Postoperative troponin surveillance to detect myocardial infarction: an observational cohort modelling study.

BACKGROUND: Clinical presentation of postoperative myocardial infarction (POMI) is often silent. Several international guidelines recommend routine troponin surveillance in patients at risk. We compared how these different guidelines select patients for surveillance after noncardiac surgery with our established risk stratification model. METHODS: We used outcome data from two prospective studies: Measurement of Exercise Tolerance before Surgery (METS) and Troponin Elevation After Major non-cardiac Surgery (TEAMS). We compared the major American, Canadian, and European guideline recommendations for troponin surveillance with our established risk stratification model. For each guideline and model, we quantified the number of patients requiring monitoring, % POMI detected, sensitivity, specificity, diagnostic odds ratio, and number needed to screen (NNS). RESULTS: METS and TEAMS contributed 2350 patients, of whom 319 (14%) had myocardial injury, 61 (2.5%) developed POMI, and 14 (0.6%) died. Our risk stratification model selected fewer patients for troponin monitoring (20%), compared with the Canadian (78%) and European (79%) guidelines. The sensitivity to detect POMI was highest with the Canadian and European guidelines (0.85; 95% confidence interval [CI] 0.74-0.92). Specificity was highest using the American guidelines (0.91; 95% CI 0.90-0.92). Our risk stratification model had the best diagnostic odds ratio (2.5; 95% CI 1.4-4.2) and a lower NNS (21 vs 35) compared with the guidelines. CONCLUSIONS: Most postoperative myocardial infarctions were detected by the Canadian and European guidelines but at the cost of low specificity and a higher number of patients undergoing screening. Patient selection based on our risk stratification model was optimal.

Postoperative myocardial injury phenotypes and self-reported disability in patients undergoing noncardiac surgery: a multicentre observational study.

BACKGROUND: Postoperative myocardial injury (PMI) comprises a spectrum of mechanisms resulting in troponin release. The impact of different PMI phenotypes on postoperative disability remains unknown. METHODS: This was a multicentre prospective cohort study including patients aged ≥50 yr undergoing elective major noncardiac surgery. Patients were stratified in five groups based on the occurrence of PMI and clinical information on postoperative adverse events: PMI classified as myocardial infarction (MI; according to fourth definition), PMI plus adverse event other than MI, clinically silent PMI (PMI without adverse events), adverse events without PMI, and neither PMI nor an adverse event (reference). The primary endpoint was 6-month self-reported disability (assessed by WHO Disability Assessment Schedule 2.0 [WHODAS]). Disability-free survival was defined as WHODAS ≤16%. RESULTS: We included 888 patients of mean age 69 (range 53-91) yr, of which 356 (40%) were women; 151 (17%) patients experienced PMI, and 625 (71%) experienced 6-month disability-free survival. Patients with PMI, regardless of its phenotype, had higher preoperative disability scores than patients without PMI (difference in WHODAS; ß: 3.3, 95% confidence interval [CI]: 0.5-6.2), but scores remained stable after surgery (ß: 1.2, 95% CI: -3.2-5.6). Before surgery, patients with MI (n=36, 4%) were more disabled compared with patients without PMI and no adverse events (ß: 5.5, 95% CI: 0.3-10.8). At 6 months, patients with MI and patients without PMI but with adverse events worsened in disability score (ß: 11.2, 95% CI: 2.3-20.2; ß: 8.1, 95% CI: 3.0-13.2, respectively). Patients with clinically silent PMI did not change in disability score at 6 months (ß: 1.39, 95% CI: -4.50-7.29, P=0.642). CONCLUSIONS: Although patients with postoperative myocardial injury had higher preoperative self-reported disability, disability scores did not change at 6 months after surgery. However, patients experiencing myocardial infarction worsened in disability score after surgery.

Pathological findings associated with the updated European Society of Cardiology 2022 guidelines for preoperative cardiac testing: an observational cohort modelling study.

BACKGROUND: In 2022, the European Society of Cardiology updated guidelines for preoperative evaluation. The aims of this study were to quantify: (1) the impact of the updated recommendations on the yield of pathological findings compared with the previous guidelines published in 2014; (2) the impact of preoperative B-type natriuretic peptide (NT-proBNP) use for risk estimation on the yield of pathological findings; and (3) the association between 2022 guideline adherence and outcomes. METHODS: This was a secondary analysis of MET-REPAIR, an international, prospective observational cohort study (NCT03016936). Primary endpoints were reduced ejection fraction (EF<40%), stress-induced ischaemia, and major adverse cardiovascular events (MACE). The explanatory variables were class of recommendations for transthoracic echocardiography (TTE), stress imaging, and guideline adherence. We conducted second-order Monte Carlo simulations and multivariable regression. RESULTS: In total, 15,529 patients (39% female, median age 72 [inter-quartile range: 67-78] yr) were included. The 2022 update changed the recommendation for preoperative TTE in 39.7% patients, and for preoperative stress imaging in 12.9% patients. The update resulted in missing 1 EF <40% every 3 fewer conducted TTE, and in 4 additional stress imaging per 1 additionally detected ischaemia events. For cardiac stress testing, four more investigations were performed for every 1 additionally detected ischaemia episodes. Use of NT-proBNP did not improve the yield of pathological findings. Multivariable regression analysis failed to find an association between adherence to the updated guidelines and MACE. CONCLUSIONS: The 2022 update for preoperative cardiac testing resulted in a relevant increase in tests receiving a stronger recommendation. The updated recommendations for TTE did not improve the yield of pathological cardiac testing.

Factors affecting adherence to recommendations on pre-operative cardiac testing: A cohort study.

BACKGROUND: Cardiac risk evaluation prior to noncardiac surgery is fundamental to tailor peri-operative management to patient's estimated risk. Data on the degree of adherence to guidelines in patients at cardiovascular risk in Europe and factors influencing adherence are underexplored. OBJECTIVES: The aim of this analysis was to describe the degree of adherence to [2014 European Society of Cardiology (ESC)/European Society of Anaesthesiology (ESA) guidelines] recommendations on rest echocardiography [transthoracic echocardiography (TTE)] and to stress imaging prior to noncardiac surgery in a large European sample and to assess factors potentially affecting adherence. DESIGN: Secondary analysis of a multicentre, international, prospective cohort study (MET-REPAIR). SETTING: Twenty-five European centres of all levels of care that enrolled patients between 2017 and 2020. PATIENTS: With elevated cardiovascular risk undergoing in-hospital elective, noncardiac surgery. MAIN OUTCOME MEASURES: (Non)adherence to each pre-operative TTE and stress imaging recommendations classified as guideline-adherent, overuse and underuse. We performed descriptive analysis. To explore the impact of patients' sex, age, geographical region, and hospital teaching status, we conducted multivariate multinominal regression analysis. RESULTS: Out of 15 983 patients, 15 529 were analysed (61% men, mean age 72 ±â€Š8 years). Overuse (conduction in spite of class III) and underuse (nonconduction in spite of class I recommendation) for pre-operative TTE amounted to 16.6% (2542/15 344) and 6.6% (1015/15 344), respectively. Stress imaging overuse and underuse amounted to 1.7% (241/14 202) and 0.4% (52/14 202) respectively. Male sex, some age categories and some geographical regions were significantly associated with TTE overuse. Male sex and some regions were also associated with TTE underuse. Age and regions were associated with overuse of stress imaging. Male sex, age, and some regions were associated with stress imaging underuse. CONCLUSION: Adherence to pre-operative stress imaging recommendation was high. In contrast, adherence to TTE recommendations was moderate. Both patients' and geographical factors affected adherence to joint ESC/ESA guidelines. TRIAL REGISTRATION: NCT03016936.

Risk assessment for major adverse cardiovascular events after noncardiac surgery using self-reported functional capacity: international prospective cohort study.

BACKGROUND: Guidelines endorse self-reported functional capacity for preoperative cardiovascular assessment, although evidence for its predictive value is inconsistent. We hypothesised that self-reported effort tolerance improves prediction of major adverse cardiovascular events (MACEs) after noncardiac surgery. METHODS: This is an international prospective cohort study (June 2017 to April 2020) in patients undergoing elective noncardiac surgery at elevated cardiovascular risk. Exposures were (i) questionnaire-estimated effort tolerance in metabolic equivalents (METs), (ii) number of floors climbed without resting, (iii) self-perceived cardiopulmonary fitness compared with peers, and (iv) level of regularly performed physical activity. The primary endpoint was in-hospital MACE consisting of cardiovascular mortality, non-fatal cardiac arrest, acute myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care or resulting in a prolongation of stay on ICU/intermediate care (≥24 h). Mixed-effects logistic regression models were calculated. RESULTS: In this study, 274 (1.8%) of 15 406 patients experienced MACE. Loss of follow-up was 2%. All self-reported functional capacity measures were independently associated with MACE but did not improve discrimination (area under the curve of receiver operating characteristic [ROC AUC]) over an internal clinical risk model (ROC AUCbaseline 0.74 [0.71-0.77], ROC AUCbaseline+4METs 0.74 [0.71-0.77], ROC AUCbaseline+floors climbed 0.75 [0.71-0.78], AUCbaseline+fitnessvspeers 0.74 [0.71-0.77], and AUCbaseline+physical activity 0.75 [0.72-0.78]). CONCLUSIONS: Assessment of self-reported functional capacity expressed in METs or using the other measures assessed here did not improve prognostic accuracy compared with clinical risk factors. Caution is needed in the use of self-reported functional capacity to guide clinical decisions resulting from risk assessment in patients undergoing noncardiac surgery. CLINICAL TRIAL REGISTRATION: NCT03016936.

ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation.

BACKGROUND: In recent years, there has been increasing focus on the use of cardiac biomarkers in patients undergoing noncardiac surgery. AIMS: The aim of this focused guideline was to provide updated guidance regarding the pre-, post- and combined pre-and postoperative use of cardiac troponin and B-type natriuretic peptides in adult patients undergoing noncardiac surgery. METHODS: The guidelines were prepared using Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology. This included the definition of critical outcomes, a systematic literature search, appraisal of certainty of evidence, evaluation of biomarker measurement in terms of the balance of desirable and undesirable effects including clinical outcomes, resource use, health inequality, stakeholder acceptance, and implementation. The panel differentiated between three different scopes of applications: cardiac biomarkers as prognostic factors, as tools for risk prediction, and for biomarker-enhanced management strategies. RESULTS: In a modified Delphi process, the task force defined 12 critical outcomes. The systematic literature search resulted in over 25,000 hits, of which 115 full-text articles formed the body of evidence for recommendations. The evidence appraisal indicated heterogeneity in the certainty of evidence across critical outcomes. Further, there was relevant gradient in the certainty of evidence across the three scopes of application. Recommendations were issued and if this was not possible due to limited evidence, clinical practice statements were produced. CONCLUSION: The ESAIC focused guidelines provide guidance on the perioperative use of cardiac troponin and B-type natriuretic peptides in patients undergoing noncardiac surgery, for three different scopes of application.

Associations between intraoperative hypotension, duration of surgery and postoperative myocardial injury after noncardiac surgery: a retrospective single-centre cohort study.

BACKGROUND: Studies of intraoperative hypotension typically specify a blood pressure threshold associated with adverse outcomes. Such thresholds are likely to be study-biased, investigator-biased, or both. We hypothesised that a newly developed modelling method without a threshold, which is biologically more plausible than a threshold-based approach, would reveal a continuous association between exposure to intraoperative hypotension and adverse outcomes. METHODS: Single-centre, retrospective cohort study of subjects ≥60 yr old undergoing noncardiac surgery. We modelled intraoperative hypotension using three different approaches: (1) unweighted, (2) weighted for degree of hypotension (depth), and (3) weighted for duration of hypotension. The primary outcome was myocardial injury, defined as elevated troponin I (>60 ng L-1) measured during the first 3 days after surgery. The associations between the three models, postoperative myocardial injury, and mortality (secondary outcome) were reported as penalised adjusted odds ratios (ORs) scaled between the 75th and 25th percentiles. RESULTS: Myocardial injury occurred in 1812/15 452 (12%) procedures, with 554/15 452 (3.6%) procedures resulting in death before discharge from hospital. The unweighted lower blood pressure measure (OR: 0.26, 95% confidence interval [CI]: 0.12-0.53) and the depth-weighted measure (OR: 4.4, 95% CI: 2.6-7.4) were associated with myocardial injury. The duration-weighted measure was not associated with myocardial injury (OR: 0.89, 95% CI: 0.61-1.3). The unweighted measure (OR 0.08, 95% CI: 0.01-0.40) and the depth-weighted measure (OR: 12, 95% CI, 3.8-35) were associated with in-hospital mortality, but not the duration-weighted measure (OR: 1.3, 95% CI: 0.53-3.0). CONCLUSIONS: Intraoperative hypotension appears to have a graded association with postoperative myocardial injury and mortality, with depth appearing to contribute more than duration.

Outlying End-Tidal Carbon Dioxide During General Anesthesia Is Associated With Postoperative Pulmonary Complications: A Multicenter Retrospective Observational Study From US Hospitals Between 2010 and 2017.

BACKGROUND: Postoperative pulmonary complications (PPCs) occur in up to 33% of patients who undergo noncardiothoracic surgery. Emerging evidence suggests that permissive hypercapnia may reduce the risk of lung injury. We hypothesized that higher intraoperative end-tidal carbon dioxide (Etco2) concentrations would be associated with a decreased risk of PPCs. METHODS: This retrospective, observational, multicenter study included patients undergoing general anesthesia for noncardiothoracic procedures (January 2010-December 2017). The primary outcome was PPC within 30 postoperative days. Secondary outcomes were PPC within 1 week, postoperative length of stay, and inhospital 30-day mortality. The association between these outcomes, median Etco2, and 4 time-weighted average area-under-the-curve (TWA-AUC) thresholds (<28, <35, <45, and >45 mm Hg) was explored using a multivariable mixed-effect model and by plotting associated risks. RESULTS: Among 143,769 cases across 11 hospitals, 10,276 (7.1%) experienced a PPC. When compared to a baseline median Etco2 of 35 to 40 mm Hg, a median Etco2 >40 mm Hg was associated with an increase in PPCs within 30 days (median Etco2, 40-45 mm Hg; adjusted OR, 1.16 [99% confidence interval {CI}, 1.00-1.33]; P value = .008 and median Etco2, >45 mm Hg; OR, 1.64 [99% CI, 1.33-2.02]; P value < .001). The occurrence of any Etco2 value <28 mm Hg (ie, a positive TWA-AUC < 28 mm Hg) was associated with PPCs (OR, 1.40 [95% CI, 1.33-1.49]; P value < .001), mortality, and length of stay. Any Etco2 value >45 mm Hg (ie, a positive TWA-AUC >45 mm Hg) was also associated with PPCs (OR, 1.24 [95% CI, 1.17-1.31]; P < .001). The Etco2 range with the lowest incidence of PPCs was 35 to 38 mm Hg. CONCLUSIONS: Both a very low (<28 mm Hg) and a high Etco2 (>45 mm Hg) were associated with PPCs within 30 days. The lowest PPC incidence was found in patients with an Etco2 of 35 to 38 mm Hg. Prospective studies are needed to clarify the relationship between postoperative PPCs and intraoperative Etco2.

The comparative and added prognostic value of biomarkers to the Revised Cardiac Risk Index for preoperative prediction of major adverse cardiac events and all-cause mortality in patients who undergo noncardiac surgery.

BACKGROUND: The Revised Cardiac Risk Index (RCRI) is a widely acknowledged prognostic model to estimate preoperatively the probability of developing in-hospital major adverse cardiac events (MACE) in patients undergoing noncardiac surgery. However, the RCRI does not always make accurate predictions, so various studies have investigated whether biomarkers added to or compared with the RCRI could improve this. OBJECTIVES: Primary: To investigate the added predictive value of biomarkers to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Secondary: To investigate the prognostic value of biomarkers compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Tertiary: To investigate the prognostic value of other prediction models compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. SEARCH METHODS: We searched MEDLINE and Embase from 1 January 1999 (the year that the RCRI was published) until 25 June 2020. We also searched ISI Web of Science and SCOPUS for articles referring to the original RCRI development study in that period. SELECTION CRITERIA: We included studies among adults who underwent noncardiac surgery, reporting on (external) validation of the RCRI and: - the addition of biomarker(s) to the RCRI; or - the comparison of the predictive accuracy of biomarker(s) to the RCRI; or - the comparison of the predictive accuracy of the RCRI to other models. Besides MACE, all other adverse outcomes were considered for inclusion. DATA COLLECTION AND ANALYSIS: We developed a data extraction form based on the CHARMS checklist. Independent pairs of authors screened references, extracted data and assessed risk of bias and concerns regarding applicability according to PROBAST. For biomarkers and prediction models that were added or compared to the RCRI in ≥ 3 different articles, we described study characteristics and findings in further detail. We did not apply GRADE as no guidance is available for prognostic model reviews. MAIN RESULTS: We screened 3960 records and included 107 articles.   Over all objectives we rated risk of bias as high in ≥ 1 domain in 90% of included studies, particularly in the analysis domain. Statistical pooling or meta-analysis of reported results was impossible due to heterogeneity in various aspects: outcomes used, scale by which the biomarker was added/compared to the RCRI, prediction horizons and studied populations.  Added predictive value of biomarkers to the RCRI Fifty-one studies reported on the added value of biomarkers to the RCRI. Sixty-nine different predictors were identified derived from blood (29%), imaging (33%) or other sources (38%). Addition of NT-proBNP, troponin or their combination improved the RCRI for predicting MACE (median delta c-statistics: 0.08, 0.14 and 0.12 for NT-proBNP, troponin and their combination, respectively). The median total net reclassification index (NRI) was 0.16 and 0.74 after addition of troponin and NT-proBNP to the RCRI, respectively. Calibration was not reported. To predict myocardial infarction, the median delta c-statistic when NT-proBNP was added to the RCRI was 0.09, and 0.06 for prediction of all-cause mortality and MACE combined. For BNP and copeptin, data were not sufficient to provide results on their added predictive performance, for any of the outcomes. Comparison of the predictive value of biomarkers to the RCRI  Fifty-one studies assessed the predictive performance of biomarkers alone compared to the RCRI. We identified 60 unique predictors derived from blood (38%), imaging (30%) or other sources, such as the American Society of Anesthesiologists (ASA) classification (32%). Predictions were similar between the ASA classification and the RCRI for all studied outcomes. In studies different from those identified in objective 1, the median delta c-statistic was 0.15 and 0.12 in favour of  BNP and NT-proBNP alone, respectively, when compared to the RCRI, for the prediction of MACE. For C-reactive protein, the predictive performance was similar to the RCRI. For other biomarkers and outcomes, data were insufficient to provide summary results. One study reported on calibration and none on reclassification. Comparison of the predictive value of other prognostic models to the RCRI   Fifty-two articles compared the predictive ability of the RCRI to other prognostic models. Of these, 42% developed a new prediction model, 22% updated the RCRI, or another prediction model, and 37% validated an existing prediction model. None of the other prediction models showed better performance in predicting MACE than the RCRI. To predict myocardial infarction and cardiac arrest, ACS-NSQIP-MICA had a higher median delta c-statistic of 0.11 compared to the RCRI. To predict all-cause mortality, the median delta c-statistic was 0.15 higher in favour of ACS-NSQIP-SRS compared to the RCRI. Predictive performance was not better for CHADS2, CHA2DS2-VASc, R2CHADS2, Goldman index, Detsky index or VSG-CRI compared to the RCRI for any of the outcomes. Calibration and reclassification were reported in only one and three studies, respectively. AUTHORS' CONCLUSIONS: Studies included in this review suggest that the predictive performance of the RCRI in predicting MACE is improved when NT-proBNP, troponin or their combination are added. Other studies indicate that BNP and NT-proBNP, when used in isolation, may even have a higher discriminative performance than the RCRI. There was insufficient evidence of a difference between the predictive accuracy of the RCRI and other prediction models in predicting MACE. However, ACS-NSQIP-MICA and ACS-NSQIP-SRS outperformed the RCRI in predicting myocardial infarction and cardiac arrest combined, and all-cause mortality, respectively. Nevertheless, the results cannot be interpreted as conclusive due to high risks of bias in a majority of papers, and pooling was impossible due to heterogeneity in outcomes, prediction horizons, biomarkers and studied populations. Future research on the added prognostic value of biomarkers to existing prediction models should focus on biomarkers with good predictive accuracy in other settings (e.g. diagnosis of myocardial infarction) and identification of biomarkers from omics data. They should be compared to novel biomarkers with so far insufficient evidence compared to established ones, including NT-proBNP or troponins. Adherence to recent guidance for prediction model studies (e.g. TRIPOD; PROBAST) and use of standardised outcome definitions in primary studies is highly recommended to facilitate systematic review and meta-analyses in the future.

Reticulated Platelets as Predictor of Myocardial Injury and 30 Day Mortality After Non-cardiac Surgery.

OBJECTIVE: A pre-operative marker for identification of patients at risk of peri-operative adverse events and 30 day mortality might be the percentage of young, reticulated platelets (pRP). This study aimed to determine the predictive value of pre-operative pRP on post-operative myocardial injury (PMI) and 30 day mortality, in patients aged ≥ 60 years undergoing moderate to high risk non-cardiac surgery. METHODS: The incidence of PMI (troponin I > 0.06 µg/L) and 30 day mortality was compared for patients with normal and high pRP (≥2.82%) obtained from The Utrecht Patient Orientated Database. The predictive pRP value was assessed using logistic regression. A prediction model for PMI or 30 day mortality with known risk factors was compared with a model including increased pRP using the area under the receiving operator characteristics curve (AUROC). RESULTS: In total, 26.5% (607/2289) patients showed pre-operative increased pRP. Increased pRP was associated with more PMI and 30 day mortality compared with normal pRP (36.1% vs. 28.3%, p < .001 and 8.6% vs. 3.6%, p < .001). The median pRP was higher in patients suffering PMI and 30 day mortality compared with not (2.21 [IQR: 1.57-3.11] vs. 2.07 [IQR: 1.52-1.78], p = .002, and 2.63 [IQR: 1.76-4.15] vs. 2.09 [IQR: 1.52-3.98], p < .001). pRP was independently related to PMI (OR: 1.28 [95% CI: 1.04-1.59], p = .02) and 30 day mortality (OR: 2.35 [95% CI: 1.56-3.55], p < .001). Adding increased pRP to the predictive model of PMI or 30 day mortality did not increase the AUROC 0.71 vs. 0.72, and 0.80 vs. 0.81. CONCLUSION: In patients undergoing major non-cardiac surgery, increased pre-operative pRP is related to 30 day mortality and PMI.

Effects of dobutamine and phenylephrine on cerebral perfusion in patients undergoing cerebral bypass surgery: a randomised crossover trial.

BACKGROUND: Patients undergoing cerebral bypass surgery are prone to cerebral hypoperfusion. Currently, arterial blood pressure is often increased with vasopressors to prevent cerebral ischaemia. However, this might cause vasoconstriction of the graft and cerebral vasculature and decrease perfusion. We hypothesised that cardiac output, rather than arterial blood pressure, is essential for adequate perfusion and aimed to determine whether dobutamine administration resulted in greater graft perfusion than phenylephrine administration. METHODS: This randomised crossover study included 10 adult patients undergoing cerebral bypass surgery. Intraoperatively, patients randomly and sequentially received dobutamine to increase cardiac index or phenylephrine to increase mean arterial pressure (MAP). An increase of >10% in cardiac index or >10% in MAP was targeted, respectively. Before both interventions, a reference phase was implemented. The primary outcome was the absolute difference in graft flow between the reference and intervention phase. We compared the absolute flow difference between each intervention and constructed a random-effect linear regression model to explore treatment and carry-over effects. RESULTS: Graft flow increased with a median of 4.1 (inter-quartile range [IQR], 1.7-12.0] ml min-1) after dobutamine administration and 3.6 [IQR, 1.3-7.8] ml min-1 after phenylephrine administration (difference -0.6 ml min-1; 95% confidence interval [CI], -14.5 to 5.3; P=0.441). There was no treatment effect (0.9 ml min-1; 95% CI, 0.0-20.1; P=0.944) and no carry-over effect. CONCLUSIONS: Both dobutamine and phenylephrine increased graft flow during cerebral bypass surgery, without a preference for one method over the other. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, NL7077 (https://www.trialregister.nl/trial/7077).

Blood Pressure and End-tidal Carbon Dioxide Ranges during Aneurysm Occlusion and Neurologic Outcome after an Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Hypocapnia, hypotension, and hypertension during aneurysm occlusion in patients with an aneurysmal subarachnoid hemorrhage may lead to a poor prognosis, but evidence for end-tidal carbon dioxide (ETCO2) and mean arterial pressure (MAP) targets is lacking. Within the ranges of standardized treatment, the authors aimed to study the association between hypocapnia (PaCO2 < 35 mmHg), hypotension (MAP < 80 mmHg), and hypertension (MAP >100 mmHg) during general anesthesia for aneurysm occlusion and neurologic outcome. METHODS: This retrospective observational study included patients who underwent early aneurysm occlusion after an aneurysmal subarachnoid hemorrhage under general anesthesia. ETCO2 and MAP were summarized per patient as the mean and time-weighted average area under the curve for various absolute (ETCO2 < 30, < 35, < 40, < 45 mmHg; and MAP < 60, < 70, < 80, > 90, > 100 mmHg) and relative thresholds (MAP < 70%, < 60%, < 50%). Clinical outcome was assessed with the Glasgow Outcome Scale at discharge and at three months, as primary and secondary outcome measure, respectively. RESULTS: Endovascular coiling was performed in 578 patients, and 521 underwent neurosurgical clipping. Of these 1,099 patients, 447 (41%) had a poor neurologic outcome at discharge. None of the ETCO2 and MAP ranges found within the current clinical setting were associated with a poor neurologic outcome at discharge, with an adjusted risk ratio for any ETCO2 value less than 30 mmHg of 0.95 (95% CI, 0.81 to 1.10; P < 0.496) and an adjusted risk ratio for any MAP less than 60 mmHg of 0.94 (95% CI, 0.78 to 1.14; P < 0.530). These results were not influenced by preoperative neurologic condition, treatment modality and timing of the intervention. Comparable results were obtained for neurologic outcome at three months. CONCLUSIONS: Within a standardized intraoperative treatment strategy in accordance with current clinical consensus, hypocapnia, hypotension, and hypertension during aneurysm occlusion were not found to be associated with a poor neurologic outcome at discharge in patients with an aneurysmal subarachnoid hemorrhage.

An observational study of end-tidal carbon dioxide trends in general anesthesia.

PURPOSE: Despite growing evidence supporting the potential benefits of higher end-tidal carbon dioxide (ETCO2) levels in surgical patients, there is still insufficient data to formulate guidelines for ideal intraoperative ETCO2 targets. As it is unclear which intraoperative ETCO2 levels are currently used and whether these levels have changed over time, we investigated the practice pattern using the Multicenter Perioperative Outcomes Group database. METHODS: This retrospective, observational, multicentre study included 317,445 adult patients who received general anesthesia for non-cardiothoracic procedures between January 2008 and September 2016. The primary outcome was a time-weighted average area-under-the-curve (TWA-AUC) for four ETCO2 thresholds (< 28, < 35, < 45, and > 45 mmHg). Additionally, a median ETCO2 was studied. A Kruskal-Wallis test was used to analyse differences between years. Random-effect multivariable logistic regression models were constructed to study variability. RESULTS: Both TWA-AUC and median ETCO2 showed a minimal increase in ETCO2 over time, with a median [interquartile range] ETCO2 of 33 [31.0-35.0] mmHg in 2008 and 35 [33.0-38.0] mmHg in 2016 (P <0.001). A large inter-hospital and inter-provider variability in ETCO2 were observed after adjustment for patient characteristics, ventilation parameters, and intraoperative blood pressure (intraclass correlation coefficient 0.36; 95% confidence interval, 0.18 to 0.58). CONCLUSIONS: Between 2008 and 2016, intraoperative ETCO2 values did not change in a clinically important manner. Interestingly, we found a large inter-hospital and inter-provider variability in ETCO2 throughout the study period, possibly indicating a broad range of tolerance for ETCO2, or a lack of evidence to support a specific targeted range. Clinical outcomes were not assessed in this study and they should be the focus of future research.

RéSUMé: OBJECTIF: Malgré une accumulation de données probantes suggérant des avantages de taux plus élevés de dioxyde de carbone en fin d'expiration (ETCO2) chez les patients chirurgicaux, nous ne disposons pas encore d'assez de données pour formuler des lignes directrices sur les cibles peropératoires idéales de l'ETCO2. Comme nous ne savons effectivement pas avec certitude quels taux peropératoires d'ETCO2 sont actuellement utilisés et si ces taux ont changé au fil du temps, nous avons étudié l'évolution de la pratique en utilisant la base de données du MPOG (Multicenter Perioperative Outcomes Group). MéTHODES: Cette étude multicentrique rétrospective observationnelle a inclus 317 445 patients adultes ayant reçu une anesthésie générale pour des procédures non cardiothoraciques entre janvier 2008 et septembre 2016. Le critère d'évaluation principal était une aire sous la courbe moyenne pondérée en fonction du temps (ASC-mT) pour quatre seuils d'ETCO2 (< 28, < 35, < 45 et > 45 mmHg). De plus, une ETCO2 médiane a été étudiée. Un test de Kruskal-Wallis a permis d'analyser les différences entre les années. Des modèles de régression logistique multifactorielle à effet aléatoire ont été construits pour étudier la variabilité. RéSULTATS: L'ASC-mT et l'ETCO2 médiane ont montré une augmentation minime de l'ETCO2 au fil du temps, avec une valeur médiane [plage interquartile] de l'ETCO2 de 33 [31,0 à 35,0] mmHg en 2008 et 35 [33,0 à 38,0] mmHg en 2016 (P < 0,001). Une grande variabilité entre les hôpitaux et prestataires de l'ETCO2 a été observée après ajustement pour les caractéristiques des patients, les paramètres de ventilation et la pression artérielle peropératoire (coefficient de corrélation intracatégorie : 0,36; intervalle de confiance à 95 % : 0,18 à 0,58). CONCLUSIONS: Entre 2008 et 2016, les valeurs peropératoires de l'ETCO2 n'ont pas varié d'une manière importante sur le plan clinique. Il est intéressant de noter que nous avons trouvé une grande variabilité de l'ETCO2 entre hôpitaux et prestataires tout au long de la période d'étude témoignant peut-être d'une vaste plage de tolérance de l'ETCO2 ou d'un manque de données probantes pour soutenir une valeur cible spécifique. L'évolution clinique n'a pas été analysée au cours de cette étude et elle devra être le centre d'intérêt de futures recherches.

Unexpected Cardiac Computed Tomography Findings in Patients With Postoperative Myocardial Injury.

BACKGROUND: Postoperative myocardial injury (PMI) is a strong predictor of mortality after noncardiac surgery. PMI is believed to be attributable to coronary artery disease (CAD), yet its etiology is largely unclear. We aimed to quantify the prevalence of significant CAD in patients with and without PMI using coronary computed tomography angiography (CCTA). METHODS: This prospective cohort study included patients of 60 years or older without a history of cardiac disease and with and without PMI after intermediate- to high-risk noncardiac surgery. PMI was defined as any serum troponin I level ≥60 ng/L on the first 3 postoperative days. Main exclusion criteria were known cardiac disease and postoperative ischemic symptoms or electrocardiography abnormalities. Noninvasive imaging consisted of a postoperative CCTA. Main outcome was CAD defined as >50% coronary stenosis on CCTA. RESULTS: The analysis included 66 patients. Median peak troponin levels in the PMI (n = 46) and control group (n = 20) were 150 (interquartile range, 120-298) vs 15 (interquartile range, 10-31) ng/L (P < .01). CAD was found in 23 patients with PMI (50%) vs 3 without PMI (15%; relative risk, 3.3; 95% confidence interval, 1.1-9.8). Remarkably, pulmonary embolism was present in 15 patients with PMI (33%) versus in 4 without PMI (20%; relative risk, 1.6; 95% confidence interval, 0.6-4.3). None of the patients died within 30 days. CONCLUSIONS: In patients without a history of cardiac disease, PMI after noncardiac surgery was associated with CAD. In addition, a clinically silent pulmonary embolism was found in one-third of patients with PMI. This urges further research to improve clinical workup using imaging and may have important clinical implications.

Kinetics of troponin I in patients with myocardial injury after noncardiac surgery.

BACKGROUND: Myocardial injury after noncardiac surgery, as measured by troponin elevation, is strongly associated with mortality. However, it is unknown in which patients prognosis can be improved. The presence of kinetic changes of troponin may be associated with a worse prognosis and warrant more aggressive management. Therefore, we aimed to study the kinetics of troponin in patients with postoperative myocardial injury, and to determine the added predictive value of kinetic changes of troponin on mortality. METHODS: This cohort study included patients with myocardial injury after noncardiac surgery. Troponin I (TnI) was measured on the first three postoperative days. The primary outcome was all-cause 1-year mortality. We studied both absolute and relative TnI changes, and determined the delta TnI that was associated with mortality to distinguish a rise-and-fall TnI pattern from a stable TnI pattern. Next, we determined the added predictive value of a rise-and-fall TnI pattern for mortality. RESULTS: In total, 634 patients were included. The risk ratio (RR) for mortality increased significantly with an absolute delta TnI of ≥200 ng/L (RR 1.5, 99.4% CI 1.0-2.2, p=0.003). Using this delta TnI to define a rise-and-fall pattern, 459 patients (72%) had a stable TnI pattern and 175 patients (28%) had a rise-and-fall pattern. When added to a model including the highest TnI value and variables from the revised cardiac risk index (RCRI), the TnI pattern did not increase the predictive value for mortality. CONCLUSIONS: A postoperative TnI rise-and-fall pattern was associated with 1-year mortality, but had no added value in addition to the highest TnI level to predict 1-year mortality. Therefore, postoperative TnI kinetics are not useful for further mortality risk stratification in patients with myocardial injury after noncardiac surgery.

Relationship Between Preoperative Evaluation Blood Pressure and Preinduction Blood Pressure: A Cohort Study in Patients Undergoing General Anesthesia.

BACKGROUND: For outcomes research where changes in intraoperative blood pressure are a possible causative factor, it is important to determine an appropriate source for a reference value. We studied to what extent preinduction blood pressure values in the operating room differ from those obtained during preoperative evaluation outside the operating room. METHODS: Cohort study including 4408 patients aged 60 years or older undergoing noncardiac surgery. The outcome was the difference between the preinduction mean blood pressure (MBP) and the MBP obtained during preoperative evaluation. A difference of ≥10 mm Hg was considered clinically relevant. A paired samples t test was used to estimate the difference. Linear regression was used to obtain estimates adjusted for patient characteristics, comorbidity, medications, type of surgery, and preoperative blood pressure. RESULTS: Complete data were available for 3660 (83%) patients. There were 2228 (61%) patients with a difference of ≥10 mm Hg between the preinduction and preoperative MBP. The overall mean difference between both MBPs was 11 mm Hg (95% confidence interval, 10-11) with important variability among individuals. Patients with higher preoperative MBP values had smaller differences. After adjusting for patient characteristics, comorbidity, medications, type of surgery, and preoperative blood pressure, the difference decreased an estimated 5.0 mm Hg (95% confidence interval, 4.7-5.4) for every increase of 10 mm Hg in preoperative MBP. Patient characteristics, comorbidity, type of surgery, or medication were not strongly associated with the difference. CONCLUSIONS: The average preinduction blood pressure was higher than the preoperative blood pressure. This difference between the measurements can be explained by stress-induced effects and regression to the mean. To define an optimal reference value for research purposes or to arrive at a clinical perioperative blood pressure target, one should consider that there is important variability both within and between patients.