title: Randomized, controlled trial of individualized heparin and protamine management in infants undergoing cardiac surgery with cardiopulmonary bypass.
abstract: OBJECTIVE
  We sought to determine whether infants (younger than 1 year old) had similar clinical benefits with individualized anticoagulation management as older children and adult undergoing cardiopulmonary bypass (CPB).
  
  
  BACKGROUND
  Individualized heparin and protamine management in older children and adults undergoing CPB has been associated with improved clinical outcomes.
  
  
  METHODS
  Ninety infants younger than 1 year of age undergoing CPB were enrolled in a randomized, controlled trial comparing weight-based anticoagulation management using activated clotting time (ACT) to individualized management with Hemostasis Management System Plus. Manufacturer's guidelines were followed for the first 33 patients. A modified protocol was used for the last 57 patients with adjustments for coagulation system immaturity and hemodilution on CPB.
  
  
  RESULTS
  The hemostasis management system (HMS) device consistently underestimated plasma anti-Xa levels, leading to an overestimated required heparin dose. After a blinded interim analysis revealed poor outcomes in the experimental HMS group using manufacturer guidelines, the safety committee suspended the study pending protocol modifications. The use of the HMS device following the modified protocol resulted in more stable anti-Xa levels during CPB with improved post-operative outcomes including reduced need for transfusions (71 ml/kg vs. 80 ml/kg; p = 0.003), ventilation time (33 h vs. 49 h; p = 0.04), intensive care (88 h vs. 99 h; p = 0.003), and hospital length of stay (192 h vs. 216 h; p < 0.001), compared with the weight-based protocol.
  
  
  CONCLUSIONS
  This study supports the use of the HMS device, with a modified protocol for infants younger than 1 year of age, for anticoagulation management during CPB. Clinical guidelines for the use of the HMS device should be modified for infants younger than 1 year of age.
authors.affiliation: Labatt Family Heart Centre, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. colleen.gruenwald@sickkids.ca
authors.forename: Colleen E
authors.initials: CE
authors.lastname: Gruenwald
authors.forename: Cedric
authors.initials: C
authors.lastname: Manlhiot
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Chan
authors.forename: Lynn
authors.initials: L
authors.lastname: Crawford-Lean
authors.forename: Celeste
authors.initials: C
authors.lastname: Foreman
authors.forename: Helen M
authors.initials: HM
authors.lastname: Holtby
authors.forename: Glen S
authors.initials: GS
authors.lastname: Van Arsdell
authors.forename: Ross
authors.initials: R
authors.lastname: Richards
authors.forename: Helen
authors.initials: H
authors.lastname: Moriarty
authors.forename: Brian W
authors.initials: BW
authors.lastname: McCrindle
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D005260:Female; D006488:Hemostasis, Surgical; D006493:Heparin / Q000627:therapeutic use*; D006494:Heparin Antagonists / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D011479:Protamines / Q000627:therapeutic use*; D016037:Single-Blind Method
chemical_list: D000925:Anticoagulants; D006494:Heparin Antagonists; D011479:Protamines; D006493:Heparin