Hepatic impairment leads to changed pharmacokinetics of many drugs; the main effects are increased oral bioavailability (due to reduced first pass effect) and reduced clearance (due to impaired metabolism). These effects can have variable impact on clinical practice depending on the specific drugs. Some drugs can also cause or worsen hepatic impairment. There is limited evidence for most statements. ANZCA chapter 11.6.2, p 415.

Condition specific perioperative analgesic issues

The following opioids do usually not require dose adjustment in hepatic impairment: ANZCA TABLE 11.6 page 419-421.

• Alfentanil
• Buprenorphine
• Fentanyl
• Morphine
• Oxycodone
• Sufentanil

Medications that require caution in hepatic impairment: ANZCA TABLE 11.6 page 419-421

• Dextropropoxyphene: Dose adjustment
• Methadone: Increased half-life
• Pethidine: Increased toxicity; NOT recommended
• Tramadol: Dose adjustment in severe impairment
• Local anaesthetics (amides) have reduced clearance and may require dose reduction with prolonged or repeated use.
• Paracetamol has reduced clearance and should be used in reduced doses in severe liver impairment, although data are inconsistent.

Summary

There is limited evidence about administration of analgesics in patients with hepatic impairment, however, consideration should be given to choice and dose regimen of each analgesic.

Supplementary reading

1. Beringer RM, Thompson JP, Parry S, Stoddart PA. Intravenous paracetamol overdose: two case reports and a change to national treatment guidelines. Arch Dis Child. 2011 Mar;96(3):307-8.
2. Bosilkovska M, Walder B, Besson M, Daali Y, Desmeules J. Analgesics in patients with hepatic impairment: pharmacology and clinical implications. Drugs. 2012 Aug 20;72(12):1645-69.