title: More codeine fatalities after tonsillectomy in North American children.
abstract: In 2009 we reported the fatal case of a toddler who had received codeine after adenotonsillectomy for obstructive sleep apnea syndrome. The child was an ultra-rapid metabolizer of cytochrome P4502D6 (CYP2D6). We now report 3 additional fatal or life-threatening cases from North America. In the 2 fatal cases, functional gene duplications encoding for CYP2D6 caused a significantly greater production of potent morphine from its parent drug, codeine. A severe case of respiratory depression in an extensive metabolizer is also noted. These cases demonstrate that analgesia with codeine or other opioids that use the CYP2D6 pathway after adenotonsillectomy may not be safe in young children with obstructive sleep apnea syndrome.
authors.affiliation: Schulich School of Medicine, University of Western Ontario, London, Canada.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Kelly
authors.forename: Michael
authors.initials: M
authors.lastname: Rieder
authors.forename: John
authors.initials: J
authors.lastname: van den Anker
authors.forename: Becky
authors.initials: B
authors.lastname: Malkin
authors.forename: Colin
authors.initials: C
authors.lastname: Ross
authors.forename: Michael N
authors.initials: MN
authors.lastname: Neely
authors.forename: Bruce
authors.initials: B
authors.lastname: Carleton
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Parvaz
authors.initials: P
authors.lastname: Madadi
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
mesh_terms: D000233:Adenoidectomy / Q000401:mortality*; D000483:Alleles; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D001996:Bronchopneumonia / Q000139:chemically induced / Q000401:mortality; D002675:Child, Preschool; D003061:Codeine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D020440:Gene Duplication / Q000235:genetics; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000235:genetics; D009020:Morphine / Q000493:pharmacokinetics / Q000633:toxicity; D011183:Postoperative Complications / Q000139:chemically induced* / Q000401:mortality*; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000601:surgery*; D014068:Tonsillectomy / Q000401:mortality*
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D019389:Cytochrome P-450 CYP2D6; D003061:Codeine