Empirical Vancomycin Dosing in Pediatric Patients with Congenital Heart Disease and the Impact of Cardiopulmonary Bypass on Trough Concentrations.

Abstract

To determine the optimal vancomycin dosing regimen to achieve empirical goal trough concentrations in pediatric patients with congenital heart disease and to examine the impact of cardiopulmonary bypass on vancomycin dosing requirements. Patients younger than 18 years admitted to the pediatric cardiovascular intensive care unit (CVICU) at our institution from October 1, 2012-December 31, 2014, who received at least one dose of vancomycin, were reviewed retrospectively. Included patients had a steady-state vancomycin trough concentration drawn during the study period. The first steady-state vancomycin trough drawn after being initiated on empirical vancomycin therapy was analyzed for each patient. Excluded patients were those who received mechanical circulatory support, any form of renal replacement therapy, or had a serum creatinine result greater than 1.0 mg/dl on the day of vancomycin initiation. Overall, 77 patients met inclusion criteria, of which 57.1% had undergone cardiopulmonary bypass (CPB) before CVICU admission. Median age was 62 days (interquartile range [IQR] 8.3-176 days). Median daily vancomycin dose was 36.25 mg/kg/day (IQR 29-40 mg/kg/day), resulting in a median steady-state trough of 10.0 μg/ml (IQR 6.3-12.9 μg/ml). Therapeutic troughs occurred in 50.6% of patients; supratherapeutic and subtherapeutic concentrations were attained in 18.2% and 31.2% of patients, respectively. A subgroup analysis of patients who were post-CPB revealed that the only additional variable to affect vancomycin trough concentrations was aortic cross-clamp time (median 56 min, IQR 0-123.3 min, p=0.02). Empirical vancomycin dosing to achieve troughs of 8-15 μg/dl in patients with congenital heart disease without evidence of significant acute kidney injury should be 30 mg/kg/day for neonates, 35-40 mg/kg/day for infants, and 45 mg/kg/day in children, with adjustments required for patients with elevated creatinine or significant aortic cross-clamp time. The receipt and duration of CPB did not affect total daily vancomycin dose requirements.