Kidney Disease

One of the jobs of the kidneys is to remove waste products produced by normal body function. These waste products can be toxic. In the case of kidney failure, the kidneys can’t remove waste products effectively. As the toxins build up a person’s energy gradually decreases and the desire to rest increases. In the final days or weeks of life most people sleep.

A common symptom of kidney failure is delirium. This is a mental state that’s marked by confusion and restlessness. It develops because the toxins that are accumulating are affecting the brain. In the final days of kidney failure, it’s not possible to fix this, so the only effective way to control delirium is to provide sedation. This can be hard for family, since it means there’s no more interaction with the patient. Usually the person must be kept in deep sleep, since mild sedation can worsen the confusion. As hard as this is for family, it may be the only way to ensure a comfortable and calm final few hours or days. Even if the person is sedated it’s worth continuing to talk to him or her. It’s thought that people who aren’t alert are still aware and can hear to some degree. Conversation can be calming and meaningful for visitors and patients alike.

Pain is not common with kidney failure. Some people have other illnesses that need pain treatment, but it’s usually not because of the kidneys. If there is pain to be treated, it’s best to avoid morphine. Morphine has by-products that build up when the kidneys aren’t working well, and this can cause confusion and opioid toxicity. Toxicity from an opioid can cause twitching, irritation and general confusion. Hydromorphone (Dilaudid®) is usually a better pain medication in this case because its by-products take longer to build up, and it’s easy to administer and to adjust dosages. Another option is fentanyl by intravenous infusion, as dosages can be adjusted more quickly than with a fentanyl patch. Methadone may be used, but it can only be given by mouth, which is not useful when people are not alert.

People with kidney failure may have nausea, which can be managed well with anti-nausea medications.

The length of time someone can live with acute kidney failure is influenced by many variables. If the person has been having dialysis and it is stopped, then the person can live for as little as a few days or as many as about ten days. Other medical conditions can influence this and it becomes very difficult to estimate.

This is not a straightforward issue, as the evidence supporting one opioid over another is often based on the experience and advice of experts rather than on solid data from prospective, randomized, double-blind trials.

Both morphine and hydromorphone (Dilaudid) have active metabolites that are known to accumulate in the context of renal insufficiency. Morphine-6-glucuronide and morphine-3-glucuronide are derived from morphine, and hydromorphone-3-glucuronide from hydromorphone. These active metabolites are renally excreted. The 3-glucuronide metabolites have been implicated in the development of opioid-induced neurotoxicity (OIN), and have been described as "anti-analgesic." They may result in a syndrome of hyperalgesia, delirium, myoclonus, and ultimately seizures and death.

One of the early indications of OIN is an escalation of pain that takes on a more widespread and diffuse nature than previously, and which worsens in spite of rapid escalation of opioid doses. In fact, the pain is escalating as a result of the increasing opioid doses, rather than in spite of the increases. There is often an accompanying agitated delirium, where restlessness and calling out are misinterpreted as pain, resulting in further increases of the opioid that is actually causing the problem.

Between morphine and hydromorphone, hydromorphone is generally preferred in renal insufficiency. Despite the lack of literature to support this, problems related to hydromorphone’s 3-glucuronide metabolite seem to appear more slowly than with morphine. However, OIN will still develop over days or weeks due to metabolite accumulation.

Fentanyl and methadone have no known active metabolites, and are preferred opioids in renal insufficiency. However, there are case reports of opioid-induced neurotoxicity even with these drugs, although it is uncommon.

Reference

King S, Forbes K, Hanks GW, Ferro CJ, Chambers EJ. A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: a European palliative care research collaborative opioid guideline project. Palliat Med. 2011;25(5):525-552.