Abstract

Previous work from our group has reported that the volume of distribution is increased in neonates with sepsis (Lingvall et al, 2005). Our aim was to determine the effect of various intravenous volume expanders administered to neonates with suspected sepsis on the volume of distribution of gentamicin. A case–control study of 1 : 3 septic versus non-septic infants was undertaken with 29 confirmed septic neonates. Controls were matched by gestational age and sex. Data were collected for any intravenous fluids that were known volume expanders including those administered via intravenous bolus and also via continuous intravenous infusion. A pharmacokinetic analysis was performed using NONMEM, version 5. A one compartment first order elimination model was developed. The covariates investigated included cumulative continuous infusion fluid volume, cumulative bolus fluid received and total intravenous fluid administration per patient. The base model estimated clearance of 0.086 l/h and volume of distribution of 1.14 litres, which is consistent with reported literature values. No improvement to the model was seen when the intravenous fluid covariates were included. The final covariate model was: clearance 1.21 l/h per 70 kg, volume of distribution 31.2 litres per 70 kg + 0.152 (sepsis). Previous studies have reported that the increased administration of intravenous fluids to septic patients affects the volume of distribution of drugs. In this study, none of the covariates associated with the intravenous volume expanders improved the pharmacokinetic model, suggesting that those volume expanders do not affect the volume of distribution of gentamicin in this group of septic neonates.