Pharmacological management of acute agitation in palliative care

For pharmacological management of acute behavioural disturbance, see the following topics in the Psychotropic guidelines:

In an emergency, when death appears to be imminent, see management in Catastrophic terminal events in palliative care. See also Emergencies in palliative care.

Choice of initial drug regimen for acute agitation in palliative care is guided by factors listed in Factors influencing choice of initial drug regimen for pharmacological management of acute agitation in palliative care.

Figure 1. Factors influencing choice of initial drug regimen for pharmacological management of acute agitation in palliative care. [NB1]

clinical scenario:

  • if delirium is likely, an antipsychotic is preferred
  • if anxiety is prominent, or alcohol or benzodiazepine withdrawal is likely, a benzodiazepine is preferred.

urgency of the situation—consider the time to onset of action and route of administration of the drug.

comorbidities—haloperidol (and less frequently reported, olanzapine) can aggravate motor features in Parkinson disease or ‘Parkinson plus’ disorders (eg Lewy body dementia); for these patients, use a benzodiazepine or seek expert advice.

treatment setting—intravenous routes or more frequent dosing can be considered in monitored acute care settings (eg emergency department, intensive care unit)

Note: NB1: Also consider the patient and practical factors (eg drug availability, access) influencing drug choice listed in Principles of drug therapy for symptoms in the last days of life.

If an antipsychotic is appropriate for symptomatic management of acute agitation in palliative care, consider:

1haloperidol 0.5 to 1 mg subcutaneously, intramuscularly or intravenously, as a single dose haloperidol

OR

1olanzapine 2.5 mg orally, as an orally disintegrating formulation (eg wafer), as a single dose; 5 mg may be required for younger patients olanzapine

OR

1olanzapine 2.5 mg intramuscularly1, as a single dose; 5 mg may be required for younger patients. olanzapine

If a benzodiazepine is appropriate for symptomatic management of acute agitation in palliative care, and the patient is being treated in a monitored acute care setting (eg an emergency department, intensive care unit), consider:

1midazolam 1 to 2 mg intravenously, repeated at 5- to 10-minute intervals as required; seek specialist advice if 3 doses do not improve acute agitation midazolam

OR

1midazolam 2.5 to 5 mg subcutaneously, repeated at 15-minute intervals as required; seek specialist advice if 3 doses do not improve acute agitation midazolam

OR

2clonazepam 0.2 to 0.5 mg subcutaneously, repeated at 30-minute intervals as required; seek specialist advice if 3 doses do not improve acute agitation3 clonazepam

OR

2clonazepam 0.2 to 0.5 mg sublingually, repeated at 30-minute intervals as required2; seek specialist advice if 3 doses do not improve acute agitation3. clonazepam

If a benzodiazepine is appropriate for symptomatic management of acute agitation in palliative care, and the patient is not being treated in a monitored acute care setting (eg patient is being treated in an inpatient ward or residential aged-care facility), the interval between benzodiazepine doses is increased to reduce the risk of toxicity. Consider:

1midazolam 2.5 to 5 mg subcutaneously, repeated 1-hourly as required; seek specialist advice if 3 doses do not improve acute agitation midazolam

OR

2clonazepam 0.2 to 0.5 mg subcutaneously, repeated 2-hourly as required; seek specialist advice if 3 doses do not improve acute agitation3 clonazepam

OR

2clonazepam 0.2 to 0.5 mg sublingually, repeated 2-hourly as required2; seek specialist advice if 3 doses do not improve acute agitation3. clonazepam

For information on the ongoing management of agitation caused by delirium, see Delirium in palliative care.

1 Olanzapine is not approved for intravenous or subcutaneous use in Australia, but some research supports its use by these routes. The short-acting intramuscular formulation of olanzapine can be administered intravenously or subcutaneously.Return
2 Two to five drops of clonazepam 2.5 mg/mL oral liquid is equivalent to clonazepam 0.2 to 0.5 mg. Do not count drops directly into the mouth; count drops into a spoon first.Return
3 Clonazepam has a long half-life (30 to 40 hours) and ongoing use of frequent doses can result in accumulation and excessive sedation. Once symptoms have improved, reduce the frequency of as-required doses. Alternatively, midazolam has a shorter half-life and can be used for as-required doses.Return