Implementation of buffy-coat-derived pooled platelet concentrates for internal quality control of light transmission aggregometry: a proof of concept study.

Essentials In platelet function testing, standardized internal controls (IQC) are not commercially provided. Platelet function testing was performed daily on aliquoted pooled platelet concentrates. Pooled platelet concentrates showed stability for control purposes from Monday to Friday. Pooled platelet concentrates provide the necessary steadiness to serve as IQC material. SUMMARY: Background Standardized commercially available control material for internal quality control (IQC) of light transmission aggregometry (LTA) is still lacking. Moreover, the availability of normal blood donors to provide fresh platelets is difficult in small laboratories, where 'volunteers' may be in short supply. Objectives To evaluate the implementation of buffy-coat-derived pooled platelet concentrates (PCs) for IQC material for LTA. Methods We used buffy-coat-derived pooled PCs from the blood bank as IQC material for LTA. On each weekend one PC was prepared (> 200 mL) and aliquoted from the original storage bag on a daily basis in four baby bags (40-50 mL), which were delivered from Monday to Friday to our laboratory. The IQC measurements of at least 85 work-weeks (from Monday to Friday) were evaluated with this new IQC material. LTA was performed on a four-channel Chronolog 700 Aggregometer (Chronolog Corporation, Havertown, PA, USA) (agonists: collagen, adenosine diphosphate [ADP], arachidonic acid [AA] and thrombin receptor activator peptide-6 [TRAP-6]). Results The medians of platelet aggregation from IQC measurements with collagen, ADP and AA from Monday to Friday were 68.0-59.5, 3.0-2.0 and 51.0-50.0%, respectively, and the mean of platelet aggregation with TRAP-6 was 71.2-66.4%. Conclusions Buffy-coat-derived pooled PCs serve as a reliable and robust IQC material for LTA measurements and would be beneficial for the whole laboratory procedure and employees' safety.

Platelet function testing to time surgery in patients on dual antiplatelet therapy?

In patients pretreated with P2Y12 receptor inhibitors who need to undergo non-emergent cardiac or major non-cardiac surgery, current guidelines of the European Society of Cardiology recommend postponing surgery for at least five days after last intake of clopidogrel or ticagrelor, and for seven days after last intake of prasugrel, unless there is high risk of ischemic events. However, a fixed five to seven days preoperative waiting period may be challenged, in the presence of inter-individual variability in on-treatment platelet reactivity. Therefore, Society of Thoracic Surgeons guidelines suggest to base decisions about a surgical delay on platelet function although both, the optimal platelet function assay and a bleeding cutoff have not yet been defined by large scale multicenter trials. This review aims to provide an overview on current knowledge of P2Y12 receptor induced platelet inhibition and surgery related bleeding and the potential role of platelet function analysis to time surgery.

Role of N-terminal pro B-type natriuretic peptide in identifying patients at high risk for adverse outcome after emergent non-cardiac surgery.

BACKGROUND: Patients undergoing emergency surgery continue to be at very high risk, but accurate risk identification for the individual patient remains difficult. This study tested the usefulness of perioperative N-terminal pro B-type natriuretic peptide (NT-proBNP) for in-hospital and long-term risk stratification. METHODS: We conducted a prospective single-centre observational cohort study in an Austrian university hospital. Two hundred and ninety-seven consecutive patients >50 yr of age undergoing a variety of emergency non-cardiac procedures were included. The primary endpoint was a composite of non-fatal myocardial infarction (MI), acute heart failure, or death between index surgery and 3 yr follow-up. The secondary endpoint was in-hospital major adverse cardiac events (MACE), defined as non-fatal MI, acute heart failure, or cardiac death. RESULTS: During a median follow-up of 34 months (inter-quartile range: 16-39), 31% of subjects reached the primary endpoint. A preoperative NT-proBNP ≥725 pg ml(-1) was associated with a 4.8-fold univariate relative risk [95% confidence interval (CI): 3.1-7.6] and a postoperative NT-proBNP ≥1600 pg ml(-1) was associated with a four-fold univariate relative risk (95% CI: 2.7-6.2) for reaching the primary endpoint. Moreover, preoperative NT-proBNP remained a significant and independent (hazards ratio 1.91, 95% CI 1.08-3.37, P=0.027) predictor in a multivariate Cox proportional hazards model. A preoperative NT-proBNP ≥1740 pg ml(-1) was associated with a 6.9-fold univariate relative risk (95% CI: 3.5-13.4) for MACE during the index hospital stay, but did not remain significant in a multivariate logistic regression model. CONCLUSIONS: Preoperative NT-proBNP can help identify patients at high risk for adverse long-term outcome after emergency surgery.

[Platelet function: new drugs, new assays : possible impacts on operative medicine?]. / Thrombozytenfunktion - neue Medikamente, neue Assays : Mögliche Auswirkungen auf die operative Medizin?

Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is a well-established strategy to prevent thrombotic complications in patients with acute coronary syndromes (ACS) and after percutaneous coronary interventions (PCI). Current practice guidelines for antiplatelet therapy advocate a 1 to 12-month dual antiplatelet therapy after bare metal stent PCI and an up to 12-month dual antiplatelet therapy after PCI in patients with ACS and drug-eluting stent PCI. Premature withdrawal of dual antiplatelet therapy carries a substantial risk of stent thrombosis but perioperative continuation of dual antiplatelet therapy is associated with an increased risk of bleeding, particularly in patients treated with the new potent drugs prasugrel and ticagrelor. Based on the various available assays, the lack of validated cut-offs and the disappointing results of targeted antiplatelet therapy as demonstrated by the GRAVITAS trial, current guidelines of international societies recommend platelet function testing only for selected high risk patients despite the known association between clopidogrel low responsiveness and ischemic events. However, for individual patients taking clopidogrel, platelet function monitoring may be considered to safely shorten the preoperative waiting period, to assess the risk of bleeding and transfusion and to initiate specific therapy in bleeding patients.

The influence of clinical risk factors on pre-operative B-type natriuretic peptide risk stratification of vascular surgical patients.

The role of the revised cardiac risk index in risk stratification has recently been challenged by studies reporting on the superior predictive ability of pre-operative B-type natriuretic peptides. We found that in 850 vascular surgical patients initially risk stratified using B-type natriuretic peptides, reclassification with the number of revised cardiac risk index risk factors worsened risk stratification (p < 0.05 for > 0, > 2, > 3 and > 4 risk factors, and p = 0.23 for > 1 risk factor). When evaluated with pre-operative B-type natriuretic peptides, none of the revised cardiac risk index risk factors were independent predictors of major adverse cardiac events in vascular patients. The only independent predictor was B-type natriuretic peptide stratification (OR 5.1, 95% CI 1.8-15 for the intermediate class, and OR 25, 95% CI 8.7-70 for the high-risk class). The clinical risk factors in the revised cardiac risk index cannot improve a risk stratification model based on B-type natriuretic peptides.

Different effects of abciximab and cytochalasin D on clot strength in thrombelastography.

Maximum amplitude (MA) in thrombelastography (TEG) consists of a plasmatic and a platelet component. To assess the magnitude of the plasmatic component, pharmacological approaches have been proposed to eliminate the platelet component. We evaluated the individual and combined effects of abciximab and cytochalasin D on the MA of TEG. Whole blood, platelet-rich plasma (PRP) and homologous platelet-poor plasma (PPP) from 20 healthy volunteers were spiked with abciximab or cytochalasin D or a combination of both and TEGs performed. Abciximab and cytochalasin D decreased MA in all samples. MA of whole blood (18.6 +/- 3.1 mm) and PRP (33.7 +/- 3.5 mm) spiked with abciximab or cytochalasin D alone (15.0 +/- 2.9 mm and 25.0 +/- 4.0 mm) were significantly higher when compared with abciximab and cytochalasin D combined (10.4 +/- 3.0 and 20.2 +/- 3.5 mm). While MA of PRP and homologous PPP were significantly (P < 0.001) different after individual administration of abciximab and cytochalasin D, combination of both abolished this difference (20.2 +/- 3.5 mm and 20.4 +/- 3.7 mm, P = 0.372). In whole blood of critically ill patients or patients undergoing major surgery there was also a significant difference of MA between abciximab alone and in combination with cytochalasin D (16.5 +/- 11.3 mm and 11.3 +/- 7.7 mm, P < 0.001). This indicates that in contrast to individual administration of abciximab or cytochalasin D, a combination of both compounds eliminates the platelet-specific effect on MA of TEG tracings.

First clinical experience with the rapid-, short-acting amiodarone derivative E 047/1 after cardiac surgery.

BACKGROUND AND OBJECTIVE: Amiodarone is very effective against a variety of dysrhythmias but has poor pharmacodynamic properties and many undesired side-effects. Its short- and rapid-acting derivative E 047/1 may circumvent some of these drawbacks. It is easier to titrate while retaining the high efficacy of amiodarone and may have acceptable influences on haemodynamics and cardiac conduction in patients who develop serious, destabilizing ventricular tachydysrhythmias after cardiac surgery. METHODS: Testing E 047/1 was performed prospectively in two consecutive phase II open, clinical studies. Out of 504 patients scheduled for surgery using cardiopulmonary bypass for coronary artery grafting and/or valve repair, 35 developed serious, haemodynamically destabilizing ventricular dysrhythmias (Lown 2-Lown 4b) after surgery and were treated with a 1 mg kg(-1) (pilot study, n = 15) or randomized to a 2 or 3 mg kg(-1) bolus of E 047/1, followed by a 1 mg kg(-1) h(-1) continuous infusion for 2 h (n = 10 in each group). Dysrhythmias, PQ, QTc intervals and haemodynamics using the thermodilution technique were evaluated for up to 24 h after drug initiation. RESULTS: At the time of final inclusion the patients had between 6 and 12 (or more) ventricular ectopics per minute. Within the first 2-3 min of application in the pilot trial E 047/1 induced a decrease of ventricular dysrhythmias to between 0 and 4 per min, a decrease that held for the duration of treatment. The area under the curve decreased from 434 (322, 855; median, quartiles) to 114 (9, 477, P < 0.01) events per hour. In the randomized trial, E 047/1 administered in either dose rapidly reduced ventricular dysrhythmias at least as effectively as in the pilot trial 565 (478, 701) to 33 (8, 238, P < 0.05) after a 2 mg bolus; 482 (339, 482) to 95 (13, 540, P < 0.01) events per hour after a 3 mg bolus. Approximately 4-6 h after drug termination, dysrhythmias reappeared in the majority of patients. In only three patients did the incidence of dysrhythmias return to inclusion criteria levels. In contrast to the pilot trial, in the randomized trial there was a slight increase of mean pulmonary artery pressure, central venous pressure and pulmonary arterial wedge pressure and a slight decrease of LCWI in both groups. E 047/1 did not cause QTc prolongation. CONCLUSIONS: E 047/1 appears to be a safe alternative to amiodarone in the perioperative setting of cardiac surgery when serious, destabilizing dysrhythmias occur.

Coronary artery plaque burden and perioperative cardiac risk.

BACKGROUND: Electron-beam computed tomography-derived coronary calcium score correlates with the morphologic severity of coronary artery disease, reflecting both global atherosclerotic plaque formation and coronary artery luminal narrowing. The current study examines the impact of coronary atherosclerotic plaque burden, measured by coronary calcium score, on the potential for perioperative myocardial cell injury, as assessed by cardiac troponin T elevations in patients undergoing elective vascular surgery. The authors further investigated whether perioperative myocardial cell injury in those patients adversely affects noninvasive measures of left ventricular systolic function, such as ejection fraction and wall motion score. METHODS: Fifty-one consecutive patients scheduled for vascular surgery were enrolled in this prospective study. In addition to standard preoperative evaluation, including patient history and physical examination, electron-beam computed tomography scan, 12-lead electrocardiography, and transthoracic echocardiography were performed on the day before surgery. Subsequent evaluations on postoperative days 2 and 7 included transthoracic echocardiography and 12-lead electrocardiography. Cardiac troponin T determinations were performed on the day before surgery, immediately preoperatively, and on postoperative days 1, 2, 3, and 7. RESULTS: The median coronary calcium score of the 51 patients was 997.0 (25th percentile, 202.5; 75th percentile, 1,949.5). Cardiac troponin T elevations exclusively occurred in patients with a coronary calcium score greater than 1,000. The six patients (12%) with perioperative cardiac troponin T elevations had a 2.5-fold higher coronary calcium score than those without cardiac troponin T elevation (P = 0.021). In these patients, the ejection fraction decreased from 61 +/- 10% to 52 +/- 13% (mean +/- SD) on postoperative day 2 and was 54 +/- 16% on postoperative day 7 (P = 0.022). CONCLUSION: A high electron-beam computed tomography coronary calcium score, reflecting substantial coronary plaque burden, carries an increased risk for myocardial cell injury after vascular surgery. In these patients, myocardial damage may result in deterioration of global systolic left ventricular function.

Thromboelastography for monitoring prolonged hypercoagulability after major abdominal surgery.

UNLABELLED: Despite clinical and laboratory evidence of perioperative hypercoagulability, there are no consistent data evaluating the extent, duration, and specific contribution of platelets and procoagulatory proteins by in vitro testing. We tested the hypothesis that the parallel use of standard and abciximab-cytochalasin D-modified thromboelastography (TEG) can assess 7 days' postoperative hypercoagulability and can estimate the independent contribution of procoagulatory proteins and platelets. Thromboelastograms were performed before surgery, at the end of surgery, 6 h after surgery, and on postoperative days 1, 2, 3, and 7; they were analyzed for the reaction time and the maximal amplitude (MA). We calculated the elastic shear modulus of standard MA (G(t)) and modified MA (G(c)), which reflect total clot strength and procoagulatory protein component, respectively. The difference was an estimate of the platelet component (G(p)). There was a 10% perioperative increase of standard MA, corresponding to a 50% increase of G(t) (P < 0.0001) and an 86%-90% contribution of the calculated G(p) to G(t). We conclude that serial standard and modified thromboelastography may reveal prolonged postoperative hypercoagulability and the independent contribution of platelets and procoagulatory proteins to clot strength. IMPLICATIONS: Postoperative hypercoagulability, occurring for at least 1 wk after major abdominal surgery, may be demonstrated by standard and modified thromboelastography. This hypercoagulability is not reflected by standard coagulation monitoring and seems to be predominantly caused by increased platelet reactivity.

[Coronary arterial stent implantation proceeding noncardiac surgical procedures. Is it safe; can we recommend it?]. / Koronararterielle Stentimplantation vor nichtkardiochirurgischen Eingriffen. Wiegen wir uns fälschlich in Sicherheit?

Patients undergoing non-cardiac surgical procedures who carry coronary artery stents have to be classified as high risk patients. Perioperative myocardial infarction and severe bleeding are possible. Therefore, anaesthetic management directed by invasive monitoring, ECG ST analysis, transesophageal echocardiography and referral to an intensive care unit are absolutely justified. The urgency of the surgical procedure, perioperative risk and an antiplatelet regimen have to be discussed with the patient and the surgeon in advance. In the case of cardiac complications, rapid therapy by an interventional cardiologist must be available.

Perioperative myocardial cell injury: the relationship between troponin T and cortisol.

STUDY OBJECTIVE: To investigate whether there is an association between Troponin T (TnT), reflecting myocardial cell injury, and cortisol, reflecting the degree of surgical trauma and associated stress, in light of our recent evaluation of TnT as a marker of perioperative myocardial cell injury. DESIGN: Prospective, cohort study. PATIENTS: 70 patients (67.4 +/- 8.7 yrs) with definite or at-risk coronary artery disease (CAD) undergoing elective noncardiac surgery (vascular n = 38, abdominal n = 21, orthopedic n = 8) with general (n = 63) or regional (n = 4) anesthesia with postoperative on-demand analgesia. MEASUREMENTS AND MAIN RESULTS: Morning blood samples for TnT (upper limit of normal: <0.2 ng/mL), CK-MB (reference range

Minimally invasive versus conventional aortic valve operations: a prospective study in 120 patients.

BACKGROUND: Risk evaluation comparing the minimally invasive and standard aortic valve operations has not been studied. METHODS: Four surgeons were randomly assigned to perform the minimally invasive (L-shaped sternotomy) (group 1) or the conventional (group 2) operation in 120 patients exclusively. RESULTS: In both groups (n = 60) a CarboMedics prothesis was implanted in 90% of patients. There was no significant difference in the cross-clamping period (group 1, 60 minutes; range, 35 to 116 minutes), in the duration of extracorporal circulation (group 1, 84 minutes; range, 51 to 179 minutes) or in the time from skin-to-skin (group 1, 195 minutes; range, 145 to 466 minutes). Patients in group 1 were extubated earlier (p<0.001), the postoperative blood loss was less (p<0.001), and the need for analgesics was reduced (p<0.05). In 5 patients in group 1 a redo operation was required for bleeding (p>0.05), 3 patients in group 1 required a redo operation because of paravalvular leakage or endocarditis (p>0.05), the 30-day mortality rate was 1.6%. Overall the survival rate was 95% in group 1 and 97% in group 2 (mean follow-up, 294 days; range, 30 to 745 days). CONCLUSION: The advantages of minimally invasive aortic valve operation include reduced trauma from incision and duration of ventilation, decreased blood loss and postoperative pain, the avoidance of groin cannulation, and a cosmetically attractive result. Simple equipment is used with a high degree of effectiveness and with no sacrifice of safety. Our study demonstrated the practicability and reliability of this new method.

DA1-receptor stimulation by fenoldopam in the treatment of postcardiac surgical hypertension.

BACKGROUND: Besides adequate analgesia, sedation and ventilation, postcardiac surgical hypertension has to be treated frequently with vasoactive drugs to avoid possible complications. In this study the hemodynamic effects of the DA1-receptor agonist fenoldopam (F) are compared to those of the Ca-channel antagonist nifedipine (N). METHODS: Postoperatively, 64 CABG-patients with a mean arterial pressure (MAP) of more than 105 mmHg over 10 min were investigated. Patients with compromised ventricular function, insufficient surgical repair, arrhythmia or an ECG unable to detect myocardial ischemia were excluded. The study drugs (initial dosage: F: 0.8; N: 0.3 micrograms.kg-1.min-1) were given continuously via a central venous catheter to reduce and to maintain the MAP between 80 and 95 mmHg. Hemodynamic parameters were determined using thermodilution technique. RESULTS: A significant reduction of the MAP (F: from 121 +/- 11 to 83 +/- 4, N: from 119 +/- 8 to 82 +/- 9 mmHg) and of the calculated systemic vascular resistance (SVR) (F: 2110 +/- 500 to 970 +/- 200, N:1980 +/- 660 to 1020 +/- 300 dyn.s.cm-5) were noted in both groups, whereby in the F group the therapeutic goal could be achieved more quickly with the dosage regimen chosen. As a result, a marked increase of heart rate, cardiac index and stroke volume index could be observed, which was more pronounced due to the initially stronger decrease of SVR with F. There was also a stronger decrease of pulmonary vascular resistance in the F group, but the indices of right ventricular function did not differ between the groups. CONCLUSION: Fenoldopam seems to be an efficient alternative to nifedipine, especially because of its more rapid onset of action.

[The artificial heart and neuromonitoring? Technical and clinical aspects]. / Kunstherz und Neuromonitoring? Technische und klinische Aspekte.

There is a steady progress in the development of artificial heart and circulatory assist devices. There is also no doubt that further advances in energy systems, materials, and electronics will provide for smaller and more reliable electrically driven blood pumps, but the present engineering design appears to be adequate to provide devices satisfactory for initial clinical use. Due to problems in the availability of suitable donor hearts, the concept of replacing the natural heart with an artificial heart as a "bridge to transplantation" has gained attention in recent years. The present paper shows technical and clinical aspects of multivariable electrophysiologic neuromonitoring in a patient with an artificial heart assist device in the intensive care unit. The data (EEG, 40 Hz brain oscillations, brainstem auditory- and somatosensory evoked potentials) are discussed with respect to the influence of the artificial heart on their quality and reliability. Reasons for artifacts and problems of interpretation are shown.

Perioperative ventricular dysrhythmias in patients with structural heart disease undergoing noncardiac surgery.

UNLABELLED: Noncardiac surgical patients with preoperative ventricular dysrhythmias and structural heart disease may be at increased risk of adverse cardiac outcome. We evaluated how anesthesia and surgery affect the course of ventricular dysrhythmias (premature ventricular beats [PVB] and repetitive forms of ventricular beats [RFVB]: couplets and nonsustained ventricular tachycardia) noted preoperatively in patients with structural heart disease and whether the frequency of ventricular dysrhythmias affects cardiac outcome. In a prospective study, 70 patients scheduled for noncardiac surgery with structural heart disease and RFVB on preoperative Holter electrocardiogram were continuously monitored intraoperatively and for 3 days postoperatively. Holter tracings were analyzed for rhythm, medians of total PVB and RFVB per hour. Preoperative RFVB recurred intraoperatively in 35% and postoperatively in 87% of patients. There was a significant intra- and postoperative decrease of total PVB per hour (P < 0.05) and RFVB per hour (P < 0.01). Frequency of ventricular dysrhythmias in the five patients suffering adverse outcome (unstable angina, n = 1; congestive heart failure, n = 4) did not significantly differ from those with good outcome. We conclude that in noncardiac surgical patients with structural heart disease and RFVB, the frequency of ventricular dysrhythmias is not associated with adverse cardiac outcome. IMPLICATIONS: Using continuous electrocardiogram monitoring, we investigated whether the frequency of perioperative ventricular dysrhythmias independently affects outcome in patients with structural heart disease undergoing noncardiac surgery. The incidence of perioperative dysrhythmia in patients with an adverse outcome (8%) did not differ from those with a good outcome.

Postoperative myocardial ischaemia in patients with recent myocardial infarction.

Fifteen patients (10 men and five women; mean age 67.3 yr) with a history of a recent (less than 1 yr) myocardial infarction underwent ambulatory ECG monitoring for 5 days after non-cardiac surgery. The duration, number and severity of ischaemic episodes were maximal within the first 12 h after surgery and again on the 3rd day after operation. The difference in the duration of ischaemic episodes between the 2nd and 3rd days after operation was statistically significant (P less than 0.05). There were no perioperative myocardial infarctions and all patients were discharged from hospital.