Perioperative copeptin: predictive value and risk stratification in patients undergoing major noncardiac surgery-a prospective observational cohort study.

PURPOSE: Biomarkers can aid in perioperative risk stratification. While preoperative copeptin has been associated with adverse events, intraoperative information is lacking and this association may rather reflect a baseline risk. Knowledge about correlations between postoperative copeptin measurements and clinically relevant outcomes is scarce. We examined the association of perioperative copeptin concentrations with postoperative all-cause mortality and/or major adverse cardiac and cerebrovascular events (MACCE) at 12 months and 30 days as well as with perioperative myocardial injury (PMI). METHODS: We conducted a prospective observational cohort study of adults undergoing noncardiac surgery with intermediate to high surgical risk in Basel, Switzerland, and Düsseldorf, Germany from February 2016 to December 2020. We measured copeptin and cardiac troponin before surgery, immediately after surgery (0 hr) and once between the second and fourth postoperative day (POD 2-4). RESULTS: A primary outcome event of a composite of all-cause mortality and/or MACCE at 12 months occurred in 48/502 patients (9.6%). Elevated preoperative copeptin (> 14 pmol·L-1), immediate postoperative copeptin (> 90 pmol·L-1), and copeptin on POD 2-4 (> 14 pmol·L-1) were associated with lower one-year MACCE-free and/or mortality-free survival (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.62 to 5.2; HR, 2.07; 95% CI, 1.17 to 3.66; and HR, 2.47; 95% CI, 1.36 to 4.46, respectively). Multivariable analysis continued to show an association for preoperative and postoperative copeptin on POD 2-4. Furthermore, elevated copeptin on POD 2-4 showed an association with 30-day MACCE-free survival (HR, 2.15; 95% CI, 1.18 to 3.91). A total of 64 of 489 patients showed PMI (13.1%). Elevated preoperative copeptin was not associated with PMI, while immediate postoperative copeptin was modestly associated with PMI. CONCLUSION: The results of the present prospective observational cohort study suggest that perioperative copeptin concentrations can help identify patients at risk for all-cause mortality and/or MACCE. Other identified risk factors were revised cardiac risk index, body mass index, surgical risk, and preoperative hemoglobin. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02687776); first submitted 9 February 2016.

RéSUMé: OBJECTIF: Les biomarqueurs peuvent aider à la stratification du risque périopératoire. Bien que la copeptine préopératoire ait été associée à des événements indésirables, les informations peropératoires font défaut; plutôt, cette association pourrait refléter un risque de base. Les connaissances sur les corrélations entre les mesures postopératoires de la copeptine et les résultats cliniquement pertinents sont rares. Nous avons examiné l'association entre les concentrations de copeptine périopératoires et la mortalité postopératoire toutes causes confondues et/ou les événements indésirables cardiaques et cérébrovasculaires majeurs (EICCM/MACCE) à 12 mois et 30 jours ainsi qu'en cas de lésion myocardique périopératoire (LMP/PMI). MéTHODE: Nous avons réalisé une étude de cohorte observationnelle prospective d'adultes bénéficiant d'une chirurgie non cardiaque à risque chirurgical intermédiaire à élevé à Bâle, en Suisse, et à Düsseldorf, en Allemagne, de février 2016 à décembre 2020. Nous avons mesuré la copeptine et la troponine cardiaque avant la chirurgie, immédiatement après la chirurgie (0 h) et une fois entre le deuxième et le quatrième jour postopératoire (JPO 2-4). RéSULTATS: Un événement constituant un critère d'évaluation principal d'un composite de mortalité toutes causes confondues et/ou de MACCE à 12 mois est survenu chez 48/502 patient·es (9,6 %). Une élévation de la copeptine préopératoire (> 14 pmol·L−1), de la copeptine postopératoire immédiate (> 90 pmol·L−1) et de la copeptine aux JPO 2 à 4 (> 14 pmol·L−1) était associée à une survie sans MACCE et/ou sans mortalité à un an plus faible (rapport de risque [RR], 2,89; intervalle de confiance [IC] à 95 %, 1,62 à 5,2; RR, 2,07; IC 95 %, 1,17 à 3,66; et RR, 2,47; IC 95 %, 1,36 à 4,46, respectivement). L'analyse multivariée a aussi montré une association entre la copeptine préopératoire et postopératoire aux JPO 2 à 4. De plus, un taux élevé de copeptine aux JPO 2 à 4 a montré une association avec la survie sans MACCE à 30 jours (RR, 2,15; IC 95 %, 1,18 à 3,91). Au total, 64 des 489 patient·es présentaient une LMP (13,1 %). Un taux élevé de copeptine préopératoire n'a pas été associé à la LMP, tandis que la copeptine postopératoire immédiate était modestement associée à la LMP. CONCLUSION: Les résultats de la présente étude de cohorte observationnelle prospective suggèrent que les concentrations périopératoires de copeptine peuvent aider à identifier les personnes à risque de mortalité toutes causes confondues et/ou de MACCE. Les autres facteurs de risque identifiés étaient l'indice de risque cardiaque révisé, l'indice de masse corporelle, le risque chirurgical et l'hémoglobine préopératoire. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT02687776); première soumission le 9 février 2016.

Quantification of metabolic equivalents (METs) by the MET-REPAIR questionnaire: A validation study in patients with a high cardiovascular burden.

STUDY OBJECTIVE: Quantifying functional capacity is a core component of preoperative cardiovascular risk assessment. Lower metabolic equivalents (METs) are associated with higher morbidity/mortality in non-surgical and surgical populations. However, actually measuring METs preoperatively is rare. We sought to determine the correlation of self-reported METs using the questionnaire of the MET: REevaluation for Perioperative cArdIac Risk (MET-REPAIR) study and objectively measured METs by gold-standard cardiopulmonary exercise testing (CPET). DESIGN: Single-center prospective validation study. SETTING: University hospital. PATIENTS: We enrolled adult patients aged ≥45 undergoing out-patient cardiac rehabilitation. INTERVENTION: Patients completed the MET-REPAIR Questionnaire and the Duke Activity Status Index (DASI), had blood samples drawn, and underwent undergoing routine CPET. MEASUREMENTS: We compared measured METs by CPET to 1) self-reported METs (the MET-REPAIR Questionnaire), 2) the DASI score, 3) stand-alone questions, and 4) N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations. MAIN RESULTS: 140 patients were recruited. Measured METs by CPET correlated with 1) self-reported METs by the MET-REPAIR Questionnaire (ρ = 0.489, "fair"), 2) self-reported physical activity by the DASI (ρ = 0.487, "fair"), 3) the self-reported continual stair climbing ability (one of the stand-alone questions; ρ = 0.587, "fair") and 4) NT-proBNP concentrations (ρ = -0.353, "poor"). The area under the receiver operating characteristic curve (AUROC) for the ability to perform more than 4 METs were: highest for flights of stairs (0.841 [95%CI 0.735-0.948], p < 0.05 to rest, optimum: 3 flights), not significantly different between MET-REPAIR Questionnaire and DASI (0.666 [95%CI 0.551-0.781], optimum: 6 METs vs. 0.704 [95%CI 0.578-0.829], optimum: 32.2 points or 6.7 METs, p = 0.405), and not significant for NT-proBNP: (0.623 [95%CI 0.483-0.763]). CONCLUSIONS: The MET-REPAIR Questionnaire correlates with measured METs; all utilized forms of self-reported physical activity overestimate measured METs. NT-proBNP correlates poorly with measured METs.

Peri-operative copeptin concentrations and their association with myocardial injury after vascular surgery: A prospective observational cohort study.

BACKGROUND: Copeptin levels in conjunction with cardiac troponin may be used to rule out early myocardial infarction in patients presenting with chest pain. Raised pre-operative copeptin has been shown to be associated with postoperative cardiac events. However, very little is known about the peri-operative time course of copeptin or the feasibility of very early postoperative copeptin measurement to diagnose or rule-out myocardial injury. OBJECTIVES: In this preparatory analysis for a larger trial, we sought to examine the time course of peri-operative copeptin and identify the time at which concentrations returned to pre-operative levels. Second, in an explorative analysis, we sought to examine the association of copeptin in general and at various time points with myocardial injury occurring within the first 48 h. DESIGN: Preparatory analysis of a prospective, observational cohort study. SETTING: Single university centre from February to July 2016. PATIENTS: A total of 30 consecutive adults undergoing vascular surgery. INTERVENTION: Serial peri-operative copeptin measurements. MAIN OUTCOME MEASURE: We measured copeptin concentrations before and immediately after surgery (0 h), then at 2, 4, 6 and 8 h after surgery and on the first and second postoperative day. Postoperative concentrations were compared with pre-operative levels with a Wilcoxon signed-rank test. Second, we explored an association between postoperative copeptin concentrations and myocardial injury by the second postoperative day. Myocardial injury was defined as a 5 ng l increase between pre-operative and postoperative high-sensitivity cardiac troponin T with an absolute peak of at least 20 ng l. RESULTS: Immediate postoperative copeptin concentrations (median [interquartile range]) increased nearly eight-fold from pre-operative values (8.5 [3.6 to 13.8] to 64.75 pmol l [29.6 to 258.7]; P < 0.001). Copeptin concentrations remained elevated until returning to baseline on the second postoperative day. Postoperative copeptin was significantly higher in patients experiencing myocardial injury than in those who did not (P = 0.02). The earliest most promising single time point for diagnosis may be immediately after surgery (0 h). The receiver-operating characteristics curve for immediate postoperative copeptin and myocardial injury by the second postoperative day was 0.743 (95% confidence interval 0.560 to 0.926). CONCLUSION: Copeptin concentrations are greatly increased after vascular surgery and remain so until the 2nd postoperative day. Postoperative copeptin concentrations appear to be higher in patients who go on to exhibit myocardial injury. Immediate postoperative copeptin concentrations show promise for eliminating or identifying those at risk of myocardial injury. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02687776, Mauermann/Lurati Buse.

Perioperative Myocardial Injury After Noncardiac Surgery: Incidence, Mortality, and Characterization.

BACKGROUND: Perioperative myocardial injury (PMI) seems to be a contributor to mortality after noncardiac surgery. Because the vast majority of PMIs are asymptomatic, PMI usually is missed in the absence of systematic screening. METHODS: We performed a prospective diagnostic study enrolling consecutive patients undergoing noncardiac surgery who had a planned postoperative stay of ≥24 hours and were considered at increased cardiovascular risk. All patients received a systematic screening using serial measurements of high-sensitivity cardiac troponin T in clinical routine. PMI was defined as an absolute high-sensitivity cardiac troponin T increase of ≥14 ng/L from preoperative to postoperative measurements. Furthermore, mortality was compared among patients with PMI not fulfilling additional criteria (ischemic symptoms, new ECG changes, or imaging evidence of loss of viable myocardium) required for the diagnosis of spontaneous acute myocardial infarction versus those that did. RESULTS: From 2014 to 2015 we included 2018 consecutive patients undergoing 2546 surgeries. Patients had a median age of 74 years and 42% were women. PMI occurred after 397 of 2546 surgeries (16%; 95% confidence interval, 14%-17%) and was accompanied by typical chest pain in 24 of 397 patients (6%) and any ischemic symptoms in 72 of 397 (18%). Crude 30-day mortality was 8.9% (95% confidence interval [CI], 5.7-12.0) in patients with PMI versus 1.5% (95% CI, 0.9-2.0) in patients without PMI (P<0.001). Multivariable regression analysis showed an adjusted hazard ratio of 2.7 (95% CI, 1.5-4.8) for 30-day mortality. The difference was retained at 1 year with mortality rates of 22.5% (95% CI, 17.6-27.4) versus 9.3% (95% CI, 7.9-10.7). Thirty-day mortality was comparable among patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infarction (280/397, 71%) versus those with at least 1 additional criterion (10.4%; 95% CI, 6.7-15.7, versus 8.7%; 95% CI, 4.2-16.7; P=0.684). CONCLUSIONS: PMI is a common complication after noncardiac surgery and, despite early detection during routine clinical screening, is associated with substantial short- and long-term mortality. Mortality seems comparable in patients with PMI not fulfilling any other of the additional criteria required for spontaneous acute myocardial infarction versus those patients who do. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02573532.

Effect of high-dose sodium selenite in cardiac surgery patients: A randomized controlled bi-center trial.

BACKGROUND & AIMS: Cardiac surgery is accompanied by oxidative stress and systemic inflammatory response, which may be associated with organ dysfunction and increased mortality. Selenium and selenoenzymes are important constituents of anti-oxidative defense. We hypothesized that high-dose sodium selenite supplementation can attenuate the postoperative inflammation and might, therefore, improve clinical outcome. METHODS: Randomized, placebo-controlled, double-blinded, bi-center study on 411 adult patients undergoing elective cardiac surgery. Patients received an intravenous bolus of 4000 µg selenium (in the form of sodium selenite) or placebo after induction of anesthesia and 1000 µg/d selenium or placebo during their intensive care unit (ICU) stay. Primary outcome measure was the Sequential Organ Failure Assessment (SOFA) score on the second postoperative day. Secondary endpoints included the change in perioperative selenium levels, change of inflammatory and cardiac markers, use of vasoactive medication, incidence of acute kidney injury, ICU and hospital length of stay, and mortality. RESULTS: The perioperative administration of high-dose sodium selenite prevented the postoperative drop of blood and serum selenium levels, reduced the number of patients depending on postoperative vasoactive support but failed to reduce the postoperative SOFA score and its related organ-specific scores compared to placebo. Except for an increase of postoperative procalcitonin and bilirubin levels in the sodium selenite group, other inflammatory markers, organ function variables and clinical endpoints remained unchanged. CONCLUSIONS: The perioperative administration of high-dose sodium selenite in cardiac surgery patients prevented the postoperative fall of blood selenium levels and reduced the need for postoperative vasoactive support by a yet unknown mechanism. TRIAL REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT01141556.

Association of Troponin Trends and Cardiac Morbidity and Mortality After On-Pump Cardiac Surgery.

BACKGROUND: Elevated, single-measure, postoperative troponin is associated with adverse events after cardiac surgery. We hypothesized that increases in troponin from the first to the second postoperative day are also associated with all-cause, 12-month mortality and major adverse cardiac events (MACE). METHODS: This observational study included consecutive adults undergoing on-pump cardiac surgery with cardiac arrest. Troponin T was measured on the first and second postoperative day and was classified as "increasing" (>10%), "unchanged" (10% to -10%), or "decreasing" (<-10%). The primary endpoint was all-cause, 12-month mortality. Secondary endpoints were all-cause 12-month mortality or MACE and both outcomes at 30 days. The main analysis was by multivariable Cox regression. RESULTS: Of 1,417 included patients, 99 (7.0%) died and 162 (11.4%) died or suffered MACE at 12 months. A significant interaction (p < 0.001) between first postoperative day troponin and the troponin trend from the first to the second postoperative day on 12-month, all-cause mortality precluded an analysis independent of first postoperative day troponin. Consequently, we stratified patients by their first postoperative day troponin (cutoff, 0.8 µg/L). Increasing troponin was associated with higher mortality in patients with first postoperative day troponin T ≥ 0.8 µg/L (hazard ratio, 1.98; 95% CI, 1.09 to 3.59; p = 0.025). CONCLUSIONS: Troponin changes from the first to the second postoperative day should not be interpreted without consideration of the first postoperative day troponin concentration. For patients with a first postoperative day troponin ≥ 0.8 µg/L, an increase by more than 10% from the first to the second postoperative day was significantly associated with all-cause, 12-month mortality and other adverse events.

Absolute Postoperative B-Type Natriuretic Peptide Concentrations, but Not Their General Trend, Are Associated With 12-Month, All-Cause Mortality After On-Pump Cardiac Surgery.

BACKGROUND: B-type natriuretic peptide (BNP) is a predictor of mortality after on-pump cardiac surgery. However, previous limited and heterogeneous studies have focused on peak concentrations at 3 to 5 days after surgery and may not offer clinicians much help in early decision-making. After confirming the predictive value of first-postoperative-day BNP in a preliminary analysis, we explored the association between isolated second-postoperative-day BNP concentrations, second-day BNP concentrations in conjunction with first-day BNP concentrations, and the change in BNP (ie, ΔBNP) from the first to the second postoperative day and 12-month, all-cause mortality. METHODS: We included consecutive patients undergoing on-pump cardiac surgery in this observational, secondary analysis of prospectively collected data. We analyzed biomarkers on the first and second postoperative day. ΔBNP was defined as BNP on the second postoperative day minus BNP on the first postoperative day. The primary end point was 12-month, all-cause mortality. The secondary end point was a composite of major adverse cardiac events (MACEs) at 12 months and/or all-cause mortality at 12 months. MACE was defined as nonfatal cardiac arrest, myocardial infarction, and congestive heart failure. The association between BNP and outcomes was examined by receiver operating characteristic curves, as well as univariate and multivariable logistic regression, adjusting for the EuroSCORE II, cross-clamp time, and first-postoperative-day troponin T. RESULTS: We included 1199 patients in the preliminary analysis focused on BNP on postoperative day 1. In the analyses examining BNP variables requiring second-postoperative-day BNP measurement (n = 708), we observed 66 (9.3%) deaths, 48 (6.8%) MACE, and 104 (14.7%) deaths and/or MACE. Both first- and second-postoperative-day BNP were significant independent predictors of all-cause, 12-month mortality per 100 ng/L increase (adjusted odds ratio [aOR], 1.040 [95% confidence interval (CI), 1.019-1.065] and 1.064 [95% CI, 1.031-1.105], respectively). When used in conjunction with one another, first-day BNP was not significant (aOR, 1.021 [95% CI, 0.995-1.048]), while second-day BNP remained significant (aOR, 1.046 [95% CI, 1.008-1.091]). The ΔBNP per 100 ng/L increase was not associated with 12-month, all-cause mortality in the univariable (OR, 0.977 [95% CI, 0.951-1.007]) or multivariable analysis (aOR, 0.989 [95% CI, 0.962-1.021]). CONCLUSIONS: Both absolute concentrations of first- and second-postoperative-day BNP are independent predictors of 12-month, all-cause mortality. When modeled together, second-postoperative-day BNP is more predictive of 12-month, all-cause mortality. Although intuitively appealing, the change in BNP from the first to the second postoperative day is a complex variable and should not routinely be used for prognostication.

Postoperative High-Sensitivity Troponin and Its Association With 30-Day and 12-Month, All-Cause Mortality in Patients Undergoing On-Pump Cardiac Surgery.

BACKGROUND: Troponin T is a predictor of cardiac morbidity and mortality after cardiac surgery with most data examining fourth generational troponin T assays. We hypothesize that postoperative high-sensitivity troponin T (hsTnT) measured in increments of the upper limit of the norm independently predicts 30-day all-cause mortality. METHODS: We included consecutive patients undergoing on-pump cardiac surgery from February 2010 to March 2012 in a prospective cohort that measured hsTnT at 0600 of the first and second postoperative day. Our primary end point was 30-day, all-cause mortality. The secondary end point was 12-month, all-cause mortality in patients surviving the first 30 days. We divided hsTnT into 5 predetermined categorizes based on the upper limit of the norm (ULN). We used Cox regression to examine an association of hsTnT independent of the EuroSCORE II at both 30 days as well as at 12 months in patients surviving the first 30 days. We assessed the area under the receiver operating characteristics curve and the net reassignment improvement for examining the benefit of adding of hsTnT to the EuroSCORE II for prognostication and restratification of 30-day, all-cause mortality. RESULTS: We included 1122 of 1155 eligible patients (75% male; mean age 66 ± 11 years). We observed 58 (5.2%) deaths at 30 days and another 35 (3.4%) deaths at 12 months in patients surviving 30 days. HsTnT categorized by ULN exhibited a graded response for the mortality. Furthermore, hsTnT remained an independent predictor of all-cause mortality at 30 days (adjusted hazard ratio 1.019 [1.014-1.024] per 10-fold increase in ULN) as well as at 12 months (adjusted hazard ratio 1.019 [1.007-1.032]) in patients surviving the first 30 days. The addition of hsTnT to the EuroSCORE II significantly increased the area under the receiver operating characteristics curve (area under curve: 0.816 [95% confidence interval, 0.754-0.878] versus area under curve: 0.870 [95% confidence interval, 0.822-0.917], respectively; P = .012). Finally, adding hsTnT to the EuroSCORE II improved restratification by the net reassignment improvement, primarily by improving rule-out of events. CONCLUSIONS: This analysis suggests that, similar to previous assays, higher postoperative concentrations of hsTnT are independently associated with all-cause mortality in patients undergoing on-pump cardiac surgery.

Significance of new Q waves and their location in postoperative ECGs after elective on-pump cardiac surgery: An observational cohort study.

BACKGROUND: The clinical significance of new pathological Q waves after on-pump cardiac surgery is uncertain. OBJECTIVES: To determine whether or not either the occurrence per se or the location of new pathological Q waves after on-pump cardiac surgery is associated with 12-month, all-cause mortality and/or major adverse cardiac events (MACEs). DESIGN: Observational cohort study. SETTING: Single university hospital from January 2007 to October 2010. PATIENTS: Consecutive adult patients undergoing elective on-pump cardiac surgery with MACE-free survival until at least the 7th postoperative day and available ECGs both preoperatively and on the 7th postoperative day (n = 1464). We conducted a subgroup analysis in patients undergoing isolated coronary artery bypass grafting (n = 740). MAIN OUTCOME MEASURE: Our primary endpoint was 12-month, all-cause mortality and/or MACE, defined as acute coronary syndrome, cardiac arrest, congestive heart failure or re-vascularisation at 12 months. Using logistic regression, we examined the prognostic value of new pathological Q waves according to the Minnesota ECG Code, adjusting for the EuroSCORE II, cardiopulmonary bypass time and peak postoperative troponin T concentrations. RESULTS: We included 1464 patients (74% men; mean ±â€ŠSD age 66 ±â€Š10 years) and observed 103 (7.0%) all-cause deaths and/or MACEs at 12 months. A total of 236 patients (16.1%) had definite or probable new pathological Q waves according to the Minnesota ECG Code. The occurrence of new pathological Q waves per se was not associated with our primary endpoint [adjusted odds ratio, 0.970 (95% confidence interval, 0.540 to 1.648)]. However, the occurrence of a new pathological Q wave in V1 to V5 (anterior) was a strong independent predictor for poor outcome [adjusted odds ratio, 3.461 (95% confidence interval, 1.501 to 7.242)]. CONCLUSION: The current analysis suggests that for patients undergoing elective on-pump cardiac surgery, only new pathological Q waves in V1 to V5 (anterior) in the 7th postoperative day ECG are associated with 12-month, all-cause mortality and/or MACE. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00468598.

Incremental Value of Preoperative Copeptin for Predicting Myocardial Injury.

BACKGROUND: Copeptin, a novel marker of endogenous stress, has shown diagnostic and prognostic value in nonsurgical patients with a suspected coronary event. We aimed to assess the incremental value of copeptin in addition to established preoperative risk indices to predict the occurrence of postoperative myocardial injury. METHODS: This secondary analysis of prospectively collected data included adults undergoing noncardiac surgery with risk factors for adverse perioperative cardiac events based on preoperative risk stratification. We examined preoperative copeptin in patients without elevated preoperative troponin and its association with myocardial injury by receiver operator characteristic curves, logistic regression, and net reassignment indices. RESULTS: Of the 190 patients included, 33 (17.4%) experienced myocardial injury within 48 hours, and 17 (8.9%) experienced cardiac death and/or major adverse cardiac events within the first postoperative year. Preoperative copeptin showed an area under the receiver operator characteristic curve of .66 (95% confidence interval, .55-.76) for myocardial injury and an optimal cutoff of 9.6 pmol/L. This cutoff was an independent predictor of myocardial injury, with an odds ratio of 4.67 (95% confidence interval, 2.06-11.19) when adjusted for age, sex, and the revised cardiac risk index. The net reassignment improvement for myocardial injury was between 39% and 50% for both events and nonevents when adding copeptin to established preoperative risk indices. No significant difference in major adverse cardiac event and/or cardiac death was observed. CONCLUSIONS: Copeptin (≥9.6 pmol/L) was associated with significantly higher rates of myocardial injury and improved risk stratification in patients scheduled for noncardiac surgery with nonelevated preoperative troponin.

Efficacy and safety of carbetocin applied as an intravenous bolus compared to as a short-infusion for caesarean section: study protocol for a randomised controlled trial.

BACKGROUND: The two most commonly used uterotonic drugs in caesarean section are oxytocin and carbetocin, a synthetic oxytocin analogue. Carbetocin has a longer half-life when compared to oxytocin, resulting in a reduced use of additional uterotonics. Oxytocin is known to cause fewer cardiovascular side effects when administered as a short-infusion compared to as an intravenous bolus. Based on these findings, we aim at comparing carbetocin 100 mcg given as a slow intravenous bolus with carbetocin 100 mcg applied as a short-infusion in 100 ml 0.9 % sodium chloride in women undergoing a planned or unplanned caesarean delivery. We hypothesise uterine contraction not to be inferior to a bolus application (primary efficacy endpoint) and greater haemodynamic stability to be achieved after a short-infusion than after a bolus administration, as measured by heart rate and mean arterial blood pressure (primary safety endpoint). METHODS/DESIGN: This is a prospective, double-blind, randomised controlled, investigator-initiated, non-inferiority trial taking place at the University Hospital Basel, Switzerland. Uterine tone is quantified by manual palpation by the obstetrician using a linear analogue scale from 0 to 100 at 2, 3, 5 and 10 minutes after cord clamping. We will evaluate whether the lower limit of the confidence interval for the difference of the maximal uterine tone within the first 5 minutes after cord clamping between both groups does not include the pre-specified non-inferiority limit of -10. Both haemodynamic secondary endpoints will be analysed using a linear regression model, adjusting for the baseline value and the dosage of vasoactive drug given between cord clamping and 1 minute thereafter, in order to investigate superiority of a short-infusion as compared to a bolus application. We will follow the extension of CONSORT guidelines for reporting the results of non-inferiority trials. DISCUSSION: Haemodynamic stability and adequate uterine tone are important outcomes in caesarean sections. The results of this trial may be used to optimise these factors and thereby increase patient safety due to a reduction in cardiovascular side effects. TRIAL REGISTRATION: Clinicaltrials.gov NCT02221531 on 19 August 2014 and www.kofam.ch SNCTP000001197 on 15 November 2014.

Troponin T and B-type natriuretic peptide after on-pump cardiac surgery: prognostic impact on 12-month mortality and major cardiac events after adjustment for postoperative complications.

BACKGROUND: The independent predictive value of troponin T (TNT) after on-pump cardiac surgery was established in several studies. However, adjustment was limited to preoperative risk factors without considering perioperative complications. Data on the prognostic value of postoperative B-type natriuretic peptide (BNP) are scarce. Our aim was to assess the independent value of TNT and BNP to predict 12-month outcome after cardiac surgery with adjustment for preoperative risk estimates and postoperative complications and to report risk stratification gains when considering the European System for Cardiac Operative Risk Evaluation (EuroSCORE) combined with postoperative biomarkers. METHODS AND RESULTS: This prospective cohort study included consecutive patients undergoing on-pump cardiac surgery between 2007 and 2010. We evaluated postoperative TNT and BNP, the EuroSCORE, and postoperative complications as predictors of adverse events using Cox regression. The primary end point was death or major adverse cardiac events within 1 year after surgery. We calculated the net reclassification index of TNT and BNP in addition to the EuroSCORE. We enrolled 1559 patients, of whom 176 (11.3%) experienced an event. The adjusted hazard ratio of TNT >0.8 µg/L was 2.13 (95% confidence interval, 1.47-3.15) and of BNP >790 ng/L was 2.44 (95% confidence interval, 1.65-3.62). The net reclassification index of the addition of TNT and BNP to the EuroSCORE was 0.276 (95% confidence interval, 0.195-0.348). CONCLUSIONS: Postoperative TNT and BNP are strong predictors of 1-year events after on-pump cardiac surgery independent of preoperative risk factors and postoperative complications. Updating the preoperative EuroSCORE risk with postoperative TNT and BNP after surgery allows for improved prediction of 1-year death or major adverse cardiac events.

Randomized comparison of sevoflurane versus propofol to reduce perioperative myocardial ischemia in patients undergoing noncardiac surgery.

BACKGROUND: Volatile anesthetics provide myocardial preconditioning in coronary surgery patients. We hypothesized that sevoflurane compared with propofol reduces the incidence of myocardial ischemia in patients undergoing major noncardiac surgery. METHODS AND RESULTS: We enrolled 385 patients at cardiovascular risk in 3 centers. Patients were randomized to maintenance of anesthesia with sevoflurane or propofol. We recorded continuous ECG for 48 hours perioperatively, measured troponin T and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) on postoperative days 1 and 2, and evaluated postoperative delirium by the Confusion Assessment Method. At 6 and 12 months, we contacted patients by telephone to assess major adverse cardiac events. The primary end point was a composite of myocardial ischemia detected by continuous ECG and/or troponin elevation. Additional end points were postoperative NT-proBNP concentrations, major adverse cardiac events, and delirium. Patients and outcome assessors were blinded. We tested dichotomous end points by χ(2) test and NT-proBNP by Mann-Whitney test on an intention-to-treat basis. Myocardial ischemia occurred in 75 patients (40.8%) in the sevoflurane and 81 (40.3%) in the propofol group (relative risk, 1.01; 95% confidence interval, 0.78-1.30). NT-proBNP release did not differ across allocation on postoperative day 1 or 2. Within 12 months, 14 patients (7.6%) suffered a major adverse cardiac event after sevoflurane and 17 (8.5%) after propofol (relative risk, 0.90; 95% confidence interval, 0.44-1.83). The incidence of delirium did not differ (11.4% versus 14.4%; P=0.379). CONCLUSIONS: Compared with propofol, sevoflurane did not reduce the incidence of myocardial ischemia in high-risk patients undergoing major noncardiac surgery. The sevoflurane and propofol groups did not differ in postoperative NT-proBNP release, major adverse cardiac events at 1 year, or delirium.