 (95% CI, 87.35-589.92), respectively. An absolute hsTnT change of 5 ng/L or higher was associated with an increased risk of 30-day mortality (adjusted HR, 4.69; 95% CI, 3.52-6.25). An elevated postoperative hsTnT (ie, 20 to <65 ng/L with an absolute change ≥5 ng/L or hsTnT ≥65 ng/L) without an ischemic feature was associated with 30-day mortality (adjusted HR, 3.20; 95% CI, 2.37-4.32). Among the 3904 patients (17.9%; 95% CI, 17.4%-18.4%) with MINS, 3633 (93.1%; 95% CI, 92.2%-93.8%) did not experience an ischemic symptom. Conclusions and Relevance Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

Double-adjustment in propensity score matching analysis: choosing a threshold for considering residual imbalance

BackgroundDouble-adjustment can be used to remove confounding if imbalance exists after propensity score (PS) matching. However, it is not always possible to include all covariates in adjustment. We aimed to find the optimal imbalance threshold for entering covariates into regression.MethodsWe conducted a series of Monte Carlo simulations on virtual populations of 5,000 subjects. We performed PS 1:1 nearest-neighbor matching on each sample. We calculated standardized mean differences across groups to detect any remaining imbalance in the matched samples. We examined 25 thresholds (from 0.01 to 0.25, stepwise 0.01) for considering residual imbalance. The treatment effect was estimated using logistic regression that contained only those covariates considered to be unbalanced by these thresholds.ResultsWe showed that regression adjustment could dramatically remove residual confounding bias when it included all of the covariates with a standardized difference greater than 0.10. The additional benefit was negligible when we also adjusted for covariates with less imbalance. We found that the mean squared error of the estimates was minimized under the same conditions.ConclusionIf covariate balance is not achieved, we recommend reiterating PS modeling until standardized differences below 0.10 are achieved on most covariates. In case of remaining imbalance, a double adjustment might be worth considering.

Surgical ablation of atrial fibrillation: a systematic review and meta-analysis of randomized controlled trials

Aims The aim of this review was to assess the effect of concomitant surgical atrial fibrillation (AF) ablation on postoperative freedom from AF and patient-important outcomes. Methods and results We searched Cochrane CENTRAL, MEDLINE, and EMBASE databases from inception to May 2016 for randomized controlled trials (RCTs) evaluating surgical AF ablation using any lesion set vs. no surgical AF ablation in adults with AF undergoing cardiac surgery. We performed screening, risk-of-bias evaluation, and data collection independently and in duplicate. We evaluated risk of bias with the modified Cochrane tool, quality of evidence using GRADE framework, and pooled data with a random-effects model. Of the 23 included studies, only one was considered at low risk of bias. Surgical AF ablation was associated with more freedom from AF at 12 months [relative risk (RR) = 2.32, 95% confidence interval (CI) 1.92-2.80; P < 0.001, low quality]. However, no significant difference was seen in mortality (RR = 1.07, 95% CI 0.72-1.52; P = 0.41, moderate quality), stroke (RR = 1.19, 95% CI 0.59-2.39; P = 0.63, moderate quality), or pacemaker implantation (RR = 1.28, 95% CI 0.85-1.95; P = 0.24, high quality). Comparing biatrial and left-sided lesion sets showed no difference in mortality (P-interaction = 0.60) or stroke (P-interaction = 0.12). At 12 months, biatrial procedures led to more freedom from AF (RR = 2.80, 95% CI 2.13-3.68; P < 0.0001) when compared with left-sided ablation (RR = 2.00, 95% CI 1.68-2.39; P < 0.0001) (P-interaction = 0.04) Biatrial procedures appear to increase the risk for pacemaker (RR = 2.68, 95% CI 1.41-5.11; P = 0.002) compared with no ablation while left-sided ablation does not (RR = 1.08, 95% CI 0.67-1.74; P = 0.76) (P-interaction = 0.03). Conclusion Surgical AF ablation during cardiac surgery improves freedom from AF. However, impact on patient-important outcomes including mortality and stroke has not shown statistical significance in current RCT evidence. Biatrial compared with left-sided lesion sets showed no difference in mortality or stroke but were associated with significantly increased freedom from AF and risk for pacemaker requirement.

Variation in Diagnostic Testing in Icus: A Comparison of Teaching and Nonteaching Hospitals in a Regional System*

Objectives:To explore variation in the use of diagnostic testing in ICUs, with emphasis on differences between teaching and nonteaching ICUs. Design:Retrospective review of a prospective clinical ICU database. Setting:Five teaching and four nonteaching ICUs in Winnipeg, Canada, during 2006–2010. Patients:All adults admitted to the nine ICUs during the study period were eligible. After excluding subgroups restricted to teaching ICUs, inter-ICU transfers, prior ICU admission within 90 days, ICU length of stay less than 12 hours, and missing death dates, 10,262 patients were evaluated. Interventions:None. Measurements and Main Results:Our primary outcome variable (TotalTesting) was the cumulative number of nine common laboratory tests, three radiologic tests, and electrocardiograms performed in each ICU. We used multivariable median regression to identify factors associated with TotalTesting, including length of stay, demographics, admission details, type and severity of acute illness, and specific medical interventions. We estimated the predictive power of variables as the decline in pseudo-R2 (a goodness-of-fit measure for median regression) when omitting those variables from the model. Median (interquartile range) TotalTesting was 27 (18–49) in teaching ICUs and 20 (13–36) in nonteaching units. With multivariable adjustment, median TotalTesting was 7.1 higher (95% CI, 6.6–7.7) in teaching ICUs. The most influential variable was length of stay, accounting for almost half of the variation. ICU teaching status was the second most important factor, greater than the degree of physiologic derangement and details of medical management. Conclusions:After adjustment for confounding variables, patients in teaching ICUs had slightly but significantly more diagnostic tests done than those in nonteaching ICUs. In addition to increasing costs, prior studies have shown that excessive testing can cause harm in various ways and does not improve outcomes. Interventions to reduce testing should be directed to all caregivers with responsibility for ordering diagnostic tests, in both teaching and nonteaching institutions.

International Normalized Ratio Targets for Left-Sided Mechanical Valve Replacement

BACKGROUND Guidelines recommend higher international normalized ratio (INR) targets for patients with mechanical valves believed to be at higher risk for thromboembolism. Higher INR targets are associated with increased bleeding risk. We performed a systematic review and meta-analysis assessing effects of lower and higher INR targets on thromboembolic and bleeding risk in patients with mechanical heart valves. METHODS We searched Cochrane CENTRAL, MEDLINE and EMBASE for randomized controlled trials (RCTs) evaluating lower versus higher INR targets for adults with bileaflet mechanical valves. We performed title and abstract screening, full-text review, risk of bias evaluation and data collection independently and in duplicate. We pooled data using a random effects model and used the Grading of Recommendations Assessment, Development and Evaluation framework to evaluate overall quality of evidence. RESULTS We identified six RCTs (n = 5,497). Lower INR targets were associated with significantly less bleeding-22% versus 40% (relative risk [RR]: 0.54, 95% confidence interval [CI]: 0.31, 0.93, p = 0.03, very low quality). There was no difference in thromboembolism-2% in both groups (RR: 1.28, 95% CI: 0.88, 1.85, p = 0.20, very low quality) or mortality-5.5% with lower INR targets versus 8.5% (RR: 1.00, 95% CI: 0.82, 1.21, p = 0.47, moderate quality). CONCLUSION In patients with mechanical valves, higher INR targets are not supported by current evidence, which is of very low quality. In fact, our systematic review suggests that lower INR targets offer significantly lower bleeding risks with no significant difference in thromboembolic risk.

Surgical ablation of atrial fibrillation: a protocol for a systematic review and meta-analysis of randomised controlled trials

Introduction Atrial fibrillation (AF) affects 10% of patients undergoing cardiac surgery and is an independent risk factor for all-cause mortality, ischaemic stroke and heart failure. Surgical AF ablation has been shown to significantly improve maintenance of sinus rhythm, however, small to medium size trials conducted to date lack the power required to assess patient-important outcomes such as mortality, stroke, heart failure and health-related quality of life. Moreover, a recent randomised trial (RCT) suggested harm by surgical AF ablation with an almost threefold increase in the requirement for permanent pacemaker postablation. We aim to perform a systematic review and meta-analysis to evaluate efficacy and safety of surgical AF ablation compared to no surgical ablation. Methods and analysis We will search Cochrane CENTRAL, MEDLINE and EMBASE for RCTs evaluating the use of surgical AF ablation, including any lesion set, versus no surgical AF ablation in adults with AF undergoing any type of cardiac surgery. Outcomes of interest include mortality, embolic events, quality of life, rehospitalisation, freedom from AF and adverse events, including need for pacemaker and worsening heart failure. Independently and in duplicate, reviewers will screen references, assess eligibility of potentially relevant studies using predefined eligibility criteria and collect data using prepiloted forms. We will pool data using a random effects model and present results as relative risk with 95% CIs for dichotomous outcomes and as mean difference with 95% CI for continuous outcomes. We will assess risk of bias using the Cochrane Collaboration tool, and quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Ethics and dissemination Our results will help guide clinical practice by providing the most comprehensive analysis of risks and benefits associated with the procedure. Our results will be disseminated through publication in peer-reviewed journals and conference presentations. Trial registration number CRD42015025988.

Assessing the quality of evidence supporting patent foramen ovale closure over medical therapy after cryptogenic stroke

We read the recent article by Ahmad et al. with interest. This systematic review and meta-analysis compared patent foramen ovale (PFO) closure to medical therapy for patients with cryptogenic stroke. After pooling data from five studies, the authors concluded that PFO closure is superior to medical therapy (hazard ratio 0.32, 95% confidence interval 0.13–0.82, I = 73%), and called for updated guidelines reflecting these findings. When appraising the methodological rigor of the evidence, the authors concluded that the overall quality of individual trials was either ‘intermediate’ or ‘high’ and they did not provide an evaluation of their overall confidence in the body of evidence. In the approach recommended by GRADE, included trials should be dichotomized as high or low risk of bias according to the Cochrane framework. We applied this framework based on the information provided in Table 2; our judgements differed from those made by the study authors (Figure 1). In the PC, REDUCE, and RESPECT trials, the number of patients who were lost to follow-up in the intervention arm were large and exceeded the fragility index. Hence, we disagree that these trials were at low risk of attrition bias. We agree with Ahmad et al. that the open-label CLOSE, CLOSURE, and REDUCE trials were at risk of detection bias due to non-blinded adjudication. In consequence, each of the five trials in this meta-analysis is at risk of detection bias, attrition bias, or both biases; this places them at high overall risk of bias. Ahmad et al. also failed to consider other factors that affect quality of evidence. In the GRADE framework, summary findings based on randomized controlled trials start as high quality evidence but can be downgraded based on five categories—risk of bias, imprecision, inconsistency (also known as heterogeneity), indirectness, and publication bias. The summary data presented by the review authors is therefore of low quality, requiring downgrading for serious risk of bias, and substantial heterogeneity (I = 73%). Figure 1 Risk of bias summary: revised judgements about each risk of bias item for each included study. The green circles with ‘þ’ denote a low risk of bias for this study in this domain, the red circles with ‘-’ denote a high risk of bias for this study in this domain, and the yellow circles with ‘?’ denote an unclear risk of bias for this study in this domain.

When and how should we cluster and cross over: methodological and ethical issues (letter 1)

To the Editor, The editorial by Goldstein et al. expresses concern regarding the methods and ethics of our BenzodiazepineFree Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial, suggesting that waived consent cannot be justified when interventions are administered directly to individuals. In our view, however, international guidelines and current practice support the concept that trials evaluating treatments administered directly to individual patients can fulfill the requirements for a waiver of individual consent, provided that they have minimal risk. There are many completed and ongoing cluster trials that test policies related to the use of pharmacologic and other interventions where waiver of consent has been accepted. Such trials include: conventional vs incremental

Efficacy and safety of inhaled anaesthetic for postoperative sedation during mechanical ventilation in adult cardiac surgery patients: a systematic review and meta-analysis

&NA; The aim was to evaluate the efficacy and safety of volatile anaesthetic for postoperative sedation in adult cardiac surgery patients through a systematic review and meta‐analysis. We retrieved randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Web of Science, clinical trials registries, conference proceedings, and reference lists of included articles. Independent reviewers extracted data, including patient characteristics, type of intraoperative anaesthesia, inhaled anaesthetic used, comparator sedation, and outcomes of interest, using pre‐piloted forms. We assessed risk of bias using the Cochrane Tool and evaluated the strength of the evidence using the GRADE approach. Eight studies enrolling 610 patients were included. Seven had a high and one a low risk of bias. The times to extubation after intensive care unit (ICU) admission and sedation discontinuation were, respectively, 76 [95% confidence interval (CI) ‐150 to ‐ 2, I2=79%] and 74 min (95% CI ‐ 126 to ‐ 23, I2=96%) less in patients who were sedated using volatile anaesthetic. There was no difference in ICU or hospital length of stay. Patients who received volatile anaesthetic sedation had troponin concentrations that were 0.71 ng ml‐1 (95% CI 0.23‐1.2) lower than control patients. Reporting on other outcomes was varied and not suitable for meta‐analysis. Volatile anaesthetic sedation may be associated with a shorter time to extubation after cardiac surgery but no change in ICU or hospital length of stay. It is associated with a significantly lower postoperative troponin concentration, but the impact of this on adverse cardiovascular outcomes is uncertain. Blinded randomized trials using intention‐to‐treat analysis are required. PROSPERO registry number: 2016:CRD42016033874. Available from http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016033874.

Tranexamic Acid Administration During On-Pump Cardiac Surgery: A Survey of Current Practices Among Canadian Anesthetists Working in Academic Centers.

BACKGROUND: Tranexamic acid (TXA) is commonly administered during on-pump cardiac surgery to minimize bleeding. However, an optimal dosing regimen has not been described, and recent studies suggest that higher doses may be associated with seizure. Little is known about current practice among cardiac anesthetists. METHODS: We contacted all academic anesthesia departments in Canada to identify cardiac anesthetists, who represent the majority of practitioners. This group constituted our sampling frame. Information regarding participant demographics, TXA dose, and administration details were obtained by electronic survey. Responses were analyzed descriptively. To compare dose, we assumed an 80-kg patient and 3 hours of infusion time. The Kruskal-Wallis test was used to compare average dose across provinces. RESULTS: Among 341 Canadian academic cardiac anesthetists, 234 completed the survey (68.2% response rate). Among respondents, 86.3% administer TXA to all patients; 13.7% administer it to some. Most (68.4%) administer an infusion after a bolus; other modes included infusion (4.7%), single bolus (13.2%), 2 or more boluses (12.0%), or another regimen (1.7%). The mean (standard deviation) dose given was 49 mg/kg (24), with a range from 10 to 100 mg/kg. The mean dose varied across provinces from 23 to 55 mg/kg (P = .001). CONCLUSIONS: TXA is given to nearly all patients undergoing on-pump cardiac surgery at academic hospitals in Canada. However, there is significant heterogeneity in practice between individuals and across provinces. Further research is needed to determine the TXA dose that maximizes efficacy and minimizes side effects.