Appendix 1: Use of Opioids in Renal Failure

by Dr Gordon Coates

Series Context

This article is Appendix 1 of the book "How Cancer Pain is Treated: A non-technical guide for patients and their carers". You will find links to the other articles in the series at the bottom of this page. Alternatively, you may download the whole book in PDF format HERE. (All downloads are free.)

Disclaimers

This article, written by a senior medical practitioner with considerable experience in palliative medicine and hospice care, is offered purely for educational purposes. Nothing in it should be taken as therapeutic advice for any particular patient. Mention of any trade (brand) name should not be taken as an endorsement of the brand or its manufacturer.

Cautions

If you read the articles in this series carefully, and think about the information in them, in relation to a particular pain management problem affecting you or someone you love, you may sometimes be able to think of modifications to the current treatment which might be expected to improve the situation.

However, it is very dangerous to make changes to a patient's medication without first discussing them with the prescribing doctor. The doctor must always know exactly what the patient is taking, as virtually all medications can cause unwanted side effects and interact in various ways with other medications.

Importantly, this also applies to "natural", "alternative" or "complementary" therapies, many of which have significant interactions with prescribed medications. Therefore, even if you feel that the current pain management is not optimal, never make any changes without first discussing them with the doctor.

Introduction

Much of the information in this article is not of direct relevance to patients and their carers, as the problems discussed will be addressed by the doctor. However, I have decided to provide the information in non-technical terms for the sake of completeness.

The metabolic products of most opioids are normally removed by the kidneys. They therefore tend to accumulate when renal function is reduced. Many of these metabolic products become toxic as their concentrations rise, causing muscle twitching and confusion, and in extreme cases convulsions, coma or even death.

It is not uncommon for patients who need opioid analgesia to also have some degree of renal failure, either as a result of their cancer, its treatment or some other illness. It is then necessary to watch carefully for the adverse effects caused by accumulation of toxic opioid metabolites. If they become significant, it may be necessary to change to an opioid which is better tolerated in renal failure.

Weak opioids

Weak opioids, if they are ever used at all, should not be administered to patients with a significant degree of renal failure. This is partly because their ratio of wanted to unwanted effects is relatively low to start with, and partly because that ratio deteriorates further as metabolic products which are normally removed by the kidneys accumulate in the bloodstream.

Pethidine

Pethidine (meperidine, demerol etc) is also completely unsuitable in renal failure (as it is in most other situations) because its metabolites are particularly toxic. Other strong opioids vary in their suitability for patients with renal failure, or for those undergoing renal dialysis, as discussed below.

Morphine, Oxycodone and Hydromorphone

Morphine is chiefly metabolised in the liver, and the resulting metabolites[66] are then excreted by the kidneys. They naturally accumulate in the bloodstream in renal failure, when they cause drowsiness, muscle twitching, hallucinations, and, at higher concentrations, convulsions, coma, and ultimately death.

Therefore, although morphine can be used cautiously in the presence of mild renal insufficiency, it often becomes unsuitable for continued use as renal function deteriorates. This is especially likely to be the case when the glomerular filtration rate[67] (GFR) is 10 ml/minute or less. Continued opioid analgesia will then usually need to be provided by a different opioid, as discussed later.

The hepatic metabolites of oxycodone and hydromorphone are probably somewhat better tolerated than those of morphine, but they also become toxic if their concentrations rise too much as a result of renal failure. When this occurs, these two opioids must also be replaced by an alternative opioid in order to maintain satisfactory opioid analgesia.

In the case of patients undergoing renal dialysis, morphine, oxycodone, hydromorphone and their metabolic products are usually reduced in concentration after each episode of dialysis. However, the degree of clearance varies with different dialysis systems, and is difficult or impossible to predict accurately.

In some cases, dialysis might cause failure of pain control, or even precipitate opioid withdrawal symptoms. In other cases, a reduction in opioid dosage might be necessary. Therefore, unless a dialysis patient's condition remains entirely satisfactory, one of the opioids discussed below may need to be substituted.

Fentanyl

Fentanyl is removed from the bloodstream mainly by being metabolised in the liver. Its metabolic products appear to be virtually inactive, as their accumulation in renal failure does not usually cause any clinically significant problems.

In most cases, fentanyl is therefore the ideal opioid for patients in whom renal failure is severe enough to result in side effects from the accumulation of toxic metabolic products of other opioids, such as morphine, oxycodone or hydromorphone.

Fentanyl is not removed by most dialysis filters, so failure of pain control, or an opioid withdrawal syndrome, does not usually occur as a result of renal dialysis. However, close monitoring of the patient is always essential, as dialysis systems vary, and information about drug clearance is limited.

Buprenorphine

Buprenorphine is well tolerated in renal failure and during renal dialysis, as its hepatic metabolites are virtually inactive and are also excreted into the bile. However, in view of the low concentrations achieved by the currently available patches, it would usually need to be administered by continuous infusion. Its ability to precipitate opioid withdrawal must, of course, also be taken into account by the prescribing doctor in patients who were recently, or are currently, taking another opioid.

Methadone

Methadone also has the advantages of having well tolerated hepatic metabolites, and of hepatic excretion of its metabolites into the bile. However, as discussed in a previous article in this series, Medications used to Relieve Cancer Pain, methadone should only be prescribed by clinicians with considerable experience in its use because its duration of action is variable and unpredictable, even in healthy people.

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Declaration of Interest

None.

Not Copyright

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Footnotes: (Click the number of a footnote to return to its reference in the text)

[66] The most important hepatic metabolites of morphine are morphine-3-glucuronide, morphine-6-glucuronide and normorphine.

[67] Glomerular filtration rate (GFR) is usually the best measure of renal function. A fairly accurate estimate of the GFR can be derived from a simple blood test, though its exact measurement is more difficult.

Articles in the Cancer Pain Series

1. Myths and Facts about Cancer Pain

2. How Cancer Pain can be Relieved

3. Medications used to Relieve Cancer Pain

4. Optimal Use of Opioid Analgesics

5. Appendices:

Appendix 1: Use of Opioids in Renal Failure (this page)

Appendix 2: Use of Opioids in Hepatic Failure

Appendix 3: Special Medication Delivery Systems

For more free articles and ebooks by the same author, on a wide range of topics, visit http://www.wanterfall.com