Codeine, Ultrarapid-Metabolism Genotype, and Postoperative Death

TLDR

A healthy 2‑year‑old boy with sleep apnea underwent elective adenotonsillectomy. Post‑operative pain was managed with intramuscular meperidine and dimenhydrinate, followed by oral codeine and acetaminophen every 4–6 hours. The child died the next day; postmortem revealed bronchopneumonia, codeine and morphine were detected, and CYP2D6 genotyping showed a functional duplication indicating ultrarapid metabolism.

Abstract

We report on the case of a healthy 2-year-old boy weighing 13 kg, with a history of snoring and sleep-study–confirmed sleep apnea, who under -went elective adenotonsillectomy. The outpatient surgery was uncomplicated, and 6 hours after sur -gery the boy received 10 mg of meperidine and 12.5 mg of dimenhydrinate intramuscularly and was sent home with instructions for 10 to 12.5 mg of codeine and 120 mg of acetaminophen syrup to be administered orally every 4 to 6 hours as needed. On the second evening after surgery, fever and wheezing developed in the child. At 9 a.m. the next day, the child’s vital signs were absent, and resuscitation efforts failed.Postmortem examination showed evidence of chronic tracheitis, aspiration of food particles, and bilateral consolidation in the lungs that was con-sistent with bronchopneumonia. Codeine (0.70 mg per liter) and morphine (32 ng per milliliter) were detected in the femoral blood by means of gas chromatography–mass spectrometry; there was no evidence of other drugs or metabolites. Cyto -chrome P-450 2D6 (CYP2D6) genotyping revealed functional duplication of the