PMID- 36471142 OWN - NLM STAT- MEDLINE DCOM- 20230228 LR - 20231226 IS - 1496-8975 (Electronic) IS - 0832-610X (Linking) VI - 70 IP - 2 DP - 2023 Feb TI - Minimum protamine dose required to neutralize heparin in cardiac surgery: a single-centre, prospective, observational cohort study. PG - 219-227 LID - 10.1007/s12630-022-02364-4 [doi] AB - PURPOSE: Excess protamine contributes to coagulopathy following cardiopulmonary bypass (CPB) and may increase blood loss and transfusion requirements. The primary aim of this study was to find the least amount of protamine necessary to neutralize residual heparin following CPB using the gold standard assays of anti-IIa and anti-Xa activity. Secondary objectives were to evaluate whether the post-CPB activated clotting time could be used as a surrogate marker for quantifying heparin neutralization. METHODS: Twenty-eight consecutive patients undergoing elective cardiac surgery were enrolled. Protamine administration was standardized through an infusion pump at 25 mg.min(-1). Blood samples were withdrawn prior to and following administration of 150, 200, 250, and 300 mg protamine and analyzed for activated clotting time and anti-IIa and -Xa activity. RESULTS: Following a mean (standard deviation) cumulative heparin dose of 67,700 (19,400) units and a CPB duration of 113 (71) min, protamine requirements varied widely. Eight out of 25 (32%) patients showed complete neutralization of anti-IIa and -Xa activity at the first sampling point (150 mg protamine; protamine:heparin ratio, 0.3 [0.1]). A protamine:heparin ratio of 0.5 (0.2) was sufficient for heparin neutralization in > 90% of patients. After CPB, a low to mid-range activated clotting time correlated well with anti-IIa and -Xa activity. CONCLUSIONS: The protamine:heparin ratio required to neutralize residual unfractionated heparin (UFH) following CPB is variable. A protamine:heparin ratio of 0.3 was sufficient to neutralize UFH in some patients, while a ratio of 0.5 is sufficient to neutralize both residual anti-IIa and -Xa activity in most patients. Larger studies are necessary to confirm these findings and evaluate their clinical implications. STUDY REGISTRATION: ClinicalTrials.gov (NCT03787641); registered 26 December 2018. CI - (c) 2022. Canadian Anesthesiologists' Society. FAU - Taneja, Ravi AU - Taneja R AUID- ORCID: 0000-0002-5361-9208 AD - Department of Anesthesia and Perioperative Medicine, London Health Sciences Centre, London, ON, Canada. ravi.taneja@lhsc.on.ca. AD - Division of Critical Care, Department of Medicine, London Health Sciences Centre, University Hospital, B2-223, 339 Windermere Road, London, ON, N6A 5A5, Canada. ravi.taneja@lhsc.on.ca. FAU - Szoke, Daniel J AU - Szoke DJ AD - Department of Anesthesia and Perioperative Medicine, London Health Sciences Centre, London, ON, Canada. FAU - Hynes, Zachary AU - Hynes Z AD - Department of Anesthesia and Perioperative Medicine, London Health Sciences Centre, London, ON, Canada. FAU - Jones, Philip M AU - Jones PM AD - Department of Anesthesia and Perioperative Medicine, London Health Sciences Centre, London, ON, Canada. AD - Department of Epidemiology & Biostatistics, University of Western Ontario, London, ON, Canada. LA - eng SI - ClinicalTrials.gov/NCT03787641 GR - R3913A05/Anesthesia Internal Research Fund (Western University)/ PT - Journal Article PT - Observational Study TT - Dose minimale de protamine requise pour neutraliser l'heparine en chirurgie cardiaque : une etude de cohorte observationnelle prospective monocentrique. DEP - 20221205 PL - United States TA - Can J Anaesth JT - Canadian journal of anaesthesia = Journal canadien d'anesthesie JID - 8701709 RN - 9005-49-6 (Heparin) RN - 0 (Protamines) RN - 0 (Anticoagulants) SB - IM MH - Humans MH - *Heparin MH - Protamines MH - Prospective Studies MH - *Cardiac Surgical Procedures MH - Cohort Studies MH - Cardiopulmonary Bypass MH - Anticoagulants OTO - NOTNLM OT - activated clotting time OT - cardiac surgery OT - cardiopulmonary bypass OT - heparin OT - protamine EDAT- 2022/12/06 06:00 MHDA- 2023/03/03 06:00 CRDT- 2022/12/05 23:39 PHST- 2022/03/28 00:00 [received] PHST- 2022/08/12 00:00 [accepted] PHST- 2022/08/10 00:00 [revised] PHST- 2022/12/06 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2022/12/05 23:39 [entrez] AID - 10.1007/s12630-022-02364-4 [pii] AID - 10.1007/s12630-022-02364-4 [doi] PST - ppublish SO - Can J Anaesth. 2023 Feb;70(2):219-227. doi: 10.1007/s12630-022-02364-4. Epub 2022 Dec 5.