PHARMACOKINETICS OF VANCOMYCIN IN CRITICALLY ILL INFANTS UNDERGOING EXTRACORPOREAL MEMBRANE-OXYGENATION

Extracorporeal membrane oxygenation (ECMO) is a widely used therapy fo r neonates with respiratory failure. Because of sepsis, many of these infants require antibiotics like vancomycin during ECMO treatment. ECM O transiently alters renal function and increases the circulating bloo d volume by 75%. Initial vancomycin pharmacokinetics were determined i n 12 infants undergoing ECMO to determine an adequate drug administrat ion regimen. Vancomycin dosage was based on current recommendations fo r weight and gestational age. Pharmacokinetic parameters were determin ed by fitting the data to a two compartment model. This study yielded a mean steady-state volume of distribution of 1.1 +/- 0.5 (range, 0.6 to 2.1) liters/kg and a mean vancomycin clearance of 0.78 +/- 0.19 (ra nge, 0.49 to 1.07) ml/min/kg. The mean vancomycin half-life was 16.9 /- 9.5 (range, 8.8 to 42.9) h. Nomogram-calculated creatinine clearanc e was a significant predictor of vancomycin terminal rate constant and clearance. These data suggest alterations in the pharmacokinetics of vancomycin in infants on ECMO. With the goal of achieving vancomycin c oncentrations in serum above the MIC for the offending pathogen while using the least amount of the drug necessary, new administration guide lines for term infants without renal impairment undergoing ECMO should be 20 mg of vancomycin per kg at an interval of 24 h. With significan t renal impairment, the interval should be extended on the basis of co ncentrations in serum. In comparison with previously published data, t he neonates undergoing ECMO in our study demonstrated a much larger vo lume of distribution, a lower clearance, and consequently a longer van comycin half-life.