From the Guidelines
Fentanyl and hydromorphone are the safest opioids for patients with hepatic impairment.
Key Considerations
- When selecting opioids for patients with hepatic impairment, it is essential to consider the metabolism and excretion of the opioid to minimize the risk of accumulation and toxicity 1.
- Fentanyl is a suitable option as it is metabolized by cytochromes and does not produce toxic metabolites, with its blood concentration remaining unchanged in patients with liver cirrhosis 1.
- Hydromorphone is also a good choice as its half-life is stable even in patients with liver dysfunction, and it is metabolized and excreted by conjugation 1.
- Opioids such as morphine, codeine, and tramadol should be avoided or used with caution in patients with hepatic impairment due to the risk of accumulation and toxicity 1.
- Methadone should be used with caution due to its complex pharmacokinetics and pharmacodynamics, and its association with cardiac arrhythmias and QT prolongation 1.
Clinical Recommendations
- Clinicians should perform more frequent clinical observation and opioid dose adjustment in patients with hepatic impairment who receive opioids 1.
- The selection of opioid analgesics and adjustments in dosage and interval of administration should be carefully considered based on drug metabolism and liver function 1.
- A multidisciplinary approach involving experts in palliative care is needed to effectively manage pain in patients with hepatic impairment 1.
From the Research
Opioid Safety in Hepatic Impairment
The safety of opioids in patients with hepatic impairment is a significant concern due to the liver's crucial role in metabolizing these drugs. Several studies have investigated the pharmacokinetics and pharmacodynamics of opioids in patients with liver disease.
Affected Opioids
- Morphine, oxycodone, tramadol, and alfentanil have decreased clearance in moderate or severe hepatic impairment, leading to increased bioavailability and risk of accumulation 2, 3, 4.
- Codeine and tilidine rely on hepatic biotransformation to active metabolites, which may be compromised in patients with liver disease, reducing their analgesic effect 2, 3, 4.
- Pethidine (meperidine) and dextropropoxyphene have toxic metabolites that can accumulate in patients with liver disease, increasing the risk of seizures and hepatotoxicity 2, 3, 4.
Unaffected Opioids
- Fentanyl, sufentanil, and remifentanil appear to be unaffected in liver disease, making them potentially safer options for patients with hepatic impairment 2, 3, 4.
- Methadone and buprenorphine also seem to be less affected by liver disease, although caution is still necessary when using these opioids in patients with hepatic impairment 4.
Recommendations
- Lower doses and longer administration intervals should be used when administering opioids to patients with liver disease to avoid accumulation and increased adverse effects 2, 3, 4, 5, 6.
- Patients with liver disease should be closely monitored for signs of opioid toxicity, such as sedation, constipation, and encephalopathy 5, 6.
- Opioids should be used cautiously in patients with severe liver disease, and alternative pain management strategies should be considered when possible 5, 6.