Systematic Evaluation of Protamine Doze in Cardiac Surgery

NCT ID: NCT03787641

Last Updated: 2018-12-31

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-20
• Study Completion Date: 2020-02-28

Brief Summary

The precise amount of protamine required to neutralize unfractionated heparin (UFH) remains unknown. This study will systematically identify the doze needed to neutralize UFH following cardiopulmonary bypass (CPB).

Detailed Description

The precise dose of protamine needed to neutralize unfractionated heparin (UFH) is unknown. Research suggests that low dose protamine is associated with decreased need for transfusions in cardiac surgery. The ATS guidelines recommend that half of the total UFH dose given for cardiopulmonary bypass (CPB) should be neutralized with protamine. However, it is unknown if this is routinely followed by anesthesiologists. Furthermore, the reference standard for UFH has changed recently and it is unknown how this has affected the dose of protamine in the perioperative period. Protamine does have a very short life and heparin rebound occurs very commonly.

It is common practice to divert the suctioned mediastinal blood following CPB while the patient is still anticoagulated. The traditional practice is that once half dose protamine has been given, suction to the cardiotomy reservoir is turned off. All surgical field blood loss is then diverted to wall suction. The inherent risk of letting too much protamine into the CPB reservoir is that UFH therein may get neutralized and predispose to clot formation in the venous reservoir. This precludes an emergency 'crash' on to CPB, should that be required for some reason. Experience of the Investigators indicates that most surgeons will turn off suction leading to the cardiotomy reservoir once half the total protamine dose has been administered. The concern with this is that "half dose" protamine may be quite different for different anesthesiologists.

The research investigators hypothesize low dose protamine is sufficient to neutralize the effects of UFH as monitored through activated clotting time (ACT). Anesthesiologists administer varying doses of protamine to neutralize UFH in cardiac surgery and the rationale behind such decisions is unclear.

Thus, the primary objective of this study is to evaluate the dose of protamine required to neutralize UFH following CPB. Secondary objectives are 1) to assess the amount of protamine needed to neutralize UFH in intravenously administered cardiotomy reservoir blood. 2) To examine the amount of residual heparin postoperatively in the cardiac surgery ICU; 3) to examine, through semi-structured interviews, the decision-making processes involved in managing (anti)coagulation in cardiac surgery.

Conditions

Cardiac Surgery With Cardiopulmonary Bypass

Keywords

cardiopulmonary bypass; heparin; protamine; anti-IIa assay; anti-Xa assay; activated clotting time

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Protamine doze

Protamine Sulfate will be administered through an infusion pump in aliquots at a predefined rate (25 mg/min). Blood samples will be withdrawn after each aliquot and quantified for anti-Xa, IIa and ACT.

Group Type: OTHER

Protamine Sulfate

Intervention Type: DRUG

Protamine Sulfate will be administered via an infusion pump to administer a 50 mg test doze, then 100 mg after 5 min waiting period. Following blood samples, additional alliquots of 50 mg will be measured to a maximum of 300 mg.

Interventions

Protamine Sulfate

Protamine Sulfate will be administered via an infusion pump to administer a 50 mg test doze, then 100 mg after 5 min waiting period. Following blood samples, additional alliquots of 50 mg will be measured to a maximum of 300 mg.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Elective cardiac surgery patients > 18 years age who can provide written consent for the study.

Exclusion Criteria

• History of any known coagulopathies, liver dysfunction, previous cardiac surgery, preoperative abnormal coagulation profiles, recent exposure to heparin (unfractionated or low molecular weight), warfarin, clopidogrel or other direct thrombin inhibitors in the preceding 7 days.
• History of heparin resistance
• History of adverse reactions to protamine
• Patients identified as having heparin resistance
• Anticipated CPB time > 2-2.5 hrs

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

OTHER

Sponsor Role: lead

Responsible Party

Ravi Taneja

Associate Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

London Health Sciences Centre

London, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Ravi Taneja, FRCPC

Role: CONTACT

Phone: 5196858500

Email: Ravi.Taneja@lhsc.on.ca

Facility Contacts

Ravi Taneja, FRCPC

Role: primary

References

Taneja R, Szoke DJ, Hynes Z, Jones PM. Minimum protamine dose required to neutralize heparin in cardiac surgery: a single-centre, prospective, observational cohort study. Can J Anaesth. 2023 Feb;70(2):219-227. doi: 10.1007/s12630-022-02364-4. Epub 2022 Dec 5.

Reference Type: DERIVED

PMID: 36471142 (View on PubMed)

Other Identifiers

107681

Identifier Type: -

Identifier Source: org_study_id