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Opioids: Renal failure

Analgesia in patients with renal disease and who require opioids has obvious risks and prescribing their use in this population should be performed with caution. The list below show the common opioids used.

Typically Avoided:

Codeine: Metabolized by the liver to codeine-6-glucuronide (81%), norcodeine (2%), morphine (0.6%), M3G (2%), M6G (0.8%) and morphine (2.4%). Morphine and morphine-6-glucuronide are considered the active metabolites. Inadequate excretion can lead to potential respiratory depression, hypotension, and narcolepsy.

Morphine: Metabolized to normorphine (4%), morphine-3-glucuronide (55%) and an active metabolite morphine-6-glucuronide (10%) by the liver. All three are ultimately excreted by the kidneys. M6G can accumulate and cause respiratory depression, hypotension, and narcolepsy.

Hydrocodone: Parent drug and active metabolite can accumulate in Renal Failure. Metabolized to hydromorphone. This can eventually lead to hydromorhpone-3-glucuronide, which can lead to possible neuroexcitatory effects (agitation, confusion, and hallucinations).

Meperidine: Active metabolite (normeperidine) can accumulate in renal disease and can decrease the seizure threshold.

Often Used with Caution:

Oxycodone: Metabolized by the liver with metabolites being excreted by the kidneys. 10% of the parent drug is excreted unchanged by the Kidneys. Oxymorphone is the active metabolite however plasma levels are usually negligible.

Hydromorphone: Metabolized by the liver and produces an active metabolite is hydromorphone-3-glucuronide (36.8%) . This metabolite can accumulate and cause neuroexcitatory effects. Currently thought to have no analgesic properties.

Typically used:

Fentanyl, sufentanil and alfentanil are metabolized by the liver without any active metabolites.

Methadone: Fecal (10-45%) and urine excretion (20-50%) without any active metabolite. Methadone is generally considered as a safe opioid to use in kidney disease.

Remifentanil: Metabolized by nonspecific plasma esterases into inactive metabolites.

References

  1. Dean M. Opioids in renal failure and dialysis patients. J Pain Symptom Manage. 2004 Nov;28(5):497-504. PubMed Link

Other References

  1. Keys to the Cart: January 29, 2018; a 5-minute video review of ABA Keywords Link