Comparison of two infusion rates of antithrombin concentrate in cardiopulmonary bypass surgery

Abstract

Antithrombin concentrate (AT) is used to treat heparin resistance (HR) in cardiac surgery. It is usually given slowly due to the fear of anaphylaxis. This may delay cardiac catheterisation and the start of cardiopulmonary bypass (CPB). HR is often defined as the failure to reach or maintain a target activated clotting time (ACT) despite a standard dose of heparin. It is not generally possible to predict which patients will display HR, although there are known risk factors. Routine early administration of AT before heparinisation is probably not cost-effective. Infusing AT relatively quickly after demonstrating HR may be more cost-effective, while not delaying surgery. The aim of this study is to investigate the safety and side effects of a faster infusion of AT. Forty patients undergoing elective heart surgery were included and randomised to two groups in a double-blind fashion. Each group received 1000 IU of AT intravenously (IV). One group received a slow infusion (100 IU/min) before full-dose heparinisation. The other group received a fast infusion (250 IU/min). Haemodynamic and respiratory data were recorded. Any adverse effects were noted. Thrombin-antithrombin, anti-Xa and antithrombin levels in plasma were measured. No anaphylaxis occurred in either group. No differences were found regarding haemodynamics, respiration or laboratory results. Two patients experienced major haemorrhage and recovered; there were two deaths, thought to be unrelated to the study drugs. AT can be infused at a rate of 250 IU/min. This is faster than the current recommendation of 100 IU/min. This rate of infusion allows restricting AT infusion to those patients who display HR, without delaying surgery. Optimal anticoagulant therapy for CPB probably includes point-of-care measurement of ACT and plasma AT and small, but rapid, infusions of AT in heparin-resistant patients.