Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery on minimal invasive extracorporeal circulation; A prospective randomized study

Anna Gkiouliava; Helena Argiriadou; Polychronis Antonitsis; Antonis Goulas; Evangelia Papapostolou; Despoina Sarridou; Georgios T Karapanagiotidis; Kyriakos Anastasiadis

doi:10.1177/02676591231204284

Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery on minimal invasive extracorporeal circulation; A prospective randomized study

Perfusion. 2023 Sep 30:2676591231204284. doi: 10.1177/02676591231204284. Online ahead of print.

Authors

Anna Gkiouliava¹, Helena Argiriadou¹, Polychronis Antonitsis², Antonis Goulas³, Evangelia Papapostolou¹, Despoina Sarridou¹, Georgios T Karapanagiotidis², Kyriakos Anastasiadis²

Affiliations

¹ Department of Anesthesiology and Intensive Care, AHEPA University Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
² Cardiothoracic Department, AHEPA University Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
³ First Laboratory of Pharmacology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.

PMID: 37776194
DOI: 10.1177/02676591231204284

Abstract

Introduction: Individualized heparin and protamine management is increasingly used as a strategy to reduce coagulation activation and bleeding complications. While it is associated with increased heparin requirements during Cardiopulmonary Bypass (CPB), the impact on protamine administration remains controversial. We aim to investigate the effect of heparin level-guided monitoring on protamine dosing during cardiac surgery where low-anticoagulation protocols are implemented.

Methods: This is a prospective, randomized, controlled trial. A total of 132 patients undergoing elective full-spectrum cardiac surgery with Minimal Invasive Extracorporeal Circulation (MiECC) were recruited. All patients were managed by the same anaesthetic, surgical and perfusion team. Patients were randomly allocated in two groups; the individualized heparin-protamine titration (IHPT) group and the conventional heparinization and reversal group by using ACT (cACT) with a 0.75:1, protamine: heparin ratio. Titration was accomplished with the Hepcon HMS Plus (Medtronic, Minneapolis, MN) system. The primary outcome of the study was the total protamine dose used. Secondary outcomes comprised of the total heparin dose, the percentage of patients achieving target ACT, 24-h transfusion requirements, postoperative bleeding, duration of mechanical ventilation, major morbidity and length of hospital stay. Patients in each group were divided in two subgroups according to the target ACT; those operated for coronary artery bypass grafting (CABG) using a target ACT >300 s and the rest (non-CABG) patients operated with a target ACT >400 s, respectively.

Results: Protamine requirements were significantly reduced when IHPT was implemented; CABG (118 ± 24 mg vs 163 ± 61 mg; p < 0.001) and non-CABG cases (151 ± 46 mg vs 197 ± 45 mg; p < 0.001). Moreover, heparin requirements were significantly higher in the non-CABG subgroup managed with IHPT (34,539 ± 7658 IU vs 29,893 ± 9037 IU; p = 0.02). In overall, no significant differences were detected with respect to postoperative bleeding, transfusion of RBC or other blood products.

Conclusions: Individualized heparin monitoring and management reduces protamine requirements in cardiac surgery with MiECC implementing reduced anticoagulation strategy.

Trial registration: clinicaltrials.gov; NCT04215588.

Keywords: cardiac surgery; coagulation; heparin; minimal invasive extracorporeal circulation; point-of-care; protamine.

Associated data

ClinicalTrials.gov/NCT04215588