Effect of exchange transfusion on elimination of theophylline in premature neonates

Abstract

THEOPHYLLINE has been recently introduced as a treatment for apnea in premature newborn infants. Preliminary studies have revealed that in premature neonates theophylline disposition differs from that in older infants? The number of reported cases, however, is too few, and the range of pathologic conditions which may occur is too brcad to allow general deductions which could confidently be applied in clinical practice. In this study we were interested in the measurements of blood theophylline concentrations in three premature newborn infants before and after exchange transfusions. Microsamples of blood (200 to 300 t~l) were collected for theophylline assay from the umbilical artery in hepa- rinized test tubes before and 15 minutes after the exchange transfusion; all of the blood exchanged was also collected for determination of total blood theophylline. Theophylline blood levels were measured by a recently developed micromethod that consisted of a single step extraction at pH 6.0 in chloroform, evaporation, and determination of the underivatized drug on a gas-liquid chromatographic apparatus equipped with an OV-17 column and a nitrogen-phosphorus selective detector. =' The total amount of the drug cleared from the body during the procedure was calculated as the difference of the amount of theophylline in the body after transfusion substracted from that which was present before. The total amount (A,,) of theophylline in the body was calculated using the expression of Gibaldi and associates, '~ A,, = C  V~/~, where C (blood concentration) was measured and Vda was assumed to be 0.69 l/kg as reported by Aranda and associates :~ for the premature neonate. RESULTS The blood levels of theophylline before and after the exchange transfusion and the total amount exchanged are shown in Table I. Neonates 1 and 2, who had received 1 and 4 doses, respectively, had much lower theophylline blood levels than neonate 3 who had been treated for four days; it appears that the drug accumulates at this dosage schedule. The percentage of drug exchanged by the procedure ranged from 16.9 to 29.9; this is similar to the percentage estimated on theoretical calculations as being cleared from the body.