From the Guidelines
Morphine should be avoided in patients with End-Stage Renal Disease (ESRD) due to the accumulation of active metabolites that can lead to toxicity. According to the most recent and highest quality study 1, opioids primarily eliminated in urine, such as morphine, should be avoided in patients with renal impairment, unless there are no alternatives. The study recommends rotating to methadone, if not contraindicated, as this agent is excreted fecally. Alternative opioids like fentanyl or hydromorphone may be safer options for ESRD patients as they have fewer active metabolites dependent on renal clearance.
When considering the use of morphine in ESRD patients, it is essential to understand that morphine is metabolized in the liver to morphine-3-glucuronide and morphine-6-glucuronide, which are normally excreted by the kidneys. In ESRD, these metabolites accumulate, with morphine-6-glucuronide being particularly potent and potentially causing prolonged sedation, respiratory depression, and neurotoxicity including myoclonus and seizures.
Key considerations for using morphine in ESRD patients include:
- Starting with a reduced dose (25-50% of the normal dose) and extending the dosing interval to prevent accumulation
- Close monitoring for signs of opioid toxicity, including respiratory rate, level of consciousness, and neurological symptoms
- Regular dose adjustments based on dialysis schedule, as some metabolites may be partially removed during dialysis sessions
- Considering alternative opioids like fentanyl or hydromorphone, which have fewer active metabolites dependent on renal clearance.
As stated in 1 and 1, morphine use in patients with significant renal function impairment may result in the accumulation of neurotoxic metabolites, and opioid-induced neurotoxicity. Therefore, it is crucial to prioritize alternative opioids and closely monitor patients with ESRD for signs of opioid toxicity.
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
The main considerations for using morphine in patients with End-Stage Renal Disease (ESRD) are:
- Altered pharmacokinetics: Morphine clearance is decreased, and the metabolites M3G and M6G may accumulate to higher plasma levels in patients with renal failure.
- Dose adjustment: Start with a lower than usual dosage and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension 2 2.
- Monitoring: Closely monitor patients with renal impairment for adverse reactions.
From the Research
Considerations for Using Morphine in ESRD Patients
- Morphine is not recommended for use in patients with End-Stage Renal Disease (ESRD) due to the accumulation of potentially toxic metabolites 3, 4.
- The use of morphine in ESRD patients can lead to neurotoxic symptoms, making it a less desirable option for pain management 4.
- Alternative opioids such as fentanyl, methadone, and buprenorphine are considered safer options for ESRD patients, but require careful dosage adjustments and monitoring 5, 3, 4.
Key Factors in Opioid Selection for ESRD Patients
- The choice of opioid should be based on the patient's individual needs and medical history, as well as the potential for drug interactions and accumulation of toxic metabolites 6, 4.
- A thorough assessment of the patient's pain and medical history is essential to determine the most effective and safe opioid regimen 5, 7.
- Non-opioid analgesics and adjuvant medications should also be considered as part of a comprehensive pain management plan for ESRD patients 5, 6.
Safe Use of Opioids in ESRD Patients
- Opioid use in ESRD patients requires careful monitoring and dosage adjustments to minimize the risk of adverse effects 3, 4.
- Patients with ESRD should be closely monitored for signs of opioid toxicity, such as respiratory depression and sedation 4.
- The use of opioid-sparing strategies, such as non-pharmacological interventions and non-opioid analgesics, should be considered to minimize the risks associated with opioid use in ESRD patients 5, 6.