From the Guidelines
Morphine is not recommended for patients with end-stage renal disease (ESRD) due to the risk of accumulation of its active metabolites and increased toxicity. According to the most recent and highest quality study 1, morphine should be avoided in patients with renal insufficiency (GFR <30 mL/min/1.73 m2) and ESRD due to the accumulation of its active metabolites.
Key Considerations
- Morphine metabolites, such as morphine-6-glucuronide, can accumulate in kidney failure and cause prolonged sedation, respiratory depression, and neurotoxicity 1.
- Alternative opioids like fentanyl or hydromorphone may be safer options for ESRD patients as they have fewer active metabolites dependent on kidney clearance 1.
- Close monitoring for side effects such as excessive sedation, confusion, respiratory depression, and myoclonus is essential when using opioids in ESRD patients 1.
Recommendations
- Avoid using morphine in patients with ESRD and instead consider alternative opioids like fentanyl or hydromorphone 1.
- If morphine is used, doses should be reduced by 50-75% of the normal dose, with extended intervals between doses, and close monitoring for side effects is essential 1.
- Regular reassessment of pain control and side effects should guide ongoing dosing adjustments 1.
From the FDA Drug Label
Morphine pharmacokinetics are altered in patients with renal failure The AUC is increased, and clearance is decreased and the metabolites, M3G and M6G, may accumulate to much higher plasma levels in patients with renal failure as compared to patients with normal renal function. Morphine sulfate pharmacokinetics are altered in patients with renal failure. Start these patients with a lower than usual dosage of morphine sulfate tablets and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension [see Clinical Pharmacology (12.3)].
Morphine is not recommended for patients with End-Stage Renal Disease (ESRD) without careful consideration and monitoring. The drug's pharmacokinetics are altered in patients with renal failure, leading to increased levels of morphine and its metabolites, which can cause respiratory depression, sedation, and hypotension.
- Key considerations:
- Start with a lower than usual dosage
- Titrate slowly
- Monitor for signs of respiratory depression, sedation, and hypotension [2] [2]
From the Research
Opioid Use in End-Stage Renal Disease (ESRD)
- Morphine is not recommended for use in ESRD patients due to the accumulation of potentially toxic metabolites 3, 4, 5, 6.
- The use of morphine in ESRD patients can lead to neurotoxic symptoms, making it an unsuitable choice for pain management in this population.
Alternative Opioids for ESRD Patients
- Fentanyl, alfentanil, and methadone are recommended for use in ESRD patients managed conservatively, as they have a more favorable pharmacological profile 3.
- Hydromorphone and oxycodone can be used with caution and close monitoring, but may not be the best choices due to limited evidence and potential for accumulation of toxic metabolites 3, 4, 5, 6.
- Buprenorphine may be a good choice for ESRD patients, but more research is needed to confirm its safety and efficacy in this population 3, 4, 5.
Safe Use of Opioids in ESRD Patients
- Accurate pain diagnosis, opioid titration, and tailoring are mandatory to minimize risks and improve outcomes in ESRD patients 5.
- Opioid-related side effects, such as constipation, can be managed with peripherally-acting-μ-opioid-receptor-antagonists (PAMORA), which do not require dose adjustment in CKD and HD patients 5.
- Close monitoring of patients and careful dose adjustment are necessary to prevent adverse effects, such as neuroexcitatory phenomena, when using opioids like hydromorphone in ESRD patients 7.