Han Li1, Justyna Bartoszko2,3,4, Cyril Serrick1, Vivek Rao5,4, Keyvan Karkouti2,3,4,6,7. 1. Perfusion Services, University Health Network, Toronto, ON, Canada. 2. Department of Anesthesia and Pain Management, Sinai Health System, Women's College Hospital, University Health Network, Toronto, ON, Canada. 3. Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada. 4. Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada. 5. Cardiovascular Surgery, University Health Network and University of Toronto, Toronto, ON, Canada. 6. Interdepartmental Division of Critical Care, Department of Medicine, University of Toronto, Toronto, ON, Canada. 7. Institute for Health Policy, Management, and Evaluation, University of Toronto, Toronto, ON, Canada.
Abstract
PURPOSE: Optimal heparin titration during cardiopulmonary bypass (CPB) may reduce coagulation system activation and preserve hemostatic function post-CPB. Our objective was to assess if the Heparin Management System (HMS) Plus improves heparin titration, thereby leading to higher thrombin generation post-CPB compared with activated clotting time (ACT)-guided management. METHODS: We conducted a randomized controlled trial of 100 patients undergoing cardiac surgery with CPB at a single center. A total of 50 patients were randomized to conventional ACT-guided management, and 50 to the HMS Plus system. The primary outcome was change in thrombin generation post-CPB compared with baseline, as assessed by calibrated automated thrombography. Secondary outcomes included intraoperative blood loss, chest drain output up to 72 hr, and transfusions. In an exploratory analysis, we compared the quintile of patients with the highest average heparin concentration on CPB (≥ 4.0 mg⋅kg-1) with the rest of the cohort. RESULTS: A total of 100 patients were included in an intent-to-treat analysis. We observed no difference in post-CPB thrombin generation or secondary outcomes. However, patients in the HMS Plus group had higher average heparin concentrations while on CPB than patients in the conventional management group did (mean difference, -0.21; 95% confidence interval, -0.42 to -0.01). The quintile of patients with the highest average heparin concentration (4.0 mg⋅kg-1) had higher thrombin generation post-CPB than the rest of the cohort did. CONCLUSIONS: The HMS Plus system did not show significant benefits in thrombin generation, bleeding outcomes, or transfusion in patients undergoing cardiac surgery with CPB. Higher average heparin concentrations on CPB were associated with higher post-CPB thrombin generation. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03347201); first submitted 12 October 2017.
PURPOSE: Optimal heparin titration during cardiopulmonary bypass (CPB) may reduce coagulation system activation and preserve hemostatic function post-CPB. Our objective was to assess if the Heparin Management System (HMS) Plus improves heparin titration, thereby leading to higher thrombin generation post-CPB compared with activated clotting time (ACT)-guided management. METHODS: We conducted a randomized controlled trial of 100 patients undergoing cardiac surgery with CPB at a single center. A total of 50 patients were randomized to conventional ACT-guided management, and 50 to the HMS Plus system. The primary outcome was change in thrombin generation post-CPB compared with baseline, as assessed by calibrated automated thrombography. Secondary outcomes included intraoperative blood loss, chest drain output up to 72 hr, and transfusions. In an exploratory analysis, we compared the quintile of patients with the highest average heparin concentration on CPB (≥ 4.0 mg⋅kg-1) with the rest of the cohort. RESULTS: A total of 100 patients were included in an intent-to-treat analysis. We observed no difference in post-CPB thrombin generation or secondary outcomes. However, patients in the HMS Plus group had higher average heparin concentrations while on CPB than patients in the conventional management group did (mean difference, -0.21; 95% confidence interval, -0.42 to -0.01). The quintile of patients with the highest average heparin concentration (4.0 mg⋅kg-1) had higher thrombin generation post-CPB than the rest of the cohort did. CONCLUSIONS: The HMS Plus system did not show significant benefits in thrombin generation, bleeding outcomes, or transfusion in patients undergoing cardiac surgery with CPB. Higher average heparin concentrations on CPB were associated with higher post-CPB thrombin generation. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03347201); first submitted 12 October 2017.