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

Abstract

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 × 106 kallikrein inactivator (KI) units intravenous patient bolus and 0·5 × 106 KI units h−1 plus 2 × 106 KI units into pump prime, n = 25); prime group (aprotinin 2 × 106 KI units added to the pump prime, n = 24); and patient group (aprotinin 106 KI units intravenous patient bolus plus 106 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.