Unexpected urine drug testing results in a hospice patient on high-dose morphine therapy.

CASE DESCRIPTION A 41-year-old African-American woman was admitted to an inpatient hospice facility with advanced, inoperable cervical cancer. The patient was experiencing severe pain secondary to extensive local tumor invasion, osseous pelvic metastases, and sacral decubitus ulcers. Her pain was treated with an escalating-dose schedule of morphine sulfate until satisfactory analgesia was achieved with stable doses of a combination of controlled-release morphine sulfate (MSContin , Purdue Pharma LP) 400 mg orally every 8 h, and immediate-release morphine sulfate (MSIR , Purdue Pharma LP), 180 mg orally every 4 h, as needed for breakthrough pain (average 2 to 3 doses per day). The patient experienced several episodes of lifethreatening vaginal bleeding for which she was hospitalized for red blood cell transfusions and bilateral hypogastric artery embolizations. She spent the final 12 weeks of her life exclusively on the inpatient hospice unit. Approximately 3 weeks before her death, the patient underwent urine specimen collection and analysis of morphine and metabolites. GC-MS analysis revealed the presence of morphine as well as small quantities of hydromorphone. DISCUSSION During the past 2 decades, chronic opioid analgesic therapy (COAT) for chronic nonmalignant pain has gained increasing clinical acceptance. An unintended consequence of more liberal opioid prescription practices has been a dramatic increase in the abuse and diversion of these drugs. According the most recent National Survey on Drug Abuse and Health (1 ), the number of new, pastyear abusers of prescription opioids was 2 147 000 — more than the number of new abusers of any other single class of prescription or illicit drugs. Furthermore, most of these opioids originated with valid physician prescriptions. By 2002, prescription opioids surpassed cocaine and heroin as the leading cause of drug poisoning reported on death certificates (2 ). This potential for opioid abuse and diversion is a concern for physicians who prescribe these drugs. Consequently, urine drug testing is becoming an increasingly common part of the management plan of patients treated with COAT for chronic pain. Knowledge of opioid metabolism is critical to the correct interpretation of opioid-positive urine drug tests in patients on COAT. Several prescription opioids produce metabolites that are themselves prescription opioids, so the presence of a metabolite in the urine may reflect either the in vivo conversion of the prescribed opioid or the unauthorized use of a second opioid (Figure 1). Alternatively, some drugs, such as heroin, are not detectable in urine owing to their rapid metabolism; heroin administration is determined solely by the detection of metabolites, 6-acetylmorphine and morphine. Because the presence of metabolites can be interpreted as unauthorized use of prescription opioids and may result in punitive actions, including loss of opioid privileges and dismissal from medical practice, it is essential that clinicians correctly interpret urine drug-testing results. Surveys of physicians who order urine drug tests in their patients on COAT reveal, however, that relatively few clinicians are aware of these metabolic conversions (3 ). The most prevalent morphine metabolites of opioid analgesics include the UGT2B7-catalyzed, pharmacologically active 3and 6-glucuronides, with several inactive metabolites occurring in smaller quantities. The possible metabolism of morphine to hydromorDepartments of 1 Community Health and Family Medicine; and 4 Pathology, University of Florida Health Science Center, Jacksonville, FL; 2 Department of Pathology, Immunology, and Laboratory Medicine; and 3 Department of Psychiatry, University of Florida College of Medicine, Gainesville, FL. * Address correspondence to this author at: Department of Pathology, University of Florida Health Science Center/Jacksonville, 655 West 8th Street, Jacksonville, FL 32209. Fax 904-244-4290; e-mail [email protected]. Received December 18, 2008; accepted February 27, 2009. DOI: 10.1373/clinchem.2008.122754 CONSIDER