Inter-individual variation in morphine clearance in children

OBJECTIVES: The aim of the study was to determine the extent of inter-individual variation in clearance of intravenous morphine in children and to establish which factors are responsible for this variation. METHODS: A systematic literature review was performed to identify papers describing the clearance of morphine in children. The following databases were searched: Medline, Embase, International Pharmaceutical Abstracts, CINAHL, and Cochrane library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined. RESULTS: Twenty-eight studies were identified. After quality assessment, 20 studies were included. Only 10 studies gave clearance values for individual patients. The majority of the studies were in critically ill patients. Inter-individual variability of morphine clearance was observed in all age groups, but greatest in critically ill neonates (both preterm and term) and infants. In critically ill patients, the CV was 16–9 7 % in preterm neonates, 24–87 % in term neonates, 35 and 134 % in infants, 39 and 55 % in children, and 74 % in adolescents. The CV was 37 and 44 % respectively in non-critically ill neonates and infants. The mean clearance was higher in children (32 and 52 ml min(-1) kg(-1)) than in neonates (2 to 16 ml min(-1) kg(-1)). CONCLUSIONS: Large inter-individual variation was seen in morphine clearance values in critically ill neonates and infants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00228-015-1843-x) contains supplementary material, which is available to authorized users.