Analgesia in Liver Disease

Analgesia in liver disease requires balancing effective pain control against the risks of encephalopathy, kidney injury, gastrointestinal bleeding and hepatotoxicity. Undertreated pain is common in cirrhosis because of excessive fear of paracetamol, while harm more often comes from non-steroidal anti-inflammatory drugs and opioids.

Paracetamol. At therapeutic doses paracetamol does not worsen chronic liver disease. Glutathione stores may be low in malnutrition and alcohol use, so a lower daily ceiling is used.

Non-steroidal anti-inflammatory drugs. These reduce renal prostaglandins, cause diuretic resistance, acute kidney injury and hepatorenal syndrome, and raise variceal and peptic bleeding risk.

Opioids. Clearance falls and bioavailability rises. Constipation and sedation precipitate encephalopathy.

First line. Paracetamol for most acute and chronic pain.

Avoid. Non-steroidal anti-inflammatory drugs in cirrhosis with portal hypertension, ascites or kidney impairment. Topical non-steroidal gels on small areas are acceptable for short courses.

Opioid choice. - Preferred: hydromorphone and fentanyl, which have no active metabolites of concern. - Use with dose reduction: morphine and oxycodone. - Avoid: codeine and tramadol (unpredictable activation, seizures with tramadol), pethidine (neurotoxic metabolite), and methadone outside specialist care.

Neuropathic pain. Gabapentin and pregabalin are not hepatically metabolised; adjust for kidney function. Avoid amitriptyline and duloxetine in significant liver disease.

Adjuncts. Topical lidocaine 5% plaster for localised pain. Regional anaesthesia where coagulation and platelets allow.

Paracetamol. 500 mg to 1 g orally every 6 to 8 hours. Maximum 3 g daily in compensated disease; maximum 2 g daily if weight is under 50 kg, in decompensated cirrhosis, active alcohol use or malnutrition.

Opioid regimens.

Gabapentin. 100 to 300 mg orally at night, increased every 3 to 7 days; reduce maximum to 700 mg daily when creatinine clearance is 30 to 59 mL/min.

Pregabalin. 25 to 75 mg orally once or twice daily; reduce for creatinine clearance under 60 mL/min.

Laxatives. Prescribe lactulose 15 to 30 mL orally twice daily with every regular opioid, titrated to 2 to 3 soft stools daily.

Special groups. - Kidney impairment: avoid morphine; prefer fentanyl or hydromorphone. - Older adults: halve starting doses and extend intervals. - Pregnancy: paracetamol is the analgesic of choice; non-steroidal anti-inflammatory drugs are avoided after 20 weeks. - Breastfeeding: paracetamol is compatible; avoid codeine.

Monitoring. Pain score, sedation score, respiratory rate, bowel frequency and mental state at each review. Creatinine and sodium if a non-steroidal anti-inflammatory drug has been given.

Stopping. Reduce or stop opioids for drowsiness, asterixis, respiratory rate under 10 breaths/minute or constipation not controlled by laxatives. Naloxone 100 to 200 micrograms intravenously, repeated every 2 to 3 minutes, reverses severe respiratory depression.

Referral and escalation. Involve palliative care for refractory pain in end-stage liver disease. Seek specialist advice for chronic opioid therapy in transplant candidates.