Edmund H Jooste1, Rebecca Scholl2, Yi-Hung Wu3, Robert D B Jaquiss4, Andrew J Lodge5, Warwick A Ames2, H Mayumi Homi2, Kelly A Machovec2, Nathaniel H Greene2, Brian S Donahue6, Nirmish Shah7, Claudia Benkwitz8. 1. Pediatric Anesthesiology, Department of Anesthesiology, Duke University Medical Center, Durham, NC. Electronic address: edmund.jooste@dm.duke.edu. 2. Pediatric Anesthesiology, Department of Anesthesiology, Duke University Medical Center, Durham, NC. 3. Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC. 4. Department of Cardiovascular and Thoracic Surgery, UT Southwestern Medical Center and Children's Medical Center, Dallas, TX. 5. Division of Congenital Cardiac Surgery, Department of Cardiothoracic Surgery, Duke University Medical Center, Durham. 6. Division of Pediatric Cardiac Anesthesiology, Monroe Carell Jr Children's Hospital, Vanderbilt University Medical Center, Nashville, TN. 7. Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC. 8. Department of Anesthesia and Perioperative Care, UCSF Benioff Children's Hospital, San Francisco, CA.
Abstract
OBJECTIVES: To determine whether precardiopulmonary bypass (CPB) normalization of antithrombin levels in infants to 100% improves heparin sensitivity and anticoagulation during CPB and has beneficial effects into the postoperative period. DESIGN: Randomized, double-blinded, placebo-controlled prospective study. SETTING:Multicenter study performed in 2 academic hospitals. PARTICIPANTS: The study comprised 40 infants younger than 7 months with preoperative antithrombin levels <70% undergoing CPB surgery. INTERVENTIONS:Antithrombin levels were increased with exogenous antithrombin to 100% functional level intraoperatively before surgical incision. MEASUREMENTS AND MAIN RESULTS: Demographics, clinical variables, and blood samples were collected up to postoperative day 4. Higher first post-heparin activated clotting times (sec) were observed in the antithrombin group despite similar initial heparin dosing. There was an increase in heparin sensitivity in the antithrombin group. There was significantly lower 24-hour chest tube output (mL/kg) in the antithrombin group and lower overall blood product unit exposures in the antithrombin group as a whole. Functional antithrombin levels (%) were significantly higher in the treatment group versus placebo group until postoperative day 2. D-dimer was significantly lower in the antithrombin group than in the placebo group on postoperative day 4. CONCLUSION: Supplementation of antithrombin in infants with low antithrombin levels improves heparin sensitivity and anticoagulation during CPB without increased rates of bleeding or adverse events. Beneficial effects may be seen into the postoperative period, reflected by significantly less postoperative bleeding and exposure to blood products and reduced generation of D-dimers.
RCT Entities:
OBJECTIVES: To determine whether precardiopulmonary bypass (CPB) normalization of antithrombin levels in infants to 100% improves heparin sensitivity and anticoagulation during CPB and has beneficial effects into the postoperative period. DESIGN: Randomized, double-blinded, placebo-controlled prospective study. SETTING: Multicenter study performed in 2 academic hospitals. PARTICIPANTS: The study comprised 40 infants younger than 7 months with preoperative antithrombin levels <70% undergoing CPB surgery. INTERVENTIONS:Antithrombin levels were increased with exogenous antithrombin to 100% functional level intraoperatively before surgical incision. MEASUREMENTS AND MAIN RESULTS: Demographics, clinical variables, and blood samples were collected up to postoperative day 4. Higher first post-heparin activated clotting times (sec) were observed in the antithrombin group despite similar initial heparin dosing. There was an increase in heparin sensitivity in the antithrombin group. There was significantly lower 24-hour chest tube output (mL/kg) in the antithrombin group and lower overall blood product unit exposures in the antithrombin group as a whole. Functional antithrombin levels (%) were significantly higher in the treatment group versus placebo group until postoperative day 2. D-dimer was significantly lower in the antithrombin group than in the placebo group on postoperative day 4. CONCLUSION: Supplementation of antithrombin in infants with low antithrombin levels improves heparin sensitivity and anticoagulation during CPB without increased rates of bleeding or adverse events. Beneficial effects may be seen into the postoperative period, reflected by significantly less postoperative bleeding and exposure to blood products and reduced generation of D-dimers.