Trends and In-Hospital Mortality for Perioperative Myocardial Infarction After the Introduction of a Diagnostic Code for Type 2 Myocardial Infarction in the United States Between 2016 and 2018.

BACKGROUND: The frequency of perioperative myocardial infarction has been declining; however, previous studies have only described type 1 myocardial infarctions. Here, we evaluate the overall frequency of myocardial infarction with the addition of an International Classification of Diseases 10th revision (ICD-10-CM) code for type 2 myocardial infarction and the independent association with in-hospital mortality. METHODS: A longitudinal cohort study spanning the introduction of the ICD-10-CM diagnostic code for type 2 myocardial infarction using the National Inpatient Sample (NIS) from 2016 to 2018. Hospital discharges that included a primary surgical procedure code for intrathoracic, intraabdominal, or suprainguinal vascular surgery were included. Type 1 and type 2 myocardial infarctions were identified using ICD-10-CM codes. We used segmented logistic regression to estimate change in frequency of myocardial infarctions and multivariable logistic regression to determine the association with in-hospital mortality. RESULTS: A total of 360,264 unweighted discharges were included, representing 1,801,239 weighted discharges, with median age 59 and 56% female. The overall incidence of myocardial infarction was 0.76% (13,605/1,801,239). Before the introduction of type 2 myocardial infarction code, there was a small baseline decrease in the monthly frequency of perioperative myocardial infarctions (odds ratio [OR], 0.992; 95% confidence interval [CI], 0.984-1.000; P = .042), but no change in the trend after the introduction of the diagnostic code (OR, 0.998; 95% CI, 0.991-1.005; P = .50). In 2018, where there was an entire year where type 2 myocardial infarction was officially a diagnosis, the distribution of myocardial infarction type 1 was 8.8% (405/4580) ST elevation myocardial infarction (STEMI), 45.6% (2090/4580) non-ST elevation myocardial infarction (NSTEMI), and 45.5% (2085/4580) type 2 myocardial infarction. STEMI and NSTEMI were associated with increased in-hospital mortality (OR, 8.96; 95% CI, 6.20-12.96; P < .001 and OR, 1.59; 95% CI, 1.34-1.89; P < .001). A diagnosis of type 2 myocardial infarction was not associated with increased odds of in-hospital mortality (OR, 1.11; 95% CI, 0.81-1.53; P = .50) when accounting for surgical procedure, medical comorbidities, patient demographics, and hospital characteristics. CONCLUSIONS: The frequency of perioperative myocardial infarctions did not increase after the introduction of a new diagnostic code for type 2 myocardial infarctions. A diagnosis of type 2 myocardial infarction was not associated with increased in-patient mortality; however, few patients received invasive management that may have confirmed the diagnosis. Further research is needed to identify what type of intervention, if any, may improve outcomes in this patient population.

Persistent Brain Connectivity Changes in Healthy Volunteers Following Nitrous Oxide Inhalation.

Background: Nitrous oxide holds promise in the treatment of major depressive disorder. Its psychotropic effects and NMDA receptor antagonism have led to comparisons with ketamine. Despite longstanding use, persistent effects of nitrous oxide on the brain have not been characterized. Methods: Sixteen healthy volunteers were recruited in a double-blind crossover study. In randomized order, individuals underwent a 1-hour inhalation of either 50% nitrous oxide/oxygen or air/oxygen mixtures. At least two 7.5-minute echo-planar resting-state functional magnetic resonance imaging scans were obtained before and at 2 and 24 hours after each inhalation (average 130 min/participant). Using the time series of preprocessed, motion artifact-scrubbed, and nuisance covariate-regressed imaging data, interregional signal correlations were measured and converted to T scores. Hierarchical clustering and linear mixed-effects models were employed. Results: Nitrous oxide inhalation produced changes in global brain connectivity that persisted in the occipital cortex at 2 and 24 hours postinhalation (p < .05, false discovery rate-corrected). Analysis of resting-state networks demonstrated robust strengthening of connectivity between regions of the visual network and those of the dorsal attention network, across 2 and 24 hours after inhalation (p < .05, false discovery rate-corrected). Weaker changes in connectivity were found between the visual cortex and regions of the frontoparietal and default mode networks. Parallel analyses following air/oxygen inhalation yielded no significant changes in functional connectivity. Conclusions: Nitrous oxide inhalation in healthy volunteers revealed persistent increases in global connectivity between regions of primary visual cortex and dorsal attention network. These findings suggest that nitrous oxide inhalation induces neurophysiological cortical changes that persist for at least 24 hours.

Rare missense variants in the SH3 domain of PSTPIP1 are associated with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic, debilitating skin disease for which few treatment options are available. While most HS is sporadic, some rare kindred show a high-penetrance, autosomal-dominant inheritance. We wanted to identify rare variants that could contribute to HS risk in sporadic cases using candidate gene sequencing. We ultimately identified 21 genes for our capture panel. We included genes of the γ-secretase complex (n = 6) because rare variants in these genes sometimes cause familial HS. We added Notch receptor and ligand genes (n = 13) because γ-secretase is critical for processing Notch receptor signaling. Clinically, some people with PAPA (pyogenic arthritis, pyoderma gangrenosum, and acne) syndrome, a rare inflammatory disease, have concurrent HS. Rare variants in PSTPIP1 are known to cause PAPA syndrome, so we included PSTPIP1 and PSTPIP2 in the capture panel. We screened 117 individuals with HS for rare variations and calculated the expected burden using Genome Aggregation Database (gnomAD) allele frequencies. We discovered two pathogenic loss-of-function variants in NCSTN. This class of NCSTN variant can cause familial HS. There was no increased burden of rare variations in any γ-secretase complex gene. We did find that individuals with HS had a significantly increased number of rare missense variants in the SH3 domain of PSTPIP1. This finding, therefore, implicates PSTPIP1 variation in sporadic HS and further supports dysregulated immunity in HS. Our data also suggests that population-scale HS genetic research will yield valuable insights into disease pathology.

Preoperative ß-Blocker Therapy and Stroke or Major Adverse Cardiac Events in Major Abdominal Surgery: A Retrospective Cohort Study.

BACKGROUND: Perioperative ß-blocker therapy has been associated with increased risk of stroke. However, the association between ß-blocker initiation before the day of surgery and the risk of stroke is unknown. The authors hypothesized there would be no association between preoperative ß-blocker initiation within 60 days of surgery or chronic ß-blockade (more than 60 days) and the risk of stroke in patients undergoing major abdominal surgery. METHODS: Data on elective major abdominal surgery were obtained from the IBM (USA) Truven Health MarketScan 2005 to 2015 Commercial and Medicare Supplemental Databases. Patients were stratified by ß-blocker dispensing exposure: (1) ß-blocker-naïve, (2) preoperative ß-blocker initiation within 60 days of surgery, and (3) chronic ß-blocker dispensing (more than 60 days). The authors compared in-hospital stroke and major adverse cardiac events between the different ß-blocker therapy exposures. RESULTS: There were 204,981 patients who underwent major abdominal surgery. ß-Blocker exposure was as follows: perioperative initiation within 60 days of surgery for 4,026 (2.0%) patients, chronic ß-blocker therapy for 45,424 (22.2%) patients, and ß-blocker-naïve for 155,531 (75.9%) patients. The unadjusted frequency of stroke for patients with ß-blocker initiation (0.4%, 17 of 4,026) and chronic ß-blocker therapy (0.4%, 171 of 45,424) was greater than in ß-blocker-naïve patients (0.2%, 235 of 155,531; P < 0.001). After propensity score weighting, patients initiated on a ß-blocker within 60 days of surgery (odds ratio, 0.90; 95% CI, 0.31 to 2.04; P = 0.757) or on chronic ß-blocker therapy (odds ratio, 0.86; 95% CI, 0.65 to 1.15; P = 0.901) demonstrated similar stroke risk compared to ß-blocker-naïve patients. Patients on chronic ß-blocker therapy demonstrated lower adjusted risk of major adverse cardiac events compared to ß-blocker-naïve patients (odds ratio, 0.81; 95% CI, 0.72 to 0.91; P = 0.007), despite higher unadjusted absolute event rate (2.6% [1,173 of 45,424] vs. 0.6% [872 of 155,531]). CONCLUSIONS: Among patients undergoing elective major abdominal surgery, the authors observed no association between preoperative ß-blocker initiation within 60 days of surgery or chronic ß-blocker therapy and stroke.

Nitrous Oxide, a Rapid Antidepressant, Has Ketamine-like Effects on Excitatory Transmission in the Adult Hippocampus.

BACKGROUND: Nitrous oxide (N2O) is a noncompetitive inhibitor of NMDA receptors that appears to have ketamine-like rapid antidepressant effects in patients with treatment-resistant major depression. In preclinical studies, ketamine enhances glutamate-mediated synaptic transmission in the hippocampus and prefrontal cortex. In this study, we examined the effects of N2O on glutamate transmission in the hippocampus and compared its effects to those of ketamine. METHODS: Glutamate-mediated synaptic transmission was studied in the CA1 region of hippocampal slices from adult albino rats using standard extracellular recording methods. Effects of N2O and ketamine at subanesthetic concentrations were evaluated by acute administration. RESULTS: Akin to 1 µM ketamine, 30% N2O administered for 15-20 minutes resulted in persistent enhancement of synaptic responses mediated by both AMPA receptors and NMDA receptors. Synaptic enhancement by both N2O and ketamine was blocked by co-administration of a competitive NMDA receptor antagonist at saturating concentration, but only ketamine was blocked by an AMPA receptor antagonist. Synaptic enhancement by both agents involved TrkB (tropomyosin receptor kinase B), mTOR (mechanistic target of rapamycin), and NOS (nitric oxide synthase) with some differences between N2O and ketamine. N2O potentiation occluded enhancement by ketamine, and in vivo N2O exposure occluded further potentiation by both N2O and ketamine. CONCLUSIONS: These results indicate that N2O has ketamine-like effects on hippocampal synaptic function at a subanesthetic, but therapeutically relevant concentration. These 2 rapid antidepressants have similar, but not identical mechanisms that result in persisting synaptic enhancement, possibly contributing to psychotropic actions.

Normalized Subendocardial Myocardial Attenuation on Coronary Computed Tomography Angiography Predicts Postoperative Adverse Cardiovascular Events: Coronary CTA VISION Substudy.

BACKGROUND: Abnormalities in computed tomography myocardial perfusion has been associated with coronary artery disease and major adverse cardiovascular events (MACE). We sought to investigate if subendocardial attenuation using coronary computed tomography angiography predicts MACE 30 days postelective noncardiac surgery. METHODS: Using a 17-segment model, coronary computed tomography angiography images were analyzed for subendocardial and transmural attenuation and the corresponding blood pool. The segment with the lowest subendocardial attenuation and transmural attenuation were normalized to the segment with the highest subendocardial and transmural attenuation, respectively (SUBnormalized, and TRANSnormalized, respectively). We evaluated the independent and incremental value of myocardial attenuation to predict the composite of cardiovascular death or nonfatal myocardial infarction. RESULTS: Of a total of 995 coronary CTA VISION (Coronary Computed Tomographic Angiography and Vascular Events in Noncardiac Surgery Patients Cohort Evaluation Study) patients, 735 had available images and complete data for these analyses. Among these patients, 60 had MACE. Based on Revised Cardiovascular Risk Index, 257, 302, 138, and 38 patients had scores of 0, 1, 2, and ≥3, respectively. On coronary computed tomography angiography, 75 patients had normal coronary arteries, 297 patients had nonobstructive coronary artery disease, 264 patients had obstructive disease, and 99 patients had extensive obstructive coronary artery disease. SUBnormalized was an independent and incremental predictor of events in the model that included Revised Cardiovascular Risk Index and coronary artery disease severity. Compared with patients in the highest tertile of SUBnormalized, patients in the second and first tertiles had an increased hazards ratio for events (2.23 [95% CI, 1.091-4.551] and 2.36 [95% CI, 1.16-4.81], respectively). TRANSnormalized, as a continuous variable, was also found to be a predictor of MACE (P=0.027). CONCLUSIONS: Our study demonstrates that SUBnormalized and TRANSnormalized are independent and incremental predictors of MACE 30 days after elective noncardiac surgery. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01635309.

Preoperative Assessment of Anxiety and Depression Using Computerized Adaptive Screening Tools: A Pilot Prospective Cohort Study.

BACKGROUND: Serious mental health conditions (eg, anxiety and depression) are common in surgical patients, yet likely underassessed due to the time-consuming and cumbersome traditional screening process. A recently developed computerized adaptive mental health assessment tool (computerized adaptive test-mental health [CAT-MH]) allows rapid, precise, and accurate assessment of numerous mental health disorders, including anxiety and depression, without the need for a trained interviewer. The goal of this investigation was to determine the feasibility of administering CAT-MH for anxiety and depression in the preoperative setting and to obtain preliminary evidence of the prevalence of anxiety and depression in preoperative patients. METHODS: In this prospective cohort study, 100 adult patients scheduled for elective surgery were enrolled and asked to complete the CAT-MH in the preoperative clinic. Urgent and emergency surgeries were excluded as were pregnant patients. Primary feasibility outcomes were completion rate and time to completion. Secondary outcomes were prevalence estimates of anxiety and depression. RESULTS: All 100 enrolled patients completed the study. All patients were able to complete the mental health assessment (mean time: 3.6 ± 1.8 minutes standard deviation). Sixteen patients (16%) screened positive for anxiety (severity: mild, n = 7 [7%]; moderate, n = 7 [7%]); severe, n = 2 [2%]); 12 of 16 (75%) did not have a previous diagnosis of anxiety disorder. Twenty-eight (28%) patients screened positive for depression (severity: mild, n = 26 [26%]; moderate and severe, n = 1 each [1%]); 23 of 28 (82%) had no previous diagnosis of depressive disorder. Nineteen patients (19%) met the screening criteria for major depressive disorder; 14 of 19 (74%) of which had no previous diagnosis of major depressive disorder. CONCLUSIONS: The results of this pilot study support the feasibility of using CAT-MH in a preoperative evaluation and indicate that there is a substantial prevalence of undiagnosed anxiety and depression in surgical patients.

Evaluation of Appropriate Use of Preoperative Echocardiography before Major Abdominal Surgery: A Retrospective Cohort Study.

BACKGROUND: Preoperative resting echocardiography is often performed before noncardiac surgery, but indications for preoperative resting echocardiography are limited. This study aimed to investigate appropriateness of preoperative resting echocardiography using the Appropriate Use Criteria for Echocardiography, which encompass indications from the guidelines on perioperative cardiovascular evaluation and management and nonperioperative indications independent of the perioperative period. The authors hypothesized that patients are frequently tested without an appropriate indication. METHODS: Records of patients in the Truven Health MarketScan Commercial and Medicare Supplemental Databases who underwent a major abdominal surgery from 2005 to 2017 were included. These databases contain de-identified records of health services for more than 250 million patients with primary or Medicare supplemental health insurance coverage through employer-based fee-for-service, point-of-service, or capitated plans. Patients were classified based on the presence of an outpatient claim for resting transthoracic echocardiography within 60 days of surgery. Appropriateness was determined via International Classification of Diseases, Ninth Revision-Clinical Modification, and International Classification of Diseases, Tenth Revision-Clinical Modification principal and secondary diagnosis codes associated with the claims, and classified as "appropriate," "rarely appropriate," or "unclassifiable" using the Appropriate Use Criteria for Echocardiography. RESULTS: Among 230,535 patients in the authors' cohort, preoperative resting transthoracic echocardiography was performed in 6.0% (13,936) of patients. There were 12,638 (91%) studies classifiable by the Appropriate Use Criteria for Echocardiography, and 1,298 (9%) were unable to be classified. Among the classifiable studies, 8,959 (71%) were deemed "appropriate," while 3,679 (29%) were deemed "rarely appropriate." Surveillance of chronic ischemic heart disease and uncomplicated hypertension accounted for 43% (1,588 of 3,679) of "rarely appropriate" echocardiograms. CONCLUSIONS: More than one in four preoperative resting echocardiograms were considered "rarely appropriate" according to the Appropriate Use Criteria for Echocardiography. A narrow set of patient characteristics accounts for a large proportion of "rarely appropriate" preoperative resting echocardiograms.

NT-proBNP in young healthy adults undergoing non-cardiac surgery.

OBJECTIVES: N-terminal pro-brain natriuretic peptide (NT-proBNP), a standard marker for diagnosis and treatment guidance of heart failure, has previously been investigated in high-risk patients undergoing cardiac and non-cardiac surgery. However, the kinetics of NT-proBNP in healthy patients undergoing non-cardiac surgery are unknown. DESIGN & METHODS: A secondary analysis of a prospective cohort study was conducted. NT-proBNP plasma concentrations were measured preoperatively, 2-6 h, and 18-30 h after surgery in 120 patients, 18-35 years, undergoing elective non-cardiac surgery. Reasons for non-inclusion: history or symptoms of cardiac disease, kidney disease, pulmonary embolism, thrombosis, stroke, diabetes, head or chest trauma, pregnancy, incomplete panel of perioperative NT-proBNP plasma samples. Absolute and relative change of NT-proBNP plasma concentration were calculated. Changes between preoperative, 2-6 h, and 18-30 h (POD 1) NT-proBNP values, and of within-patient change in NT-proBNP were analyzed. RESULTS: In 95 patients, NT-proBNP plasma concentrations (median [IQR]) were 8 [5-26] pg/mL at baseline, 17 [5-53] pg/mL 2-6 h, and 42 [11-86] pg/mL 18-30 h after surgery. Absolute and relative NT-proBNP increase after surgery was 32 [5-74] pg/mL and 196% [61 - 592%] compared to baseline. NT-proBNP elevation above the age- and sex-specific reference range was observed in 6/95 (6%) patients prior to surgery and in 39/95 (41%) patients after surgery. CONCLUSIONS: Even after uncomplicated surgery and postoperative period, NT-proBNP concentrations markedly increase in otherwise healthy adult patients. The aetiology of postoperative NT-proBNP increase is currently unknown and may be multifactorial.

A phase 2 trial of inhaled nitrous oxide for treatment-resistant major depression.

Nitrous oxide at 50% inhaled concentration has been shown to improve depressive symptoms in patients with treatment-resistant major depression (TRMD). Whether a lower concentration of 25% nitrous oxide provides similar efficacy and persistence of antidepressant effects while reducing the risk of adverse side effects is unknown. In this phase 2 clinical trial (NCT03283670), 24 patients with severe TRMD were randomly assigned in a crossover fashion to three treatments consisting of a single 1-hour inhalation with (i) 50% nitrous oxide, (ii) 25% nitrous oxide, or (iii) placebo (air/oxygen). The primary outcome was the change on the Hamilton Depression Rating Scale (HDRS-21). Whereas nitrous oxide significantly improved depressive symptoms versus placebo (P = 0.01), there was no difference between 25 and 50% nitrous oxide (P = 0.58). The estimated differences between 25% and placebo were -0.75 points on the HDRS-21 at 2 hours (P = 0.73), -1.41 points at 24 hours (P = 0.52), -4.35 points at week 1 (P = 0.05), and -5.19 points at week 2 (P = 0.02), and the estimated differences between 50% and placebo were -0.87 points at 2 hours (P = 0.69), -1.93 points at 24 hours (P = 0.37), -2.44 points at week 1 (P = 0.25), and -7.00 points at week 2 (P = 0.001). Adverse events declined substantially with dose (P < 0.001). These results suggest that 25% nitrous oxide has comparable efficacy to 50% nitrous oxide in improving TRMD but with a markedly lower rate of adverse effects.

U.S. trends in elective and emergent major abdominal surgical procedures from 2002 to 2014 in older adults.

BACKGROUND: The U.S. population is aging and projected to undergo an increasing number of general surgical procedures. However, recent trends in the frequency of major abdominal procedures in older adults are currently unknown as improvements in non-operative interventions may obviate the need for major surgery. Thus, we evaluated the trends of major abdominal surgical procedures in older adults in the United States. METHODS: We performed a retrospective cohort study using the National Inpatient Sample from 2002 to 2014 with trend analysis using National Cancer Institute's Joinpoint Trend Analysis Software. We identified the average annual percent change (AAPC) in the yearly frequency of major abdominal surgical procedures in older adults (≥50 years of age). RESULTS: Our cohort included a total of 3,951,947 survey-weighted discharges that included a major abdominal surgery in adults ≥50 years of age between 2002 and 2014. Of these discharges, 2,529,507 (64.0%) were for elective abdominal surgeries, 2,062,835 (52.0%) were for female patients, and mean (SD) age was 61.4 (15.9) years. The frequency of major abdominal procedures (elective and emergent) decreased for adults aged 65-74 (AAPC: -1.43, -1.75, -1.11, p < 0.0001), 75-84 (AAPC: -2.75, -3.33, -2.16, p < 0.001), and ≥85 (AAPC: -4.07, -4.67, -3.47, p < 0.0001). The AAPC for elective procedures decreased for older adults aged 75-84 (AAPC = -1.65; -2.44, -0.85: p = 0.0001) and >85 (AAPC = -3.53; -4.57, -2.48: p < 0.0001). All age groups showed decreases in emergent procedures in 50-64 (AAPC = -1.76, -2.00, -1.52, p < 0.0001), 65-74 (AAPC = -3.59, -4.03, -3.14, p < 0.0001), 75-84 (AAPC = -3.90, -4.34, -3.46, p < 0.0001), ≥85 (AAPC = -4.58, -4.98, -4.17, p < 0.0001) age groups. CONCLUSIONS AND RELEVANCE: In this cohort of older adults, the frequency of emergent and elective major abdominal procedures in adults ≥65 years of age decreased with significant variation among individual procedure types. Future studies are needed to identify the generalizability of our findings to other surgical procedures.

Expert consensus on peri-operative myocardial injury screening in noncardiac surgery: A literature review.

Peri-operative myocardial injury, detected by dynamic and elevated cardiac troponin (cTn) concentrations, is a common complication of noncardiac surgery that is strongly associated with 30-day mortality. Although active screening for peri-operative myocardial injury has been suggested in recent guidelines, clinical implementation remains tentative due to a lack of examples on how to tackle such an interdisciplinary project at a local level. Moreover, consensus on which assay and cTn cut-off values should be used has not yet been reached, and guidance on whom to screen is lacking. In this article, we aim to summarise local examples of successfully implemented cTn screening practices and review the current literature in order to provide information and suggestions for patient selection, organisation of a screening programme, caveats and a potential management pathway.

Morbidity and Mortality After Acute Myocardial Infarction After Elective Major Noncardiac Surgery.

OBJECTIVES: To develop parsimonious models of in-hospital mortality and morbidity risk after perioperative acute myocardial infarction (AMI). DESIGN: Retrospective data analysis. SETTING: National Inpatient Sample (2008-2013), a 20% sample of all non-federal in-patient hospitalizations in the United States. PARTICIPANTS: Patients 45 years or older who experienced perioperative AMI during elective admission for noncardiac surgery. INTERVENTIONS: The study used a mixed principal components analysis and multivariate logistic regression to identify risk factors for in-hospital mortality after perioperative AMI. A model incorporating only preoperative risk factors, defined by the Revised Cardiac Risk Index (RCRI), was compared with a "full risk factor" model, incorporating a large set of preoperative AMI risk factors. The risk of post-AMI disposition to an intermediate care or skilled nursing facility, a marker of functional impairment, then was evaluated. MEASUREMENTS AND MAIN RESULTS: In the present study, 15,574 cases of AMI after elective noncardiac surgery were identified (0.42%, corresponding with 78,122 cases nationally), with a 12.4% in-hospital mortality rate. The "RCRI-only" model was the best-fit model of post-AMI in-hospital mortality risk, without loss of predictive accuracy compared with the "full risk factor" model (area under the receiver operator characteristic curve 0.80, 95% confidence interval [CI] [0.77-0.82] v area under the receiver operator characteristic curve 0.81, 95% CI [0.77-0.83], respectively). Post-AMI mortality risk was the highest for perioperative complications, including sepsis (odds ratio 4.95, 95% CI [4.32-5.67]). Conversely, functional impairment was best predicted by the "full-risk factor" model and depended strongly on chronic preoperative comorbidities. CONCLUSIONS: The RCRI provides a simple but adequate model of preoperative risk factors for in-hospital mortality after perioperative AMI.

Systematic review and consensus definitions for the Standardized Endpoints in Perioperative Medicine (StEP) initiative: cardiovascular outcomes.

BACKGROUND: Adverse cardiovascular events are a leading cause of perioperative morbidity and mortality. The definitions of perioperative cardiovascular adverse events are heterogeneous. As part of the international Standardized Endpoints in Perioperative Medicine initiative, this study aimed to find consensus amongst clinical trialists on a set of standardised and valid cardiovascular outcomes for use in future perioperative clinical trials. METHODS: We identified currently used perioperative cardiovascular outcomes by a systematic review of the anaesthesia and perioperative medicine literature (PubMed/Ovid, Embase, and Cochrane Library). We performed a three-stage Delphi consensus-gaining process that involved 55 clinician researchers worldwide. Cardiovascular outcomes were first shortlisted and the most suitable definitions determined. These cardiovascular outcomes were then assessed for validity, reliability, feasibility, and clarity. RESULTS: We identified 18 cardiovascular outcomes. Participation in the three Delphi rounds was 100% (n=19), 71% (n=55), and 89% (n=17), respectively. A final list of nine cardiovascular outcomes was elicited from the consensus: myocardial infarction, myocardial injury, cardiovascular death, non-fatal cardiac arrest, coronary revascularisation, major adverse cardiac events, pulmonary embolism, deep vein thrombosis, and atrial fibrillation. These nine cardiovascular outcomes were rated by the majority of experts as valid, reliable, feasible, and clearly defined. CONCLUSIONS: These nine consensus cardiovascular outcomes can be confidently used as endpoints in clinical trials designed to evaluate perioperative interventions with the goal of improving perioperative outcomes.

Frequency and Outcomes of Preoperative Stress Testing in Total Hip and Knee Arthroplasty from 2004 to 2017.

Importance: Cardiac stress testing is often performed prior to noncardiac surgery, although trends in use of preoperative stress testing and the effect of testing on cardiovascular outcomes are currently unknown. Objective: To describe temporal trends and outcomes of preoperative cardiac stress testing from 2004 to 2017. Design, Setting, and Participants: Cross-sectional study of patients undergoing elective total hip or total knee arthroplasty from 2004 to 2017. Trend analysis was conducted using Joinpoint and generalized estimating equation regression. The study searched IBM MarketScan Research Databases inpatient and outpatient health care claims for private insurers including supplemental Medicare coverage and included patients with a claim indicating an elective total hip or total knee arthroplasty from January 1, 2004, to December 31, 2017. Exposures: Elective total hip or knee arthroplasty. Main Outcomes and Measures: Trend in yearly frequency of preoperative cardiac stress testing. Results: The study cohort consisted of 801 396 elective total hip (27.9%; n = 246 168 of 801 396) and total knee (72.1%; 555 228 of 801 396) arthroplasty procedures, with a median age of 62 years (interquartile range, 57-70 years) and 58.1% women (n = 465 545 of 801 396). The overall rate of stress testing during the study period was 10.4% (n = 83 307 of 801 396). The rate of stress tests increased 0.65% (95% CI, 0.09-1.21; P = .03) annually from quarter (Q) 1 of 2004 until Q2 of 2006. A joinpoint was identified at Q3 of 2006 (95% CI, 2005 Q4 to 2007 Q4) when preoperative stress test use decreased by -0.71% (95% CI, -0.79% to 0.63%; P < .001) annually. A second joinpoint was identified at the Q4 of 2013 (95% CI, 2011 Q3 to 2015 Q3), when the decline in stress testing rates slowed to -0.40% (95% CI, -0.57% to -0.24%; P < .001) annually. The overall rate of myocardial infarction and cardiac arrest was 0.24% (n = 1677 of 686 067). Rates of myocardial infraction and cardiac arrest were not different in patients with at least 1 Revised Cardiac Risk Index condition who received a preoperative stress test and those who did not (0.60%; n = 221 of 36 554 vs 0.57%; n = 694 of 122 466; P = .51). Conclusions and Relevance: The frequency of preoperative stress testing declined annually from 2006 through 2017. Among patients with at least 1 Revised Cardiac Risk Index condition, no difference was observed in cardiovascular outcomes between patients who did and did not undergo preoperative testing.

Generalisability of randomised trials evaluating perioperative ß-blocker therapy in noncardiac surgery.

BACKGROUND: The limited applicability of evidence from RCTs in real-word practice is considered a potential bottleneck for evidence-based practice but rarely systematically assessed. Using our failure to recruit patients into a perioperative beta-blocker trial, we set out to analyse the restrictiveness and generalisability of trial eligibility criteria in a real-world cohort. METHODS: We prospectively included adult patients (≥18 yr) scheduled for elective noncardiac surgery at an academic tertiary care facility who were screened for inclusion in a planned perioperative beta-blocker RCT, which was terminated owing to recruitment failure. The primary outcome was the proportion of screened patients who matched the eligibility criteria of 36 published RCTs included in a large Cochrane meta-analysis on perioperative beta-blocker therapy. The pragmatic/explanatory level of each RCT was assessed using the PRagmatic-Explanatory Continuum Indicator Summary 2 (PRECIS-2) score, which ranges from 9 points (indicating a very explanatory study) to 45 points (indicating a very pragmatic study). RESULTS: A total of 2241 patients (54% female, n=1215; 52 [standard deviation, 20] yr) were included for the assessment of trial eligibility between October 2015 and January 2016. Only a small proportion of patients matched the inclusion and exclusion criteria for each of the 36 RCTs, ranging from 53% to 0%. The average proportion of patients who did match the eligibility criteria of all 36 RCTs was 6.5% (n=145; 95% confidence interval, 6.3-6.6). A higher PRECIS-2 score was associated with a higher proportion of matching patients (P<0.001). CONCLUSIONS: Trial eligibility criteria in perioperative beta-blocker therapy trials are overly restrictive and not generalisable to a real-world surgical population. CLINICAL TRIAL REGISTRATION: EudraCT#: 2015-002366-23.