Low activated coagulation time during cardiopulmonary bypass does not increase postoperative bleeding

The activated coagulation time (ACT) is widely used to monitor adequacy of anticoagulation during cardiopulmonary bypass despite absence of data establishing an ACT below which adverse outcomes occur. For anticoagulation before cardiopulmonary bypass, we administered a single dose of heparin (300 U/kg) to 193 patients and measured ACT and heparin levels at intervals after administration. No additional heparin was administered to any patient. Clot formation in the cardiopulmonary bypass circuit and excessive postoperative chest tube drainage were considered outcomes indicating inadequate anticoagulation. Cardiopulmonary bypass averaged 59 +/- 23 minutes (range, 30 to 138 minutes). Activated coagulation time values at every sampling period were normally distributed. In 51 patients (26.4%) ACT values were less than 400 seconds, including 4 less than 300 seconds, at some sampling time after heparinization. Patients with low ACT values did not bleed more postoperatively than those with high ACT values, nor was bleeding related to heparin level. No clots were found in any perfusion circuit. We conclude that a minimum ACT value for adequacy of heparinization is not yet defined but that it is less than 400 seconds.     

High dose thrombin time versus the activated clotting time during cardiopulmonary bypass

In this study we compared the High Dose Thrombin Time (HiTT) with the Activated Clotting Time (ACT) during cardiopulmonary bypass (CPB) in non-aprotinin treated patients. On the advice of the HiTT test manufacturer each institution should perform comparative ACT/HiTT assays in the cardiac surgery population. In previous tests our target ACT value of 480 seconds corresponds with a mean HiTT value of 190 seconds. Our results showed that after heparinization (300-400 IU/kg body weight) 8 out of 20 patients did not reach the target ACT of 480 seconds, while the HiTT results in those 8 patients were higher than our target time of 190 seconds. Four heparin pretreated patients who received 400 IU/kg heparin, had relatively low ACT values (467 +/- 14 sec.) and high HiTT values (324 +/- 47 sec.). Before and during CPB there was a poor correlation between the HiTT and ACT (r = 0.38). The results of this study show that for the individual patient the target HiTT of 190 seconds is no guarantee for reaching an adequate ACT of 480 seconds. Although the HiTT may be a very useful assay for monitoring heparin effects during CPB, the determination of the target time can be a point of discussion. In contrast of the advice of the manufacturer we therefore suggest that comparative ACT/HiTT assay should be done in every individual patient to determine a safe target HiTT time, instead of the whole group of patients.     

Cardiopulmonary bypass over 24 hours without systemic anticoagulation: new horizons?

Open chest cardiopulmonary bypass was evaluated in eight canine experiments (mean bodyweight 37 +/- 7 kg) over 24 hours using either heparin surface coated equipment without systemic anticoagulation or standard equipment with systemic heparinization (ACT greater than 400 s). Mean duration of perfusion achieved was 23 +/- 2 hours in the group perfused without systemic anticoagulation versus 21 +/- 6 hours in the group with: [table; see text] These results show, that prolonged open chest perfusion by the means of heparin surface coated equipment without systemic anticoagulation can be performed with reduced blood trauma and without transfusion of blood products for 12 hours.     

Cardiopulmonary bypass without systemic heparinization. Performance of heparin-coated oxygenators in comparison with classic membrane and bubble oxygenators

Performance characteristics of heparin-coated hollow-fiber membrane oxygenators (COATED HFMO, n = 5) were evaluated in an open-chest dog model without systemic heparinization. Four other oxygenators were evaluated with standard systemic heparinization (300 IU/kg, activated clotting time more than 400 seconds): a standard hollow-fiber membrane oxygenator (HFMO, n = 5), an inversed hollow-fiber membrane oxygenator (IHFMO, n = 5), a plate membrane oxygenator (PLATE MO, n = 5) and a bubble oxygenator (BUBBLE O, n = 5). The 25 dogs (36 +/- 12 kg) were perfused after cavo-aortic cannulation for 6 hours with a mean flow of 100 ml/kg body weight. At the end of perfusion without systemic heparin, heparin-coated equipment was replaced in three animals with standard uncoated equipment for control studies. Besides continuous hemodynamic evaluation with Mikro-Tip pressure transducers (Millar Instruments, Inc., Houston, Texas), a standard battery of analyses was performed before, after mixing, and every 30 minutes during bypass. All animals could be perfused in accordance with the protocol. Blood-gas values (pH, arterial oxygen tension, and arterial carbon dioxide tension) were maintained within physiologic ranges for all groups. After 6 hours of perfusion, plasma hemoglobin levels were as follows: 0.57 +/- 0.51 gm/L for COATED HFMO without systemic heparinization versus 2.65 +/- 1.02 gm/L for HFMO (p less than 0.05), 1.77 +/- 0.48 gm/L for IHFMO (p less than 0.05), 1.96 +/- 0.41 gm/L for PLATE O (p less than 0.05), and 1.5 +/- 0.40 gm/L for BUBBLE O (p less than 0.05) with systemic heparinization. Platelet levels were highest for COATED HFMO with 47% +/- 36% without systemic heparinization versus 33% +/- 9% for HFMO, 12% +/- 2% for IHFMO, 36% +/- 17% for PLATE O, and 19% +/- 12% for BUBBLE O with systemic heparinization. Activated clotting time for COATED HFMO without systemic heparinization was 135 +/- 75 seconds before bypass, 207 +/- 21 seconds after mixing, and 131 +/- 20 seconds after 4 hours of perfusion. There was no statistically significant increase of plasma heparin levels in the group perfused without systemic heparin. Determination of fibrin split products during perfusion without systemic heparinization did not show a significant increase. At the end of perfusion all devices were disconnected and gently rinsed with saline: There were no macroscopic clots in the COATED HFMO group perfused without systemic heparin. However, uncoated equipment introduced for control in animals perfused without systemic heparin showed major clotting.(ABSTRACT TRUNCATED AT 400 WORDS)     

Anticoagulation management in a patient with an acquired antithrombin III deficiency.

We report a case of heparin resistance and its management during cardiopulmonary bypass (CPB). A 63-year-old, 96 Kg female with a posterior myocardial infarction (MI) with previous deep venous thrombosis was treated with intravenous (IV) heparin infusion for 7 days before myocardial revascularization surgery. The patient required 1200 IU/Kg of beef lung heparin to extend the activated clotting time (ACT) in order to initiate CPB. A total of 1562 IU/Kg of heparin was administered throughout the procedure. This acquired heparin resistance was attributed to an antithrombin (AT III) deficiency, and was treated with fresh frozen plasma (FFP) to restore adequate anticoagulation. The patient's heparinized ACTs ranged between 368 seconds and 387 seconds before FFP administration as opposed to 626 seconds to 1329 seconds after treatment with FFP and additional heparin once on CBP. The patient experienced an uneventful postoperative course. Future treatment with AT III concentrate rather than FFP may reduce heparin requirements that will, in turn, reduce protamine reversal dose, postoperative bleeding attributable to heparin rebound, and its associated complications.     

Adequate anticoagulation during cardiopulmonary bypass determined by activated clotting time and the appearance of fibrin monomer.

The adequacy of anticoagulation during 2 hours of cardiopulmonary bypass at 30 degrees C in 9 rhesus monkeys was determined by measuring the whole-blood activated clotting time (ACT) and by noting the appearance of thrombin-altered fibrin (fibrin monomer) and the relative consumption of clotting factors. Factor V and VIII, the heparin cofactor, antithrombin III, prothrombin time, partial thromboplastin time, ACT, platelets, hematocrit, fibrinogen, and fibrin monomer were determined prior to heparinization and after protamine. In 6 of 9 experiments, fibrin monomer became positive in the plasma during cardiopulmonary bypass (CPB), indicating that active coagulation was occurring. In 5 of the 6 animals, initial ACT was less than 400 seconds, and fibrin monomer appeared within the first 30 minutes of bypass. In 1 animal with an initial ACT of 439 seconds, fibrin monomer appeared after 60 minutes of bypass, at which time the ACT was less than 400 seconds. An abnormal level of fibrin monomer was not detected in 5 pediatric patients with an ACT greater than 450 seconds during CPB. Our experimental study and clinical data suggest that the lower limit, as measured by the ACT, for anticoagulant effect to provide coagulation-free CPB is at least 400 seconds.     

Fresh frozen plasma: a solution to heparin resistance during cardiopulmonary bypass

The reasons for the highly variable response of patients to heparin remain incompletely understood. Empirical maintenance of the activated clotting time (ACT) at levels of 400 to 480 seconds appears to be safe for cardiopulmonary bypass (CPB). For patients with ACT responses lower than predicted for initial heparin doses, titration with additional heparin has been customary. In 44 patients undergoing cardiopulmonary bypass, 20 patients were identified as having initial ACTs of 300 seconds or less after receiving 300 units per kilogram of heparin. In 11 of them, ACTs were titrated to 400 to 480 seconds with additional heparin. Nine were given 2 units of fresh frozen plasma shortly after institution of CPB. In this group, there was significant augmentation of the ACT immediately after infusion of plasma. No differences in total heparin dosages given during CPB were found between 24 control patients with initially acceptable ACTs and the group receiving fresh frozen plasma. In contrast, more heparin was necessary in the patients with a low ACT titrated with heparin alone. Data also indicated that protamine sulfate requirements were substantially lower after administration of plasma than were those in either the control or the heparin-titrated, low ACT group. Fresh frozen plasma appears to "normalize" the heparin-ACT dose-response curve in heparin-resistant patients and to lessen total heparin requirements during CPB.     

Heparin concentration and hemostatic alterations with low systemic heparinization during CPB using heparin-coated circuits

Extracorporeal circulation with heparin coated circuits allows reduction of systemic heparin. The authors investigated the effects of this method on the hemostatic and fibrinolytic systems and heparin concentration simultaneously. Ten patients undergoing coronary artery bypass surgery were studied. The dose of heparin was 100 IU.kg-1, and the target activated clotting time (ACT) was more than 300 seconds. Blood samples were obtained at the following times; before and after giving heparin, 10 and 40 minutes after the start of extracorporeal circulation, after cross-clamp release, and after giving protamine, and heparin concentration, ACT, thrombin-antithrombin complex (TAT), plasmin alpha 2 plasmin inhibition complex (PIC), and D-dimer were measured. ACT was kept over 300 seconds without additional heparin administration. Heparin concentration was maintained at 1.0 IU.ml-1. However, after release of the aortic cross-clamp, TAT, PIC, D-dimer increased significantly. Despite reduced systemic heparinization, heparin concentration was maintained adequately. Thrombin generation and fibrinolytic activity showed no significant increase until the release of the aortic cross-clamp.     

Safety and efficacy of a heparin removal device: a prospective randomized preclinical outcomes study

BACKGROUND: Systemic protamine sulfate for heparin reversal after cardiopulmonary bypass (CPB) is associated with uncommon, but life-threatening adverse reactions. METHODS: In a prospective randomized 3-day outcomes study, a heparin removal device (HRD) group (n = 12; 60-, 80-, 100-kg subgroups) was compared with a matched systemic Protamine group (Protamine; n = 6) for safety and efficacy using an adult swine model of CPB (60 minutes, 28 degrees C). RESULTS: HRD run time was 25 to 38 minutes depending on weight without complications. After HRD, heparin concentration decreased from 4.77 +/- 0.17 to 0.45 +/- 0.06 U/mL (activated clotting time [ACT] 776 +/- 83 to 180 +/- 12 seconds), and in Protamine, 3.94 +/- 0.63 to 0.13 +/- 0.02 U/mL (ACT 694 +/- 132 to 101 +/- 5 seconds) (p = 0.01 between groups, but no significant differences 60 minutes later). No significant difference between HRD and Protamine to 72 hours was seen in plasma-free hemoglobin C3a, heparin concentration, thromboelastogram index, platelet count, activated partial thromboplastin time, anti-thrombin III, fibrinogen, ACT, and tissue histology. CONCLUSIONS: In a prospective randomized outcomes study, HRD achieved predictable reversal of systemic heparinization after CPB with no difference in safety or outcomes compared with protamine.     

The in vitro effects of antithrombin III on the activated coagulation time in patients on heparin therapy

Heparin requires antithrombin III (AT) to achieve anticoagulation, and patients on continuous small-dose heparin preoperatively experience decreased levels of AT-causing heparin resistance. When this occurs, 2-4 units of fresh frozen plasma ( approximately 1000 units of AT) are often administered to increase AT levels and restore heparin responsiveness. We evaluated purified human AT concentrate (Thrombate III; Bayer, Inc., Elkhart, IN) to restore in vitro anticoagulation responses in patients receiving heparin. Blood samples were obtained from cardiac surgery patients including 22 patients receiving heparin and 21 patients not receiving heparin preoperatively. Heparin was added to blood in final concentrations of 4.1, 5.4, and 6.8 U/mL (equivalent to 300, 400, and 500 U/kg), and kaolin-activated clotting times (ACTs) were determined with and without AT at a final concentration of 0.2 units/mL to mimic fresh frozen plasma administration. The mean duration of preoperative heparin therapy was 4.0 days (range 2-10 days). AT activity was 69% +/- 9% in patients receiving heparin and 92% +/- 8% in patients not receiving heparin (P < 0.01). Heparin >4.1 U/mL failed to further increase ACT values in all patients. Attempts to increase ACT in patients receiving heparin may require supplemental AT administration. Purified AT even in small doses significantly prolongs the ACT response to heparin. Implications: In vitro addition of antithrombin III (0.2 U/mL) to heparinized blood samples (4.1-6.8 units of heparin/mL) from patients on previous heparin therapy increases sensitivity to supplemental heparin as reflected by significantly prolonged activated clotting time.     

Prevention of heparin-induced thrombocytopenia during open heart surgery with iloprost (ZK36374)

Recurrent thrombocytopenia, thrombosis, or sudden death may develop in patients with heparin-induced thrombocytopenia who are reexposed to heparin. Three patients came to us in whom a diagnosis of heparin-induced thrombocytopenia had been made on the basis of clinical and serologic evidence; these patients required reexposure to heparin because of urgent cardiac surgery. Therefore, we evaluated the ability of iloprost (ZK36374), a new analogue of prostacyclin, to prevent heparin-dependent activation of platelets and thereby permit obligatory heparinization for safe extracorporeal circulation. Before operation, we demonstrated that iloprost prevented both heparin-dependent platelet aggregation and tritiated (3H)-serotonin release in vitro. Therefore a continuous infusion of iloprost was begun 1 hour before heparinization and was continued throughout cardiopulmonary bypass and for an additional 15 minutes after protamine administration. The mean platelet count of 130,000/microliters before operation remained stable, and no spontaneous platelet aggregation was observed in samples of platelet-rich plasma obtained before cardiopulmonary bypass but after heparin administration. Similarly, after heparin administration but before bypass, platelet responsiveness to adenosine diphosphate remained unchanged when compared with preoperative values. Plasma levels of platelet factor 4 increased from 26 +/- 1 ng/ml (mean +/- standard error) to 843 +/- 383 ng/ml after heparin administration but actually decreased throughout cardiopulmonary bypass to 52 +/- 25 ng/ml. Beta-thromboglobulin levels increased from 103 +/- 16 to 244 +/- 94 ng/ml with heparinization. The mean bleeding time was 10.5 minutes preoperatively and 13.3 minutes postoperatively. The mean amount of postoperative chest tube drainage (duration: 12 hours) was 432 +/- 67 ml. Thus, despite the confirmed presence of heparin-dependent platelet-activating factor in the plasma of these three patients, iloprost prevented heparin-induced platelet activation during cardiopulmonary bypass while preserving platelet function, as would be desired for postoperative hemostasis.     

Low dose systemic heparinization combined with heparin-coated extracorporeal circulation. Effects related to platelets

BACKGROUND: A heparin coated cardiopulmonary bypass system combined with full and low dose systemic heparinization in coronary bypass surgery was investigated in a prospective, randomised study. Roller pumps, coronary suction and an open cardiotomy reservoir were used. METHODS: One hundred and nineteen patients were divided into 3 groups: group A (n=39) had a standard uncoated extracorporeal circulation (ECC)-set and systemic heparin was given in an initial dose of 400 IE/kg body weight. During ECC activated clotting time (ACT) was kept at = or >480 sec. Group B (n=42) had the same ECC-set completely coated with low molecular weight heparin, i.v. heparin was administered in the same dose as in group A, ACT was again kept at = or >480 sec. Group C (n=38) had the same coated ECC set as group B, but i.v. heparin was reduced to 150 IE/kg and during ECC ACT was maintained of = or >240 sec. RESULTS: Platelet decrease was significantly less in both groups utilizing coated circuitry as compared to control group A. Activation of thrombocytes as marked by b-thromboglobulin (not PF4) was significantly decreased in patients treated with coated circuits combined with low dose systemic heparinization and postoperative bleeding was significantly reduced. CONCLUSIONS: We conclude that in heparin coated extracorporeal circulation combined with either full dose or reduced systemic heparinization compared to uncoated circuits platelet count reduction is significantly less. Platelet activation as marked by b-thromboglobulin and postoperative blood loss are decreased with coated equipment and low i.v. heparinization.     

Reduction and elimination of systemic heparinization during cardiopulmonary bypass.

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.     

Kaolin-based activated coagulation time measured by sonoclot in patients undergoing cardiopulmonary bypass

OBJECTIVES: In vivo data for the kaolin-based ACT test from the Sonoclot Analyzer (SkACT, Sienco Inc, Arvada, CO) are lacking. The aim of this study was to compare SkACT with an established kaolin-based ACT from Hemochron (HkACT) and anti-Xa activity in patients undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective observational study. SETTING: Community hospital. PARTICIPANTS: Fifty patients scheduled for elective cardiac surgery. INTERVENTIONS: Blood samples were taken before CPB at baseline (T0) and after heparinization (T1 and T2), on CPB after administration of aprotinin (5, 15, 30, 60 minutes; T3-T6), and at the end after protamine infusion (T7). MEASUREMENTS AND MAIN RESULTS: A total of 375 blood samples were analyzed. ACT measurements were comparable for SkACT and HkACT at each measurement time point. Overall bias +/- standard deviation between SkACT and HkACT was -19 +/- 75 seconds (-2.4% +/- 11.7%). Mean bias between SkACT and HkACT at each time point ranged from -35 to 3 seconds (-4.5% to 2.6%) and showed no statistical significance over time. Heparin sensitivity of SkACT and HkACT, defined as (ACT(Tx)-ACT(T0))/(anti-Xa(Tx)-anti-Xa(T0)), significantly increased for measurements during CPB (p < 0.001) but without significant difference between the 2 methods. Test variability was comparable for both ACT measurement techniques. Overall test variability was 7.5% +/- 7.4% for SkACT and 7.8% +/- 11% for HkACT. CONCLUSIONS: Accuracy and performance of SkACT and HkACT were comparable for heparin monitoring in patients undergoing CPB for elective cardiac surgery. However, both tests were affected significantly after initiating CPB and aprotinin infusion.     

Heparin-coated circuits (Duraflo II) with reduced versus full anticoagulation during coronary artery bypass surgery

BACKGROUND: Introduction of completely heparin-coated cardiopulmonary bypass (CPB) circuits combined with reduced systemic anticoagulation has been shown to reduce postoperative bleeding and requirements for allogeneic transfusions after cardiac surgery. However, some uncertainty exists whether this effect is due to the reduced amount of heparin or to the heparinized surface itself. Therefore, a retrospective study was undertaken, comparing two different anticoagulation protocols applied to coronary artery bypass patients treated with identical heparin-coated CPB equipment. METHOD: Over a 12 month period all coronary artery bypass patients operated with extracorporeal circulation were subjected to a Duraflo II heparin-coated circuit (Baxter Healthcare Corp, Bentley Laboratories Division, Irvine, Calif) and full heparin dose (activated clotting time [ACT] > 480 seconds; Group F, n = 651). Over the next 24 months, all coronary patients who were treated with an identical circuit combined with reduced systemic heparinization (ACT > 250 seconds) were included in Group R (n = 675). Except for the different anticoagulation protocols, all treatment regimens before, during, and after the operation remained unchanged throughout the study period. RESULTS: There were no statistically significant differences in any major demographic or operative parameters. In Group R, the postoperative bleeding was mean 665 +/- 257 ml versus 757 +/- 367 ml in Group F (p < 0.0001), and the perioperative decrease in hemoglobin concentration was significantly lower in Group R (22 +/- 1.2 gm/L versus 25 +/- 1.3 gm/L, p < 0.0001). The time for postoperative ventilatory support was shorter in Group R (1.7 +/- 1.3 hours versus 1.9 +/- 1.1 hours in Group F, p = 0.0006), and the incidence of new episodes of atrial fibrillation after the operation was lower (26.4% in Group R versus 32.8% in Group F, p = 0.01). There were no significant differences in the incidences of perioperative myocardial infarction, stroke, transient neurological disturbances, physical rehabilitation, or mortality. No technical or coagulation problems were recorded in either group. CONCLUSION: The use of Duraflo II coated circuits for CPB combined with reduced anticoagulation decrease postoperative bleeding and hemoglobin loss compared with full heparin dose treatment. In addition, the intubation time was shorter and the incidence of postoperative atrial fibrillation was lower in the patients treated with low heparin doses.     

Heparin-Coated Extracorporeal Circulation with Full and Low Dose Heparinization: Comparison of Thrombin Related Coagulatory Effects

Thrombin related coagulatory effects of a heparin-coated cardiopulmonary bypass system combined with full and low dose systemic heparinization were investigated in a prospective, randomized study in coronary bypass surgery patients. One hundred nineteen patients were divided into 3 groups. Group A (n = 39) had a standard uncoated extracorporeal circulation (ECC) set, and systemic heparin was administered in an initial dose of 400 IU/kg body weight. During ECC activated clotting time (ACT) was maintained at > or =480 s. Group B (n = 42) had the same ECC set completely coated with low molecular weight heparin. Intravenous heparin was given in the same dose as in Group A, and ACT was kept at the same level. Group C (n = 38) had the same coated ECC set as Group B, but intravenous heparin was reduced to 150 IU/kg, and during ECC, ACT was set to be > or =240 s. The same ECC components were used in all 3 groups including roller pumps, coronary suction, and an open cardiotomy reservoir. Thrombin generation as indicated by F1/F2 was significantly elevated at an ECC duration >60 min if heparin-coated ECC combined with low dose systemic heparinization was employed. Complexed thrombin (TAT) was significantly elevated after administration of protamine. Release of D-dimers indicating fibrinolysis was not significantly different between groups. Signs of clinical thromboembolism, i.e., postoperative neurological deficit, occurred in 2 patients in Group A and 1 patient in Group C. We conclude that heparin-coated extracorporeal circulation combined with reduced systemic heparinization intraoperatively leads to significantly increased thrombin generation, but not to increased fibrinolysis.     

Superior hemodynamics in left heart bypass without systemic heparinization

Open-chest left heart bypass was performed in 10 canine experiments (30 +/- 9 kg) by a servo controlled roller pump for 6 h at a pump flow of 50 ml/min per kg bodyweight. The surfaces of the tubing sets were either standard (with systemic heparinization) or with end-point attached heparin (no systemic heparin). Besides continuous monitoring of hemodynamics, a standard battery of blood samples was taken before bypass, after 10 min and every hour thereafter. There is no evidence of increased fibrin production in the group with end-point attached heparin surfaces perfused without systemic heparinization. Superior hemodynamics in left heart bypass performed without systemic heparinization appear to be due to improved hemostasis, reduced blood loss and therefore reduced transfusion requirements. Left heart bypass with heparin-coated equipment has been successfully used for resection of a thoracoabdominal aneurysm in six patients.     

Stabilized Infective Endocarditis and Altered Heparin Responsiveness During Cardiopulmonary Bypass

Background  Although active infective endocarditis (IE) is known as a risk factor for decreased heparin responsiveness during cardiopulmonary bypass (CPB), evidence is lacking in patients with stabilized IE. We investigated whether heparin responsiveness was still altered in stabilized IE patients undergoing cardiac surgery in a prospective, controlled trial. Methods  A total of 16 patients with stabilized IE without signs of active inflammation (IE group) and 48 patients without systemic infection (control group) undergoing valve surgery were included. Heparin responsiveness was assessed using the heparin sensitivity index (HSI), whereas heparin resistance was defined as an activated clotting time (ACT) occurring less than 400 s after the initial heparinization. Results  Preoperative antithrombin III activity was lower and fibrinogen level was higher in the IE group. ACT after initial heparinization was shorter in the IE group. The HSI was lower and the number of patients with HSI <1.0 was greater in the IE group. Heparin resistance occurred more frequently in the IE group. Conclusions  Heparin responsiveness during CPB was significantly reduced in the IE group, and it seems to be associated with preoperative hypercoagulability and reduced antithrombin III activity. Therapeutic measures such as the administration of antithrombin III concentrate should be considered in these patients even when they are in a stabilized condition without active inflammation.     

Reduced blood loss and transfusion requirements with low systemic heparinization: preliminary clinical results in coronary artery revascularization

In coronary artery revascularization, low systemic heparinization was compared to full systemic heparinization during perfusion with heparin surface-coated cardiopulmonary bypass equipment. Twelve patients were randomly assigned to two groups and perfused with low [activated clotting time (ACT) > 180 s] or full (ACT > 480 s) systemic heparinization. A standard battery of blood samples was taken before the procedure, after heparinization, and at regular intervals during and after cardiopulmonary bypass. No differences were seen between the two groups in regard to age, body surface area, preoperative hematocrit, duration of bypass, bypass hypothermia, cross-clamp time, and number of bypasses per patient. However, there were more internal thoracic artery (ITA) grafts in the group with low systemic heparinization (1.5 ± 0.8 ITA grafts per patient versus 0.8 ± 0.4 ITA grafts per patient with full heparinization; p < 0.05). The oxygenator gradient at the end of perfusion (before weaning) was 107 ± 40 mmHg for low versus 110 ± 10 mmHg for full heparinization (difference not significant). The total amount of heparin used was 7200 ± 1030 IU for low versus 51 400 ± 9700 IU for full (p < 0.05). Postoperative hematocrit was 35.0 ± 2.0% for low versus 24.7 ± 2.7% for full (p < 0.05). Total chest tube drainage was 428 ± 153 ml/m² for low versus 935 ± 414 ml/m² for full (p < 0.05). Homologous transfusions of blood products were necessary in 3/6 patients for low versus 6/6 patients for full (p < 0.10). The total volume of packed red cells transfused was 221 ± 228 ml/m² for low versus 842 ± 366 ml/m² for full (p < 0.05). Final hematocrit at day 7 was 31.0 ± 2.0% for low versus 33.0 ± 3.0% for full (difference not significant). Full systemic heparinization can be avoided during clinical cardiopulmonary bypass by the use of heparin-coated perfusion equipment. A low dose of heparin, similar to the amounts given during vascular surgery, results in reduced blood loss and transfusion requirements.