Absorption
- Porto-caval shunts and reduced hepatic blood flow mean a lower hepatic extraction ratio
- This can increase the bioavailability of drugs by reducing first-pass metabolism
Distribution
- Ascites and increased TBW leads to an increase in the volume of distribution of drugs
- Impaired albumin production reduces drug protein binding, increasing the available/free fraction
Metabolism
- Reduced hepatic extraction ratio reduces metabolism of drugs with high hepatic extraction ratios e.g. morphine, midazolam, propofol, lidocaine
- Reduced Phase 1 and Phase 2 metabolic reactions increse the duration of action of hepatically metabolised drugs
Excretion
- The presence of hepatorenal syndrome may impair elimination of renally-excreted drugs
Specific effects on anaesthetic drugs
| Drug class | Effect of hepatic impairment |
| Opioids | Enhanced effects owing to reduced metabolism Use short-acting agents or remifentanil and use with caution |
| Barbiturates | Impaired metabolism and increased free drug availability |
| Propofol | Reduced doses required |
| Suxamethonium | Reduced plasma cholinesterase production prolongs action |
| Aminosteroid NMBA | Impaired metabolism leads to prolonged duration of action |
| (Cis-)atracurium | Probably the preferred NMBA owing to lack of hepatic excretion May need increased dose as higher VD and altered protein binding Altered pH in liver disease may affect speed of Hoffman degradation |
| Benzodiazepines | Reduced metabolism significantly enhances effects; should be avoided |
| Fluid therapy | Cautious approach due to increased risk of overload/pulmonary oedema Avoid Hartmann's as lactate metabolism impaired |