What is the recommended first-line approach for managing agitation in a general inpatient hospice setting?

Management of Agitation in General Inpatient Hospice

For agitation in hospice patients, use a combination of haloperidol and a benzodiazepine (lorazepam or midazolam) as first-line pharmacologic treatment after addressing reversible causes. 1

Initial Non-Pharmacologic Approach

Before administering medications, rapidly assess and address reversible causes 1:

• Explore patient concerns and anxieties through brief therapeutic communication 1
• Treat medical causes: hypoxia, urinary retention, constipation, pain, metabolic derangements 1, 2
• Assess for medication-induced causes: anticholinergics, steroids, opioid neurotoxicity, benzodiazepine or alcohol withdrawal 2
• Ensure adequate lighting and orientation (explain location, identity, your role) 1

Pharmacologic Management Algorithm

For Patients Able to Swallow

First-line: Lorazepam 0.5-1 mg orally every 2-4 hours as needed (maximum 4 mg in 24 hours) 1

• Reduce to 0.25-0.5 mg in elderly or debilitated patients (maximum 2 mg in 24 hours) 1
• Oral tablets can be used sublingually 1

If agitation persists or is severe, add haloperidol 0.5-1 mg orally 1, 2

• Can repeat every 1-2 hours as needed 1, 2
• Maximum 10 mg daily (5 mg daily in elderly) 1

For Patients Unable to Swallow

First-line: Midazolam 2.5-5 mg subcutaneously every 2-4 hours as needed 1

• If needed more than twice daily, consider subcutaneous infusion via syringe driver starting with midazolam 10 mg over 24 hours 1
• Reduce to 5 mg over 24 hours if eGFR <30 mL/min 1

Add haloperidol 0.5-1 mg subcutaneously for persistent agitation 1, 2

• Can administer same dose subcutaneously as oral route 1
• Subcutaneous infusion of 2.5-10 mg over 24 hours is an option 1

For Refractory Agitation

If initial doses fail to control agitation within 15-60 minutes 3, 4:

• Continue haloperidol 0.5-2 mg every 1 hour until episode controlled 2
• Add lorazepam 0.5-2 mg every 4-6 hours if agitation remains refractory to high-dose neuroleptics 2
• The combination prevents paradoxical excitation that can occur when delirious patients receive benzodiazepines alone 2

Alternative: Consider intramuscular administration if oral/subcutaneous routes are inadequate 2, 5

• IM haloperidol 2-5 mg provides more rapid and reliable absorption 2, 5
• Can repeat as often as every hour, though 4-8 hour intervals may be satisfactory 5

Evidence Supporting Combination Therapy

The combination of haloperidol plus midazolam is superior to haloperidol alone for hospice agitation 3:

• Controls 84% of agitation episodes with first dose versus 64% with haloperidol alone (p=0.002) 3
• Median time to control: 15 minutes with combination versus 60 minutes with haloperidol alone (p<0.001) 3
• In palliative care protocols, 91% of agitation episodes controlled with first dose of combination therapy 6

Critical Safety Monitoring

Obtain or review baseline ECG when using haloperidol, especially in combination with other QT-prolonging agents 2:

• Haloperidol causes mean QT prolongation of 7ms at usual doses 2
• Monitor for electrolyte abnormalities, bradycardia, other QT-prolonging medications 2

Monitor for extrapyramidal symptoms with haloperidol 2:

• Acute dystonia, akathisia, Parkinsonian symptoms occur in approximately 20% of patients 2
• Discontinue antipsychotics immediately once distressful symptoms resolve 1

Watch for excessive sedation, particularly with combination therapy 3, 4

Important Clinical Pitfalls

Avoid using antipsychotics in anticholinergic or sympathomimetic intoxication, as they can exacerbate agitation through anticholinergic side effects 1, 2

Do not use antipsychotics routinely for delirium without agitation 1 - reserve for patients with significant distress from hallucinations/delusions or agitation that may cause physical harm 1, 2

For severe distress or immediate danger to others, consider higher starting oral haloperidol dose of 1.5-3 mg 1