What is the best subcutaneous analgesia for end-of-life patients with Impaired Renal Function, to avoid constipation?

From the Guidelines

For end-of-life patients with very poor renal function requiring subcutaneous analgesia while avoiding constipation, fentanyl is the preferred option. Fentanyl is metabolized primarily in the liver with inactive metabolites, making it safe for patients with renal impairment 1. A typical starting dose would be 12.5-25 mcg/hour via continuous subcutaneous infusion, titrated according to pain response.

Some key points to consider when selecting an opioid for these patients include:

• Avoiding opioids with active metabolites that can accumulate in renal failure, such as morphine, hydromorphone, and codeine, due to the risk of neurotoxicity and respiratory depression 1
• Considering the use of opioids with minimal impact on bowel motility, such as fentanyl and alfentanil, to reduce the risk of constipation
• Using caution when prescribing opioids in patients with fluctuating renal function, due to the potential for accumulation of renally cleared metabolites 1

In addition to selecting an appropriate opioid, a prophylactic bowel regimen should be considered to minimize the risk of constipation. This may include:

• A stool softener, such as docusate sodium 100mg twice daily
• A stimulant laxative, such as senna 8.6mg daily or bisacodyl 5-10mg daily 1
• Avoiding the use of bulk laxatives, which may not be effective in advanced disease and can worsen constipation 1

Overall, the goal is to provide effective pain management while minimizing the risk of adverse effects, such as constipation, in end-of-life patients with poor renal function. Fentanyl is a safe and effective option for these patients, and should be considered as the first-line treatment for subcutaneous analgesia.

From the FDA Drug Label

After oral administration of a single 4 mg dose (2 mg hydromorphone immediate-release tablets), exposure to hydromorphone (C max and AUC 0-48) is increased in patients with impaired renal function by 2-fold in moderate (CLcr = 40 to 60 mL/min) and 3-fold in severe (CLcr < 30 mL/min) renal impairment compared with normal subjects (CLcr > 80 mL/min) Patients with moderate renal impairment should be started on a lower dose. Starting doses for patients with severe renal impairment should be even lower Patients with renal impairment should be closely monitored during dose titration

• Hydromorphone may not be the best option for end-of-life patients with impaired renal function due to increased exposure and risk of adverse effects.
• Fentanyl has insufficient information to make recommendations regarding its use in patients with impaired renal function, and its use should be with caution.
• There is no clear evidence to support the use of either hydromorphone or fentanyl as the best subcutaneous analgesia for end-of-life patients with impaired renal function to avoid constipation 2 3.
• However, considering the information available, hydromorphone may be a more suitable option if dose adjustments are made according to renal function, but this should be done with caution and close monitoring.

From the Research

Subcutaneous Analgesia for End-of-Life Patients with Impaired Renal Function

To avoid constipation in end-of-life patients with impaired renal function, the choice of subcutaneous analgesia is crucial. The following points highlight the key considerations:

• Fentanyl is recommended for use in patients with end-stage renal disease due to its large apparent volume of distribution, short plasma half-life, and extensive biotransformation without active metabolites 4, 5.
• Methadone is also considered safe for use in patients with end-stage renal disease 5.
• Hydromorphone is not recommended due to limited evidence, although it may be a better choice than morphine or diamorphine 6, 7.
• Morphine and diamorphine are not recommended because of known accumulation of potentially toxic metabolites 6.

Management of Opioid-Induced Constipation

In addition to choosing the right analgesia, managing opioid-induced constipation is essential:

• Laxatives and stool softeners are commonly used to treat opioid-induced constipation 8.
• Newer agents, such as methylnaltrexone, linaclotide, lubiprostone, and naloxegol, are available but not widely used in hospice organizations 8.
• A bowel regimen should be prescribed to patients on admission to hospice, and guidelines or protocols for managing opioid-induced constipation should be in place 8.

Key Considerations

When selecting a subcutaneous analgesia for end-of-life patients with impaired renal function, consider the following:

• The patient's renal function and the potential for accumulation of toxic metabolites 6, 7.
• The risk of constipation and the need for a bowel regimen 8.
• The use of alternative drugs, such as fentanyl or methadone, which may be safer in patients with impaired renal function 4, 5.