Calculating the protamine-heparin reversal ratio: A pilot study investigating a new method

There is no consensus as to the dosage of protamine required to reverse a given dose of heparin. The amounts advised vary widely. The hypothesis was investigated that doses of protamine smaller than those usually recommended could be used following cardiac surgery to successfully reverse heparin activity as measured by the activated coagulation time (ACT). A group of 18 patients scheduled for cardiopulmonary bypass (CPB) were investigated with their informed consent. A baseline ACT was measured before anticoagulation with heparin. At the end of CPB, an initial neutralizing dose (IND) of protamine (2 mg/kg) was administered. The ACT was measured after 5 minutes and a further dose of protamine (2 mg/kg) was then administered to make up the full dose. The heparin activity (HA) before and after the IND of protamine reversal was calculated according to the method described by Bull.¹ The IND of protamine (2 mg/kg) was expressed as a ratio of the change in HA (the latter also expressed as mg/ kg). The average ± standard deviation (SD) preoperative ACT was 155 ± 21 seconds with a range of 130 to 199 seconds. Following heparin administration the ACT increased to 701 ± 152 seconds. After the IND of protamine, the average ACT of 160 ± 31 (range, 121 to 250) was not statistically (NS) significantly different from the starting value. A further dose of 2 mg/kg of protamine (“full-dose”) decreased (NS) the ACT only minimally to an average of 151 ± 18 (range, 128 to 206) seconds. The HA before and after the IND of protamine reversal was 3.81 ± 1.11 mg/ kg (range, 2.34 to 6.19) and 0.06 ± 0.38 mg/kg (range, -0.37 to +1.16). This change in HA was caused by an average dose of 2.01 ± 0.09 mg/kg of protamine (ie, 1 mg of heparin activity was reversed by 0.6 ± 0.14 mg of protamine). It is concluded that the proper dose of protamine required to reverse heparin is less than usually recommended and can be calculated using this new ratio.