Consider and appropriately treat reversible causes, which may include:

• Urinary retention
• Constipation
• Biochemical abnormalities: hypercalcaemia, hyponatraemia, hypo/hyperglycaemia
• Renal failure
• Liver failure
• Cerebral tumour
• Infection
• Hypoxia
• Anxiety and depression
• Drug-related causes:
  • opioids
  • corticosteroids and withdrawal
  • benzodiazepines and withdrawal
  • SSRI withdrawal
  • Nicotine or alcohol withdrawal
  • digoxin toxicity

Drugs should only be prescribed if necessary. Reassurance, helping to orientate the patient and alleviate their fear may be all that is required.

Sedation should only be necessary if the patient is very distressed and not amenable to reassurance, or is a danger to themselves or others.

Where delirium and psychotic features are predominant:

Antipsychotics are the drugs of choice for delirium.

See 4.2 Drugs used in psychoses and related disorders

1st line - Haloperidol

For patients with mild to moderate distress:

• start with haloperidol 500 micrograms (oral or SC) single dose and repeat 2 hourly when required
• if necessary, increase the dose progressively e.g. up to 1mg, then 1.5mg

For patients with severe distress and/or an immediate danger to self and others:

• start with 1.5 - 3mg single dose, possibly combined with a benzodiazepine, and repeat 2 hourly when required
• if necessary, increase the dose further e.g. 5mg

Patients may require the administration of their haloperidol via a continuous subcutaneous infusion (CSCI):

• 2.5-10mg/24 hours via CSCI

The maintenance dose is usually based on the initial cumulative dose needed to settle the patient. This is usually 5mg or less over 24 hours.

Continue to review the dose needed, particularly if the underlying cause can be resolved.

2nd line - Levomepromazine

• 12.5mg oral or subcutaneous single dose plus 12.5 - 50mg/ 24 hours via CSCI if necessary.

Levomepromazine is more sedating than haloperidol

Atypical antipsychotics

The use of atypical antipsychotics may be appropriate in those patients intolerant of haloperidol or levomepromazine. Please seek specialist advice.

See 4.2 Drugs used in psychoses and related disorders

Olanzapine

• 2.5mg oral or SC when required and at bedtime
• if necessary increase to 5-10mg at bedtime
• available in orodispersible tablets

Where anxiety is a predominant feature:

Although antipsychotics are first-line treatment for delirium, in patients with advanced cancer agitation and restlessness may represent an anxiety state. In these cases, benzodiazepines may be more appropriate and effective.

Lorazepam

• 0.5 - 1mg sublingually when required
• See 4.8.2 Drugs used in status epilepticus

Diazepam

1. 2 - 10mg orally or rectally once daily at night when required
2. See 4.1.2 Anxiolytics

Midazolam

• 2.5 - 10mg subcutaneous when required plus 10 - 60mg/24 hours subcutaneous infusion where necessary

In cases of extreme distress, where urgent control of symptoms is needed, diazepam or midazolam can be given as a titrated, slow intravenous injection.

Benzodiazepines used alone carry an increased risk of paradoxical agitation, especially in the elderly.

Occasionally the combination of an antipsychotic and benzodiazepine is more successful than either alone:

• haloperidol 3mg oral plus lorazepam 1mg sublingual or
• levomepromazine 25mg - 50mg plus midazolam 30mg/24 hours via CSCI

For the management of agitation and distress in the last few hours or days of life, see section on Care of the dying person