title: Contribution of morphine and morphine-6-glucuronide to respiratory depression in a child.
abstract: A morphine plasma concentration/respiratory rate relationship has been described for both adults and children although that of its metabolite, morphine-6-glucuronide, remains uncertain. We describe this relationship in a child with end-stage renal failure who received repeat morphine administration over two days. An EMAX model for additive morphine and morphine-6-glucuronide respiratory effects described respiratory rate better than models describing either alone. Failure to clear morphine-6-glucuronide renally led to respiratory depression episodes occurring later than those predicted by modelling morphine levels only. These findings support the use of alternative analgesics (e.g. fentanyl) that are cleared by non-renal pathways and have no active metabolites in patients with end-stage renal disease.
authors.affiliation: Department of Anaesthesiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. j.hannam@auckland.ac.nz
authors.forename: J A
authors.initials: JA
authors.lastname: Hannam
authors.forename: B J
authors.initials: BJ
authors.lastname: Anderson
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D002648:Child; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009020:Morphine / Q000009:adverse effects* / Q000493:pharmacokinetics; D009022:Morphine Derivatives / Q000009:adverse effects*; D012119:Respiration / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine