Riboflavin to treat nucleoside analogue-induced lactic acidosis

Abstract

Fetal blood was obtained by transabdominal cardiac puncture. In each case, a detailed transvaginal ultrasound was done to confirm gestational age and to assess spontaneous and reflex fetal movements. Written consent was obtained from each woman after receiving complete information on the procedure. This study was approved by the University College London Hospitals Committee on the Ethics of Human Research. The fetal samples were collected between 5 and 20 min following intravenous (IV) administration of a bolus of 3 mg/kg of propofol (Diprivan 1%, Zeneca, Macclesfield, UK) to the mother. Peripheral maternal venous blood was collected simultaneously. Anaesthesia was maintained by spontaneous breathing of 70% nitrous oxide with 0·5–1% isoflurane in oxygen via a laryngeal mask. The propofol concentration was determined by high-performance liquid chromatography with fluorescence. The method has a lower limit of sensitivity of 0·1 g/mL and the intra-assay and interassay coefficients of variation were both 5%. No spontaneous fetal movements or reflux responses were observed in any case during the time interval between induction of anaesthesia and the surgical procedure or during the sampling procedure. Propofol was detected in all maternal and fetal serum samples. No propofol was found in coelomic or amniotic fluid samples at any stage of gestation. Propofol concentration decreased exponentially with time in both maternal (r=0·73, p<0·0001) and fetal (r=0·58, p<0·0001) serum. Maternal serum concentration of propofol was always higher than fetal serum concentration. In 14 matched samples, the mean propofol concentration was 1·96 g/mL (95% CI 1·49–2·42) in maternal serum and 0·90 g/mL (95% CI 0·68–1·11) in fetal serum. Over the 20 min interval between injection and sampling, little change was observed in the fetal/maternal propofol concentration ratio. This finding can be explained by the fact that propofol binds 97–98% to albumin, which is in much lower concentration in fetal serum during the first half of pregnancy. Overall, the pharmacodynamics of propofol found in pregnant women at 12–18 weeks of gestation are similar to those described at term 1–3 indicating that our data can be extrapolated to the period of gestation between 24 and 37 weeks and that our model can be used to study the placental transfer of other analgesic drugs in early pregnancy. Propofol has no known teratogenic effect in humans and our results also indicate that, during short maternal general