Validation of a method for heparin reversal with protamine in patients undergoing cardiac surgery.

While guidelines for protamine administration have been published by several cardiac surgical societies, a number of different approaches are currently used. These include: 1. Giving protamine in a fixed 1:1 ratio (1mg. protamine to 1 mg or 100 International Units of heparin) based on the initial dose of heparin. 2. A fixed ratio of 1:1 based on the total dose of heparin administered during the case. 3. A ratio based on either the total dose of heparin given throughout the case or the initial heparin dose, depending on the individual anaesthetist/institution( waring from 0.5:1 to 1:1). Doses of protamine derived from a heparin:activated clotting time (ACT) dose-response curve and estimated blood volume will be estimated for each patient, allowing the effective heparin concentration to be estimated at each ACT measured. This approach is aligned with clinical practice, as the estimated dose of protamine will be within the range normally used. The post-protamine ACT is used to assess that an appropriate dose of protamine has been used, and this will be confirmed by viscoelastic testing. The pre-protamine ACT will be used to estimate the appropriate dose of protamine for heparin reversal after rewarming and before re-infusion of pump blood. Viscoelastic testing with the Clotpro or TEG6s will allow comparison of the clot times with and without heparinase to determine effectiveness of this predicted protamine dose in reversing heparin effect. Inadequate reversal will be treated with additional protamine in the usual manner by anaesthetic and surgical team. The ACT is measured routinely throughout the cardiac surgical procedure. The creation of the heparin:ACT dose-response curve will require no additional blood samples over and above those that are normally used to confirm that an appropriate level of coagulation has been reached, apart from one blood sample taken prior to heparinisation. The volume of blood required is less than 5 mL. The cardiac surgical procedures are those that require bypass, with anticoagulation achieved by using heparin. The duration varies depending on surgical difficulty but is usually longer than two hours. There will be no additional time require for performance of blood tests. If the dose of protamine estimated is the correct dose, total time will be reduced. The minimum and maximum dose of heparin to be administered depends on the anaesthetist carrying out the procedure, and is not relevant to the calculation of protamine for the purpose of this study, as the dose of protamine is estimated by individual patient's response to the heparin as shown by the current ACT. The minimum dose of heparin to be administered will be in the order of 10,000 units, the maximum dose may be as high as to 80,000 units. Heparinase is not administered to the patient, it ia component of the viscoelastic tests to compare the clotting time in a single sample of blood with and without the presence of heparin. Heparin is given after the first incision and prior to going on to bypass. Protamine is administered after rewarming, before re-infusion of pump blood. An ACT will be measured five minutes after the protamine is given. Viscoelastic testing is performed at this time to confirm that the heparin has bene reversed, and to determine if there are other factors that might contribute to ongoing bleeding. Heparin and protamine are given by slow intravenous injection. Infusions are not used. The purpose of this study is to determine how well the approach taken determines the appropriate dose of protamine to reverse active heparin based on the ACT before protamine is administered. The drugs used are those normally used in performing this surgery. Observation of the patient throughout the perioperative patient are the responsibility of the anaesthetic and surgical team performing the procedure, and is not a requirement of this study.