From the Guidelines
In patients with liver failure, fentanyl is the preferred opioid due to its minimal hepatic metabolism and lack of active metabolites, allowing for easier titration and reduced risk of accumulation and toxicity 1. When considering opioid choice in liver failure, it is essential to prioritize medications with minimal hepatic metabolism to avoid accumulation and toxicity.
- Fentanyl is advantageous as it undergoes primarily non-hepatic metabolism and has a short half-life, making it easier to titrate 1.
- Opioids to avoid include morphine, codeine, and meperidine, as they produce active metabolites that can accumulate in liver failure, potentially causing prolonged sedation, respiratory depression, and neurotoxicity.
- When administering opioids to patients with liver failure, it is recommended to start with lower doses, extend dosing intervals, and carefully titrate based on clinical response while monitoring for signs of opioid toxicity such as excessive sedation and respiratory depression 1. Key considerations for opioid use in liver failure include:
- Instituting a bowel regimen with stimulant or osmotic laxative in all patients receiving sustained opioid administration unless there are contraindications such as small bowel obstruction 1.
- Monitoring for neuroexcitatory effects, such as myoclonus, especially when using opioids chronically or in patients with renal failure, electrolyte disturbances, and dehydration 1.
- Rotating opioid to a lower dose of another opioid with a different structure may reduce myoclonus within 24 h, with fentanyl being a potential option due to its lack of active metabolites 1.
From the Research
Opioid Choice in Liver Failure
The choice of opioid in patients with liver failure is crucial due to the impaired pharmacokinetics of these drugs. Several studies have investigated the effects of liver failure on opioid metabolism and the potential risks associated with their use.
- The liver is the major site of biotransformation for most opioids, and liver insufficiency can lead to decreased drug clearance and increased oral bioavailability 2, 3, 4.
- Some opioids, such as morphine, oxycodone, tramadol, and alfentanil, have decreased clearance in moderate or severe hepatic impairment, increasing the risk of accumulation and adverse effects 3, 4, 5.
- The use of certain opioids, such as pethidine (meperidine), is not recommended in patients with liver disease due to the risk of toxic metabolites and seizures 3, 4.
- Fentanyl, sufentanil, and remifentanil are considered safe options in patients with liver failure, as their pharmacokinetics are unaffected by liver disease 2, 3, 4, 5.
- Codeine and tramadol rely on hepatic biotransformation to active metabolites, and their analgesic effect may be reduced in patients with liver disease 3, 5.
- Lower doses and/or longer administration intervals should be used when administering opioids to patients with liver disease to avoid the risk of accumulation and adverse effects 6, 5.
Specific Opioid Considerations
- Morphine: clearance is reduced in liver failure, and its use is not recommended in patients with liver and renal failure 2, 3, 4.
- Alfentanil: plasma clearance and elimination are reduced in patients with liver failure, and its use is not recommended 2.
- Remifentanil: considered the opioid of choice in patients with liver and renal failure due to its unaffected pharmacokinetics 2.
- Fentanyl and sufentanil: pharmacokinetic effects are not affected in liver and renal failure, but continuous infusion of fentanyl may result in accumulation and prolonged opioid effects 2.