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Objective: To compare two heparin managements for a cardiopulmonary bypass (CPB) procedure with heparin-coated equipment. The hypothesis was that a lower heparin dose may reduce blood loss and homologous transfusion requirements and influence the speed of postoperative recovery., Design: Prospective, randomized, and open study., Setting: Operating room and intensive care unit in a university hospital., Participants: Twenty-four patients undergoing first-time elective coronary artery surgery., Interventions: Heparin-coated CPB equipment (Duraflo II; Baxter-Bentley) was used in all patients. The study group (n = 12) received low-dose (100 IU/kg i.v. and 0 to 1,000 IU/L priming; target level of activated coagulation time [ACT] over 180 seconds during CPB; suction in a red cell washing device); and the control group (n = 12) received high-dose (300 IU/kg i.v. and 5,000 IU/L priming; ACT over 480 seconds; standard cardiotomy suction) heparin management., Measurements and Main Results: ACT remained above 200 seconds after the initial heparin dose in the study group for the CPB duration up to 99 minutes. In 11 of 12 patients in the control group, additional heparin was required during CPB. Total doses of heparin and protamine (mean 8,017 v 50,508 IU and 83 v 325 mg, respectively; p < 0.0001), volume of homologous blood transfusion (median 600 v 1450 mL; p < 0.025), and blood products exposure (median 0.5 v 5.0 units/patients; p < 0.05) were significantly lower in the study group. Postoperative chest drainage showed a trend to lower volume loss (median 705 v 930 mL; p < 0.08) in patients managed with low-dose heparin. Oxygenator resistance during CPB, perioperative laboratory analyses (oxygen and metabolic data, hematocrit, platelet count, prothrombin, thrombin, activated partial thromboplastin time, fibrinogen, D-dimers, creatine kinase, and myocardial band of creatine kinase concentration), fluid balance, and the time periods required for extubation, stay in the intensive care unit, and hospital discharge were not different between the groups. There were no evidences of myocardial infarction in any of 24 patients, and all recovered after the procedure., Conclusion: Low-dose heparin management enabled uneventful procedures with heparin-coated CPB equipment, significantly decreased protamine and homologous blood requirements, but did not reduce chest drainage or influence the postoperative course and recovery in patients after coronary artery surgery.

Heparin surface-coated perfusion equipment with improved thromboresistance was evaluated in 104 consecutive patients undergoing open heart operation in a prospective, randomized trial with low versus full systemic heparinization. Surgical procedures included coronary artery revascularization in 47 of 54 (87%) for low versus 44 of 50 patients (88%; not significant [NS]) for full, valve repair/replacement in 8 of 54 (15%) for low versus 5 of 50 patients (10%; NS) for full, left ventricular aneurysm repair in 1 of 54 (2%) for low versus 2 of 50 patients (4%; NS) for full, and other in 3 of 54 (6%) for low versus 3 of 50 patients (6%; NS) for full. Cross-clamp time was 39.2 +/- 10.7 minutes for low versus 39.5 +/- 10.5 minutes for full (NS). Cardiopulmonary bypass time was 68.6 +/- 20.1 minutes for low versus 69.3 +/- 16.6 minutes for full (NS). Lowest activated coagulation time during perfusion was 255 +/- 75 seconds for low versus 537 +/- 205 seconds for full (p < 0.0005). In the low group, the target activated coagulation time of more than 180 seconds was not reached during perfusion in 4 of 54 patients (7%), the lowest value being 164 seconds. No oxygenator failure occurred. Hospital mortality was 0 of 54 (0%) for low versus 1 of 50 patients (2%) for full (NS). Bleeding required surgical revision in 0 of 54 (0%) for low versus 4 of 50 patients (8%) for full (p = 0.05). Drainage (24 hours) was 790 +/- 393 mL for low versus 1,039 +/- 732 mL for full (p < 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

The need for improvements in materials and equipment for extracorporeal circulation has been obvious for years. Among the surfaces with biologically active compounds, those with heparin binding have been found sufficiently thromboresistant and particularly suitable for different types of artificial perfusion. Partial left heart bypass (LHBP) was performed in 10 anesthetized, acutely instrumented, and open-chested mongrel dogs (weight 23 to 50 kg) with a servo-controlled roller pump. The pump flow was maintained at 50 mL/kg/min for 6 hours. Heparin surface-coated equipment was used without additional heparin. For LHBP with a standard circuit, the total amount of heparin during the study period was (mean +/- SD) 487 +/- 124 IU/kg. The right atrial, pulmonary artery, and left ventricular end-diastolic pressures, cardiac output, left ventricular output, right and left ventricular stroke work, pulmonary gas exchange, and acid-base balance changed similarly with both systems. Blood loss (204 +/- 78 v 1,240 +/- 586 mL, P < 0.0005), volume substitution requirements (647 +/- 48 v 1,860 +/- 764 mL, P < 0.0025), and oxygen extraction ratio (mean 25.4 to 32.0 v 25.4 to 56.4%, P < 0.025) were significantly lower, and mean aortic pressure (mean 65 to 69 v 62 to 38 mmHg, P < 0.025) and hemoglobin concentration (mean 9.1 to 8.1 v 9.4 to 3.9 g/dL, P < 0.05) were significantly higher during 6 hours of LHBP without systemic heparinization. Low but stable oxygen delivery was provided with heparin-coated LHBP, whereas it showed a descending trend (mean 14.0 to 10.8 v 13.4 to 5.5 mL/kg/min, P < 0.1) with the standard circuit.(ABSTRACT TRUNCATED AT 250 WORDS)

Left heart bypass (LHBP) with heparin coated perfusion equipment including an arterial filter (pore size: 40 microns) was performed in five canine experiments after full systemic heparinization (heparin 300 IU/kg; activated coagulation time [ACT] > 480 sec). The heparin coated filter was replaced after 45 min with a second heparin coated filter. Protamine (1:1) was added after 45 min and perfusion was continued for another 45 min before the second filter was replaced with an uncoated control filter. In addition to continuous hemodynamic monitoring, all filters were disassembled and analyzed morphometrically with a scanning electron microscope (deposits on screens were expressed as percent of surface covered with fibrin or number of cells/100 micron 2, respectively). For the first heparin coated filter (ACT > 480), 0.3 +/- 0.5% of the surface was covered with fibrin, 0.7 +/- 0.7% with platelets, and 0.02 +/- 0.0% with red cells. For the second heparin coated filter exposed to neutralization of heparin with protamine, surface coverage was fibrin in 22 +/- 15%, platelets in 3.2 +/- 0.8%, and red cells in 0.2 +/- 0.1% (p < 0.05 for all comparisons with filter 1). For uncoated control filters (ACT = 120), surface coverage was fibrin in 31 +/- 33%, platelets in 3.7 +/- 2.9%, and red cells in 0.2 +/- 0.1% (not significant [NS] for all comparisons with filter 2). Although all arterial filters used in this study remained patent throughout the scheduled period, it became clear that protamine given during perfusion reduces the antithrombotic activity of bonded heparin. Hence, protaminization during perfusion with heparin coated equipment cannot be recommended.

Perfusion during cardiopulmonary bypass with low-dose heparin (activated clotting time, > 180 sec) versus full-dose heparin (activated clotting time, > 480 sec) combined with high-dose aprotinin was evaluated prospectively. Fifteen patients undergoing elective myocardial revascularization were randomly assigned to 1 of 2 groups. No significant differences between the groups were found for age, sex, body surface area, preoperative hematocrit level, duration of cardiopulmonary bypass, aortic cross-clamp time, mean number of bypasses per patient, or mean number of arterial grafts per patient. In all patients, heparin-coated cardiopulmonary bypass equipment was used, including heparinized hollow-fiber membrane oxygenators and tubing sets. In each group, protamine sulfate was given equivalent to the heparin loading dose; additional doses were administered according to the ACT. The mean total dosage of heparin was 9.5 +/- 1.4 x 10(3) IU for the group given low systemic heparinization (Group 1) compared with 34.6 +/- 3.4 x 10(3) IU for the group given full systemic heparinization in combination with high-dose aprotinin (Group 2) (p < 0.0001). The mean amount of aprotinin administered in Group 2 was 5.6 +/- 0.3 x 10(6) KIU; aprotinin was not used in Group 1. The mean protamine dosage necessary in Group 1, 7.0 +/- 0.9 x 10(3) IU, was significantly less than the 22.9 +/- 3.2 x 10(3) IU needed in Group 2 (p < 0.0001). In Group 1, shed blood recovery was achieved by a red-cell spinning device; in Group 2, cardiotomy suction was used. The total chest tube drainage (i.e., postoperative blood loss) per patient in Group 1 totaled 432 +/- 162 mL/m2; in Group 2, it was 311 +/- 111 mL/m2 (difference not significant). Transfusion requirements comprised a mean volume of 143 +/- 165 mL/m2 concentrated homologous red blood cells per patient in Group 1 and 416 +/- 128 mL/m2 in Group 2 (p < 0.01). Heparin-coated perfusion equipment allowed a significantly lower dosage of systemic heparin and protamine in Group 1 than that in Group 2, and a lower dosage in Group 2 than that in previous studies. Postoperative blood loss appeared to be similar between groups. The combination of heparin-coated perfusion equipment with low systemic heparinization and a red-cell spinning device provides promising results.

After extensive experimental evaluation, heparin-coated perfusion equipment was clinically evaluated with low or no systemic heparinization in three different groups of patients (n = 47). In group 1, resection of descending thoracic aortic aneurysms (n = 24) was performed with heparin-coated equipment used for left heart bypass (n = 12) or partial cardiopulmonary bypass (n = 12) for proximal unloading and distal protection (heparin 5000 IU, autotransfusion). All devices remained functional throughout the procedures and no systemic emboli were detected. The sole death (1 of 24, 4%) occurred in a patient with ruptured thoracoabdominal aortic aneurysm requiring operation in extremis. Paraparesis with spontaneous recovery occurred in one patient (1 of 24, 4%). In group 2, coronary artery revascularization randomized for low (activated clotting time greater than 180 seconds) versus full (activated clotting time greater than 480 seconds) systemic heparinization was prospectively analyzed in 22 patients. All patients recovered without sequelae, and no myocardial infarction was diagnosed. Low dose of heparin (8041 +/- 1270 IU versus 52,500 +/- 17,100 IU; p less than 0.0005) resulted in reduced protamine requirements (7875 +/- 1918 IU versus 31,400 +/- 14,000 IU; p less than 0.0005), reduced blood loss (831 +/- 373 ml versus 2345 +/- 1815 ml; p less than 0.01), reduced transfusion requirements of homologous blood products (281 +/- 415 ml versus 2731 +/- 2258 ml; p less than 0.001), and less patients transfused (5 of 12 versus 10 of 10; p less than 0.05). Lower D-dimer levels in the group perfused with low systemic heparinization (0.50 +/- 0.43 mg/L versus 1.08 +/- 0.59 mg/L; p less than 0.05) were attributed to the absence of cardiotomy suction in this group. In group 3, rewarming in accidental hypothermia by cardiopulmonary bypass was successfully performed without systemic heparinization in a patient with hypothermic cardiac arrest (23.3 degrees C) and intracranial trauma. We conclude that systemic heparinization for clinical cardiopulmonary bypass can be reduced and eliminated in selected patients if perfusion equipment with improved biocompatibility is used. Bypass-induced morbidity can be reduced.

Heparin surface coated ventricular assist devices (VADs) were evaluated without systemic heparinization and compared with uncoated control VADs with systemic heparinization (bovine experiments, n = 8; bodyweight, 75 +/- 6 kg). No heparin was given in the study group, whereas heparin (300 IU/kg) was given before cannulation in the control group. Mean activated clotting time (ACT) was 127 +/- 12 sec before and 122 +/- 17 sec after 6 hours of left ventricular assist for coated (NS) versus 184 +/- 114 sec before and 650 +/- 240 sec after for uncoated (p less than 0.05) VADs. No difference was observed in platelet depletion, plasma hemoglobin, lactic dehydrogenase (LDH) production, mixed venous oxygen saturation, and VAD clot score. No VAD occlusions occurred. Ventricular assist can be achieved without systemic heparinization if VADs are improved.

Clinical application of heparin-coated cardiopulmonary bypass equipment during perfusion with low systemic heparinization is reported with special emphasis on patients refusing any transfusion of homologous blood or blood products. Using the described technique, coronary artery revascularization was successfully performed in three Jehovah's witnesses. During perfusion, the activated clotting time (ACT) was maintained above 180 seconds. Prebypass haematocrit was 38 +/- 3% and dropped to 22 +/- 1% after seven days. Hence, cardiopulmonary bypass with low systemic heparinization may further reduce bypass induced morbidity and improve the final outcome in selected patients.