Principles of analgesic use in patients with cirrhosis

Although the general principles of assessing and managing pain apply to patients with cirrhosis, analgesic choice may need to be modified. For more information on assessing and managing pain, see:

This topic discusses the use of oral and some parenteral analgesics in adults and children with cirrhosis. Inhaled analgesics (eg nitrous oxide) and drugs used for painful procedures (eg ketamine) are beyond the scope of this topic.

Pain related to distension caused by ascites is managed with diuretic therapy or paracentesis rather than analgesics—see Ascites.

Tips for prescribing analgesics for patients with cirrhosis are shown in Tips for prescribing analgesics for patients with cirrhosis.

In patients with compensated cirrhosis most analgesics, including paracetamol, can be used in the usual doses because liver synthetic function is preserved. However, nonsteroidal anti-inflammatory drugs (NSAIDs) and oral naloxone-containing preparations should be avoided because patients may have unrecognised portal hypertension, which makes them more susceptible to the adverse effects of these drugs.

Note: Avoid NSAIDs preparations in all patients with cirrhosis.

Patients with decompensated cirrhosis have decreased liver function, which can affect the bioavailability, biotransformation, half-life and protein binding of many analgesics. Additionally, the adverse effects of analgesics (especially opioids) can worsen the complications of decompensated cirrhosis. Choosing the optimal analgesic and dose in these patients can be complex—seek expert advice if necessary.

Note: Paracetamol can be used for patients with cirrhosis.
Figure 1. Tips for prescribing analgesics for patients with cirrhosis.

[NB1]

For patients with cirrhosis (compensated or decompensated):

  • paracetamol can be used. Dosage adjustment should be considered for patients with decompensated cirrhosis or multiple conditions associated with glutathione depletion [NB2]
  • avoid NSAIDs—these drugs can precipitate kidney dysfunction (including hepatorenal syndrome) in patients with established portal hypertension. NSAIDs can also cause gastrointestinal bleeding, and worsen platelet function, sodium retention and oedema
  • avoid oral naloxone-containing preparations (eg oxycodone+naloxone)—the bioavailability of oral naloxone is increased in patients with cirrhosis and, when given in combination with an opioid, reduces opioid efficacy.

For patients with decompensated cirrhosis:

  • start with low doses of analgesics and consider increasing the dosing interval
  • avoid long-acting formulations or drugs when starting therapy. The half-life of many drugs is already prolonged in patients with decompensated cirrhosis and use of long-acting drugs or formulations increases the risk of drug accumulation
  • paracetamol can be used but dosage reduction is required. The recommended total dose is 2 to 3 g per day for adults
  • avoid codeine because it requires hepatic transformation to morphine, further reducing its limited analgesic efficacy
  • opioids can precipitate or worsen hepatic encephalopathy by causing constipation and sedation; always monitor for these effects. To manage sedation, decrease the dose or frequency of the opioid, or stop therapy if opioid toxicity is suspected. For constipation, increase laxative dosage
  • a gabapentinoid (gabapentin, pregabalin) or tricyclic antidepressant (TCA) can be used for neuropathic pain in adults with decompensated cirrhosis. Gabapentinoids and TCAs commonly cause sedation; use low starting doses and increase the dosage carefully in this patient group. If a TCA is used, nortriptyline is preferred because it is the least sedating TCA; monitor the patient for reduced frequency of bowel motions because TCAs can cause constipation. Gabapentin and pregabalin may require dose reduction in patients with concurrent kidney impairment. Serotonin and noradrenaline reuptake inhibitors (SNRIs) should be avoided; note that duloxetine can cause liver injury. For more information see Adjuvants in pain management and Neuropathic pain.
Note:

NB1: This box addresses oral and some parenteral analgesics, but does not cover inhaled analgesics or analgesics used for painful procedures.

NB2: There is anecdotal evidence that liver toxicity can occur when therapeutic doses of paracetamol (4 g per day) are used in adults with intrahepatic glutathione depletion. Intrahepatic glutathione depletion can occur in people who are malnourished, cachectic or frail, or have alcoholism or decompensated cirrhosis. Liver toxicity is more likely when more than one of these conditions is present. Although cautious dosing is often advised in these people, there is a lack of consistent clinical evidence to support dose reduction. Dose reduction can be considered for complex patients (eg patients with decompensated cirrhosis or multiple conditions associated with glutathione depletion) but should not be undertaken routinely—expert advice may be needed. Inappropriate dose reductions can result in inadequate analgesia and, consequently, use of more harmful analgesics.

For paracetamol dosing for children at risk of glutathione depletion, seek expert advice.