Blood transfusion during versus after cardiopulmonary bypass is associated with postoperative morbidity in neonates undergoing cardiac surgery.

INTRODUCTION: Cardiac surgery on neonates for the correction of congenital heart defects is usually associated with the transfusion of packed red blood cells (PRBCs) into the cardiopulmonary bypass (CPB) circuit. We hypothesised that such transfusions of stored PRBCs directly into the arterial system may increase postoperative morbidity when compared to intravenous transfusion. PATIENTS AND METHODS: In this retrospective cohort study, data from 122 consecutive neonates who received transfusions of PRBCs in the course of corrective surgery for congenital heart defects were analysed. Group assignment was according to the timing of the first transfusion: during CPB (On-CPB) or after weaning from CPB (Post-CPB). Chi Square and rank sum tests were applied to compare clinical characteristics. Times until extubation and release from the intensive care unit were analysed by Kaplan-Meier curves and by multivariate Cox regression. RESULTS: Transfusion of PRBCs during CPB was associated with greater 48 hour blood loss (mean±standard deviation, 86±125 versus 32±16 mL/kg, p<0.001), longer duration of mechanical ventilation (214±268 versus 99±75 h, p<0.001) and longer stay on the intensive care unit (10.9±12.1 versus 5.3±3.5 days, p<0.001). However, the groups also differed in many characteristics, such as bodyweight, complexity of surgery or preoperative haemoglobin concentration, which may also affect outcome. Yet, multivariate analyses confirmed an independent association of transfusion On-CPB with an adverse clinical outcome. CONCLUSIONS: Our results are consistent with the hypothesis that the transfusion of PRBCs during CPB may increase postoperative morbidity. However, due to the limitations of this retrospective analysis, further studies are needed to confirm a causal relationship between the timing of the transfusion and the clinical outcome and to elucidate putative mechanisms of such an association.

Temporal and spatial dispersion of human body temperature during deep hypothermia.

BACKGROUND: Clinical temperature management remains challenging. Choosing the right sensor location to determine the core body temperature is a particular matter of academic and clinical debate. This study aimed to investigate the relationship of measured temperatures at different sites during surgery in deep hypothermic patients. METHODS: In this prospective single-centre study, we studied 24 patients undergoing cardiothoracic surgery: 12 in normothermia, 3 in mild, and 9 in deep hypothermia. Temperature recordings of a non-invasive heat flux sensor at the forehead were compared with the arterial outlet temperature of a heart-lung machine, with the temperature on a conventional vesical bladder thermistor and, for patients undergoing deep hypothermia, with oesophageal temperature. RESULTS: Using a linear model for sensor comparison, the arterial outlet sensor showed a difference among the other sensor positions between -0.54 and -1.12°C. The 95% confidence interval ranged between 7.06 and 8.82°C for the upper limit and -8.14 and -10.62°C for the lower limit. Because of the hysteretic shape, the curves were divided into phases and fitted into a non-linear model according to time and placement of the sensors. During cooling and warming phases, a quadratic relationship could be observed among arterial, oesophageal, vesical, and cranial temperature recordings, with coefficients of determination ranging between 0.95 and 0.98 (standard errors of the estimate 0.69-1.12°C). CONCLUSION: We suggest that measured surrogate temperatures as indices of the cerebral temperature (e.g. vesical bladder temperature) should be interpreted with respect to the temporal and spatial dispersion during cooling and rewarming phases.

Mast cells promote lung vascular remodelling in pulmonary hypertension.

Left heart disease (LHD) frequently causes lung vascular remodelling and pulmonary hypertension (PH). Yet pharmacological treatment for PH in LHD is lacking and its pathophysiological basis remains obscure. We aimed to identify candidate mechanisms of PH in LHD and to test their relevance and therapeutic potential. In rats, LHD was induced by supracoronary aortic banding. Whole genome microarray analyses were performed, candidate genes were confirmed by RT-PCR and Western blots and functional relevance was tested in vivo by genetic and pharmacological strategies. In lungs of LHD rats, mast cell activation was the most prominently upregulated gene ontology cluster. Mast cell gene upregulation was confirmed at RNA and protein levels and remodelled vessels showed perivascular mast cell accumulations. In LHD rats treated with the mast cell stabiliser ketotifen, or in mast cell deficient Ws/Ws rats, PH and vascular remodelling were largely attenuated. Both strategies also reduced PH and vascular remodelling in monocrotaline-induced pulmonary arterial hypertension, suggesting that the role of mast cells extends to non-cardiogenic PH. In PH of different aetiologies, mast cells accumulate around pulmonary blood vessels and contribute to vascular remodelling and PH. Mast cells and mast cell-derived mediators may present promising targets for the treatment of PH.

An imaging spectroscopy approach for measurement of oxygen saturation and hematocrit during intravital microscopy.

OBJECTIVE: Oxygen supply and partial pressure are key determinants of tissue metabolic status and are also regulators of vascular function including production of reactive oxygen species, vascular remodeling, and angiogenesis. The objective of this study was to develop an approach for the determination of oxygen saturation and hematocrit for individual microvessels in trans- and epi-illumination intravital microscopy. METHODS: A spectral approach was used, taking advantage of the availability of commercial imaging systems that allow digital recording of intravital images at a number of predetermined wavelengths within a relatively short time. The dependence of validity and precision of saturation measurements on critical experimental variables (reference spectra, number and selection of wavelengths, exposure time, analysis area, analysis model) was evaluated. In addition, a software approach for two-dimensional analysis of images was developed. RESULTS: Exposure times per wavelength of about 200 ms and use of up to 50 wavelengths evenly spaced from 500 to 598 nm allow automatic discrimination of microvessels from tissue background (segmentation) with reliable determination of oxygen saturation (in trans- and epi-illumination) and hematocrit (in transillumination). CONCLUSIONS: The present imaging spectroscopy approach allows detailed assessment of oxygen transport and other functional parameters at the microcirculatory level.

EEG-based indices of anaesthesia: correlation between bispectral index and patient state index?

BACKGROUND AND OBJECTIVE: Both the bispectral and the patient state indices are derived from the electroencephalogram and have been proposed as a measure of the same clinical target, the hypnotic component of anaesthesia. The present study evaluated whether there is concordance between the bispectral and the patient state indices with regard to end-points measured simultaneously in patients undergoing surgery under general anaesthesia. METHODS: Fifty-seven patients scheduled for elective abdominal, orthopaedic (Groups 1 and 2) or cardiac surgery (Group 3) under general anaesthesia were enrolled in the study. Anaesthesia was performed using remifentanil/ sevoflurane (Group 1, 19 patients), remifentanil/propofol (Group 2, 19 patients) or sufentanil/propofol/isoflurane (Group 3, 19 patients). The bispectral and the patient state indices were simultaneously recorded. Pearson's correlation between these two indices was calculated for the complete data and each group. The percentage of bispectral index values in the recommended range for general anaesthesia (45-60) that were confirmed by levels of patient state index (25-50) was calculated and vice versa. RESULTS: Overall correlation between the bispectral and the patient state indices was 0.667, 0.671 in Group 1, 0.650 in Group 2 and 0.675 in Group 3 (P < 0.01). For values of the bispectral index between 45 and 60, only 40% of corresponding patient state index values were between 25 and 50. For patient state index values of 25-50, only 50% of the corresponding bispectral index values were in the range of 45-60. CONCLUSIONS: Concordance between the bispectral and patient state indices is relatively weak, whereas both are thought to reflect the same clinical target, the hypnotic component of anaesthesia. As a consequence, further studies are required to compare reliability of both indices as indicators of different levels of hypnosis.

Quality of perioperative AEP--variability of expert ratings.

BACKGROUND: Previous studies suggest that auditory evoked potentials (AEP) may be used to monitor anaesthetic depth. However, during surgery and anaesthesia, the quality of AEP recordings may be reduced by artefacts. This can affect the interpretation of the data and complicate the use of the method. We assessed differences in expert ratings of the signal quality of perioperatively recorded AEPs. METHODS: Signal quality of 180 randomly selected AEP, recorded perioperatively during a European multicentre study, was rated independently by five experts as 'invalid' (0), 'poor' (1), or 'good' (2). Average (n=5) quality rating was calculated for each signal. Differences between quality ratings of the five experts were calculated for each AEP: inter-rater variability (IRV) was calculated as the difference between the worst and best classification of a signal. RESULTS: Average signal quality of 57% of the AEPs was rated as 'invalid', 39% as 'poor', and only 4% as 'good'. IRV was 0 in only 6%, 1 in 62%, and 2 in 32% of the AEP, that is in 32% one expert said signal quality was good, whereas a different expert thought the identical signal was invalid. CONCLUSIONS: There is poor agreement between experts regarding the signal quality of perioperatively recorded AEPs and, as a consequence, results obtained by one expert may not easily be reproduced by a different expert. This limits the use of visual AEP analysis to indicate anaesthetic depth and may affect the comparability of AEP studies, where waveforms were analysed by different experts. An objective automated method for AEP analysis could solve this problem.

In situ analysis of coronary terminal arteriole diameter responses: technical report of a new experimental model.

INTRODUCTION: To date, investigation of coronary arteriole vasomotor activity has been limited to arterioles >30- 40 microm. Here, we introduce a new experimental model to allow for in situ microscopy of terminal coronary arterioles. METHODS: Rat hearts were perfused in a closed loop system (priming volume 20 ml) which was placed on a computer-controlled microscope stage. FITC-dextran and tetrodotoxin (TTX, 50 microM) were added. Tilting of the microscope by 90 degrees allowed for visual access to the ventricular surface. Arterioles were identified by the flow direction of fluorescent beads (1 microm). Images were recorded on video tape, and arteriole diameters were measured offline. Stability of the preparation and maintenance of coronary flow reserve were analyzed. Responses of coronary flow and arteriole diameters to the vasodilators papaverine and Na-nitroprusside were recorded. RESULTS: In TTX-arrested control hearts coronary flow and terminal arteriole diameters were stable for 2 h. Administration of papaverine and Na-nitroprusside increased coronary flow from 6.4 +/- 0.7 to 13.3 +/- 1.3 ml/min, decreasing coronary resistance by 52 +/- 3%. Terminal coronary arteriole diameters increased from 12.0 +/- 0.9 to 13.6 +/- 1.0 microm, decreasing hindrance of this vessel segment by 45 +/- 11%. CONCLUSION: Preservation of coronary terminal arteriolar tone and adequate responsiveness to vasodilators in the TTX-arrested isolated heart were demonstrated. Thus, this model may serve to complement our understanding of coronary microvascular control mechanisms by extending observations to the terminal arteriolar bed.

[Coronary artery bypass grafting in patients with highly impaired ventricular function. Long-term outcome]. / Koronarbypassoperation bei hochgradig eingeschränkter Ventrikelfunktion - Langzeitergebnisse.

BACKGROUND AND OBJECTIVE: Left ventricular function is the most important predictor of survival in patients with coronary artery disease. It is also an important indicator for hospital mortality after operation for end-stage coronary artery disease. In our study we investigated, how preoperative ventricular dysfunction influences long term survival after coronary bypass surgery. PATIENTS AND METHODS: Between 4/1986 and 12/2000, 1751 patients (1440 men/311 women) with left ventricular ejection fraction (LVEF) 10-30% underwent coronary bypass grafting (CABG) at the Deutsches Herzzentrum Berlin. The age of the patients was calculated to an average of 59,2 years. The prime criterion for CABG was ischemia ("hibernating myocardium") diagnosed by myocardial scintigraphy, echocardiography and in some cases with magnetic resonance imaging and positron emission tomography. RESULTS: Operative mortality for the group was 7,1%. The actuarial survival rate was 87,6% after 2 years, 76,0% after 5, and 53,3% after 9. 455 had LVEF 10-20%, in these actuarial survival was 79,8% after 2 years, 63,0% after 5 and 45,7% after 9 years. CONCLUSION: We conclude that CABG can be used successfully to improve life expectancy of patients with end-stage coronary artery disease. CABG leads to acceptable prognosis for these high-risk patients when the myocardium is preoperatively identified as being viable.

OPS imaging of human microcirculation: a short technical report.

Despite the pivotal role of microcirculation in numerous diseases, techniques for the direct assessment of human microcirculation are limited. A new approach based on orthogonal polarization spectral (OPS) imaging (Cytoscan microscope) allows noninvasive observation of human microcirculation in all accessible tissue surfaces. Limitations remain: application of pressure with the instrument affects blood flow, lateral movement of tissue precludes continuous investigation of a given microvascular region, and blood flow velocities above 1 mm/s cannot be measured. We addressed these problems by (a) constructing an attachment to the probe, preventing direct contact of the instrument with the observed tissue area and allowing fixation of the tissue, and (b) implementing a double-flash spatial correlation technique extending the measuring range for blood flow velocities up to approximately 40 mm/s. The modified approach was tested in vitro and in vivo. Velocity readings correlated well with velocities of an external standard (r(2) = 0.99, range 1.9-33.8 mm/s). Pulsatile flow patterns synchronous with heart rate with maximal velocities of about 10 mm/s could be detected in arterioles of the human sublingual mucosa. The modified instrument may prove useful to investigate the microcirculation in the context of research, diagnosis and therapy control.

Initial reperfusion with magnesium after cardioplegic arrest attenuates myocardial reperfusion injury.

BACKGROUND: Magnesium's effect on calcium ion concentrations may attenuate myocardial reperfusion injury. The aim of this study was therefore to investigate the effects on the recovery of myocardial function of initial reperfusion with varying Mg(2+) concentrations following cardioplegic arrest. METHODS: Isolated guinea pig hearts underwent 3.5 hours of cardioplegic arrest in St. Thomas Hospital II solution (STH) or Bretschneider HTK solution (HTK) at 24 degrees C. Control hearts were reperfused with normal Krebs-Henseleit solution (KHS). In the therapy groups, hearts were initially reperfused with 5, 10, or 20 mM Mg(2+) for 15 minutes, followed by 30 minutes of perfusion with KHS. RESULTS: During initial reperfusion, elevated Mg(2+) concentrations markedly reduced rate-pressure product, dP/dt and O 2 demand. Release of LDH and CK was reduced in the therapy groups pretreated with Bretschneider HTK. After Mg(2+) washout, left ventricular function recovery and compliance was improved after HTK but not after STH cardioplegia. Following both STH and HTK cardioplegia, Mg(2+) reperfusion reduced reperfusion arrhythmias. CONCLUSIONS: The combination of HTK cardioplegia with 15 min initial Mg(2+) (5 and 10 mM, but not 20 mM) reperfusion was clearly superior to HTK followed by immediate Krebs-Henseleit reperfusion as well as STH cardioplegia with or without initial Mg(2+) reperfusion. The high Mg(2+) concentrations in the STH solution might mask beneficial effects of Mg(2+) reperfusion.

Autologous plasma and platelet sequestration at the beginning of cardiopulmonary bypass: a pilot investigation in five patients undergoing extended vascular surgery in deep hypothermia.

Platelet dysfunction and loss of procoagulants and platelets leads to impaired hemostasis after cardiopulmonary bypass (CPB). Preoperative platelet sequestration delays surgery, and the large volume shifts, necessary to harvest therapeutically effective components, may be associated with hemodynamic instability. We performed platelet and plasma sequestration after the initiation of CPB during the cooling period in patients undergoing surgery in deep hypothermic cardiac arrest. Five patients who underwent major vascular surgery in deep hypothermia were enrolled in this pilot study. Platelet and plasma sequestration was performed during cooling with the CATS cell saver using the plasma sequestration set. Before processing, 2 x 1,000 ml of blood were concentrated by means of hemofiltration to reduce dilution effects of CPB. The autologous platelet concentrates were rotated at 24 degrees C, and the plasma was stored at room temperature. The harvested plasma and platelets were re-transfused during modified ultrafiltration after CPB. Platelet count, 20 mmol/L ADP stimulated platelet aggregation, and fibrinogen levels were measured preoperatively in the harvested material and in patient blood before and after transfusion. A heparinase thromboelastogram (TEG) was performed preoperatively before and after re-transfusion. There was a significant increase in the ADP stimulated platelet aggregation, platelet count, fibrinogen level, and maximum amplitude of the TEG after re-transfusion of the harvested material. No patient needed transfusion of fresh frozen plasma or random donor platelet concentrates. No patient needed re-exploration due to hemorrhage. The data presented provide evidence that autologous plasma and platelet sequestration during CPB initiation is effective. The harvested material reveals a high platelet count and fibrinogen level and preserves functional integrity.

[Cellular pathophysiology of pulmonary hypertension]. / Zelluläre Pathophysiologie der pulmonalen Hypertonie.

Pulmonary hypertension comprises a group of diseases with heterogeneous etiology characterized by an increase of hydrostatic pressure in the pulmonary vascular bed. While secondary pulmonary hypertension predominantly results from acute or chronic left ventricular failure, characteristic gene defects or predisposing risk factors lead to various forms of primary pulmonary hypertension. Despite its diverse pathogenesis, pulmonary hypertension exhibits a uniform cellular pathophysiology in the pulmonary microcirculation. The dysfunction of lung vascular endothelial cells, which are the front line in response to hemodynamic changes in the pulmonary circulation, is the pathophysiological driving force of pulmonary hypertension. Endothelial dysfunction is characterized by a reduced production of vasodilative, anti-proliferative mediators and an increased release of vasoconstrictive, proliferative factors. This apparent imbalance not only enhances pulmonary vasoconstriction, but supports pathologic remodeling processes in the vascular intima and media. In addition, the pulmonary endothelium recruits platelets and leukocytes, thus, contributing to further release of vasoconstrictive and proliferative mediators and characteristic thrombus formation. These endothelium-derived pathomechanisms amplify each other, further enhance pulmonary vascular resistance, and finally result in fixation of the hypertensive state. Hence, pulmonary hypertension not only describes an alteration of lung hemodynamics, but comprises a complex set of pathophysiological events in both lung parenchymal cells and circulating blood cells. For development of new therapeutical strategies, the multifactorial character of the disease should be considered.

Cariporide (HOE 642) attenuates leukocyte activation in ischemia and reperfusion.

UNLABELLED: Cariporide (HOE 642) ameliorates myocardial ischemia/reperfusion (I/R) injury, by the well established reduction of cytosolic [Ca(2+)] in cardiac myocytes through inhibition of Na(+)/H(+) exchange. However, postischemic inflammation also contributes to I/R injury. We tested the hypothesis that cariporide also modulates the inflammatory response. The effect of cariporide on L-selectin expression by human leukocytes in vitro and leukocyte adhesion and emigration in the reperfused rat cremaster muscle in vivo were studied. The rat cremaster muscle was exteriorized for intravital videomicroscopy, induction of ischemia (90 min), and reperfusion (90 min). Eleven rats were pretreated with cariporide (9 mg/kg body weight IV) whereas 11 rats received saline. Leukocyte adhesion was quantified offline. Human venous blood was incubated with cariporide (3 micromol/L) or saline, stimulated with formyl- methionine-leucine-phenylalanine (10(-10)-10(-6) mol/L), and granulocyte L-selectin expression was analyzed by flow cytometry. Cariporide reduced leukocyte rolling and adhesion by approximately 35% and 45%, respectively, after 30 min of reperfusion. Leukocyte extravasation was decreased by approximately 85% after 90 min. Cariporide increased L-selectin shedding at each formyl-methionine-leucine-phenylalanine concentration, reducing the 50% effective dose from 9.95 to 4.68 nmol/L. Thus, cariporide may ameliorate I/R injury not only by the known reduction of cytosolic [Ca(2+)] in cardiomyocytes, but also by attenuating leukocyte-dependent inflammatory responses. Promotion of L-selectin shedding from activated leukocytes may present a mechanism underlying this newly detected effect. IMPLICATIONS: This study provides evidence that inhibition of Na(+)/H(+) exchange by cariporide (HOE 642) attenuates the postischemic inflammatory response. Leukocyte adhesion and emigration, assessed by in vivo microscopy, were markedly reduced in rat cremaster muscle, possibly because of increased L-selectin shedding of activated leukocytes as demonstrated by flow cytometry.

Intraoperative radiofrequency maze ablation for atrial fibrillation: the Berlin modification.

BACKGROUND: The Cox-maze procedure combined with an operation for organic heart disease is highly successful in the elimination of chronic atrial fibrillation. However, it prolongs significantly the aortic cross-clamp and operating time. In this study, a simplified left atrial maze procedure, which is a short procedure performed using a surgical radiofrequency ablation probe, is added to elective open heart procedures in patients with atrial fibrillation. METHODS: Forty-eight adults with atrial fibrillation (duration, 6 months to 36 years) underwent elective open heart operations (isolated valve procedures or coronary artery bypass grafting, n = 27 patients; combined procedures, n = 21 patients) combined with intraoperative radiofrequency ablation of the left atrium. The postoperative follow-up period ranged from 1 to 11 months (mean, 4 months). Possible predictors for persistent postoperative atrial fibrillation were determined among 40 variables by univariate and multivariate analyses. RESULTS: Intraoperative radiofrequency ablation prolonged the aortic cross-clamp time for 6 to 14 minutes (mean, 11 minutes). Freedom from atrial fibrillation was 100% intraoperatively, 25% at 1 week after operation (12 of 48 patients), 59% at 1 month postoperatively (16 of 27 patients), 64% at 3 months postoperatively (16 of 25 patients), and 92% at 6 months postoperatively (12 of 13 patients). The only predictor of postoperative atrial fibrillation was the presence of coronary artery disease (odds ratio, 7.5; 80% confidence interval, 2.24-25.13). CONCLUSIONS: Intraoperative radiofrequency ablation of the left atrium combined with an operation for organic heart disease effectively eliminates atrial fibrillation without significant prolongation of the aortic cross-clamp and operative time. The presence of coronary artery disease decreases the success rate during the first 6 postoperative months.

Predictors of survival 1 hour after implantation of an intra-aortic balloon pump in cardiac surgery.

From July 1996 to March 2000, 391 patients with intraoperative cardiac low-output syndrome who underwent surgery with heart-lung bypass and had an intra-aortic balloon pump (IABP) implanted were analyzed in a prospective study. Of these 391 patients, 153 (39%) were operated on in an emergency situation, and 238 (61%) patients had elective surgeries. The perioperative mortality was 34% (133 patients). Clinical parameters were analyzed 1 hour after IABP support began. Statistical multivariate analysis showed that patients with an adrenaline requirement higher than 0.5 microg/kg/min, a left atrial pressure higher than 15 mmHg, output of less than 100 mL/hour, and mixed venous saturation (SvQ2) of less than 60% had poor outcomes. Using this data, we developed an IABP score to predict survival early after IABP implantation in cardiac surgery. We conclude that the success or failure of perioperative IABP support can be predicted early after implantation of the balloon pump. In patients with low-output syndrome despite IABP support, implantation of a ventricular assist system should be considered.

Evaluation of post-cardiopulmonary bypass coagulation disorders by differential diagnosis with a multichannel modified thromboelastogram: a pilot investigation.

We assessed a modified multichannel thromboelastogram for differentiation of the causes of coagulopathy after cardiopulmonary bypass and its suitability as a therapy guide. Thirty adult patients undergoing surgery with cardiopulmonary bypass, who revealed a coagulopathy as observed by a prolonged activated clotting time of >150 sec after the application of protamine, were enrolled. Therapy was based on the results obtained by the computerized four-channel thromboelastogram with baseline, heparinase (2 IU/mL), heparinase/abciximab (5 microg/mL), and heparinase/fresh frozen plasma (25%) channels. The mean activated clotting time before therapy was 162.2+/-7.8 sec. Based on differential diagnosis with the modified multichannel thromboelastogram, two patients received protamine (30 mg), five desmopressin (0.4 microg/kg), 19 patients three units of fresh frozen plasma, two patients platelet transfusions, and two patients both protamine (30 mg) and three units of fresh frozen plasma. After therapy, there was a significant (p < .01) decrease of the activated clotting time to a mean value of 127+/-8.3 sec. Therapy based on the synoptic modified multichannel thromboelastogram analysis provides a guide for effective therapy of coagulopathy. However, elaboration is desirable, and larger clinical trials are necessary for a final evaluation of the protocol.

Assessment of the resonance thromboelastograph CS-3 for differentiation of coagulation disorders: a pilot in vitro investigation of simulated post-cardiopulmonary bypass coagulopathies.

Resonance thromboelastography (RTG), a further development of the thromboelastogram (TEG), has been designed for improved differentiation of the effect of the plasmatic coagulation factors (increasing F-leg) and platelets (decreasing P-leg) on clot formation. It is based on the effect of clot elasticity on the resonance of a swinging wire. We assessed the RTG for its ability to differentiate coagulation disorders that frequently occur after cardiac surgery. The RTG was performed with a CS-3 Analyzer. Samples from 10 healthy volunteers were investigated after the following preparations: (1) baseline values, (2) dilution to a hematocrit of 30% and 20% with either hydroxyl ethyl starch (HES) 10% or plasma; (3) addition of 0.25, 0.5, and 1.0 IU/mL porcine heparin with and without heparinase; and (4) addition of 1.0, 3.0, 4.0, and 5.0 microg/mL of the antiplatelet agent abciximab (ReoPro). Increasing concentrations of abciximab led to a slower decrease or in the case of higher concentrations, to a persistent elevation of the platelet leg of the RTG. Dilution of the hematocrit with plasma had no effect on the fibrin and platelet leg; whereas, dilution with HES 10% led to an inhibition of the fibrin and platelet leg. Dilution of the plasmatic coagulation factors resulted in an inhibition of both the fibrin and the platelet leg. The addition of 0.25 and 0.5 IU/mL of heparin led to an increased coagulation time and inhibition of the fibrin and platelet legs. These effects were eliminated by the addition of heparinase. The RTG enables the evaluation of platelet function under the condition of a nonimpaired plasma coagulation system. Depletion of plasma coagulation factors and the administration of small amounts of heparin do not enable the distinction between residual effects of an anticoagulant, coagulation factor deficiency, or impaired platelet function. However, the heparin effects can be eliminated by the addition of heparinase. Further improvement may be achieved using a modified RTG by adding plasma coagulation factors in one channel for an improved evaluation of platelet function, even under the condition of a loss of procoagulants.

Some new perspectives in heparin-induced thrombocytopenia type II.

We conclude that HIT II is a serious complication, particularly in patients undergoing cardiovascular surgery that involves CPB. New tests might contribute to the earlier diagnosis of this disease. However, the reduction of immunization by the use of alternative anticoagulants whenever possible seems to be the most effective strategy for the reduction of HIT II-associated complications. If HIT II is diagnosed. r-hirudin is effective as an acute therapy (especially in combination with GP IIb/IIIa inhibitors) and also for further anticoagulation. If patients must undergo CPB, all current alternative anticoagulation concepts are associated with relevant drawbacks that put the patient at an increased risk for post-operative bleeding and/or CPB thrombosis. Currently, r-hirudin is most probably the best option for this purpose. However, when there is impaired renal function, the persistent anticoagulant effect is associated with hemorrhage. Further studies must evaluate whether extracorporeal elimination procedures, such as hemofiltration or plasmapheresis, are effective in avoiding such complications. Otherwise, the combination of UFH with a potent antiplatelet agent, especially with short-acting GP IIb/IIIa antagonists, is an attractive alternative.

Anaphylactic reactions to aprotinin reexposure in cardiac surgery: relation to antiaprotinin immunoglobulin G and E antibodies.

BACKGROUND: Aprotinin, a serine proteinase inhibitor, reduces bleeding during cardiac surgery. As aprotinin is derived from bovine lung, it has antigenic properties. This investigation examined the incidence of anaphylactic reactions in patients reexposed to aprotinin and the relation to preformed antiaprotinin immunoglobulin (Ig)G and IgE antibodies. METHODS: This prospective observational study conducted at five centers in Germany evaluated patients undergoing repeat cardiac surgery reexposed to aprotinin between 1995 and 1996. Antiaprotinin IgG and IgE antibody measurements, using a noncommercial enzyme-linked immunosorbent assay and an immunofluorescence assay, respectively, were performed preoperatively and postoperatively. An anaphylactic reaction was defined as major changes from baseline within 10 min of aprotinin administration of systolic pressure 20% or greater, heart rate 20% or greater, inspiratory pressure greater than 5 cm H2O, or a skin reaction. RESULTS: In 121 cases (71 adults, 46 children), a mean aprotinin reexposure interval of 1,654 days (range, 16-7,136 days) was observed. Preoperative antiaprotinin IgG (optical density ratio > 3) and IgE antibodies (radioallergosorbent test [RAST] score < 3) were detected in 18 and 9 patients, respectively. High concentrations of each (IgG, optical density ratio > 10; IgE, RAST score > or = 3) were detected in five patients. Three patients (2.5%; 95% confidence interval, 0.51-7.1%) experienced an anaphylactic reaction after aprotinin exposure, followed by full recovery; these patients had reexposure intervals less than 6 months (22, 25, and 25 days) and the highest preoperative IgG concentrations of all patients (P < 0.05). Assay sensitivity was 100%, as no anaphylactic reactions occurred in IgG-negative patients (95% confidence interval, 0.0-3.1%); assay specificity was 98%. Preoperative IgE measurements were quantifiable in two of three reactive patients and in three nonreacting patients. CONCLUSIONS: Quantitative detection of antiaprotinin IgE and IgG lacks specificity for predictive purposes; however, quantitation of antiaprotinin IgG may identify patients at risk for developing an anaphylactic reaction to aprotinin reexposure.