Morphine intoxication by morphine-6-glucuronide, a pharmacologically active morphine metabolite, in chronic renal failure

History and admission findings:A 57-year-old woman with metastasizing ovarian cancer and chronic renal failure was admitted for morphine treatment of an acute lumbospinal pain syndrome, ambulant treatment with analgesics having failed provide adequate pain relief. On admission due to pain the concious patient presented with reduced general condition and lumbal pain sensitive to tapping. Lasegue's sign was positive on both sides, no other disturbed neurological functions were found. Treatment and course: On the 7(th) day of morphine administration she became somnolent and breathing became markedly depressed, indicating overdosage, metabolic and intracranial causes having been excluded. Naloxone, an opioid antagonist, was given i.v. and the:breathing pattern improved. But drowsiness continued for another 48 hours and only regressed after repeated doses of naloxone. Conclusions: Morphine-6-glucuronide (M6G), formed from morphine in the liver, accumulates in blood and penetrates the blood-brain barrier, binding with strong affinity to opiate receptors and exerts a strong analgesic effect. As M6G is excreted by the kidney, its concentration rises in renal failure and can lead to severe intoxication. Morphine dosage must therefore be carefully controlled in patients with renal failure.