HART: Systematic Evaluation of Protamine Doze in Cardiac Surgery

Sponsor

Lawson Health Research Institute (Other)

Overall Status

Unknown status

CT.gov ID

NCT03787641

Collaborator

(none)

100

Enrollment

Location

Arm

17.3

Anticipated Duration (Months)

5.8

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Cardiac Surgery With Cardiopulmonary Bypass	Drug: Protamine Sulfate	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Sysytematic Evaluation of Heparin and Protamine in Cardiac Surgery

Actual Study Start Date :

Sep 20, 2018

Anticipated Primary Completion Date :

Dec 31, 2019

Anticipated Study Completion Date :

Feb 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: 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.	Drug: 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.

Arm

Intervention/Treatment

Other: 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.

Drug: 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.

Outcome Measures

Primary Outcome Measures

Change in heparin activity [Duriing surgery (at baseline, before and after protamine adminitration following cardiopulmonary bypass). Samples will also be quantified at Intensive Care Unit (ICU) admission and 4 hours following ICU admission.]
The functional activity is ideally measured via its ability to accelerate the inhibition of activated coagulation enzymes IIa (thrombin) and Xa respectively. These tests are available commercially as ELISA kits. Briefly, an excess of coagulation factor IIa or Xa respectively is added to the sample and residual anti-IIa/Xa activity is quantified with a synthetic chromogenic substrate.
Change in Activated Clotting time (ACT) [Duriing surgery (at baseline, before and after protamine adminitration following cardiopulmonary bypass).]
ACT is the standard point of care test used in cardiac surgery. Blood is added to a tube containing predefined amount of coagulation accelerator (available commercially) and heparin activity is measured by prolongation or neutralization of ACT

Secondary Outcome Measures

Rationale for choosing a certain doze of protamine [During surgery. (Average cardiac surgery lasts for 4-6 hours)]
Anesthesiologists will undergo semi-structured face to face interviews and asked their rationale for choosing a certain doze of protamine

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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