Martin Grapow

Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery : A randomized controlled trial

Objective:Cardiac surgery is frequently followed by postoperative delirium, which is associated with increased 1-year mortality, late cognitive deficits, and higher costs. Currently, there are no recommendations for pharmacologic prevention of postoperative delirium. Impaired cholinergic transmission is believed to play an important role in the development of delirium. We tested the hypothesis that prophylactic short-term administration of oral rivastigmine, a cholinesterase inhibitor, reduces the incidence of delirium in elderly patients during the first 6 days after elective cardiac surgery. Design:Double-blind, randomized, placebo-controlled trial. Setting:One Swiss University Hospital. Patients:One hundred twenty patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. Intervention:Patients were randomly assigned to receive either placebo or 3 doses of 1.5 mg of oral rivastigmine per day starting the evening before surgery and continuing until the evening of the sixth postoperative day. Measurements and Main Results:The primary predefined outcome was delirium diagnosed with the Confusion Assessment Method within 6 days postoperatively. Secondary outcome measures were the results of daily Mini-Mental State Examinations and clock drawing tests, and the use of a rescue treatment consisting of haloperidol and/or lorazepam in patients with delirium. Delirium developed in 17 of 57 (30%) and 18 of 56 (32%) patients in the placebo and rivastigmine groups, respectively (p = 0.8). There was no treatment effect on the time course of Mini-Mental State Examinations and clock drawing tests (p = 0.4 and p = 0.8, respectively). There was no significant difference in the number of patients receiving haloperidol (18 of 57 and 17 of 56, p = 0.9) or lorazepam (38 of 57 and 35 of 56, p = 0.6) in the placebo and rivastigmine groups, respectively. Conclusion:This negative or, because of methodologic issues, possibly failed trial does not support short-term prophylactic administration of oral rivastigmine to prevent postoperative delirium in elderly patients undergoing elective cardiac surgery with cardiopulmonary bypass.

Modifiable and Nonmodifiable Risk Factors for Postoperative Delirium After Cardiac Surgery With Cardiopulmonary Bypass

OBJECTIVES Postoperative delirium after cardiac surgery is associated with increased morbidity and mortality as well as prolonged stay in both the intensive care unit and the hospital. The authors sought to identify modifiable risk factors associated with the development of postoperative delirium in elderly patients after elective cardiac surgery in order to be able to design follow-up studies aimed at the prevention of delirium by optimizing perioperative management. DESIGN A post hoc analysis of data from patients enrolled in a randomized controlled trial was performed. SETTING A single university hospital. PARTICIPANTS One hundred thirteen patients aged 65 or older undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS None. MEASUREMENTS AND MAINS RESULTS: Screening for delirium was performed using the Confusion Assessment Method (CAM) on the first 6 postoperative days. A multivariable logistic regression model was developed to identify significant risk factors and to control for confounders. Delirium developed in 35 of 113 patients (30%). The multivariable model showed the maximum value of C-reactive protein measured postoperatively, the dose of fentanyl per kilogram of body weight administered intraoperatively, and the duration of mechanical ventilation to be independently associated with delirium. CONCLUSIONS In this post hoc analysis, larger doses of fentanyl administered intraoperatively and longer duration of mechanical ventilation were associated with postoperative delirium in the elderly after cardiac surgery. Prospective randomized trials should be performed to test the hypotheses that a reduced dose of fentanyl administered intraoperatively, the use of a different opioid, or weaning protocols aimed at early extubation prevent delirium in these patients.

The prognostic value of troponin release after adult cardiac surgery — a meta-analysis

To assess the accuracy of increased troponin (Tn) concentrations for the prediction of mid-term (> or = 12 months) mortality after coronary artery bypass graft (CABG) and valve surgery, we performed a systematic review identifying all studies reporting on the association between postoperative troponin release and mortality after cardiac surgery. Studies were identified through 30 April 2008 by electronic searches of the MEDLINE, EMBASE and BIOSIS databases. Two reviewers independently selected studies, assessed methodological quality and extracted the data. We primarily considered mid-term (> or = 12 months) and secondarily short-term (< or = 30 days) all-cause mortality. A bivariate random-effects model was used to study determinants and to pool measures of prognostic accuracy of Tn. Seventeen studies fulfilled the inclusion criteria with a total of 237 mid-term deaths in 5189 patients and 296 short-term deaths in 9703 patients. The diagnostic odds ratio of increased Tn concentrations was 5.46 (95% confidence interval (CI) 2.0-14.6) for mid-term mortality and 6.57 (95% CI 4.3-10.1) for short-term mortality after adult cardiac surgery. Alternatively expressed, for troponin elevation, the sensitivity was 0.45 (0.26-0.67) and the specificity 0.87 (0.73-0.90) to predict mid-term mortality. The sensitivity was 0.59 (0.48-0.69) and the specificity 0.82 (0.72-0.89) for short-term mortality. Between-study variability was high. In conclusion, this meta-analysis provides evidence for an association between postoperative Tn release with mid- and short-term all-cause mortality after adult cardiac surgery. However, differences in populations, timing of Tn testing, Tn subunit and Tn assays make definitive conclusions about effect size and cut-off values difficult.

Pre-analytical effects of pneumatic tube transport on impedance platelet aggregometry.

Point-of-care platelet monitoring is increasingly used in cardiac patients treated with antiplatelet agents. The validity of a new assay needs to be evaluated not only for reproducible data in clinical samples, but also for other pre-analytical conditions that may influence measurements. The aim of this study was to evaluate the influence of a pneumatic tube system (PTS) for specimen transport on impedance platelet aggregometry. We evaluated 50 consecutive patients scheduled for coronary artery bypass surgery under oral therapy with 100 mg/d acetylsalicylic acid (aspirin). In each patient, three blood samples for platelet function analysis were taken before induction of anesthesia. The first sample was measured in the operating room (OR) area and designated as the reference value. The second sample was again measured by the same operator in the OR area using a random PTS transport. The third sample was sent to the central laboratory by PTS where it was measured by a local technician. Platelet function was assessed in whole blood by impedance aggregometry with a Multiplate™ analyzer using thrombin-related activation peptide (TRAP test) and arachidonic acid (ASPI test) (Dynabite GmbH, Munich, Germany). Mean ± SD for TRAP test was 1009 ± 196 in the reference measurement. Bias ± 95% limit of agreement between the reference measurement and a second measurement for TRAP test were 126 ± 284 (n = 25) for untransported and 181 ± 316 (n = 25) for PTS transported samples. In the reference measurements, 48/50 (96%) of TRAP values were within the normal range. After PTS transport, 35/50 (70%) of TRAP measurements in the central laboratory were within the normal range (p < 0.001). Mean ± SD for ASPI test was 175 ± 137. Bias ± 95% limit of agreement for ASPI test were 12 ± 109 (n = 25) for untransported and 68 ± 250 (n = 25) for PTS transported samples. In the reference measurements, 7/50 (14%) ASPI values were above the cut-off level and defined as reduced aspirin responsiveness. After PTS transport, only 1/50 (2%) of the patients showed reduced aspirin responsiveness in the central laboratory measurements (p = 0.031). In conclusion, PTS transport had a significant influence on platelet function testing by the Multiplate™ analyzer. Significantly fewer test results indicated normal platelet function in TRAP test and reduced aspirin responsiveness in ASPI test after PTS transport. Therefore, clinical decisions regarding platelet function and aspirin responsiveness should not be based on blood specimens transported by a PTS system.

A new cable-tie based sternal closure system: description of the device, technique of implantation and first clinical evaluation

BackgroundWire closure still remains the preferred technique despite reasonable disadvantages. Associated complications, such as infection and sternal instability, cause time- and cost-consuming therapies. We present a new tool for sternal closure with its first clinical experience and results.MethodsThe sternal ZipFixTM System is based on the cable-tie principle. It primarily consists of biocompatible Poly-Ether-Ether-Ketone implants and is predominantly used peristernally through the intercostal space. The system provides a large implant-to-bone contact for better force distribution and for avoiding bone cut through.Results50 patients were closed with the ZipFixTM system. No sternal instability was observed at 30 days. Two patients developed a mediastinitis that necessitated the removal of the device; however, the ZipFixTM were intact and the sternum remained stable.ConclusionsIn our initial evaluation, the short-term results have shown that the sternal ZipFixTM can be used safely and effectively. It is fast, easy to use and serves as a potential alternative for traditional wire closure.

A rifampicin-containing antibiotic treatment improves outcome of staphylococcal deep sternal wound infections

BACKGROUND Deep sternal wound infection (DSWI) is a severe complication after cardiac surgery, mostly caused by staphylococci. Little is known about the optimal antibiotic management. METHODS A 10 year retrospective analysis of 100 patients with staphylococcal DSWI after cardiac surgery in a tertiary hospital. Treatment failure was defined as sternal wound dehiscence or fistula at the end of the prescribed antibiotic therapy, 12 months later, or DSWI-related death. RESULTS Most patients were male (83%) and the median age was 72 years [interquartile range (IQR) 63-76]. Coronary artery bypass was the most frequent preceding procedure (93%). The median time to diagnosis of DSWI was 13 days (IQR 10-18) after surgery. Clinical presentation consisted of wound discharge in 77% of patients. Coagulase-negative staphylococci were isolated in 54 and Staphylococcus aureus in 46 patients. All patients received antibiotics and 95% underwent surgical debridement. The median duration of antibiotic treatment was 47 days (IQR 41-78). During follow-up, 21 out of 100 patients experienced treatment failure. Of these, 8/21 patients (38%) died from DSWI after a median of 12 days (IQR 8-30). In the multivariate analysis, a rifampicin-containing antibiotic regimen was the only factor associated with lower risk of treatment failure (hazard ratio 0.26, 95% confidence interval 0.10-0.64, P = 0.004). Prolonged treatment (12 weeks instead of 6 weeks) did not alter outcome (P = 0.716) in patients without prosthetic valve endocarditis. CONCLUSIONS Treatment of rifampicin-susceptible staphylococcal DSWI with a rifampicin-containing antibiotic regimen may improve the outcome. After surgical debridement an antibiotic treatment of 6 weeks may be adequate for staphylococcal DSWI.

12-Month Outcome After Cardiac Surgery: Prediction by Troponin T in Combination With the European System for Cardiac Operative Risk Evaluation

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 microg/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 < 0.0001). CONCLUSIONS Postoperative TNT increase (per 0.1 microg/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.

A new cable-tie-based sternal closure device: infectious considerations

OBJECTIVES To determine the difference in sternal infection and other infectious events between conventional wire and cable-tie-based closure techniques post-sternotomy in a collective of patients after cardiac surgery. METHODS The sternal ZipFix™ (ZF) system consists of a biocompatible poly-ether-ether-ketone (PEEK) cable-tie that surrounds the sternum through the intercostal space and provides a large implant-to-bone contact. Between 1 February 2011 and 31 January 2012, 680 cardiac operations were performed via sternotomy at our institution. After the exclusion of operations for active endocarditis and early mortality within 7 days, 95 patients were exclusively closed with ZF and could be compared with 498 who were closed with conventional wires (CWs) during the same period. A multivariable logistic regression analysis, including body mass index, renal impairment and emergency as suspected confounders and inverse propensity weights was performed on the infection rate. RESULTS Total infection rate was 6.1%, with a total of 36 diagnosed sternal infections (5 in ZF and 31 in CW). Comparing ZF with CW with regard to sternal infection, there is no statistically significant difference related to the device (odds ratio: 0.067, confidence interval: 0.04-9.16, P=0.72). The propensity modelling provided excellent overlap and the mean propensity was almost the same in both groups. Thus, we have observed no difference in receiving either ZF or CW. No sternal instability was observed with the ZF device, unlike 4/31 patients in the CW group. The overall operation time is reduced by 11 min in the ZF group with identical perfusion and clamping times. CONCLUSIONS Our study underlines a neutral effect of the sternal ZipFix™ system in patients regarding sternal infection. Postoperative complications are similar in both sternal closure methods. The cable-tie-based system is fast, easy to use, reliable and safe.

Automated fastener versus manually tied knots in minimally invasive mitral valve repair: impact on operation time and short- term results

BackgroundThis study compares the influence of two different annuloplasty attachment suture applications, namely the use of an automated fastener versus manually tied knots using a traditional knot pusher, on total operation time, on cardiopulmonary-bypass time and on cross-clamp time, and on short-term outcome.MethodsSixty patients underwent isolated minimally invasive mitral valve repair in Carpentier Type-II mitral disease with implantation of an annuloplasty ring in combination with correction of the prolapsing leaflet using artificial chords. The first 30 patients after implementation of a novel automated fastener were compared with the last 30 patients corrected with a traditional knot pusher. No significant differences with regard to demographic data (age, gender, NYHA class, ejection fraction, BMI, cardiovascular risk factors) between the two groups were found. All patients received isolated mitral valve repair in the first run. Bretschneider HTK was used for cardioplegic cardiac arrest in all patients.ResultsTransesophageal and transthoracic echocardiography at the end of operation and at discharge revealed no (n = 25), trace (n = 28) or mild (n = 7) residual regurgitation with no evidence of ring dehiscence and without any significant clinical differences between the groups. Cross-clamp, cardiopulmonary-bypass and total- operation time were significantly reduced in the automated fastener group compared to the group using a traditional knot pusher (87.1 ± 17.9 vs. 101.3 ± 17.8; p < 0.01, 138.1 ± 25.6 vs. 152.7 ± 24.9; p < 0.05, and 203.9 ± 31.02 vs. 223.8 ± 29.01; p < 0.01, respectively).ConclusionOur short-term results indicate a safe, reliable and fast application of the novel automated fastener device in combination with significant time savings in cardioplegic arrest and cardiopulmonary bypass.

Proteome analysis in cardiovascular pathophysiology using Dahl rat model.

Dahl salt-sensitive (DS) and salt-resistant (DR) inbred rat strains represent a well established animal model for cardiovascular research. Upon prolonged administration of high-salt-containing diet, DS rats develop systemic hypertension, and as a consequence they develop left ventricular hypertrophy, followed by heart failure. The aim of this work was to explore whether this animal model is suitable to identify biomarkers that characterize defined stages of cardiac pathophysiological conditions. The work had to be performed in two stages: in the first part proteomic differences that are attributable to the two separate rat lines (DS and DR) had to be established, and in the second part the process of development of heart failure due to feeding the rats with high-salt-containing diet has to be monitored. This work describes the results of the first stage, with the outcome of protein expression profiles of left ventricular tissues of DS and DR rats kept under low salt diet. Substantial extent of quantitative and qualitative expression differences between both strains of Dahl rats in heart tissue was detected. Using Principal Component Analysis, Linear Discriminant Analysis and other statistical means we have established sets of differentially expressed proteins, candidates for further molecular analysis of the heart failure mechanisms.