Smartphone Monitoring for Accurate Reversal Therapy: Dosing Optimization Study Evaluation.

Recent high-quality evidence demonstrates that traditional 1:1 protamine-to-heparin dosing strategies are suboptimal and contribute to increased bleeding complications due to protamine overdosing. The study’s objective is to improve protamine dosing for heparin reversal by validating a technique based on the relationship between activated clotting time (ACT) and heparin concentration. This validation will enable a more accurate dosing regime for protamine, which can be monitored at the point of care using ROTEM viscoelastic testing. Participants’ blood is taken and tested during their cardiac surgery, and depending on blood results from point of care using Activated Clotting Time (ACT) and ROTEM viscoelastic testing, the dose of protamine administered will be adjusted. ACT is routinely used during cardiac surgery in order to ensure adequate heparinisation and reversal at the end of surgery. The only additional tests will be ROTEM testing of these blood samples before heparin administration and before protamine administration. The protamine dose adjustment occurs normally as a result of ROTEM and ACT testing if inadequate heparin reversal is noted at the end of the cardiac procedure. The iPhone app used to indicate likely doses of protamine has been validated in a pilot project (1. Cumpston PH, Duffy R. Effective Heparin Administration and Reversal in Cardiac Surgery: A Pilot Study. Cardiology Research. 2024;6(1):1–10.) in which ACT was used to estimate circulating heparin concentration. That study used TEG as the device for viscoelastic testing. ROTEM will be used to validate the approach taken in this study. The initial preheparin and postheparin ACT results and the dose of heparin are used to estimate the individual patient's heparin:ACT dose-response, which then enables the ACT to determine an approximate heparin concentration based on the ACT and the patient's estimated blood volume. The dose of protamine is estimated using the algorithm at the end of cardiac bypass and after rewarming by inputting the ACT, which results in an estimation of the total circulating heparin. This allows the appropriate dose of protamine to return the ACT to the pre-heparin ACT. The interventions occur only during cardiac surgery and are very similar to routine practice. The ROTEM results evaluate the coagulation state of the patient and help identify any problems relating to coagulation that may be due to causes other than inadequate heparin reversal. Blood samples for the study (ACT and ROTEM) will be taken during cardiac surgery: before the start of cardiac bypass, before heparin administration (T1), after initial heparin has been given (T2), after bypass is stopped and the patient rewarmed just before protamine is given (T3) and after protamine has been given (T4). The results will be recorded in a proprietary application with audit logging and stored in an encrypted database at these times for later analysis. The patients will be unconscious (anaesthetised) at these times. The interventions will be carried out out by the anaesthetist.