Management | Right Decisions

Pain

Good quality evidence on commonly used pain relief medication is limited.
Undertake comprehensive assessment of pain, choosing appropriate analgesia commensurate with severity of pain (refer to Pain assessment guideline).
Use lowest effective dose (reduced dosage and/or extended dose interval), titrate slowly and monitor for toxicity.
Use transdermal and slow release opioids with caution, and only if liver function and pain control are stable.
Ensure judicious management of bowels to minimise risk of constipation and encephalopathy.

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Drug	Recommendations in liver disease	Comment
Paracetamol	Consider standard dose 1g four times a day for patients with normal lean body weight Consider dose reduction if less than 50kg or concern about nutritional status In severe impairment use maximum 2g/24 hours orally	Avoid intravenous use
NSAIDs	Avoid use	Interfere with platelet aggregation; prolong bleeding time; increase risk of gastrointestinal haemorrhage Increased risk of NSAID-induced renal impairment
Codeine	Avoid use	Reduced/unpredictable analgesic effect
Dihydrocodeine	Avoid use	Reduced/unpredictable analgesic effect
QT Tramadol	Avoid if severe hepatic impairment	Moderate hepatic impairment - increase dose interval (for example to 12 hourly) Severe hepatic impairment – risk of lowering seizure threshold
Morphine or Diamorphine	Use with caution	First-line strong opioid of choice Dose reduction may be necessary (refer to Choosing and changing opioids guideline)
Oxycodone	Use with caution	Second-line strong opioid of choice Dose reduction may be necessary (refer to Choosing and changing opioids guideline)
Hydromorphone	Use with caution	Dose reduction may be necessary (refer to Choosing and changing opioids guideline)
Alfentanil	Use with caution	Dose reduction may be necessary (refer to Choosing and changing opioids guideline)
Buprenorphine	Use with caution	Avoid transdermal products unless hepatic function and pain are stable Use if transdermal product preferred and analgesic requirement not sufficient to require transdermal fentanyl (refer to Buprenorphine information sheet)
Fentanyl	Use with caution	Avoid transdermal products unless hepatic function and pain are stable (refer to Fentanyl information sheet)
Tapentadol*	Avoid if severe hepatic impairment Use with specialist palliative care advice	Avoid use or reduce dose and extend dose interval
QT Methadone	Use with caution and seek specialist palliative care advice	Requires careful and very slow titration N.B: Complex pharmacokinetics means the accumulation can occur in people with normal hepatic function
QT Pregabalin	Not affected by hepatic impairment	Caution due to potential for sedation
Gabapentin	Not affected by hepatic impairment	Caution due to potential for sedation
QT †Amitriptyline	Avoid in severe liver failure	Use with caution in mild to moderate hepatic impairment – start slow, watch for sedation and constipation
†Clonazepam	No data	Caution with moderate hepatic impairment Contra-indicated in severe hepatic impairment
†Ketamine	Use with caution and seek specialist palliative care advice	Dose reduction necessary.

*Tapentadol as an immediate release tablet is not recommended by the Scottish Medicine Consortium (SMC), while the prolonged release tablets are accepted for restricted use for the management of severe chronic pain in adults, which can be adequately managed only with opioid analgesics. This is restricted to use in patients in whom morphine sulphate modified release has failed to provide adequate pain control or is not tolerated. Refer to SMC guidance for prolonged release tablets and for immediate release tablets.

Nausea and vomiting

Refer to Nausea and vomiting guideline.
Consider specific causes in liver disease:
- mechanical gut dysmotility (extra-luminal from hepatomegaly or ascites (which may also cause early satiety); intra-luminal from gut wall oedema)
- centrally mediated (raised bilirubin; other toxins)
- drugs (especially diuretics).
Consider regular rather than ‘as required’ prescription for persistent symptoms.
Consider route of administration (subcutaneous route may be required).

Recommendations on the use of anti-emetics in liver disease

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Drug	Recommendations in liver disease	Comment
QT Domperidone	Use with caution	Dose reduce by 50%
Metoclopramide	Use with caution	Dose reduce by 50%
Cyclizine	Use with caution	Avoid in those at risk of decompensation or with encephalopathy Slows gut transit – ensure laxatives co-prescribed
QT †Haloperidol	Use with caution	Start low and titrate slowly
QT †Levomepromazine	Use with caution	Sedating – caution in those at risk of encephalopathy
QT Ondansetron	Use with caution	Reduced clearance in hepatic impairment Slows gut transit – ensure laxatives co-prescribed Maximum dose of 8mg daily in moderate to severe hepatic impairment

Agitation

Consider delirium of any cause (refer to Delirium guideline).
Consider and address specific causes in liver disease:
- hepatic encephalopathy
- alcohol/drug withdrawal.
Consider non-pharmacological management if appropriate.
Ensure patient safety, comfort and dignity are paramount.
Consider overall goals of care and prognosis.
If terminal agitation, refer to Care in the last days of life guideline.

Recommendations on the use of medications for agitation in liver disease

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Drug	Recommendations in liver disease	Comment
QT †Haloperidol	Use with caution	Consider if agitated delirium Start low and titrate slowly
Lorazepam	Generally safe in cirrhosis	Oral lorazepam may be given sublingually Relatively long half-life
†Midazolam	Use with caution	Use if agitation severe or oral route not available
Diazepam	Avoid	Increased half-life in cirrhosis
QT †Levomepromazine	Use with caution	Sedating – caution in those at risk of encephalopathy.

Pruritus

Refer to Pruritus guideline.
Cholestatic pruritus is not histamine dependent so is managed differently to uraemic or opioid-induced itch.
Address cause and employ simple, non-pharmacological measures, including topical preparations to combat dry skin such as emollients.
Severity of pruritus is not necessarily proportionally related to degree of biliary obstruction.

Recommendations on the use of medications for pruritus in liver disease

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Drug	Recommendations in liver disease	Comment
Colestyramine	No dose reduction required in hepatic impairment; avoid in complete biliary obstruction	Avoid taking other medications from 1 hour before to 4 to 6 hours after administration, to minimise interference with absorption
†Rifampicin	Use with caution	Enzyme inducer, so may reduce effect of analgesics
QT †Sertraline	Use with caution Avoid in severe hepatic impairment	May inhibit platelet function
Chlorphenamine	Use with caution Avoid in severe hepatic impairment	Causes sedation without necessarily addressing itch

Ascites

The development of ascites is a poor prognostic indicator in patients with liver disease and carries a mortality of 50% at 2 years.
Patients with refractory ascites (diuretic resistant or diuretic intolerant) have a median survival of 6 months.
Ascites carries a high symptom burden with associated pain, nausea, need for hospital admission and limitation of function and mobility.
Peer reviewed detailed guidance on the management of ascites in cirrhosis and its related complications is available in the EASL Clinical Practice Guidelines (see references).
Standard treatment includes sodium-restricted diet and the use of diuretics, predominantly aldosterone inhibitors, sometimes in combination with a loop diuretic.
Use of diuretics may be limited by renal impairment and hyponatraemia.
Recurrent large volume paracentesis is usually safe and is the first recommended intervention for refractory ascites if there are no contra-indications. Individual patient assessment is recommended. This may be carried out as a day case procedure, however the requirement for close monitoring and infusion of albumin solution limits the practicality of this being performed in the community.
Small volume paracentesis (drainage of less than 5 litres) does not require albumin infusion and may be more suited to community settings.
Transjugular Intrahepatic Portosystemic Shunt (TIPSS), or liver transplantation, should be considered in patients with refractory ascites. Hepatic encephalopathy is a contra‑indication to TIPSS.
Indwelling peritoneal catheters are sometimes used in the management of malignant ascites. There are small published case series of use in refractory ascites due to cirrhosis. Use is limited by risk of infection. There are insufficient data at present regarding the risks and efficacy of this procedure and this cannot be routinely recommended.

Hepatic encephalopathy

Hepatic encephalopathy when present may significantly impair a person’s quality of life due to:
- poor sleep patterns
- lack of ability to concentrate
- impairment of independent living.
Confusion and agitation due to encephalopathy may cause distress to family members and care givers.
West Haven classification of hepatic encephalopathy:
- Grade 1: trivial lack of awareness. Shortened attention span. Impaired addition or subtraction. Hypersomnia, insomnia, or inversion of sleep pattern. Euphoria, depression, or irritability. Mild confusion. Slowing of ability to perform mental tasks. Asterixis can be detected.
- Grade 2: lethargy or apathy. Minimal disorientation. Inappropriate behaviour. Slurred speech. Obvious asterixis. Drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behaviour, and intermittent disorientation, usually regarding time.
- Grade 3: somnolent but can be aroused, unable to perform mental tasks, gross disorientation about time and place, marked confusion, amnesia, occasional fits of rage, present but incomprehensible speech.
- Grade 4: Coma with or without response to painful stimuli.
Peer reviewed guidelines on the management of encephalopathy are available (see references).
Treatment includes the reversal of underlying precipitants, where possible and appropriate.
Lactulose may be given via nasogastric tube if the patient is too drowsy to swallow.
Consideration should be given to the appropriateness of inserting a nasogastric tube on an individual patient basis.
Sedating and analgesic drugs may precipitate or worsen encephalopathy but, particularly in the last days of life, this must be balanced against the control of distressing symptoms.