PICS: Heparin Antagonization by Protamine in Cardiac Surgery: Pharmacokinetic/Pharmacodynamic Study
Study Details
Study Description
Brief Summary
Protamine is currently used during cardiac surgery to neutralize unfractionated heparin (UFH) at the end of extra-corporeal circulation (ECC). The optimal dose of protamine is currently unknown, and the administration of protamine is done empirically.
Protamine and UFH pharmacokinetics are characterized by a large inter-individual variability. A dose of protamine proportional to the amount of UFH administrated during the surgery may be therefore not adapted to most of the patients and exposed them to a risk of under or over dosage.
In this study, research investigators hypothesize that an accurate characterization of the pharmacokinetic/pharmacodynamic (PK/PD) relationship of protamine may help to optimize propose an optimal dosing regimen.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| cardiac surgery with extracorporeal circulation during the operation Intervention Blood sample : - Choay Heparin (pharmacokinetic) concentration: t = 5, 15, 30 minutes after the start of the heparin injection + t = 5, 30, 60 minutes after the start of extracorporeal circulation protamine dosage: t = 2, 5, 8, 10 and 15 min after protamine injection anti-X activity t = 0 before administration and at time 2, 5, 8, 10 and 15 min then at time 1, 3, 5, 6 and 7 hours after protamine injection thrombin generation test (TGT) activity (thrombinography) : t = 2, 5, 8, 10 and 15 min after protamine injection |
Other: Blood samples PK/ PD protamine
PK/ PD protamine
|
Outcome Measures
Primary Outcome Measures
- PK/PD Protamine [1 day]
Pharmacokinetics (PK) : plasma concentration of protamine measured by liquid chromatography coupled with mass spectrometry. Pharmacodynamics (PD) :The effect of protamine corresponds to the kinetics of the disappearance of UFH in the blood. To do this, the investigators measure its concentration using an anti-Xa activity measurement technique.
Secondary Outcome Measures
- PK/PD Protamine [1 day]
PK: evolution of protamine concentrations over time (plasma concentration of protamine measured by liquid chromatography coupled with mass spectrometry). PD: ts neutralizing effect evaluated by thrombinography .
- postoperative blood loss: [1 day]
quantities of blood loss in pleural and mediastinal drains during the first 24 hours postoperatively.
- ratios between the amount of UFH present at the protamine injection and the dose of protamine administered. [1 day]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Patients benefiting from scheduled or emergency at the Saint-Etienne University Hospital (coronary artery bypass grafting, valve replacements, aortic dissections).
Exclusion Criteria:
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Patients with a contraindication to UFH
-
Patients with a contraindication to protamine
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Patients requiring early resurgery.
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Patients receiving an injection of antithrombin III.
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Pregnant women.
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Patient for whom aprotinin use is planned during surgery.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | CHU Saint-Etienne | Saint-Étienne | France | 42055 |
Sponsors and Collaborators
- Centre Hospitalier Universitaire de Saint Etienne
Investigators
- Principal Investigator: Julien LANOISELÉE, MD, CHU SAINT-ETIENNE
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 19CH046
- 2019-000859-14