Esther Seeberger

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 &khgr;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. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00286585.

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 &mgr;g/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.

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.

The influence of pre-admission hypoglycaemic therapy on cardiac morbidity and mortality in type 2 diabetic patients undergoing major non-cardiac surgery: a prospective observational study*

It remains unclear whether type 2 diabetics treated with either insulin or oral hypoglycaemic agents have the same incidence of cardiac morbidity and mortality after major non‐cardiac surgery. We prospectively studied 360 type 2 diabetic patients undergoing major non‐cardiac surgery of which 105 were treated with insulin only, 171 were treated with oral hypoglycaemics only and 84 were treated with a combination of insulin and oral hypoglycaemics. All‐cause mortality after 30 days and after 12 months was highest in the insulin (10% and 26%) and lowest in the oral hypoglycaemics group (2% and 13%; p = 0.02 and 0.007, respectively). Insulin treatment was independently associated with increased mortality after 30 days (hazard ratio 3.93; 95% CI 1.22–12.64; p = 0.022) and 12 months (hazard ratio 2.03; 95% CI 1.16–3.58; p = 0.014) after multivariate adjustment for age, sex and the revised cardiac risk index (insulin treatment excluded). The increased mortality in insulin‐treated diabetic patients may be due to a more progressive disease state in these patients rather than the treatment modality itself.

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 ± SD age 66 ± 10 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.

Efficacy and safety of carbetocin given as an intravenous bolus compared with short infusion for Caesarean section - double-blind, double-dummy, randomized controlled non-inferiority trial

Background. Carbetocin is a synthetic oxytocin‐analogue, which should be administered as bolus according to manufacturers recommendations. A higher speed of oxytocin administration leads to increased cardiovascular side‐effects. It is unclear whether carbetocin administration as short infusion has the same efficacy on uterine tone compared with bolus administration and whether haemodynamic parameters differ. Methods. In this randomized, double‐blind, non‐inferiority trial, women undergoing planned or unplanned Caesarean section (CS) under regional anaesthesia received a bolus and a short infusion, only one of which contained carbetocin 100 mcg (double dummy). Obstetricians quantified uterine tone two, three, five and 10 min after cord‐clamping by manual palpation using a linear analogue scale from 0 to 100. We evaluated whether the lower limit of the 95% CI of the difference in maximum uterine tone within the first five min after cord‐clamping did not include the pre‐specified non‐inferiority limit of ‐10. Results. Between December 2014 and November 2015, 69 patients were randomized to receive carbetocin as bolus and 71 to receive it as short infusion. Maximal uterine tone was 89 in the bolus and 88 in the short infusion group (mean difference ‐1.3, 95% CI ‐5.7 to 3.1). Bp, calculated blood loss, use of additional uterotonics, and side‐effects were comparable. Conclusions. Administration of carbetocin as short infusion does not compromise uterine tone and has similar cardiovascular side‐effects as a slow i.v. bolus. In accordance with current recommendations for oxytocin, carbetocin can safely be administered as short ‐infusion during planned or unplanned CS. Clinical trial registration. ClinicalTrials.gov NCT02221531 and www.kofam.ch SNCTP000001197.

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.

Response to Letters Regarding Article, “Randomized Comparison of Sevoflurane Versus Propofol to Reduce Perioperative Myocardial Ischemia in Patients Undergoing Noncardiac Surgery”

We thank the authors of the letters for their interest in our publication.1 Their comments focused on the following issues: (1) hypothesized effect; (2) study end points, including methods and duration of the ischemia assessment; (3) factors potentially masking the preconditioning effect of sevoflurane (eg, opioids), and (4) inclusion of patients undergoing orthopedic surgery.

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.

Troponin T and brain natriuretic peptide after on-pump cardiac surgery: impact on 12-month mortality and major cardiac events after adjustment for postoperative complications: 4AP7-10

Results and discussion: Eight patients received successful LAA closure. RT3D TEE helped the measurement of LAA size, the evaluation of LAA shape, the selection of intra-atrial septum (IAS) puncture site, and the assurance of occluder implantation. The most valuable ability of RT-3D TEE over other image modalities is it could select IAS puncture site fast, precisely, and conveniently. In this study we preferred to puncture IAS more posteriorly and inferiorly, instead of the center of IAS. All patients had no or trivial flow into LAA after the occluder implantation. One patient had significant pericardial ef fusion thus pigtail drainage and transfusion were required, af ter LAA closure he was hemodynamically stable and discharged without permanent complications or any significant discomfort. Conclusion: RT-3D TEE is a helpful guidance tool and monitor in percutaneous transcatheter LAA closure with great convenience and safety, especially in the selection of IAS puncture site. References: 1. Landmesser U, Holmes DR, Jr. Lef t atrial appendage closure: a percutaneous transcatheter approach for stroke prevention in atrial fibrillation. European heart journal 2012;33:698-704. 2. Alli O, Holmes DR, Jr. Lef t atrial appendage occlusion for stroke prevention. Current problems in cardiology 2012;37:405-41. 3. Chatterjee S, Alexander JC, Pearson PJ, Feldman T. Lef t atrial appendage occlusion: lessons learned from surgical and transcatheter experiences. The Annals of thoracic surgery 2011;92:2283-92. 4AP7-10