Safety of aprotinin in congenital heart operations: results from a large multicenter database

Background: Aprotinin was used frequently in children undergoing congenital heart operations with the aim of reducing bleeding, until it was taken off the market after adult studies reported increased renal failure and death. We evaluated the safety of aprotinin in a large multicenter cohort of children undergoing congenital heart operations.

Methods: The Pediatric Health Information Systems Database was used to evaluate aprotinin in children (aged 0 to 18 years) undergoing congenital heart operations at 35 children's hospitals from 2003 to 2007. Propensity scores were constructed to account for potential confounders of age, sex, race, prematurity, genetic syndrome, type of operation (Risk Adjustment in Congenital Heart Surgery-1 category), center, and center volume. Multivariable analysis, adjusting for propensity score and individual covariates was performed to evaluate in-hospital mortality, postoperative renal failure requiring dialysis, and length of stay. Subanalysis was performed in the high-risk cohort undergoing reoperation.

Results: The study included 30,372 patients (56% male) who were a median age of 7 months (interquartile range, 36 days to 3.2 years). Overall, 44% received aprotinin. Multivariable analysis found no difference in postoperative mortality (odds ratio, 1.00; 95% confidence interval [CI], 0.99 to 1.01), dialysis (odds ratio, 1.00; 95% CI, 0.99 to 1.01), or length of stay (least square mean difference, -0.44 days; 95% CI, -1.01 to 0.13) between aprotinin recipients and nonrecipients. No difference was found in mortality or dialysis in patients undergoing reoperation. Aprotinin recipients in the reoperation subgroup had significantly reduced length of stay (least square mean difference, -2.05 days; 95% CI -3.29 to -0.81),

Conclusions: These data suggest aprotinin is not associated with increased mortality or dialysis in children undergoing congenital heart operations and that further evaluation of aprotinin in this population could be undertaken without undue risk.