PRODOSE Algorithmic Protamine Dosing for Reversal of Heparin after CPB
Research type
Research Study
Full title
Algorithmic Protamine Dosing for Reversal of Heparin after Cardiopulmonary Bypass (PRODOSE)
IRAS ID
231790
Contact name
Florian Falter
Contact email
Sponsor organisation
Papworth Hospital NHS Foundation Trust
Duration of Study in the UK
1 years, 3 months, 1 days
Research summary
Open-heart surgery is routinely conducted using a heart-lung machine. In order to conduct operations involving heart-lung machines safely a patient’s coagulation system needs to be reliably supressed to avoid clot formation. If a clot forms outside the body in the CPB circuit, it often has fatal consequences.
In the vast majority of cases (>99%) the desired suppression of the blood clotting system is achieved by administering heparin. Although relatively short acting, with a half-life of about 150min for a full adult dose, heparin needs to be reversed after weaning from the heart-lung machine in order to avoid catastrophic bleeding post-operatively.
Heparin reversal is achieved by using protamine, a drug derived from salmon sperm. Protamine is the only drug licensed for heparin reversal. Although generally safe to use, it is known to cause severe side effects in a reasonable number of cases. These range from dangerously low blood pressure in the body’s main circulation to very high blood pressure in the lung circulation, which leads to poor gas exchange in the lungs. Severe anaphylactic reactions have also been described. More and more research is showing that high doses of protamine can impact on the clotting system and can increase bleeding.
There is controversy about the right dosing of protamine. Traditionally a pragmatic and empirical ‘1:1’ formula is used reversing every 1000U of heparin given with 1mg of protamine. This dosing regime does not take the decay of heparin during the time spent on the heart-lung machine into account and has the potential to expose patients to unnecessarily high doses of protamine.
Our group was previously able to demonstrate in a pilot project that using a pharmacokinetic algorithm, which takes heparin decay into account, is able to reduce the protamine dose given to patients without increased bleeding or the need to give more blood transfusions.
We have continued to develop and refine this algorithm to make it as relevant as possible to human physiology. We are seeking to test the hypothesis that using our formula can reduce patients’ risk of the unwanted side effects of protamine by reducing its dose.
REC name
East of England - Cambridge South Research Ethics Committee
REC reference
17/EE/0460
Date of REC Opinion
9 Jan 2018
REC opinion
Further Information Favourable Opinion