Protamine—the need to determine the dose

Abstract

SummaryA simple method of protamine titration using the Hemochron system was compared with an empirical dose protocol for reversal of heparinisation following cardiopulmonary bypass in 40 patients undergoing elective myocardial revascularisation. Protamine titration revealed a wide range for protamine requirement and resulted in a signiJcant reduction in protamine dose compared with the empirical dose protocol ( p < 0.01). Heparin reversal was assessed as adequate in all patients. The titration technique was easy and straightforward to use in the operating theatre Key wordsBlood, coagulation; protamine, heparin.Heparinisation is required for the safe performance of cardiopulmonary bypass, but at the end of the procedure, residual heparin needs to be reversed with protamine sulphate. Conventional protocols calculate the dose of protamine empirically, based on the patient's weight or the dose of heparin administered. There is considerable variation in the individual's response to heparin and protamine and this empirical approach cannot guarantee optimal heparin reversal.Protamine has well documented side effects.' Hypotension is common but may be limited by adequate maintenance of the cardiac filling pressure. Cardiac output is usually well maintained if left ventricular function is good.2 More serious reactions such as anaphylaxis or pulmonary vasoconstriction occur less frequently but may be catastrophic. Protamine causes thrombocytopaenia, may impair platelet aggregation, and exerts an anticoagulant effect due to an interaction with t h r~m b i n .~ It is therefore undesirable to give more protamine than is necessary for heparin reversal.Titration of the protamine requirement may allow more accurate dose calculation and thus avoid the problems of over-or underdosing. Recently, a simple titration method has been described using activated clotting time (ACT) mea~urernent.~ The use of sample tubes prefilled with fixed amounts of protarnine allows the construction of a twopoint dose-response line from which the required protamine dose can be calculated. However, this method has not been evaluated in a controlled clinical trial, nor with any laboratory tests, to assess the adequacy of heparin reversal. This study was designed to compare, in patients following cardiopulmonary bypass, the protamine dose determined from a similar, simple protamine titration slope with that calculated from an empirical method. MethodLocal ethics committee approval was obtained for this study. Informed consent was obtained from patients undergoing elective myocardial revascularisation operations. Patients presenting for reoperation, concomitant valve or left ventricular aneurysm surgery were excluded from the study, as were those who required the use of an intra-aortic counterpulsation device, a cell saver/haemoconcentrator or the administration of clotting factors during surgery. The anaesthestic technique was determined by the individual anaesthetist but the same type of cardiopulmonary bypass equipment was used in each case.A baseline...

The British Society for Haematology Guidelines on the use and monitoring of heparin 1992: second revision. BCSH Haemostasis and Thrombosis Task Force.

“…A standard dose is usually given, but it is more sophisticated, though more time consuming, to titrate the dose of protamine with ACT measurements using ACT tubes to which known amounts of protamine have been added. 38 Protamine, unlike heparin, may have toxic effects on the cardiopulmonary circulation and it is usual to adminster protamine cautiously after bypass.…”

In vitro comparative study of activated clotting time in fresh human whole blood with various levels of coagulability using two devices

“…The anticoagulant medicine heparin and its chelating agent protamine have been used during open-heart surgery to prevent blood clots in extracorporeal circulation [1,2]. While coagulation is being controlled, several diagnostic parameters such as activated clotting time (ACT), prothrombin time (PT), and activated partial thromboplastin time (aPTT) are often measured [3,4].…”