FAST FACT AND CONCEPT #161: Opioid Use in Renal Failure

Authors: Robert Arnold MD, Peg Verrico RPh, Sara N Davison MD

Chronic pain is common in chronic kidney disease impacting 50% of hemodialysis patients;82% of whom experience moderate to severe pain. The absorption, metabolism, and renal clearance of opioids are complex in renal failure. However, with the appropriate selection and titration of opioids, patients with renal failure can achieve analgesia with minimal risk of adverse effects. This Fast Fact reviews recommendations for opioid use in the setting of renal failure and in patients receiving chronic dialysis.

NOT RECOMMENDED FOR USE

Meperidine is not recommended in renal failure due to accumulation of normeperidine, which may cause seizures.

Codeine has been reported to cause profound toxicity which can be delayed and may occur after trivial doses. We recommend that codeine be avoided in patients with a Glomerular Filtration Rate (GFR) < 30 mL/min.

Dextropropoxyphene is associated with central nervous system (CNS) and cardiac toxicity and is not recommended for use in patients with renal failure.

Morphine is not recommended for chronic use in renal insufficiency (GFR< 30 mL/min) due to the rapid accumulation of active, nondialyzable metabolites that are neurotoxic. If morphine must be used, avoid long-acting preparations and monitor closely for toxicity (see FF #57, 58).

USE WITH CAUTION

Oxycodone is metabolized in the liver with 19% excreted unchanged in the urine. There are reports of accumulation of both the parent compound and metabolites in renal failure resulting in CNS toxicity and sedation.

Hydromorphone, as the parent drug, does not substantially accumulate in hemodialysis patients. Conversely, an active metabolite, hydromorphone-3-glucuronide, quickly accumulates between dialysis treatments, but appears to be effectively removed during hemodialysis. With careful monitoring, hydromorphone may be used safely in dialysis patients. However, it should be used with caution in patients with a GFR < 30mL/min who have yet to start dialysis or who have withdrawn from dialysis.

SAFEST IN RENAL INSUFFICIENCY

Fentanyl is considered relatively safe in renal failure as it has no active metabolites. However, very little pharmacokinetic data exist regarding fentanyl in end stage renal disease. While some studies have shown decreased clearance in renal failure, most studies do not show drug accumulation. Fentanyl is not dialyzable due to high protein binding and a high volume of distribution.

Methadone is considered relatively safe in renal failure. It has no active metabolites and limited plasma accumulation in renal failure due to enhanced elimination in the feces. However, precautions regarding the use of methadone exist (See FF# 75, 86); it does not appear to be removed by dialysis.

OPIOID DOSING

Given the lack of pharmacokinetic and pharmacodynamic data of opioids in renal failure, it is difficult to advocate for specific analgesic treatment algorithms. However, t he following guide has been proposed (Broadbent, 2003)for the initial dosing of the safer opioids in renal failure.

• Cl CR = > 50 mL/min: Normal dosing
• Cl CR = 10-50 mL/min: 75% of normal
• Cl CR = < 10 mL/min: 50% of normal

The “normal opioid dose” for any given patient is the dose that adequately relieves pain without unacceptable adverse effects (see FF#20). While opioids can be used in renal insufficiency, they require closer monitoring and constant reassessment to ensure that accumulation of active metabolites does not result in toxicity. This should not preclude the effective use of opioids in these patients.

References:

1. Chambers EJ, Germain M, and Brown E, eds. Supportive Care for the Renal Patient. Publisher: Oxford University Press; 2004.
2. Davison SN. Pain in hemodialysis patients: prevalence, cause, severity, and management. American Journal of Kidney Diseases 2003; 42(6):1239-1247.
3. Murphy EJ. Acute pain management pharmacology for the patient with concurrent renal or hepatic disease. Anaesthesia & Intensive Care 2005; 33(3):311-22.
4. Dean M. Opioids in renal failure and dialysis patients. Journal of Pain Symptom Management 2004; 28(5):497-504.
5. Broadbent A, Khor K, Heaney A. Palliation and chronic renal failure: opioid and other palliative medications – dosage guidelines. Progress in Palliative Care 2003; 11(4):183-90.

Fast Facts were edited by David Weissman MD, Palliative Care Center, Medical College of Wisconsin until January 2007.  For comments/questions write to the current editor, Drew Rosielle MD: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Arnold , R, Verrico, P and Davison, S. Fast Fact and Concept #161 Opioids use in renal failure. August 2006. End-of-Life / Palliative Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information. This information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is used.

Purpose: Self-Study Guide, Teaching

Audience(s)

ACGME Competencies: Medical Knowledge; Patient Care

Keyword(s): Pain>opioids; renal diseases and dialysis

Specific Disease and Organ System Category(s): Renal diseases and dialysis