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BackgroundDespite the adoption of strict infection prevention and control measures, many hospitals have reported outbreaks of multidrug-resistant organisms (MDRO) during the Coronavirus 2019 (COVID-19) pandemic. Following an outbreak of carbapenem-resistantAcinetobacter baumannii(CRAB) in our institution, we sought to systematically analyse characteristics of MDRO outbreaks in times of COVID-19, focussing on contributing factors and specific challenges in controlling these outbreaks.MethodsWe describe results of our own CRAB outbreak investigation and performed a systematic literature review for MDRO (includingCandida auris)outbreaks which occurred during the COVID-19 pandemic (between December 2019 and March 2021). Search terms were related to pathogens/resistance mechanisms AND COVID-19. We summarized outbreak characteristics in a narrative synthesis and contrasted contributing factors with implemented control measures.ResultsThe CRAB outbreak occurred in our intensive care units between September and December 2020 and comprised 10 patients (thereof seven with COVID-19) within two distinct genetic clusters (both ST2 carrying OXA-23). Both clusters presumably originated from COVID-19 patients transferred from the Balkans. Including our outbreak, we identified 17 reports, mostly caused byCandida auris(n = 6) or CRAB (n = 5), with an overall patient mortality of 35% (68/193). All outbreaks involved intensive care settings. Non-adherence to personal protective equipment (PPE) or hand hygiene (n = 11), PPE shortage (n = 8) and high antibiotic use (n = 8) were most commonly reported as contributing factors, followed by environmental contamination (n = 7), prolonged critical illness (n = 7) and lack of trained HCW (n = 7). Implemented measures mainly focussed on PPE/hand hygiene audits (n = 9), environmental cleaning/disinfection (n = 9) and enhanced patient screening (n = 8). Comparing potentially modifiable risk factors and control measures, we found the largest discrepancies in the areas of PPE shortage (risk factor in 8 studies, addressed in 2 studies) and patient overcrowding (risk factor in 5 studies, addressed in 0 studies).ConclusionsReported MDRO outbreaks during the COVID-19 pandemic were most often caused by CRAB (including our outbreak) andC. auris.Inadequate PPE/hand hygiene adherence, PPE shortage, and high antibiotic use were the most commonly reported potentially modifiable factors contributing to the outbreaks. These findings should be considered for the prevention of MDRO outbreaks during future COVID-19 waves.

A 60-year-old woman presented with extensive swelling in the throat and impending airway obstruction. Following a well-established 2-step flexible bronchoscopic intubation procedure, a computed tomography scan identified a large hematoma compromising the airway. Laboratory testing confirmed the diagnosis of acquired hemophilia A (AHA), a rare condition that can potentially be life-threatening, particularly when it results in airway obstruction. The risk of fatal bleeding is substantial when difficult airway management guidelines call for a surgical airway. This case report describes the essentials of hemostatic treatment of AHA and our approach to the management of a difficult airway.

BACKGROUND Postoperative complications in surgery are a significant burden, not only for the patients but also economically. While several predicting factors have already been identified, it is still not well known if increased levels of inflammatory markers in the immediate perioperative phase correlate with a higher incidence of postoperative complications. This study aimed to evaluate which patient characteristics and intraoperative parameters correlate with increased plasma values of monocyte chemoattractant protein 1 (MCP-1) and interleukin 6 (IL-6) of thoracic surgery patients. A second goal was to explore whether MCP-1 and IL-6 are associated with the incidence of postoperative complications. We hypothesized that there is a positive association between inflammatory markers and the occurrence of complications within 6 months after surgery. METHODS This is a substudy of a recent randomized controlled trial, which defined the effect of desflurane versus propofol anesthesia on morbidity and mortality in patients undergoing thoracic surgery. MCP-1 and IL-6 were determined in plasma obtained before and 30 minutes after 1-lung ventilation, 6 hours after surgery, and on postoperative days 1 and 2. Complications were recorded for 6 months. Mixed linear models were used to examine factors associated with MCP-1 and IL-6 levels. Logistic regression models and receiver operating characteristic curves were used to determine the association between MCP-1 and IL-6 and postoperative complications. RESULTS In the original study, 460 patients were included, MCP-1 and IL-6 levels were determined in 428 patients. MCP-1 was positively associated with the duration of surgery (P = .016), whereas IL-6 levels increased with both the length (P < .001) and invasiveness of lung surgery (thoracoscopic wedge resection or lobectomy versus open lobectomy, P = .005; thoracoscopic wedge resection or lobectomy versus pneumonectomy, P = .021). In an exploratory approach, elevated IL-6 plasma peaks were associated with the occurrence of severe complications defined as Clavien-Dindo score grade ≥IVa during the postoperative phase up to 6 months after thoracic surgery (P = .006). CONCLUSIONS In summary, this substudy reveals factors, which correlate with high MCP-1 and IL-6 values. Moreover, higher IL-6 seems to be associated with postoperative severe complications. Perioperative IL-6 monitoring might be helpful for risk estimation in the perioperative setting of patients after lung surgery.

Background Early definitive airway protection and normoventilation are key principles in the treatment of severe traumatic brain injury. These are currently guided by end tidal CO2 as a proxy for PaCO2. We assessed whether the difference between end tidal CO2 and PaCO2 at hospital admission is associated with in-hospital mortality.Method We conducted a retrospective observational cohort study of consecutive patients with traumatic brain injury who were intubated and transported by Helicopter Emergency Medical Services to a Level 1 trauma center between January 2014 and December 2019. We assessed the association between the CO2 gap—defined as the difference between end tidal CO2 and PaCO2—and in-hospital mortality using multivariate logistic regression models.Results 105 patients were included in this study. The mean ±SD CO2 gap at admission was 1.64 (± 1.09) kPa and significantly greater in non-survivors than survivors (2.26 ±1.30 kPa vs. 1.42 ±0.92 kPa, p2 and PaCO2 at admission was low (Pearson's r=.287). The mean CO2 gap after 24 hours was only 0.64 ±0.82 kPa, and no longer significantly different between non-survivors and survivors. The multivariate logistic regression model showed that the CO2 gap was independently associated with increased mortality in this cohort and associated with a 2.7-fold increased mortality for every 1 kPa increase in the CO2 gap (OR 2.692, 95% CI 1.293 to 5.646, p=.009).Conclusions This study demonstrates that the difference between EtCO2 and PaCO2 is significantly associated with in-hospital mortality in patients with traumatic brain injury. EtCO2 was significantly lower than PaCO2, making it an unreliable proxy for PaCO2 when aiming for normocapnic ventilation. The higher-than-expected CO2 gap will lead to iatrogenic hypoventilation when normocapnic ventilation is aimed at, and might thereby increase in-hospital mortality.

While analyzing clinical data where an anesthetic was titrated based on an objective measure of drug effect, we observed paradoxically that greater effect was associated with lesser dose. With this study we sought to find a mathematical explanation for this negative correlation between dose and effect, to confirm its existence with additional clinical data, and to explore it further with Monte Carlo simulations. Automatically recorded dosing and effect data from more than 9,000 patients was available for the analysis. The anesthetics propofol and sevoflurane and the catecholamine norepinephrine were titrated to defined effect targets, i.e., the processed electroencephalogram (Bispectral Index, BIS) and the blood pressure. A proportional control titration algorithm was developed for the simulations. We prove by deduction that the average dose-effect relationship during titration to the targeted effect will associate lower doses with greater effects. The finding of negative correlations between propofol and BIS, sevoflurane and BIS, and norepinephrine and mean arterial pressure confirmed the titration paradox. Monte Carlo simulations revealed two additional factors that contribute to the paradox. During stepwise titration toward a target effect, the slope of the dose-effect data for the population will be "reversed," i.e., the correlation between dose and effect will not be positive, but will be negative, and will be "horizontal" when the titration is "perfect." The titration paradox must be considered whenever data from clinical titration (flexible dose) studies are interpreted. Such data should not be used naively for the development of dosing guidelines.

Background Internationally, propofol is commonly titrated by target-controlled infusion (TCI) to maintain a processed electroencephalographic (EEG) parameter (eg, bispectral index [BIS]) within a specified range. The overall variability in propofol target effect-site concentrations (CeT) necessary to maintain adequate anesthesia in real-world conditions is poorly characterized, as are the patient demographic factors that contribute to this variability. This study explored these issues, hypothesizing that the variability in covariate-adjusted propofol target concentrations during BIS-controlled anesthesia would be substantial and that most of the remaining interpatient variability in drug response would be due to random effects, thus suggesting that the opportunity to improve on the Schnider model with further demographic data is limited. Methods With ethics committee approval and a waiver of informed consent, a deidentified, high-resolution, intraoperative database consisting of propofol target concentrations, BIS values, and vital signs from 13,239 patients was mined to identify patients who underwent general endotracheal anesthesia using propofol (titrated to BIS), fentanyl, remifentanil, and rocuronium that lasted at least 1 hour. The propofol target concentrations and BIS values 30 minutes after incision (CeT30 and BIS30) were considered representative of stable intraoperative conditions. The data were plotted and analyzed by descriptive statistics. Confidence intervals were computed using a bootstrap method. A linear model was fit to the data to test for correlation with factors of interest (eg, age and weight). Results A total of 4584 patients met inclusion criteria and were entered into the analysis. Of the propofol target concentrations, 95% were between 1.5 and 3.5 µg·mL-1. Higher BIS30 values were correlated with higher propofol concentrations. Except for age, all the patient-related variables analyzed entered the regression model linearly. Only 10.2% of the variability in CeT30 was explained by the patient factors of age and weight combined. Conclusions Our hypothesis was confirmed. The variability in covariate-adjusted propofol CeT30 titrated to BIS in real-world conditions is considerable, and only a small portion of the remaining variability in drug response is explained by patient demographic factors. This finding may have important implications for the development of new pharmacokinetic (PK) models for propofol TCI.

Viele Patientinnen und Patienten, denen ein operativer Eingriff bevorsteht, nehmen gerinnungshemmende Medikamente ein. Taglich stellt sich somit die Frage, ob diese abgesetzt, unverandert weitergefuhrt oder durch andere Substanzen ersetzt werden sollen.

International guidelines propose a stepwise workup for the assessment/risk stratification of patients undergoing non-cardiac surgery and guide further testing or treatment/optimization of underlying cardiovascular disease when appropriate. Despite optimal surgical and medical care, around one million patients worldwide will die annually shortly after having undergone a surgical procedure. A major contributor to this postoperative mortality are “silent myocardial ischemic events” which often go unrecognized. Routine measurement of cardiac biomarkers is an important step in the identification of high risk patients and in improving their perioperative care. Once an ischemic event has occurred, a multidisciplinary approach should guide management (e.g. optimization of anti-ischemic and plaque stabilizing therapy, anticoagulation, antiplatelet therapy or invasive strategies), keeping in mind the fragile balance between risk of ischemic events and bleeding.

Zusammenfassung. Patienten, die unter einer gerinnungshemmenden Behandlung stehen und sich einem Eingriff unterziehen müssen, bedürfen einer genauen interdisziplinären Beurteilung, um das Risiko thromboembolischer Ereignisse einerseits und Blutungen andererseits gegeneinander abzuwägen und daraus eine angepasste Strategie abzuleiten. In dieser Arbeit befassen sich die Autoren mit den aktuell eingesetzten antithrombotischen Medikamenten, deren Verwendung im klinischen Alltag, sowie dem Umgang im perioperativen Umfeld.

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.

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.

Perioperative coagulation management is becoming increasingly frequent in the daily routine of the anesthesiologist and with the plethora of new substances on the market also increasingly complex. The perioperative setting poses unique challenges requiring an individualized evaluation and management of antithrombotic therapy. This review shall summarize the newest developments in this domain.New data in patients with atrial fibrillation have led to a paradigm change in the perioperative management of antithrombotics. The role of bridging therapy has been downgraded in the guidelines, which only foresee bridging in patients with high thromboembolic risk. Furthermore, direct oral anticoagulants are now a cornerstone in antithrombotic therapy, calling for specific perioperative management. The new reversal agents idarucizumab, and potentially in the future andexanet alfa and ciraparantag, will play an increasingly important role in the treatment of major bleeding in this group of patients.With the new evidence and treatment options available, perioperative coagulation management is experiencing a Renaissance, opening many interesting new doors, but also presenting the clinician with new challenges.

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.

Perioperative morbidity and mortality remains a substantial problem and is strongly associated with patients&rsquo, cardiac comorbidities. Guidelines for the cardiovascular assessment and management of patients at risk of cardiac issues while undergoing non-cardiac surgery are traditionally based on the exclusion of active or unstable cardiac conditions, determination of the risk of surgery, the functional capacity of the patient, and the presence of cardiac risk factors. In the last two decades, strong evidence showed an association between cardiac biomarkers and adverse cardiac events, with newer guidelines incorporating this knowledge. This review describes a biomarker-based risk-stratification pathway and discusses potential treatment strategies for patients suffering from postoperative myocardial injury or infarction.

A 60-year-old woman presented with extensive swelling in the throat and impending airway obstruction. Following a well-established 2-step flexible bronchoscopic intubation procedure, a computed tomography scan identified a large hematoma compromising the airway. Laboratory testing confirmed the diagnosis of acquired hemophilia A (AHA), a rare condition that can potentially be life-threatening, particularly when it results in airway obstruction. The risk of fatal bleeding is substantial when difficult airway management guidelines call for a surgical airway. This case report describes the essentials of hemostatic treatment of AHA and our approach to the management of a difficult airway.

Aims of the study Improvements to guidelines and efforts to train and equip laypersons and medical professionals are expected to result in improvements in the outcomes of patients experiencing out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate changes in the survival and neurological outcomes of patients before and after the implementation of the 2010 guidelines. Methods In a retrospective chart review, we analysed the outcomes of 182 patients who suffered bystander-witnessed, out-of-hospital ventricular fibrillation or pulseless ventricular tachycardia of cardiac aetiology. These definitions were based on the Utstein style. Survival at hospital discharge (study period 2006 to 2015), 1-year survival (study period 2011 to 2015), neurological outcome (cerebral performance category [CPC] score) and the corresponding changes over time were evaluated. In addition, the results were compared with results obtained from a systematic review of the literature. Results Of 1423 confirmed OHCAs, 182 fulfilled our inclusion criteria. 91 were treated between 2006 and 2010, and 91 from 2011 to 2015. Thirty-one (34%) survived until hospital discharge in the first time period, 44 (48%) in the second time period (p = 0.071); 26/31 (83%) and 40/44 (91%) respectively had a CPC score of 1n2. Between 2011 and 2015, the 1-year survival rate of the patients discharged from hospital was 36/44 (82%). All of these 36 patients (100%) had a favourable neurological outcome (CPC 1n2). These results were well within the range reported in the literature, although this range is wide (11 to 52% for survival at discharge and 6 to 47% for survival at 1 year). Conclusions Survival was found to be at the upper range of the results retrieved by the systematic literature review. However, we found no significant improvements over time. The neurological outcomes of the survivors were favourable. The generalisability of this study is limited by its small sample size. To further improve outcomes, more public health measures, such as a functioning chain of survival, are required (e.g. an effective first responder network).

How to improve outcomes for patients sustaining myocardial injury during and after noncardiac surgery.

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.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.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.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.

Background One-lung ventilation during thoracic surgery is associated with hypoxia–reoxygenation injury in the deflated and subsequently reventilated lung. Numerous studies have reported volatile anesthesia–induced attenuation of inflammatory responses in such scenarios. If the effect also extends to clinical outcome is yet undetermined. We hypothesized that volatile anesthesia is superior to intravenous anesthesia regarding postoperative complications. Methods Five centers in Switzerland participated in the randomized controlled trial. Patients scheduled for lung surgery with one-lung ventilation were randomly assigned to one of two parallel arms to receive either propofol or desflurane as general anesthetic. Patients and surgeons were blinded to group allocation. Time to occurrence of the first major complication according to the Clavien-Dindo score was defined as primary (during hospitalization) or secondary (6-month follow-up) endpoint. Cox regression models were used with adjustment for prestratification variables and age. Results Of 767 screened patients, 460 were randomized and analyzed (n = 230 for each arm). Demographics, disease and intraoperative characteristics were comparable in both groups. Incidence of major complications during hospitalization was 16.5% in the propofol and 13.0% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.75; 95% CI, 0.46 to 1.22; P = 0.24). Incidence of major complications within 6 months from surgery was 40.4% in the propofol and 39.6% in the desflurane groups (hazard ratio for desflurane vs. propofol, 0.95; 95% CI, 0.71 to 1.28; P = 0.71). Conclusions This is the first multicenter randomized controlled trial addressing the effect of volatile versus intravenous anesthetics on major complications after lung surgery. No difference between the two anesthesia regimens was evident.

Die Rhabdomyolyse ist eine seltene, aber bekannte Komplikation der Therapie mit Statinen. Das Risiko wird durch die gleichzeitige Gabe von Medikamenten, welche den Metabolismus und Abbau durch das CYP3A4 System inhibieren, deutlich erhoht. Wir berichten uber einen Fall von Myoglobin induziertem akutem Nierenversagen nach gleichzeitiger Gabe von Simvastatin und Amiodaron. Das Risiko der Rhabdomyolyse wird hauptsachlich durch die Dosis des Statins bestimmt, sodass bei gleichzeitiger Einnahme von CYP3A4 inhibierenden Medikamenten eine maximale Tagesdosierung von 20 mg empfohlen wird um schwerwiegende Medikamenteninteraktionen zu vermeiden.

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).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.Of 1,417 included patients, 99 (7.0%) died and 162 (11.4%) died or suffered MACE at 12 months. A significant interaction (p0.001) 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).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.

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

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.

Several studies have evaluated preoperative B-type natriuretic peptides (NPs) for predicting mortality after surgery; however, the number of deaths in each study was small, limiting the power of these studies. We conducted a systematic review and meta-analysis of studies addressing preoperative NP levels to predict mortality after cardiac and noncardiac surgery.

Background There is uncertainty regarding the prognostic value of troponin and creatine kinase muscle and brain isoenzyme measurements after noncardiac surgery. Methods The current study undertook a systematic review and meta-analysis. The study used six search strategies and included noncardiac surgery studies that provided data from a multivariable analysis assessing whether a postoperative troponin or creatine kinase muscle and brain isoenzyme measurement was an independent predictor of mortality or a major cardiovascular event. Independent investigators determined study eligibility and abstracted data in duplicate. Results Fourteen studies, enrolling 3,318 patients and 459 deaths, demonstrated that an increased troponin measurement after surgery was an independent predictor of mortality (odds ratio [OR] 3.4, 95% confidence interval [CI] 2.2-5.2), but there was substantial heterogeneity (I(2) = 56%). The independent prognostic capabilities of an increased troponin value after surgery in the 10 studies that assessed intermediate-term (≤ 12 months) mortality was an OR = 6.7 (95% CI 4.1-10.9, I(2) = 0%) and in the 4 studies that assessed long-term (more than 12 months) mortality was an OR = 1.8 (95% CI 1.4-2.3, I(2) = 0%; P < 0.001 for test of interaction). Four studies, including 1,165 patients and 202 deaths, demonstrated an independent association between an increased creatine kinase muscle and brain isoenzyme measurement after surgery and mortality (OR 2.5, 95% CI 1.5-4.0, I(2) = 4%). Conclusions An increased troponin measurement after surgery is an independent predictor of mortality, particularly within the first year; limited data suggest an increased creatine kinase muscle and brain isoenzyme measurement also predicts subsequent mortality. Monitoring troponin measurements after noncardiac surgery may allow physicians to better risk stratify and manage their patients.

Background Experimental studies and investigations in patients with cardiac diseases suggest that opioids at clinical concentrations have no important direct effect on myocardial relaxation and contractility. In vivo data on the effect of remifentanil on myocardial function in humans are scarce. This study aimed to investigate the effects of remifentanil on left ventricular (LV) function in young healthy humans by transthoracic echocardiography (TTE). We hypothesized that remifentanil does not impair systolic, diastolic LV function, or both. Methods Twelve individuals (aged 18-48 yr) without any history or signs of cardiovascular disease and undergoing minor surgical procedures under general anaesthesia were studied. Echocardiographic examinations were performed in the spontaneously breathing subjects before (baseline) and during administration of remifentanil at a target effect-site concentration of 2 ng ml−1 by target-controlled infusion. Analysis of systolic function focused on fractional area change (FAC). Analysis of diastolic function focused on peak early diastolic velocity of the mitral annulus (e′) and on transmitral peak flow velocity (E). Results Remifentanil infusion at a target concentration of 2 ng ml−1 did not affect heart rate or arterial pressure. There was no evidence of systolic or diastolic dysfunction during remifentanil infusion, as the echocardiographic measure of systolic function (FAC) was similar to baseline, and measures of diastolic function remained unchanged (e′) or improved slightly (E). Conclusion Continuous infusion of remifentanil in a clinically relevant concentration did not affect systolic and diastolic LV function in young healthy subjects during spontaneous breathing as indicated by TTE

Objectives Right ventricular dysfunction occurs very soon after conventional coronary bypass surgery with cardiopulmonary bypass and might not recover within 1 year after the operation. It has been postulated that performing coronary surgery without cardiopulmonary bypass might preserve right ventricular function. We hypothesized that right ventricular global and overall systolic functions are better preserved 3 months after off-pump surgery than after conventional coronary bypass surgery. Methods Fifty patients scheduled for elective coronary bypass surgery were randomly assigned to conventional or off-pump surgery. Right ventricular function was assessed by means of transthoracic echocardiographic analysis the day before the operation and 3 months later. Right ventricular myocardial performance index was used as a marker of global right ventricular function, and right ventricular fractional area change was used as a marker of overall right ventricular systolic function. Peak systolic velocities of the lateral tricuspid annulus were studied to assess regional systolic function of the right ventricular free wall. Results Surgical intervention was completed according to randomization in 48 of 50 patients. Demographic and perioperative characteristics were similar in the 2 groups. Over the study period, right ventricular myocardial performance index and right ventricular fractional area change did not change in comparison with the baseline values in both groups. Peak systolic velocity of the lateral tricuspid annulus was decreased significantly in both groups 3 months after the operation. There were no significant intergroup differences in any echocardiographic marker of right ventricular function. Conclusions Global right ventricular function was not better preserved 3 months after off-pump surgery than after conventional coronary bypass surgery.

Background The prognostic value of troponin T for midterm outcome in cardiac surgery is insufficiently known. We aimed to assess the value of troponin T to predict 12-month outcome after cardiac surgery, as a single predictor and in combination with the European system for cardiac operative risk evaluation (EuroSCORE). Methods This cohort study included consecutive patients undergoing on-pump cardiac surgery between January 2005 and December 2006. We evaluated postoperative troponin T (TNT) on days 1 and 2 and the EuroSCORE as predictor variables. The primary composite endpoint was all-cause mortality or any major adverse cardiac event (MACE) at 12 months. Logistic regression was used to study the prognostic effect of TNT in a univariate analysis and after adjustment for EuroSCORE. The area under the receiver-operator curve (AUC) was calculated to report the discriminatory performance of the models. Results Seven hundred forty-one patients were available for analysis. Within 12 months after surgery, 92 (12.4%) patients had a MACE, 48 (6.5%) of whom died. A multivariate model of continuous TNT and the continuous logistic EuroSCORE showed a significant independent association between TNT and the composite endpoint (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.02 to 1.04 per 0.1 μg/L increase in TNT). The AUC for the prediction of the composite endpoint of the model combining TNT and the EuroSCORE was 0.72; when based on EuroSCORE alone it was 0.64 ( p Conclusions Postoperative TNT increase (per 0.1 μg/L) is a strong independent predictor of 12-month outcome after on-pump cardiac surgery. Updating the preoperative EuroSCORE risk with postoperative TNT allows for better prediction of 12-month MACE and all-cause mortality.

Damit die Patienten in einem möglichst stabilen Zustand zur Operation kommen, sollen alle Begleiterkrankungen optimal behandelt und medikamentös eingestellt sein. Entsprechend gilt heute die Empfehlung (fast) die gesamte chronische Medikation bis zum Vortag eines operativen Eingriffes unverändert weiterzugeben. Die präoperative Phase soll darüber hinaus zum Anlass genommen werden, die Güte der chronischen Medikation zu überdenken. Sind alle internistisch-kardiologischen Indikationen für den Einsatz von β-Rezeptor-Blockern, ACE-Hemmern und Statinen ausgeschöpft? Ist der Diabetes bestmöglich eingestellt, die Therapie der Schilddrüsen-Dysfunktion noch optimal? Ergibt sich ein Handlungsbedarf, sollen die Anpassungen möglichst frühzeitig vorgenommen und die Dosierungen sorgfältig titriert werden. Einzig im Hinblick auf einen bevorstehenden Eingriff sollen hingegen keine ansonsten nicht indizierte Therapien begonnen werden. Der Umgang mit gerinnungshemmenden Substanzen verlangt nach einem differenzierten Vorgehen. Hier muss die Indikation für die Therapie genauso beachtet werden wie die Gefährlichkeit allfälliger Blutungskomplikationen. Nach akuten kardiovaskulären Ereignissen, insbesondere nach perkutaner Koronarintervention, müssen bis zur Durchführung von (Wahl-) Operationen wenn immer möglich Wartezeiten eingehalten werden, deren Dauer je nach Ereignis und Behandlungsmodalität zwischen wenigen Wochen bis zu einem Jahr liegt.

Transmitral inflow patterns have been used for detection of myocardial ischaemia. However, its diagnostic value has not been tested in anaesthetized and mechanically ventilated patients undergoing coronary artery bypass graft surgery.Transmitral inflow patterns were studied by transoesophageal Doppler echocardiography in 43 patients undergoing coronary artery bypass graft surgery without cardiopulmonary bypass after opening of the sternum (baseline) and during grafting of the left anterior descending artery. Peak early (E) and peak late (A) transmitral velocities and their ratio (E/A) were recorded. Myocardial ischaemia was defined by standard criteria using two-dimensional echocardiography and seven-lead electrocardiogram.Thirty-one patients (64 +/- 8 yr, 9 women) fulfilled the predefined inclusion criteria for analysis. During distal revascularization, 16 patients showed myocardial ischaemia and 15 did not. The use of vasoactive drugs, haemodynamic findings and transmitral inflow patterns were similar in both groups at baseline and during grafting. In the ischaemic group, E was 67.1 +/- 13.9 cm s-1 at baseline and 69.5 +/- 23.2 cm s-1 during grafting, and the E/A ratios were 1.3 +/- 0.3 and 1.4 +/- 0.9, respectively. In the non-ischaemic group, E was 64.0 +/- 17.1 cm s-1 at baseline and 60.9 +/- 14.8 cm s-1 during grafting, and the E/A ratios were 1.4 +/- 0.7 and 1.2 +/- 0.3, respectively.Analysis of Doppler findings of transmitral inflow patterns did not allow for detection of myocardial ischaemia during surgical revascularization of the myocardium.

Background Thoracic epidural analgesia is a well established technique for postoperative pain relief after major abdominal and thoracic surgery. Safety remains a major concern because of serious adverse events including epidural haematoma, abscess and permanent neurological deficit. Objective The aim of this study was to evaluate the incidence and the long-term outcome of serious adverse events associated with thoracic epidural analgesia. Design Retrospective cohort study. Setting The study was conducted at a single institution, a tertiary care teaching hospital. Data were collected over a 10-year period from 2003 until 2012. Patients Data from 7430 patients were prospectively entered into a standardised acute pain service database. A total of 7273 study participants met the inclusion criteria and were included in the final analyses. The inclusion criteria involved surgical patients receiving a postoperative thoracic epidural analgesia catheter treatment for pain control. Exclusion criteria were defined as obstetric, non-surgical, non-epidural analgesia patients and epidural analgesia catheters that had not been placed by an anaesthesiologist. Main outcome measures The database was queried for serious adverse events which were defined as spinal or epidural haemorrhage; spinal or epidural abscess; permanent neurological deficits; cardiac arrest; death and incomplete removal of the epidural analgesia catheter. Patients' charts were comprehensively reviewed in case of a major adverse event. Patients with an unclear outcome received a mailed questionnaire or were contacted by telephone to determine long-term sequelae. Results Seven serious adverse events were identified: epidural abscess [n = 1; incidence 1 : 7273 (0.014%, 95% confidence interval, CI, 0 to 0.08%)], persistent neurological damage [n = 1; incidence 1 : 7273 (0.014%, 95% CI, 0 to 0.08%)], cardiac arrest [n = 1; incidence 1 : 7273 (0.014%, 95% CI, 0 to 0.08%)] and catheter breakage leaving a catheter fragment in situ [n = 4; incidence 1 : 1818 (0.055%, 95% CI, 0.01 to 0.14%)]. Apart from the one patient with persistent neurologic deficit, the patients with serious adverse events associated with thoracic epidural analgesia in our cohort suffered no long-term consequences. Conclusion In our single-centre study of thoracic epidural analgesia, serious adverse events occurred in 0.1% cases (1 : 1000), whereas long-term outcome was compromised in 0.014% (1.4 : 10 000) which is similar to the serious adverse event rates and outcomes reported in the current literature.

Background. The effects of anaesthetics on left ventricular (LV) diastolic function in patients with pre-existing diastolic dysfunction are not well known. We hypothesized that propofol but not sevoflurane will worsen the pre-existing LV diastolic dysfunction. Methods. Of 24 randomized patients, 23 fulfilled the predefined echocardiographic criterion for diastolic dysfunction. They received general anaesthesia with sevoflurane 1 MAC (n=12) or propofol 4 μg ml−1 (n=11). Echocardiographic examinations were performed at baseline and in anaesthetized patients under spontaneous breathing and under positive pressure ventilation. Analysis focused on peak early diastolic velocity of the mitral annulus (Ea). Results. During spontaneous breathing, Ea was higher in the sevoflurane than in the propofol group [mean (95% CI) 7.0 (5.9-8.1) vs 5.5 (4.7-6.3) cm s−1; P

Reduced aspirin responsiveness (i.e. persistent high platelet reactivity in platelet function testing) might be associated with increased risk of myocardial ischemia and cardiac mortality in patients with coronary disease. However, the impact in patients undergoing coronary artery bypass grafting (CABG) is unclear. The aim of this prospective cohort study was to evaluate the predictive value of reduced aspirin responsiveness on cardiac and thromboembolic events in patients undergoing elective isolated CABG surgery with aspirin intake until at least two days before surgery. We included 304 patients in this prospective single-center cohort study. Impedance platelet aggregometry (Multiplate®) was performed directly before and on the first day after surgery. Reduced aspirin responsiveness was defined as area under the curve in ASPItest (AUCASPI) ≥300 U. The primary outcome was a composite of all-cause mortality and/or major adverse cardiac or thromboembolic events within 1 year. Reduced aspirin responsiveness was found in 13 and 24% of patients pre and postoperatively, respectively. There was no difference in the outcomes between patients with normal and reduced aspirin responsiveness in the preoperative measurement (log-rank test, p = 0.540). Multivariate analysis including logistic EuroSCORE I and postoperative troponin T levels did not show any association of reduced aspirin responsiveness with adverse outcome (hazard ratio, 0.576; (95% CI 0.128-2.585; p = 0.471). Similarly, postoperative reduced aspirin responsiveness was not associated with adverse events. To conclude, reduced aspirin responsiveness as evaluated by Multiplate® platelet function analyzer was not associated with increased incidence of major adverse cardiac and thromboembolic events and mortality after CABG surgery.

This study examined the feasibility of Doppler transesophageal echocardiography (TEE) to detect collateral flow to the myocardium supplied by the right coronary artery (RCA) in the inferior left ventricular wall. Forty-four patients who underwent elective coronary artery bypass grafting (CABG) were prospectively studied. Presence of collateral flow to the RCA was diagnosed on preoperative angiography using the Rentrop score and by intraoperative Doppler TEE. Agreement of the 2 methods was analyzed by calculating the kappa coefficient. Collateral flow was present on preoperative angiography in 19 patients and absent in 25 patients. Intraoperative TEE detected collateral flow in the inferior wall in 15 patients (79%) with and 3 patients (12%) without angiographic collaterals, resulting in a kappa coefficient for agreement of 0.67 (95% confidence interval 0.45 to 0.90). Baseline collateral flow disappeared after CABG in 12 of 14 patients with grafting of the RCA but persisted in all patients without such grafting. Physiologic flow in the inferior wall was detected by TEE in a total of 27 patients at baseline and in 38 patients after CABG (p = 0.0018); its peak velocity increased after surgery only in the subgroup of patients with grafting of the RCA. In conclusion, these findings indicate that Doppler TEE may detect collateral flow in the inferior left ventricular wall, and that there are typical changes in collateral and physiologic flow after CABG.

Background. There is limited knowledge of the effects of anaesthetics on left ventricular (LV) diastolic function in humans. Our aim was to evaluate these effects in humans free from cardiovascular disease. Methods. Sixty patients (aged 18–47 yr) who had no history or signs of cardiovascular disease were randomized to receive general anaesthesia with halothane, sevoflurane or propofol. Echocardiography was performed at baseline and during spontaneous respiration at 1 minimum alveolar concentration (MAC) of the inhalational agents or propofol 4 m gm l � 1 (step 1), and repeated during positive-pressure ventilation with 1 and 1.5 MAC of the inhalational agents or with propofol 4 and 6 m gm l � 1 (steps 2A and 2B). Analysis of echocardiographic measurements focused on heart rate corrected isovolumic relaxation time (IVRTc) and early diastolic peak velocity of the lateral mitral annulus (Ea). Results. IVRTc decreased from baseline to step 1 in the halothane group (82 [95% CI, 76–88] ms and 74 [95% CI, 68–80] ms respectively; P=0.02), remained stable in the sevoflurane group (78 [95% CI, 72–83] ms and 73 [95% CI, 67–81] ms; n.s.) and increased in the propofol group (80 [95% CI, 74–86] ms and 92 [95% CI, 84–102] ms; P=0.02). Ea decreased in the propofol group only (18.8 [95% CI, 16.5–19.9] cm s � 1 and 16.0 [95% CI, 14.9–17.9] cm s � 1 ; P=0.003). From step 2A to step 2B, IVRTc increased further in the propofol group (109 [95% CI, 99–121] ms and 119 [95% CI, 99–135] ms; P=0.04) but remained stable in the other two groups. Ea did not change from step 2A to step 2B. Conclusions. Halothane and sevoflurane did not impair LV relaxation, whereas propofol caused a mild impairment. However, the impairment by propofol was of a magnitude that is unlikely to cause clinical diastolic dysfunction. Br J Anaesth 2005; 94: 186–92