BACKGROUND

Recent concern about the safety of aprotinin administration to adults has led to its suspension from worldwide markets. However, few studies have examined its safety in pediatric patients. Studies in children evaluating aprotinin's safety have been hindered by the heterogeneity of pediatric patients and the inconsistency of clinical protocols. In this investigation, we retrospectively reviewed 200 neonatal cardiac surgical cases performed at our institution to examine the safety of aprotinin, focusing on postoperative renal dysfunction, using a consistent aprotinin dosing protocol.

METHODS

Two-hundred consecutive neonates scheduled for palliative or corrective congenital cardiac surgery requiring cardiopulmonary bypass (CPB) from January 1, 2005 through February 28, 2007 were included in this retrospective investigation. Preoperative, intraoperative and postoperative data were collected and analyzed. Markers of safety included 72-h postoperative renal dysfunction, need for dialysis (peritoneal or hemodialysis), thrombosis and in-hospital mortality.

RESULTS

Neonates were divided into those who received aprotinin (aprotinin group; n = 156) and those who did not (no aprotinin group; n = 44). Twenty-four and 72-h postoperative serum creatinine levels were significantly greater than baseline levels in both groups. The degree of change in creatinine levels was highly significant and similar between the two groups. A larger percentage of neonates in the aprotinin group developed renal dysfunction, although this difference was not statistically significant. Stepwise logistic regression, assessing the impact on renal dysfunction of all variables that indicated significance between neonates who did or did not receive aprotinin and between neonates who did or did not develop renal dysfunction, identified CPB time and age as significant predictors of postoperative renal dysfunction. All neonates who developed postoperative renal dysfunction had a CPB time of more than 100 min regardless of the use of aprotinin. Additionally, using this subset, similar percentages of renal dysfunction occurred in both groups. A second multivariable regression analysis to simultaneously account for the predictors of CPB time, age and aprotinin administration found CPB time to be the only significant predictor of renal dysfunction. Incidences of postoperative dialysis, postoperative thrombosis and in-hospital mortality were not statistically significantly different between the aprotinin and the no aprotinin groups.

CONCLUSION

The occurrence of postoperative renal dysfunction in neonates was more significantly predicted by the duration of CPB than by the intraoperative administration of aprotinin. CPB times of more than 100 min appeared to be a critical marker for the development of postoperative renal dysfunction. Randomized prospective trials are needed to confirm the validity of our retrospective findings.