A comparison of the effects of tranexamic acid and low-dose aprotinin on blood loss and homologous blood usage in patients undergoing cardiac surgery.

OBJECTIVES: To assess the relative efficacy of a "low-dose" aprotinin regimen and tranexamic acid on blood loss and homologous blood usage in patients undergoing primary cardiac surgery. DESIGN: The trial was prospective, randomized, and controlled. SETTING: A single center study in a regional cardiothoracic unit in the UK. PARTICIPANTS: 75 Patients, age 18 years or over, who were scheduled for routine primary cardiac surgery. INTERVENTIONS: The patients were randomly allocated to receive neither drug nor placebo, a total of 5 g of tranexamic acid, or a total of 2 x 10(6) kallikrein inhibitory units of aprotinin in the perioperative period. MEASUREMENTS AND MAIN RESULTS: The volume of blood loss and blood replacement were measured in the operative and postoperative periods. Hemoglobin concentration, platelet count, and white cell counts were determined preoperatively and at 24 hours postoperatively. Patients receiving tranexamic acid or aprotinin showed a significant reduction in postoperative blood loss (median[interquartile range] 375 mL [252 to 542] and 230 mL [137 to 547]), respectively, compared with the control group (615 mL [430 to 861]). Blood usage was also reduced in patients in both the tranexamic acid group (600 mL [415 to 800]) and the aprotinin-treated group (420 mL [350 to 887]) compared with the control group (1,050 mL [0 to 1,337]). There was no significant difference in blood loss or homologous blood use between patients treated with tranexamic acid or aprotinin. CONCLUSIONS: Tranexamic acid is as effective as low-dose aprotinin in the reduction of postoperative blood loss and homologous blood transfusion in patients undergoing primary cardiac surgery.

Reheparinisation requirements after cardiopulmonary bypass in patients treated with aprotinin.

OBJECTIVE: To determine reheparinisation requirements following protamine neutralisation after the discontinuation of cardiopulmonary bypass in a group of patients receiving "low dose" aprotinin compared with a control group. DESIGN: Randomised, placebo controlled study. SETTING: Regional cardiothoracic unit within a district general hospital. PATIENTS: 20 patients were consecutively allocated to one of two groups. All patients had a primary elective aortocoronary bypass operation using standard anaesthetic techniques and no patient was withdrawn from the study. INTERVENTIONS: Aprotinin group patients (n = 9) received aprotinin (1 x 10(6) kallikrein inactivator units (KIU)) as an intravenous bolus after the induction of anaesthesia, and 1 x 10(6) KIU was added to the pump prime. Control group patients (n = 11) received 0.9% saline placebo. MAIN OUTCOME MEASURES: Activated clotting time (ACT), heparin concentration, and heparin dose response (HDR) measured before, during, and after bypass. The HDR is an accurate method to determine the patients' in vitro response to heparin and is used to predict the dose of heparin required to attain an ACT of 400 seconds. RESULTS: Activated clotting times were similar in the two groups for the duration of the study. Heparin concentrations were zero in all patients before heparin administration and after protamine neutralisation. During bypass there was no difference between the groups. The median heparin dose response was the same in the two groups before the administration of heparin, but after the neutralisation of heparin with protamine after the discontinuation of bypass the HDR was significantly higher in the aprotinin group for up to one hour (median of 2.9 IU/ml v 1.25 in the control group at 10 minutes after protamine neutralisation, P < 0.01; 2.5 v 1.45 at 30 minutes, P < 0.05; and 2.9 v 1.6 at one hour, P < 0.001). CONCLUSION: Heparin requirements were nearly doubled in patients treated with aprotinin, who required reheparinisation for up to one hour after protamine. This relative "heparin resistance" cannot be explained by the presence of excessive protamine. Aprotinin may be a substrate for the N-carboxypeptidase that destroys protamine, thus indirectly enhancing and prolonging the activity of protamine.

Randomized placebo-controlled double-blind study of three aprotinin regimens in primary cardiac surgery.

The serine proteinase inhibitor aprotinin significantly reduces postoperative blood loss in patients requiring cardiac surgery using cardiopulmonary bypass. This study compared two low-dose regimens with administration of high-dose aprotinin and a control protocol to determine whether the dose of aprotinin could be greatly decreased but still maintain efficacy after primary cardiac surgery. Some 100 patients were randomly assigned to one of four groups: control group (0.9 per cent saline placebo, n = 25); high-dose group (aprotinin 2 x 10(6) kallikrein inactivator (KI) units intravenous patient bolus and 0.5 x 10(6) KI units h-1 plus 2 x 10(6) KI units into pump prime, n = 25); prime group (aprotinin 2 x 10(6) KI units added to the pump prime, n = 24); and patient group (aprotinin 10(6) KI units intravenous patient bolus plus 10(6) KI units added to the pump prime, n = 26). Only patients from the high-dose and patient groups had reduced intraoperative blood loss, but patients from all three aprotinin-treated groups demonstrated a significant decrease in median postoperative blood loss compared with the control group (high-dose 350 ml, prime 420 ml, patient 340 ml versus control 780 ml; P < 0.001). There was an even greater reduction in measured median postoperative haemoglobin loss within the chest drains in the treated compared with the control patients (high-dose 15 g, prime 24 g, patient 14 g versus control 47 g; P < 0.001). These decreases were statistically the same for all the treated groups; it is possible to lower the dose of aprotinin to approximately one-third of the currently recommended dosage and still obtain significantly reduced postoperative blood loss in primary cardiac surgery.

Randomised placebo controlled double blind study of two low dose aprotinin regimens in cardiac surgery.

OBJECTIVE: To determine whether two low dose aprotinin regimens produce clinically significant reductions in postoperative blood loss compared with a control group. DESIGN: A randomised double blind placebo controlled study. SETTING: A regional cardiothoracic unit in London. PATIENTS: 79 patients were consecutively allocated to one of three groups. All patients had primary elective surgery with standard anaesthetic and surgical techniques, and no patients were withdrawn from the study. INTERVENTIONS: Group K patients (n = 27) received aprotinin (10(6) kallikrein inactivator units (KIU) into the pump prime whereas group L patients (n = 27) received an intravenous bolus of aprotinin (0.5 x 10(6) KIU) after induction of anaesthesia and 10(6) KIU was added to the pump prime. A third group (group J, n = 25) received 0.9% saline placebo. MAIN OUTCOME MEASURES: After insertion of the chest drains at the end of cardiopulmonary bypass, blood losses were measured hourly until the drains were removed 18 to 24 h later. Total haemoglobin loss into the chest drains was calculated. RESULTS: Both aprotinin treated groups showed significantly less postoperative blood loss than controls (medians: group K, 400 ml; group L, 400 ml; v controls 780 ml; p < 0.001) and there was even less measured postoperative haemoglobin loss within the chest drains in both the aprotinin treated groups than in the controls (medians: group K, 16 g; group L, 19 g; v controls, 47 g; p < 0.001). CONCLUSION: In primary cardiac surgery the dose of aprotinin may be reduced by about 80% from the recommended high dose schedule and still significantly reduce postoperative blood loss compared with placebo.