Commonly prescribed opioids pose serious risks to hemodialysis (HD) patients, even at lower doses and within guideline recommendations, according to a new study.

Of 140,899 HD patients (median age 61 years, 52% men, 50% white) in the US Renal Data System database, 64% received opioids and 23% had at least 1 high-dose prescription, Julie Ishida, MD, of the University of California, San Francisco, and her colleagues reported in the Clinical Journal of the American Society of Nephrology. Among patients taking the analgesics, 11%, 5%, and 3% experienced an episode of altered mental status, fall, and fracture, respectively.

These hazards increased along with opioid dose. From periods of lower to higher use, the risks increased from 28% to 67% for altered mental status, from 28% to 45% for fall, and from 44% to 65% for fracture compared with no use of opioids.

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Investigators converted doses of all of the pain relievers to their morphine equivalent, with 60 mg as the cutoff between lower and higher use. Each 60-mg increment in opioid dose was associated with 29%, 4%, and 4% higher risks for altered mental status, fall, and fracture, respectively.

By specific medication, the investigators found a significantly higher risk for altered mental status with all agents. Hydromorphone, hydrocodone, oxycodone, and tramadol were linked with a significantly higher risk of falls. The same drugs and codeine were associated with a significantly higher risk for fracture. In all of the analyses, the researchers adjusted for demographics, comorbidities, medication burden, and concomitant medications with the same adverse effects, such as sedatives and hypnotics.

HD patients often experience pain, and they may be more susceptible to opioid-related complications due to multiple comorbidities, polypharmacy, uremia, and reduced renal clearance of active drug metabolites, according to background information provided by the authors.

Dr Ishida’s team noted that guidelines on opioid use in HD have been based on limited evidence. Most guidelines advise against prescribing morphine and codeine. Hydrocodone, oxycodone, and tramadol should be “used with caution.” Fentanyl, methadone, and hydromorphone are considered safer choices. In the current study, codeine was overprescribed. Fentanyl, methadone, and hydromorphone were underprescribed.

“Thus, opioid use in patients on hemodialysis may not be as safe as guidelines suggest, and the benefit-to-risk ratio of their use in this population should be carefully considered,” Dr Ishida and her colleagues concluded. “Future research and strategies to predict and mitigate the risks of opioid use in patients on hemodialysis are warranted.”

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Ishida JH, McCulloch CE, Steinman MA, Grimes BA, and Johansen KL. Opioid analgesics and adverse outcomes among hemodialysis patients. Clin J Am Soc Nephrol. doi:10.2215/CJN.09910917