Prolonged central apnoea after intravenous morphine administration in a 12 ‐year‐old male with a UGT1A1 loss‐of‐function polymorphism

Adverse eventRepeated and prolonged episodes of central apnoea and hypoxia after receiving intravenous morphine for analgesia and ketamine for sedation.Drug implicatedIntravenous morphine sulfate.The patientPreviously healthy 12 ‐year‐old male with no history of sleep apnoea who presented with distal tibia and fibula fracture.Evidence that links drug to eventPharmacogenomic testing revealed that the patient was homozygous for the T allele at the rs887829 SNP inUGT1A1, an enzyme involved in the metabolism of morphine. This polymorphism is a loss ‐of‐function variant, leading to impaired metabolism of morphine.MechanismMorphine is metabolized by UDP ‐glucuronosyltransferase (UGT)‐2B7 and UGT1A1 to form its major metabolites morphine‐3‐glucuronide (M3G) and morphine‐6‐glucuronide (M6G). Our patient was a poor metabolizer through UGT1A1, likely leading to increased respiratory depression as morphine has greater respiratory depressant effects compared to its metabolites.ImplicationsWhen appropriate, physicians should enquire about prior receipt of opioids, in both the patient and family, to be better prepared for potential adverse reactions. In the patient with excessive sedation or respiratory depression to standard doses of morphine, genetic testing may be warranted, especially if there is a family or past history that supports a metabolic defect in morphine metabolism and/or excretion.

Source: British Journal of Clinical Pharmacology - November 12, 2018 Category: Drugs & Pharmacology Authors: Michael S. Toce, Hyun Kim, Sarita Chung, Baruch S. Krauss Tags: CASE REPORT Source Type: research