title: High-dose aprotinin reduces activation of hemostasis, allogeneic blood requirement, and duration of postoperative ventilation in pediatric cardiac surgery.
abstract: BACKGROUND
  Though multiple studies have affirmed the effectiveness of aprotinin in reducing blood loss in adult cardiac surgery, the possible benefit in pediatric cardiac surgery is controversial.
  
  
  METHODS
  In a double-blind, randomized, and placebo-controlled study, the efficacy of aprotinin in attenuating the hemostatic and inflammatory activation during cardiopulmonary bypass in 60 patients weighing less than 10 kg was investigated. Secondary endpoints were the influence of aprotinin on the reduction of blood loss and allogeneic blood requirement, as well as postoperative oxygenation and length of mechanical ventilation. Aprotinin was administered in a high-dose of 3 x 10(4) KIU/kg plus a bolus of 5 x 10(5) KIU (not weight adjusted) added to the pump prime.
  
  
  RESULTS
  Aprotinin plasma concentration at the end of cardiopulmonary bypass (CPB) was with 184 +/- 45 KIU/mL, within the targeted range of 200 KIU/mL. Coagulation and fibrinolysis were suppressed (F1.2 1 hour after CPB: 5.35 +/- 2.9 nmol/L vs 14.5 +/- 23.1 nmol/L; D-dimer 1 hour after CPB: 0.63 +/- 0.6 ng/mL vs 2.3 +/- 3.1 ng/mL; p < 0.05), inflammatory markers (interleukin [IL]-6, IL-8, IL-10) increased over time without significant differences between the groups, and only complement C3a activation was significantly attenuated at the end of CPB in the aprotinin group. Chest tube drainage was significantly reduced (24 hours: median 13.5 [IQR 12.2] mL/kg vs 19.4 [8.2] mL/kg; p < 0.05). All patients received one unit of packed cells to prime the heart lung machine. A second unit was needed significantly less often in the aprotinin group (13% vs 47%; p < 0.05). Postoperative oxygenation (pO2/FIO2 172 [IQR 128] mm Hg vs 127 [74]; p < 0.05) improved, and the time on ventilator was shorter in the aprotinin group (median 45 hours [IQR 94] vs 101 [IQR 74]; p < 0.05). No side effects were attributable to the use of aprotinin.
  
  
  CONCLUSIONS
  High-dose aprotinin effectively attenuated hemostatic activation and reduced blood loss and transfusion requirement in pediatric cardiac surgery. Postoperative ventilation was also shortened in the aprotinin group.
authors.affiliation: Department of Anesthesiology, German Heart Center, Munich, Germany. moessinger@dhm.mhn.de
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Mössinger
authors.forename: Wulf
authors.initials: W
authors.lastname: Dietrich
authors.forename: Siegmund L
authors.initials: SL
authors.lastname: Braun
authors.forename: Marianne
authors.initials: M
authors.lastname: Jochum
authors.forename: Hans
authors.initials: H
authors.lastname: Meisner
authors.forename: Josef A
authors.initials: JA
authors.lastname: Richter
mesh_terms: D007611:Aprotinin / Q000008:administration & dosage* / Q000097:blood; D001803:Blood Transfusion; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D004311:Double-Blind Method; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis; D006330:Heart Defects, Congenital / Q000601:surgery*; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D007223:Infant; D007378:Interleukins / Q000097:blood; D010107:Oxygenators, Membrane; D011446:Prospective Studies; D012121:Respiration, Artificial; D013997:Time Factors
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D007378:Interleukins; C036309:fibrin fragment D; D007611:Aprotinin