Calculation Algorithm Reduces Protamine Doses Without Increasing Blood Loss or the Transfusion Rate in Cardiac Surgery: Results of a Randomized Controlled Trial

J Cardiothorac Vasc Anesth. 2019 Apr;33(4):985-992. doi: 10.1053/j.jvca.2018.07.044. Epub 2018 Aug 3.


Objectives: The aim of the study was to investigate whether the HeProCalc algorithm affects heparin and protamine dosage, postoperative blood loss, and transfusion rate.

Design: Randomized controlled trial.

Setting: University hospital.

Participants: The study comprised 210 cardiac surgery patients undergoing cardiac surgery with cardiopulmonary bypass. Twenty patients were excluded because of re-exploration for localized surgical bleeding (n = 9), violation of protocol (n = 2), aprotinin use (n = 3 and nadir body temperature <32°C (n = 6).

Interventions: Study participants were randomly assigned to either traditional heparin and protamine dosage based on body weight only (control group) or dosage based on the HeProCalc algorithm (intervention group).

Measurements and main results: The initial median heparin dose was 32,500 IU (interquartile range [IQR] 30,000-35,000) in the intervention group compared with 35,000 IU (IQR 30,000-37,500) (p = 0.025) in the control group. The total heparin dose in the intervention group was 40,000 IU (IQR 32,500-47,500) compared with 42,500 IU (IQR 35,000-50,000) in the control group (p = 0.685). The total protamine dose was 210 mg (IQR 190-240) in the intervention group compared with 350 mg (IQR 300-380) (p < 0.001) in the control group. The ratio of total protamine to initial dose of heparin in the intervention group was 0.62 compared with 1.0 (p < 0.001). The amount of chest tube bleeding after 12 postoperative hours was 320 mL (IQR 250-460) in the intervention group compared with 350 mL (IQR 250-450) (p = 0.754) in the control group. Neither the transfusion rate nor postoperative blood loss differed significantly between the 2 groups.

Conclusion: Use of the HeProCalc algorithm reduced protamine dosage and the protamine/heparin ratio after cardiopulmonary bypass compared with conventional dosage based on weight without significant effect on postoperative blood loss or the transfusion rate.

Keywords: cardiac surgery; cardiopulmonary bypass; coagulation; heparin; protamine; surgical blood loss.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Algorithms*
  • Blood Loss, Surgical / prevention & control*
  • Blood Transfusion / trends*
  • Cardiac Surgical Procedures / adverse effects
  • Cardiac Surgical Procedures / trends*
  • Dose-Response Relationship, Drug
  • Female
  • Heparin Antagonists / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Protamines / administration & dosage*
  • Single-Blind Method


  • Heparin Antagonists
  • Protamines