title: The association of renal dysfunction and the use of aprotinin in patients undergoing congenital cardiac surgery requiring cardiopulmonary bypass.
abstract: BACKGROUND
  The use of large-dose aprotinin during cardiopulmonary bypass (CPB) in adult patients has been linked to postoperative renal dysfunction, but its effect on the pediatric population undergoing complex congenital cardiac operations is not well defined.
  
  
  METHODS
  We used a retrospective cohort analysis to evaluate children undergoing cardiac surgery requiring CPB between July 2004 and July 2006. Demographic data and surgical risk quantified by the Aristotle surgical complexity level were analyzed as covariates. Renal dysfunction was defined according to the RIFLE criteria, an international consensus classification which defines three grades of increasing severity of acute kidney injury: risk (Class R), injury (Class I), and failure (Class F) based on serum creatinine values. A univariate and multivariate logistic regression analysis and a propensity score were used to analyze the data. The propensity score was developed using pretreatment covariates associated with the administration of aprotinin. A multivariate logistic regression was then used with the propensity score and intraoperative measures as covariates. A P value <0.05 was considered statistically significant.
  
  
  RESULTS
  Among 395 patients who underwent cardiac surgery, 55% received aprotinin and 45% did not. Thirty-one percent of the cohort had previous cardiac surgery; 17% were neonates. According to the RIFLE criteria, 80 of the patients (20.3%) had acute kidney injury in the postoperative period; 53 (13.4%) had risk of renal dysfunction with 23 (5.8%) having injury and four patients (0.7%) having failure. Those receiving aprotinin had a higher incidence of previous cardiac surgery (54.1% vs 5%), sepsis (6.9% vs. 0.0%), heart failure (24.8% vs 12.4%), mechanical ventilation (25.2% vs 2.8%), or mechanical circulatory support (6.0% vs. 0.6%). More patients had an Aristotle level of 4 (26.6% vs 2.8%) and were treated with diuretics (63.8% vs 26.6%), angiotensin converting enzyme inhibitors (21.1% vs 7.9%), milrinone (25.7% vs 4.5%), and inotropic support (16.1% vs 2.3%). Although there was a significant difference in the unadjusted risk of renal dysfunction, adjustment with the preoperative propensity score revealed that there was no association between aprotinin and renal dysfunction (OR 1.32; 95% CI 0.55-3.19). The duration of CPB was the only independent variable associated with the development of renal dysfunction (OR 1.0; 95% CI 1.009-1.014).
  
  
  CONCLUSIONS
  Patients who receive aprotinin are more likely to present with preoperative risk factors for the development of postoperative renal dysfunction. However, when associated risk factors are properly considered, the use of aprotinin does not seem to be associated with a higher risk of developing renal dysfunction in the immediate postoperative period in children.
authors.affiliation: Department of Cardiovascular Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Manrique
authors.forename: Edmund H
authors.initials: EH
authors.lastname: Jooste
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Kuch
authors.forename: Steven E
authors.initials: SE
authors.lastname: Lichtenstein
authors.forename: Victor
authors.initials: V
authors.lastname: Morell
authors.forename: Ricardo
authors.initials: R
authors.lastname: Munoz
authors.forename: Demetrius
authors.initials: D
authors.lastname: Ellis
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Davis
mesh_terms: D007611:Aprotinin / Q000009:adverse effects / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006330:Heart Defects, Congenital / Q000188:drug therapy / Q000601:surgery*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D007611:Aprotinin