Morphine intoxication in renal failure: the role of morphine-6-glucuronide

Patients with impaired renal function may experience severe and prolonged respiratory depression when treated with morphine. This has been attributed to accumulation of the drug during renal failure. Three patients are described who had classical signs of intoxication with morphine in the absence of measurable quantities of morphine in the plasma. The observed clinical effect is attributed to accumulation of the pharmacologically active metabolite morphine-6-glucuronide, which is usually renally excreted. It is concluded that morphine does not accumulate in patients with renal failure but that accumulation of metabolites does occur. The previously reported observations of morphine accumulation during renal failure probably result from the use of radioimmunoassays that cannot distinguish between morphine and morphine-6-glucuronide. Thus the apparent morphine concentration measured with these assays in fact reflects the total quantity of morphine and morphine-6-glucuronide present.