From the Guidelines
Morphine should be avoided or used with extreme caution when the estimated glomerular filtration rate (eGFR) falls below 15 mL/min/1.73m², as recommended by the most recent and highest quality study 1. At this level of renal impairment, morphine and its active metabolites (particularly morphine-6-glucuronide) can accumulate in the body, leading to increased risk of opioid toxicity, respiratory depression, and other adverse effects. For patients with an eGFR between 30-60 mL/min/1.73m², morphine can still be used but with dose reduction (typically 50-75% of the normal dose) and careful monitoring for signs of opioid toxicity, as suggested by 1 and 1. Some key points to consider when using morphine in patients with renal impairment include:
- Alternative opioids that may be safer in renal impairment include fentanyl, buprenorphine, or hydromorphone, as they have fewer active metabolites dependent on renal clearance, as mentioned in 1 and 1.
- The reason morphine is problematic in renal failure is that its metabolites are primarily eliminated through the kidneys, and when kidney function is severely compromised, these metabolites build up and can cause prolonged and enhanced opioid effects, potentially leading to serious complications including excessive sedation and respiratory depression.
- It is essential to carefully assess the patient's renal function and adjust the morphine dose accordingly to minimize the risk of adverse effects, as recommended by 1 and 1.
- Other studies, such as 1 and 1, provide additional guidance on managing pain and diabetes in patients with chronic kidney disease, but the primary concern with morphine use in renal impairment remains the risk of opioid toxicity and the need for careful dose adjustment and monitoring.
From the Research
Estimated Glomerular Filtration Rate (eGFR) and Morphine Use
- The use of morphine in patients with impaired kidney function is a concern due to the accumulation of its metabolites, which can cause neurotoxic symptoms 2.
- There is limited and low-quality evidence to inform the safety and analgesic effect of opioid use in reduced renal function, with morphine being the opioid for which there is the most evidence available 3.
- The current evidence suggests that morphine and hydromorphone use may be associated with neurotoxic effects in patients with renal impairment, but the quality of the studies is very low and the findings are conflicting 4.
eGFR Threshold for Avoiding Morphine
- A specific eGFR threshold for avoiding morphine is not clearly established in the available evidence.
- However, it is recommended that morphine and codeine are not used in patients with moderate-to-severe chronic kidney disease (CKD) or end-stage renal disease (ESRD) due to the risk of neurotoxicity 2.
- In patients with mild-to-moderate renal impairment, morphine and hydromorphone may be used with close monitoring for neurotoxic effects, particularly when used in high doses and for extended duration 4.
Alternative Opioids for Patients with Impaired Kidney Function
- Oxycodone and hydromorphone can be safely used in patients with CKD, but adequate dosage adjustments are required 2.
- Buprenorphine and fentanyl could be considered first-line opioids in the management of pain in CKD, but fentanyl is not appropriate in patients undergoing hemodialysis 2.
- Tapentadol does not require dosage adjustment in mild-to-moderate renal impairment conditions, but no data are available on its use in ESRD 2.