We propose a comparison between between our standard ACT based heparin management protocol for children undergoing CPB and a patient-specific heparin concentration-based heparin management protocol. We hypothesize that a heparin concentration-based anticoagulation management protocol during CPB in children will result in more effective attenuation of hemostatic activation as reflected by decreased levels of thrombin formation and, untimately, better preservation of hemostasis postoperatively.

Condition	Intervention
Primary condition: Heart defects requiring surgery with CPB	Procedure: Method of heparin management during CPB

Further Study Details: 

Primary Outcomes: Amount of heparin used compared to heparin levels and ACTs
Secondary Outcomes: Transfusion requirements and patient bleeding postoperatively.
Expected Total Enrollment:  40

40 patients will be randomly assigned to either the traditional heparin management group or the intervention group. The traditional group will be treated with an initial heparin dose of 400 units/kg and the standard amount of heparin, as dictated by the circuit size, will be added to the CPB circuit prime. An ACT target value of 480 seconds will be maintained throughout the bypass period. Should the ACT fall below 480 seconds,additional boluses of 100 units/kg of heparin will be given until the ACT returns to the target value. At the end of CPB, heparin will be neutralized by the standard reversal of 4 mg/kg of protamine.

For the intervention group, a heparin dose (HDR) response assay will be performed prior to surgical incision by the Hepcon instrument. The hepcon machine performs a patient-specific HDR assay based on body surface area, and determines a projected heparin concentration required by that patient to achieve an ACT of 480 seconds. The HDR assay provides the initial dose of heparin to give the patient as well as the amount of heparin to be added to the CPB circuit. Additional heparin doses as determined by the hepcon instrument will be administered as needed if the patient''''s heparin concentration falls below the projected reference concentration. The hepcon insturment will also calculate the protamine dose needed to reverse heparin at the end of CPB.

For comparison between groups, an assay using the hepcon machine to measure whole blood heparin concentration and an ACT will be obtained for each patient at the following intervals: after the initial heparin dose, 30 minutes after the initiation of CPB, the start of rewarming and immediately prior to the discontinuation of CPB. A sample for anti-factor Xa activity will also be obtained at each of the above time intervals to validate the heparin concentration determined by the hepcon machine to a laboratory measured value. Blood samples for biochemical markers of hemostatic activation will be collected from all patients before the initiation of CPB after the adminstration of the initial heparin dose and after the conclusion of CPB before protamine infusion. The following biochemical markers of hemostatic activation will be measured: prothrombin fragment 1.2, fibrinopeptide A, free tissue factor pathway inhibitor, factor V, factor VIII, and beta-thromboglobulin. The following measures of clinical outcome will also be recorded: amount of blood products transfused after protamine administration, time between the administration of protamine to leaving the operating room, 24-hour chest tube drainage, first post-operative weight, time to extubation and duration of ICU stay.

Ages Eligible for Study:  up to  6 Months,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. Patients undergoing elective cardiac surgical procedures requiring CPB at Children''''s Healthcare of Atlanta at Egleston.
2. Patients less than 6 months old.
3. Parent/legal guardian willing to sign consent. -

Exclusion Criteria:

1. Patients presenting for emergency surgery.
2. Patients treated preoperatively with anticoagulant therapy.
3. Patients treated with antifibrinolytics during their cardiac surgery.
4. Parent/legal guardian unwilling or unable to sign consent. -

Please refer to this study by ClinicalTrials.gov identifier  NCT00146653

Nina A Guzzetta, MD      404.785.6672    nina_guzzetta@emoryhealthcare.org

Georgia
      Children''''s Healthcare of Atlanta at Egleston, Atlanta,  Georgia,  30322,  United States

Study chairs or principal investigators

James R Zaidan, MD,  Study Chair,  Emory University   

Study ID Numbers:  286-2005
Last Updated:  September 6, 2005
Record first received:  September 2, 2005
ClinicalTrials.gov Identifier:  NCT00146653
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-09-13