What are the recommendations for controlling agitation in palliative care patients?

Management of Agitation in Palliative Care Patients

For acute agitation in palliative care, use a combination of haloperidol (2-5 mg) and midazolam (1-5 mg) administered parenterally, as this controls agitation more rapidly and effectively than haloperidol alone, with the majority of episodes controlled within 15 minutes using only the first dose. 1, 2

Initial Assessment and Non-Pharmacological Approaches

Before initiating pharmacological management, rapidly assess for reversible causes while simultaneously preparing to control dangerous agitation:

• Identify and treat underlying causes: medications (especially anticholinergics, steroids), infections, metabolic disturbances (hypercalcemia, hypomagnesemia), opioid neurotoxicity, pain, hypoxia, urinary retention, constipation, and dehydration 1, 3
• Distinguish delirium from anxiety: This distinction is critical because benzodiazepines alone can worsen delirium-related agitation 1
• Implement environmental modifications: adequate lighting, reorientation strategies, familiar environment, minimize room changes 3
• Reduce or eliminate deliriogenic medications: steroids, anticholinergics, and consider opioid rotation if neurotoxicity is suspected 1

Important caveat: While non-pharmacological interventions should be maximized, acute severe agitation requires immediate pharmacological control to prevent harm to the patient and others 1

First-Line Pharmacological Management

For Severe Agitation (Immediate Control Needed)

The combination protocol is superior to monotherapy:

• Haloperidol 2-5 mg PLUS Midazolam 1-5 mg administered intramuscularly or intravenously 1, 2
• This combination controlled 84% of agitation episodes with only the first dose, compared to 64% with haloperidol alone (p=0.002) 2
• Median time to control: 15 minutes (range 5-210 minutes) with combination versus 60 minutes (range 10-430 minutes) with haloperidol alone (p<0.001) 2
• Can be repeated as often as every hour if needed, though 4-8 hour intervals are typically satisfactory 4
• Maximum haloperidol dose: 20 mg per day 4

For Moderate Agitation or Delirium Without Severe Behavioral Disturbance

Use antipsychotics as monotherapy:

• Haloperidol: 2-5 mg IM/IV for initial control 1, 4
• Alternatives: Olanzapine, quetiapine, or risperidone for oral administration when patient can cooperate 1, 3
• Chlorpromazine: 12.5 mg IV/IM every 4-12 hours (use only in bed-bound patients due to hypotension risk) 1
• Levomepromazine: 12.5-25 mg every 8 hours, up to 300 mg/day by continuous infusion 1

Refractory Agitation Management

When high-dose neuroleptics fail to control agitation:

• Add lorazepam to the antipsychotic regimen (therapeutic levels of neuroleptics prevent paradoxical excitation from benzodiazepines) 1, 5
• Midazolam continuous infusion: Start 0.5-1 mg/hour, titrate to 1-20 mg/hour as needed 1
• Phenobarbital: 1-3 mg/kg bolus followed by 0.5 mg/kg/hour infusion, maintenance 50-100 mg/hour 1
• Consider palliative sedation after consultation with palliative care specialist and/or psychiatrist for truly refractory cases 1

Critical Safety Considerations

Benzodiazepines should NOT be used as initial monotherapy for delirium-related agitation:

• Benzodiazepines are identified as deliriogenic and can worsen confusion 1
• They increase fall risk in patients with functional mobility 1
• Exception: First-line for alcohol or benzodiazepine withdrawal 1
• When used with opioids, monitor closely for respiratory depression 5

Monitoring requirements:

• Assess for orthostatic hypotension, especially with chlorpromazine and levomepromazine 1
• Watch for extrapyramidal symptoms with all antipsychotics 1, 3
• Monitor for paradoxical agitation (can occur with any sedative) 1
• Regularly reassess mental status and adjust treatment based on response 3

Route of Administration Considerations

Parenteral routes are preferred for acute agitation:

• Subcutaneous or intramuscular administration is effective when IV access is unavailable 1
• Haloperidol and midazolam can be co-administered in the same syringe 1
• Switch to oral formulations once agitation is controlled, typically within 12-24 hours of last parenteral dose 4

Family and Staff Support

Provide comprehensive education and support:

• Give written information about delirium, including causes, symptoms, and management strategies 1, 3
• Explain that agitation is a symptom of underlying medical condition, not willful behavior 1
• Offer guidance on appropriate responses and non-pharmacological interventions family can provide 3
• Provide formal debriefing opportunities for families after resolution and for staff after challenging cases 1