title: Differential effects of aprotinin and tranexamic acid on outcomes and cytokine profiles in neonates undergoing cardiac surgery.
abstract: OBJECTIVE
  Factors contributing to postoperative complications include blood loss and a heightened inflammatory response. The objective of this study was to test the hypothesis that aprotinin would decrease perioperative blood product use, reduce biomarkers of inflammation, and result in improved clinical outcome parameters in neonates undergoing cardiac operations.
  
  
  METHODS
  This was a secondary retrospective analysis of a clinical trial whereby neonates undergoing cardiac surgery received either aprotinin (n = 34; before May 2008) or tranexamic acid (n = 42; after May 2008). Perioperative blood product use, clinical course, and measurements of cytokines were compared.
  
  
  RESULTS
  Use of perioperative red blood cells, cryoprecipitate, and platelets was reduced in neonates receiving aprotinin compared with tranexamic acid (P < .05). Recombinant activated factor VII use (2/34 [6%] vs 18/42 [43%]; P < .001), delayed sternal closure (12/34 [35%] vs 26/42 [62%]; P = .02), and inotropic requirements at 24 and 36 hours (P < .05) were also reduced in the aprotinin group. Median duration of mechanical ventilation was reduced compared with tranexamic acid: 2.9 days (interquartile range: 1.7-5.1 days) versus 4.2 days (2.9-5.2 days), P = .04. Production of tumor necrosis factor and interleukin-2 activation were attenuated in the aprotinin group at 24 hours postoperatively. No differential effects on renal function were seen between agents.
  
  
  CONCLUSIONS
  Aprotinin, compared with tranexamic acid, was associated with reduced perioperative blood product use, improved early indices of postoperative recovery, and attenuated indices of cytokine activation, without early adverse effects. These findings suggest that aprotinin may have unique effects in the context of neonatal cardiac surgery and challenge contentions that antifibrinolytics are equivalent with respect to early postoperative outcomes.
authors.affiliation: Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA. grahamem@musc.edu
authors.forename: Eric M
authors.initials: EM
authors.lastname: Graham
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Atz
authors.forename: Jenna
authors.initials: J
authors.lastname: Gillis
authors.forename: Stacia M
authors.initials: SM
authors.lastname: Desantis
authors.forename: A Lauren
authors.initials: AL
authors.lastname: Haney
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Deardorff
authors.forename: Walter E
authors.initials: WE
authors.lastname: Uber
authors.forename: Scott T
authors.initials: ST
authors.lastname: Reeves
authors.forename: Francis X
authors.initials: FX
authors.lastname: McGowan
authors.forename: Scott M
authors.initials: SM
authors.lastname: Bradley
authors.forename: Francis G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000933:Antifibrinolytic Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D007611:Aprotinin / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use*; D016063:Blood Loss, Surgical / Q000401:mortality / Q000517:prevention & control*; D006348:Cardiac Surgical Procedures / Q000009:adverse effects / Q000401:mortality; D016009:Chi-Square Distribution; D016207:Cytokines / Q000097:blood*; D017707:Erythrocyte Transfusion; D015942:Factor VIIa / Q000627:therapeutic use; D005260:Female; D006330:Heart Defects, Congenital / Q000191:economics / Q000401:mortality / Q000601:surgery*; D017722:Hospital Charges; D006801:Humans; D007231:Infant, Newborn; D018836:Inflammation Mediators / Q000097:blood*; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D017713:Platelet Transfusion; D019106:Postoperative Hemorrhage / Q000097:blood / Q000191:economics / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012121:Respiration, Artificial; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013022:South Carolina; D013997:Time Factors; D014148:Tranexamic Acid / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000933:Antifibrinolytic Agents; D016207:Cytokines; C508594:IL2 protein, human; D018836:Inflammation Mediators; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014148:Tranexamic Acid; D007611:Aprotinin; C103587:recombinant FVIIa; D015942:Factor VIIa
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