Estimation of infant dose and exposure to pethidine and norpethidine via breastmilk following patient-controlled epidural pethidine for analgesia post caesarean delivery

Introduction: There is no information about the distribution of pethidine into breastmilk and/or of exposure of the breastfed infant after patient controlled epidural analgesia (PCEA) with pethidine after caesarean delivery. Methods: We conducted an observational study among 20 women receiving pethidine PCEA after elective caesarean delivery. The mean (95% confidence interval) dose administered was 670 (346-818) mg over 41(35-46) hours. Maternal plasma and milk and neonatal plasma were collected around the time of PCEA cessation (approximately 48 hours from time of operation) and six hours later. Drug concentrations measured by liquid chromatography-tandem mass spectrometry. Absolute infant dose (AID) was calculated from the milk concentration of pethidine and norpethidine and the calculated daily milk volume. Relative infant dose (RID) was derived from the AID divided by the weight-adjusted maternal dose of pethidine used until cessation of PCEA. Infant doses via milk and infant exposure were calculated. Infant neurobehaviour was assessed using the Neonatal and Adaptive Capacity Score (NACS). Results: At the first and second sampling times, mean AIDs for pethidine were 20(14-27) μg/kg/d and 10(7-13) μg/kg/d, while mean RIDs were 0.7 (0.1-1.4) % and 0.3(0.1-0.5) % respectively.