title: Anticoagulation management during multivessel coronary artery bypass grafting: a randomized trial comparing individualized heparin management and conventional hemostasis management.
abstract: BACKGROUND
  Individualized heparin management (IHM) uses heparin dose-response curves to improve hemostasis management during cardiac surgery as compared with activated clotting time-based methods.
  
  
  OBJECTIVE
  IHM was compared with conventional hemostasis management (CHM) in a randomized, prospective study (ID DRKS00007580).
  
  
  METHODS
  One-hundred and twenty patients undergoing multivessel coronary artery bypass grafting (CABG) were enrolled. Heparin and protamine consumption, blood losses, blood transfusions and administration of hemostatic agents were recorded. Time courses of platelet counts and of coagulation parameters were determined. Coagulation was analyzed at intensive care unit (ICU) arrival by thromboelastometry.
  
  
  RESULTS
  IHM patients received significantly lower initial heparin doses (289.3IU kg(-1) [interquartile range (IQR) 221.5-376.2 IU kg(-1) ] versus 350.5 IU kg(-1) [IQR 346.8-353.7 IU kg(-1) ], P < 0.0001) but similar total heparin doses (418.5 IU kg(-1) [IQR 346.9-590.5 IU kg(-1) ] versus 435.8 IU kg(-1) [IQR 411.7-505.1 IU kg(-1) ]). IHM patients received significantly less protamine, resulting in protamine/total heparin ratios of 0.546 [IQR 0.469-0.597] versus 0.854 [IQR 0.760-0.911] in CHM patients (P < 0.0001). Activated partial thromboplastin time (50.5 s [IQR 40.0-60.0 s] versus 37.0 s [IQR 33.0-40.0 s], P < 0.0001), activated clotting time (136 s [IQR 129.0-150.5 s] versus 126.5 s [IQR 120.3-134.0 s], P = 0.0002) and INTEM clotting times (215 s [IQR 192-237] versus 201 s [IQR 191-216 s], P = 0.0397) were significantly longer in IHM patients than in CHM patients at ICU arrival, with no difference in prothrombin time (P = 0.538). IHM patients lost significantly more blood within 12 h postoperatively (420 mL [IQR 337.5-605.0 mL] versus 345 mL [IQR 230.0-482.5 mL], P = 0.0041), and required significantly more hemostatic agents to control bleeding. Red blood cell transfusion requirements and time courses of platelet counts did not differ between groups.
  
  
  CONCLUSIONS
  Multivessel CABG patients did not benefit from IHM in comparison with our established protocol based on activated clotting time.
authors.affiliation: Department of Cardio-Thoracic and Vascular Surgery, University of Ulm Medical Center, Ulm, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hoenicka
authors.affiliation: Department of Cardio-Thoracic and Vascular Surgery, University of Ulm Medical Center, Ulm, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Rupp
authors.affiliation: Department of Cardio-Thoracic and Vascular Surgery, University of Ulm Medical Center, Ulm, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Müller-Eising
authors.affiliation: Department of Cardio-Thoracic and Vascular Surgery, University of Ulm Medical Center, Ulm, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Deininger
authors.affiliation: Department of Cardio-Thoracic and Vascular Surgery, University of Ulm Medical Center, Ulm, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kunert
authors.affiliation: Department of Cardio-Thoracic and Vascular Surgery, University of Ulm Medical Center, Ulm, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Liebold
authors.affiliation: Department of Cardio-Thoracic and Vascular Surgery, University of Ulm Medical Center, Ulm, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Gorki
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001780:Blood Coagulation Tests; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D017707:Erythrocyte Transfusion; D005260:Female; D005858:Germany; D006487:Hemostasis / Q000187:drug effects*; D006490:Hemostatics / Q000008:administration & dosage; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006494:Heparin Antagonists / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care; D010976:Platelet Count; D019106:Postoperative Hemorrhage / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D011237:Predictive Value of Tests; D011479:Protamines / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D006490:Hemostatics; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin
keywords: coronary artery bypass grafting; heparin; postoperative hemorrhage; protamine sulfate; thromboelastography