Cardiopulmonary Bypass In Patients Research Articles

9. Effect of steady-state hypothermic cardiopulmonary bypass on somatosensory evoked potentials

Neurophysiological techniques are used to assess cerebral functioning in operating room and intensive care unit, but the introduction of hypothermia as a means of intraoperative neuroprotection has brought their reliability into question. The present study aimed to evaluate the effect of mild/moderate hypothermia on somatosensory evoked potentials (SSEPs)’ amplitude and latency in a cohort of cardiopulmonary bypass (CPB) patients as the temperature reached the steady-state. The amplitude and latency of four different SSEP signals – N9, N13, P14/N18, and N20/P25 – were evaluated retrospectively in 84 patients undergoing CPB during normothermic (36 ± 0.43 °C) and mild/moderate hypothermic (32 ± 1.38 °C) conditions. A paired-samples t -test was performed for each SSEP to test the differences in latencies and amplitudes between normothermic and hypothermic conditions. Compared to normothermia, hypothermia not only significantly increased the latency of all SSEPs, N9 ( P P P P P P

Influence of variations in systemic blood flow and pressure on cerebral and systemic oxygen saturation in cardiopulmonary bypass patients

BackgroundAlthough both pressure and flow are considered important determinants of regional organ perfusion, the relative importance of each is less established. The aim of the present study was to evaluate the impact of variations in flow, pressure, or both on cerebral and whole-body oxygen saturation. MethodsThirty-four consenting patients undergoing elective cardiac surgery on cardiopulmonary bypass were included. Using a randomized cross-over design, four different haemodynamic states were simulated: (i) 20% flow decrease, (ii) 20% flow decrease with phenylephrine to restore baseline pressure, (iii) 20% pressure decrease with sodium nitroprusside (SNP) under baseline flow, and (iv) increased flow with baseline pressure. The effect of these changes was evaluated on cerebral ScO2 and systemic SvO2 oxygen saturation, and on systemic oxygen extraction ratio (OER). Data were assessed by within- and between-group comparisons. ResultsDecrease in flow was associated with a decrease in ScO2 [from 63.5 (7.4) to 62.0 (8.5) %, P<0.001]. When arterial pressure was restored with phenylephrine during low flow, ScO2 further decreased from 61.0 (9.7) to 59.2 (10.2) %, P<0.001. Increase in flow was associated with an increase in ScO2 from 62.6 (7.7) to 63.6 (8.9) %, P=0.03, while decreases in pressure with the use of SNP did not affect ScO2. SvO2 was significantly lower (P<0.001) and OER was significantly higher (P<0.001) in the low flow arms. ConclusionsIn the present elective cardiac surgery population, ScO2 and SvO2 were significantly lower with lower flow, regardless of systemic arterial pressure. Moreover, phenylephrine administration was associated with a reduced cerebral and systemic oxygen saturation.

Hypothermic Versus Normothermic Cardiopulmonary Bypass in Patients With Valvular Heart Disease

The aim of this study was to test the hypothesis that normothermic cardiopulmonary bypass (CPB) is as effective as hypothermic CPB in terms of cardiac protection (cTnI level) and outcome in patients with valvular heart disease. Prospective randomized study. A tertiary cardiothoracic referral center. 140 patients who had valvular heart disease, with/without coronary artery disease, surgically treated under CPB. The patients were allocated randomly to undergo either hypothermic (temperature [T], 31 °C-32 °C) or normothermic CPB (T>36 °C). The primary endpoint was the dynamics of troponin I. The secondary endpoints were ventilation time, the need for inotropic support, intensive care unit (ICU) and hospital stay durations, complications, and mortality. There were no significant intergroup differences in dynamics of troponin I. Ventilation time was significantly lower in the hypothermic group (6 (5-9) and 8 (5-12); p = 0.01). Normothermic CPB in patients with valvular heart disease was as effective as hypothermic perfusion in terms of myocardial protection after the surgery assessed by cTnI release. The short ventilation duration in patients who underwent hypothermic CPB needs to be confirmed in a future investigation.

The Impact of Soluble Interleukin-2 Receptor as a Biomarker of Delirium

Biomarkers might help to predict the emergence of delirium. Advance warning of the threats of this condition could potentially reduce significant morbidity, mortality, and costs of hospitalizing patients. Our prospective study investigates for the first time the impact of soluble interleukin-2 receptor (sIL-2R) as a biomarker of delirium after cardiac surgery with cardiopulmonary bypass (CPB). A total of 34 patients who underwent elective cardiac surgery with CPB were enrolled. During the intensive care unit (ICU) stay and after discharge from the ICU, the delirious state was evaluated daily using the Delirium Rating Scale by Trzepacz. sIL-2R was assayed before CPB, 24 hours postoperatively, and on the day before discharge. After CPB, 11 patients (32.4%) developed delirium. A short-term delirious state (less than 1 day) was observed in 3 patients and a prolonged delirious state in 8 patients. During the study period, sIL-2R levels decreased 24 hours postoperatively and increased afterward (Friedman test; p < 0.001). As shown by the Spearman rank correlation, CPB patients with higher Delirium Rating Scale scores 72 hours, 96 hours, and 120 hours postoperatively had significant higher sIL-2R levels 24 hours postoperatively. In CPB patients with a prolonged postoperative delirious state, the sIL-2R level is statistically significantly elevated 24 hours postoperatively in comparison with CPB patients without a postoperative delirium (Mann-Whitney U: 48.5, p = 0.049). High levels of sIL-2R appear to be a useful biomarker to identify patients with high risk for a delirious state.

Emergency Conversion from Off Pump to Cardiopulmonary Bypass in Patients with Coronary Artery Bypass Graft Surgery

Introduction: As off pump Coronary artery bypass grafting surgery (CABG) is a developing method in coronary cardiac surgery, most surgeons are anxious about the danger of emergency crash conversion. In this observational study we tried to show the rate and outcome of conversion . Material and methods: In this descriptive study about 477 coronary off-pump CABG patients were operated in Ghaem hospital in Mashhad, Iran, from Jan 2012 to Jan 2013.In this group 20 patients needed to convert to Cardiopulmonary Bypass (CPB) immediately .We analyzed these 20 patients and produced the results. Results: There was no cerebrovascular accident (CVA) and no neurologic problems.There was one death among these 20 patients. There was one case of renal failure who was the same patient that expired. 75% of these 20 patients had hypertension and 45% had diabetes . Conclusion: 20 patients (4.19%) had an emergency switch to On-pump CABG and only one death occurred among 20 patients.

Might rapid implementation of cardiopulmonary bypass in patients who are failing to recover after a cardiac arrest potentially save lives?

The question addressed was whether it might be beneficial to have a rapid-response emergency cardiopulmonary bypass service for patients who suffer an in-hospital or an out-of-hospital cardiac arrest of any aetiology. Eighty-five papers were reviewed using the reported search, of which 15 represented the best evidence to answer the clinical question. The authors, journal, date, country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The concept of using emergency cardiopulmonary bypass (ECPB) for the management of cardiogenic shock and refractory cardiac arrest was developed in the late 1990s. Since this time, a large number of centres worldwide have reported success with use of ECPB for cardiac arrest refractory to conventional resuscitation techniques and for cardiogenic shock. This is a relatively new advancement in resuscitative strategy and is expanding in clinical practice. Clinical studies and experimental data reveal that ECPB is a very effective tool in the return of spontaneous circulation following refractory cardiac arrest. Resuscitation with this technique demonstrated survival benefit when compared with patients having conventional cardiopulmonary resuscitation for >10 min after witnessed in-hospital arrest, especially if the cause of arrest is of cardiac origin. The reported finding from a systematic review of 1494 patients treated with ECPB noted that the overall survival rate was 47.4%; their results indicate that the application of ECPB in cardiac arrest improves survival and the likelihood of a satisfactory neurological outcome. An additional review revealed that acceptable survival rate and neurological outcomes (30%) can be achieved with extracorporeal cardiopulmonary resuscitation in children after prolonged cardiac arrest (up to 95 min) refractory to standard resuscitation. However, no study has provided clear-cut evidence of the merits of ECPS in patients with out-of-hospital cardiac arrest, although many case reports and case series have concluded that it is an effective method. We conclude that institution of emergency cardiopulmonary bypass may save the lives of patients in whom routine attempts at resuscitation after a cardiac arrest fail, especially after >10 min. The likelihood of success is much higher for patients who have in-hospital witnessed cardiac arrest.

Activation of coagulation and fibrinolysis during coronary artery bypass grafting: a comparison between on-pump and off-pump techniques.

Coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) is associated with intense activation of hemostatic mechanisms. But the precise knowledge of the effects of eliminating CPB in patients undergoing off-pump coronary artery bypass grafting (CABG) are not well established. The present study was carried out to compare and document the changes in selected coagulation and fibrinolysis variables in patients undergoing on-pump and off-pump CABG (OPCAB). A total of 42 patients of on-pump and 31 patients of off-pump CABG were selected for the study. Platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Fibrinogen and D-dimer levels were measured immediately, 24h and 7days after operation and compared with the baseline preoperative values. Statistical analysis was done by mixed ANOVA for repeated measures and Post-hoc tests using the Bonferroni correction, Chi square and unpaired t test. All the parameters were significantly changed (P<0.05) with the time. Platelet counts, fibrinogen and D-dimer levels were significantly different between on-pump and off-pump CABG patients on immediate and 24h postoperative period and attained almost same level after 7days of operation. Fibrinogen level and platelet counts were increased after a sharp fall in the immediate post-operative period whereas D-dimer levels were persistently increased with a sharp peak of rise in the immediate post-operative period in on-pump group. On-pump surgery was associated with excessive fibrinolytic activity immediately after operation. The off-pump group demonstrated less activation of coagulation and fibrinolysis and delayed postoperative response that became almost equal to the on-pump group in the later postoperative period.

High incidence of antibodies to protamine and protamine/heparin complexes in patients undergoing cardiopulmonary bypass

AbstractProtamine is routinely used to reverse heparin anticoagulation during cardiopulmonary bypass (CPB). Heparin interacts with protamine to form ultralarge complexes that are immunogenic in mice. We hypothesized that patients exposed to protamine and heparin during CPB will develop antibodies (Abs) to protamine/heparin (PRT/H) complexes that are capable of platelet activation. Specimens from a recently completed prospective clinical trial (HIT [for heparin-induced thrombocytopenia] 5801 study; n = 500) of CPB patients were examined for PRT/H Abs at baseline, at time of hospital discharge (between days 3 through 7), and 30 days after CPB. PRT/H antibody features were characterized and correlated with adverse cardiovascular outcomes. We found a high incidence of PRT/H antibody formation (29%) in patients undergoing cardiac surgery. PRT/H Abs were of high titer (mean titer 1:14 744), showed heparin-dependent binding, and activated platelets in the presence of protamine. PRT/H Abs showed no cross-reactivity to platelet factor 4/heparin complexes, but were cross-reactive with protamine-containing insulin preparations. In the absence of circulating antigen at day 30, there were no complications of thrombocytopenia, thrombotic events, or long-term cardiovascular events. These studies show that Abs to PRT/H occur commonly after cardiac bypass surgery, share a number of serologic features with HIT Abs, including platelet activation, and may pose health risks to patients requiring drug reexposure.

ASSA13-08-12 Hyperlactatemia in Children with Congenital Heart Diseasesafter Operations with Cardiopulmonary Bypass

<h3>Background</h3> Hyperlactatemia is a well recognised marker of circulatory failure [1]. Several studies have shown a strong correlation between blood lactate levels and the risk of morbidity and mortality in varying clinical situations such as circulatory shock, septic shock, severe hypoxemia, liver failure, diabetes mellitus, and others [2]. After cardiac surgery, Hyperlactatemia is relatively common and is associated with morbidity and mortality. Hyperlactatemia occurs during cardiopulmonary bypass in patients undergoing operations for congenital cardiac disease and may be an early indicator for postoperative morbidity and mortality. It is a well-known fact that tissue hypoperfusion and inadequate oxygen delivery are associated with lactic acidosis owing to anaerobic metabolism [3]. The aim of the present study is to estimate the frequency and to reveal predictors of heperlactatemia occurrence in children with congenital heart diseases in the early postoperative period. <h3>Methods</h3> This prospective study was spent in our centre between March and September 2007. Seventy two patients with congenital heart diseases operated in artificial blood circulation conditions from 1 till 17 years old were included in to the research. The study design was approved by the centre ethical committee. Written voluntary consent to participation in the scientific programme was signed by children’s parents. The induction to anaesthesia was performed in the presence of parents and includes the following components: Ketamin 7 mg/kg; Relanium 0.25 mg/kg; Atropine 0.015 mg/kg. After an approach of proof sedative effect the child was delivered to the operation room. Myoplegia was carried out by an intravenous injection of pipikuronium bromide 0.1 mg/kg. Artificial lungs ventilation was carried by Datex Ohmeda ADU AS-5 (Finland) (IPPV-mode). <h3>Results</h3> We have obtained the following data: increase in lactate concentration &gt; 5 mmol/l was marked in 2.37% blood samples. Time intervals analysis has shown, that maximal lactate concentration were observed in 7–11 hours after operation. There were no cases of heperlactatemia after 24 hours after operation. Having investigated interrelation between lactate and glucose concentration, we have found statistically authentic differences in glucose level &gt; 9 mmol/l (r = 0.56). This interrelation was traced only in two time intervals: 1–6 and 7–11 hours after operation. <h3>Conclusions</h3> Metabolic infringements in children with congenital heart diseases operated in artificial blood circulation conditions are observed in small percent of cases. Lactate concentration peak is observed in 7–11 hours interval after operation. There is no significant interrelation between artificial circulation time and heperlactatemia intensity in early postoperative period.

Comparison of serum cystatin C and creatinine changes after cardiopulmonary bypass in patients with normal preoperative kidney function

Serum creatinine is used ubiquitously to estimate glomerular filtration rate and to diagnose acute kidney injury after cardiac surgery. Serum cystatin C is a novel biomarker that has emerged as a possible diagnostic alternative to serum creatinine. It is unclear if the dynamic changes in serum cystatin C immediately following cardiopulmonary bypass (CPB) differ from those of serum creatinine in patients with normal preoperative kidney function. We compared changes in serum levels of creatinine and cystatin C by measuring them serially in 19 patients undergoing CPB. Within-patient differences for serum creatinine and serum cystatin C were compared by repeated measures ANOVA. Serum creatinine and cystatin C levels showed significant correlation with each other. Both biomarkers showed a significant decrease after CPB, but their serum concentrations reverted to pre-CPB levels within 12 h. Serum levels of serum creatinine remained unchanged from baseline levels throughout 72-h post-CPB. In contrast, serum cystatin C levels rose further and became significantly higher compared to baseline within 48 h. Serum cystatin C remained significantly elevated at 48- and 72-h post-CPB. Processes that determine the serum concentrations of serum creatinine and cystatin C in the post-CPB period affect the two biomarkers differently, suggesting that the two are not interchangeable as diagnostic markers of glomerular filtration rate. Future studies are needed to examine if these discrepancies are related to differences in their production rates, in their ability to detect small changes in glomerular filtration rate, or to a combination of these, and to determine the effect of such differences on the diagnostic and prognostic accuracy of the two biomarkers.

Comparison of two different minimized extracorporeal circulation systems in reference to conventional cardiopulmonary bypass in patients with isolated coronary artery bypass surgery

Objective: In the last decade the minimized extracorporeal circulation (ECC) system has established in coronary artery bypass grafting. A reduction in systemic inflammatory markers and blood transfusion rate as well as lower 30-day mortality rates and lower incidences of atrial fibrillation were reported. The aim of our study was to evaluate the clinical outcome of two different ECC systems.

1118 – The impact of intra- and postoperative albumin levels as a biomarker of delirium after cardiopulmonary bypass: results of an exploratory study

Introduction Delirium is a frequently under-recognized finding in post-cardiopulmonary bypass patients that is potentially reversible but often associated with short-term complications, increased mortality and prolonged hospitalisation. Aims In this prospective study the frequency of delirium after cardiac surgery with cardiopulmonary bypass (CPB) was determined. Furthermore, we investigated the impact of intra- and postoperative levels of albumin as a biomarker of delirium. Methods 34 patients who underwent elective CPB at the Department of Cardiac Surgery, Ludwig-Maximilians-University of Munich, Germany, were enrolled in this prospective study. During the Intensive Care Unit (ICU) stay and shortly after discharge from the ICU, delirious state was evaluated daily using the Delirium-Rating-Scale. Albumin was assayed preanaesthesia, immediately after induction of anaesthesia, at the beginning of the heart-lung-apparatus period, immediately before the opening and 5 minutes after the opening of the aortic clamp, 24h and 48h postoperatively and on the day before discharge. Results After CPB, a clinical significant delirious state was observed in 11 patients (32.4%). The albumin level decreased during the surgical intervention and increased postoperatively with a maximum level at the time of discharge. CPB patients with delirious state showed a significantly lower albumin level 24h and 48h postoperatively than those without delirium. Conclusions A postoperative delirium is a frequently observed finding in post-CPB patients. A low levels of postoperative albumin seems to be an useful biomarker to identify patients with high risk of delirious state after CPB.

1119 – The impact of soluble interleukin-2 receptor as a biomarker of delirium

Introduction Much speaks in favour of searches for biomarkers that might help to predict the emergence of delirium. Advance warning of the threats of this condition could potentially reduce significant morbidity, mortality, and costs of hospitalising patients. Aims Our prospective study investigates for the first time the impact of soluble interleukin-2 receptor (sIL-2R) as a biomarker of delirium after cardiac surgery with cardiopulmonary bypass (CPB). Methods 34 patients who underwent elective CPB at the Department of Cardiac Surgery, Ludwig-Maximilians-University of Munich, Germany, were enrolled. During the ICU stay and after discharge from the ICU, the delirious state was evaluated daily using the Delirium-Rating-Scale (DRS) by P. T. Trzepacz. sIL-2R was assayed before CPB, 24 h postoperatively and on the day before discharge. Results After the CPB, 11 patients (32.4%) developed delirium. During the study period the sIL-2R level decreased at 24h postoperatively and increased afterwards. In the subgroup of patients with a postoperative delirious state longer than 24 hours the sIL-2R level is statistically significantly elevated 24h postoperatively in comparison with CPB-patients without a postoperative delirious state. Furthermore, as shown by a Spearman's rank correlation, CPB patients with higher Delirium-Rating-Scale scores 72h, 96h and 120h postoperatively had significant higher sIL-2R levels 24h postoperatively. Conclusions High levels of sIL-2R appear to be a useful biomarker to identify patients with high risk of delirious state.

Hepatic Venous Occlusion During Cardiopulmonary Bypass in Patients With Heterotaxy Syndrome: A Safe but Underutilized Option

Direct intracardiac drainage of separate right and left hepatic veins remote from each other (independent hepatic veins) in heterotaxy patients complicates procedures requiring cardiopulmonary bypass (CPB). Temporary occlusion of such independent hepatic veins during CPB is an alternative to cannulation but is rarely used because of concerns about acute congestive hepatopathy. Consequently, temporary single hepatic venous occlusion has not been well described as a safe and simple alternative to hepatic venous cannulation during CPB. We report 2 patients with the polysplenia variant of heterotaxy in whom independent hepatic veins were safely occluded for 55 and 86 minutes, respectively, in the course of intracardiac repair. Temporary hepatic venous occlusion simplified the CPB technique and minimized clutter of the operative field. The intrahepatic hemodynamics during CPB using temporary hepatic venous occlusion is illustrated.

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Introduction: During cardiac surgery requiring cardiopulmonary bypass (CPB), heparin resistance (HR) is associated with decreased antithrombin (AT) levels, which may increase operative times and potentially alter outcomes. Hypothesis: Recombinant human AT (rhAT), which may offer advantages over purified human plasma–derived AT for managing HR during CPB, will be well tolerated and safe in HR patients. Methods: An integrated safety summary of rhAT use to manage HR during CPB was obtained from a retrospective analysis of adult patients who received rhAT or placebo during CPB in either a dose-finding study of rhAT (10-200 IU/kg) or in any 1 of 3 phase 3 studies of rhAT (15 or 75 IU/kg). From study entry until hospital discharge, patients were followed for treatment-emergent adverse events (TEAEs), including severe and serious TEAEs. Results: A total of 175 patients received rhAT (n=118; mean age, 63.5 y) or placebo (n=57; mean age, 64.6 y). Overall, rhAT was well tolerated. The frequently reported TEAEs (?10% in either group) that occurred more often with rhAT than with placebo were hypotension (rhAT, 25/118 [21.2%]; placebo, 4/57 [7.0%]) and postprocedural bleeding (rhAT, 12/118 [10.2%]; placebo, 2/57 [3.5%]). Any TEAEs considered related to the study drug occurred in 22/118 (18.6%) and 6/57 (10.5%) of rhAT- and placebo-treated patients, respectively. In the rhAT group, 5 (4%) patients had 6 related serious TEAEs, most of which were associated with bleeding (postprocedural hemorrhage); all patients recovered. Although serious bleeding AEs did not occur with placebo, incidences of all bleeding TEAEs (serious and nonserious) were similar between the rhAT (28.8%) and placebo (29.8%) groups. Across the 4 studies, 3 (2.5%) deaths occurred in the rhAT group, and 1 (1.8%) in the placebo group. All were unrelated to treatment, and there were no immune reactions to any rhAT components. Conclusions: Results demonstrate that rhAT is well tolerated and has an acceptable safety profile, even at the high rhAT doses used in this integrated analysis. Our report represents the largest cohort of CPB patients with HR supplemented with AT to date.

Résultats du pontage coronaire en cas de dysfonction ventriculaire gauche (comparaison du cœur battant et de la CEC)

BackgroundThe aim of this study was to compare the results of myocardial revascularisation with or without cardiopulmonary bypass in patients with impaired left ventricular function. Patients and methodsFive hundred and sixteen consecutive patients who underwent coronary artery bypass grafting from January 2000 through December 2007 were analyzed retrospectively. One hundred and eight cases had a left ventricular EF (ejection fraction) of 45% or less. Of these patients, 78 underwent conventional coronary artery bypass (CCABG) and 30 underwent off-pump procedure (OCABG). The CCABG group received 300IU/kg of heparin while the OCABG received 100IU/kg. The off-pump coronary surgery was carried out using a tissue stabilizer Octopus II. Different pre-, per- and postoperative variables were evaluated among both groups. Statistical analysis was performed by SPSS 11.5. The variables were compared between these two groups using univariate analysis (Chi2 test, Fisher's test exact) for qualitative variable and (Student's t test, Mann-Whitney's test) for quantitative variable. ResultsPatients profiles and risk factors were similar among both groups except for age (CCABG: 57.8±9.2 year vs OCABG: 52±9.9 year; P=0.004) and left ventricular EF (CCABG: 37.4±6.3% vs OCABG: 34±7.8%; P=0.02). The number of grafts performed per patient was significantly more among patients who underwent extracorporeal circulation (CCABG: 2.53±0.7 graft/patient vs OCABG: 1.77±0.8 graft/patient; P<0.0001). The hospital mortality was more among CCABG group 9% vs 3.3% in OCABG but the difference was not significant (P=0.3). However, the operative time and the operative room stay were long in CCABG (252±61min vs 175±38min; P<0.0001 – 389±70min vs 298±54min; P<0.0001). The ventilation time was also long in CCABG (32.3±67hour vs 10.4±5.9hour; P=0.15). There was more postoperative myocardial infarction in CCABG (P=0.008), but the EF increased and was better in CCABG. ConclusionOff-pump coronary artery bypass surgery provides satisfactory operative results for most patients with reduced left ventricular function. Prospective and randomly study will be necessary before concluding.

Guidelines on the diagnosis and management of heparin‐induced thrombocytopenia: second edition

• Patients who are to receive any heparin should have a baseline platelet count (2C). • Post-operative patients including obstetric cases receiving unfractionated heparin (UFH) should have platelet count monitoring performed every 2–3 d from days 4 to 14 or until heparin is stopped (2C). • Post-cardiopulmonary bypass patients receiving low molecular weight heparin (LMWH) should have platelet count monitoring performed every 2–3 d from days 4 to 14 or until heparin is stopped (2C). • Post-operative patients (other than cardiopulmonary bypass patients) receiving LMWH do not need routine platelet monitoring (2C). • Post-operative patients and cardiopulmonary bypass patients who have been exposed to heparin in the previous 100 d and are receiving any type of heparin should have a platelet count determined 24 h after starting heparin (2C). • Medical patients and obstetric patients receiving heparin do not need routine platelet monitoring (2C). • If the platelet count falls by 30% or more and/or the patient develops new thrombosis or skin allergy or any of the other rarer manifestations of heparin-induced thrombocytopenia (HIT) between days 4 and 14 of heparin administration, HIT should be considered and a clinical assessment made (2C). • HIT can be excluded by a low pre-test probability score without the need for laboratory investigation (2B). • If the pre-test probability of HIT is not low, heparin should be stopped and an alternative anticoagulant started in full dosage whilst laboratory tests are performed (1C). • Platelet aggregation assays using platelet-rich plasma (PRP) lack sensitivity and are not recommended (2C). • Platelet activation assays using washed platelets [heparin-induced platelet activation assay (HIPA) and serotonin release assay (SRA)] have a higher sensitivity than platelet aggregation assays using PRP and are regarded as the reference standard, but are technically demanding and their use should be restricted to experienced laboratories (2C). • Non-expert laboratories should use an antigen assay of high sensitivity. Only the IgG class needs to be measured. Useful information is gained by reporting the actual optical density, degree of inhibition by high dose heparin, and the cut-off point for a positive test rather than simply reporting the test as positive or negative (1B). • In making a diagnosis of HIT, the clinician’s estimate of the pre-test probability of HIT, together with the type of assay used and its quantitative result [enzyme-linked immunosorbent assay (ELISA) only] and information on reversal using higher doses of heparin should be used to determine the post-test probability of HIT (2B). • HIT can be excluded in patients with an intermediate pre-test score who have a negative particle gel immunoassay (2B). • HIT can be excluded in all patients by a negative antigen assay of high sensitivity (1A). • Clinical decisions should be made following consideration of the risks and benefits of treatment with an alternative anticoagulant (1C). • For patients with suspected (non-low pre-test probability) or confirmed HIT, heparin should be stopped and full dose anticoagulation with an alternative anticoagulant commenced (1B). • LMWH should not be used in the treatment of HIT (1A). • Warfarin should not be used until the platelet count has recovered to the normal range. When introduced, an alternative anticoagulant must be continued until the International Normalized Ratio (INR) is therapeutic. Argatroban affects the INR and this needs to be considered when using this drug. A minimum overlap of 5 d between non-heparin anticoagulants and vitamin K antagonist (VKA) therapy is recommended (1B). Correspondence: Dr Henry Watson, British Society for Haematology, 100 White Lion Street, London, N1 9PF, UK. E-mail bcsh@b-s-h.org.uk

Metabolic Syndrome and Chronic Simvastatin Therapy Enhanced Human Cardiomyocyte Stress before and after Ischemia- Reperfusion in Cardio-Pulmonary Bypass Patients

Metabolic syndrome (MetS) is a set of metabolic alterations including high levels of low-density lipoprotein (LDL), which increase the risk of cardiomyopathy often leading to surgery. Despite inducing myopathy, statins are widely used to lower LDL. Cardiopulmonary bypass (Cpb) causes oxidative stress and metabolic injury, altering mitochondrial expression (Grp75) and endoplasmic reticulum (Grp78) chaperones, apoptotic enzymes (Bcl2 family) and increasing cardiomyocyte lipid/lipofuscin storage. We believe that cardiomyocytes from patients with MetS may be more sensitive to surgical stress, in particular after simvastatin therapy (MetS+Stat). The study group included ten patients with MetS, ten patients with Mets+Stat and ten healthy subjects. Myocardial biopsies were obtained both before and after-Cpb. Grp75, Grp78, Bax, Bcl2, lipids, lipofuscin and fibrosis were evaluated by immuno/histochemistry. MetS cardiomyocytes had higher Grp75, Bax, fibrosis and lipofuscin. MetS+Stat had lower Grp75 and higher Grp78 expressions, high Bax, fewer fibrosis and higher lipofuscin content. Cpb did not vary the fibrosis and lipids/lipofuscin content, although it influenced the chaperones and Bax expression in all groups. These changes were more profound in patients with MetS and even more so in patients with MetS+Stat. The results suggest that MetS and MetS+Stat cardiomyocytes were more highly stressed after-Cpb. Interestingly, simvastatin caused high stress even before-Cpb.

Changes in Microvascular Reactivity After Cardiopulmonary Bypass in Patients With Poorly Controlled Versus Controlled Diabetes

We investigated the effects of cardiopulmonary bypass (CPB) on peripheral arteriolar reactivity and associated signaling pathways in poorly controlled (UDM), controlled (CDM), and case-matched nondiabetic (ND) patients undergoing coronary artery bypass grafting (CABG). Skeletal muscle arterioles were harvested before and after CPB from the UDM patients (hemoglobin A1c [HbA1c]=9.0 ± 0.3), the CDM patients (HbA1c=6.3 ± 0.15), and the ND patients (HbA1c=5.2 ± 0.1) undergoing CABG surgery (n=10/group). In vitro relaxation responses of precontracted arterioles to endothelium-dependent vasodilators adenosine 5'-diphosphate (ADP) and substance P and the endothelium-independent vasodilator sodium nitroprusside (SNP) were examined. The baseline responses to ADP, substance P, and SNP of arterioles from the UDM patients were decreased as compared with microvessels from the ND or CDM patients (P<0.05). The post-CPB relaxation responses to ADP and substance P were significantly decreased in all 3 groups compared with pre-CPB responses (P<0.05). However, these decreases were more pronounced in the UDM group (P<0.05). The post-CPB response to SNP was significantly decreased only in the UDM group, not in the other 2 groups compared with pre-CPB. The expression of protein kinase C (PKC)-α, PKC-β, protein oxidation, and nitrotyrosine in the skeletal muscle were significantly increased in the UDM group as compared with those of ND or CDM groups (P<0.05). Poorly controlled diabetes results in impaired arteriolar function before and after CPB. These alterations are associated with the increased expression/activation of PKC-α and PKC-β and enhanced oxidative and nitrosative stress.

504 Subtle Differences in Commercial Heparins Can Have Serious Consequences for Cardiopulmonary Bypass Patients: a randomized controlled trial

504 Subtle Differences in Commercial Heparins Can Have Serious Consequences for Cardiopulmonary Bypass Patients: a randomized controlled trial