What are alternative medication options for managing agitation in an elderly hospice patient with rapid decline, potential impending NPO (nothing by mouth) status, and multiple episodes of agitation per day?

Alternative Medications for Agitation in a Hospice Patient with Potential NPO Status

For a hospice patient with multiple daily episodes of agitation who may become NPO, subcutaneous midazolam 2.5-5 mg every 2-4 hours as needed is the preferred alternative, with transition to a continuous subcutaneous infusion of 10 mg over 24 hours if needed more than twice daily. 1

Immediate Assessment Before Medication Changes

Before adjusting medications, systematically investigate reversible causes that commonly drive agitation in hospice patients who cannot verbally communicate discomfort 1, 2:

• Pain assessment and management - This is a major contributor to behavioral disturbances and must be addressed first 2
• Check for infections - UTIs and pneumonia are disproportionately common triggers 1, 2
• Evaluate for constipation and urinary retention - Both significantly contribute to restlessness 1, 2
• Assess for hypoxia and metabolic disturbances - These worsen confusion and agitation 1
• Review all medications - Identify anticholinergic agents that worsen agitation 2

Medication Options for Patients Able to Swallow (Current Status)

First-Line: Benzodiazepines for Anxiety/Agitation

• Lorazepam 0.25-0.5 mg orally four times daily as needed (maximum 2 mg in 24 hours in elderly/debilitated patients) 1, 3
• Oral tablets can be used sublingually (off-label) 1
• Critical caveat: Approximately 10% of elderly patients experience paradoxical agitation with benzodiazepines 2, 3

For Delirium-Related Agitation

• Haloperidol 0.5-1 mg orally at night and every 2 hours as required (maximum 5 mg daily in elderly patients) 1, 2
• Consider adding a benzodiazepine if haloperidol alone is insufficient 1
• Important: Higher doses (>1 mg initial) provide no evidence of greater effectiveness and result in significantly greater risk of sedation and side effects 4

Medication Options When Unable to Swallow (Preparing for NPO)

First-Line: Subcutaneous Midazolam

This is your primary alternative for NPO status 1:

• Initial dosing: Midazolam 2.5-5 mg subcutaneously every 2-4 hours as required 1
• Continuous infusion: If needed more than twice daily, start midazolam 10 mg over 24 hours via subcutaneous infusion 1
• Renal adjustment: Reduce to 5 mg over 24 hours if eGFR <30 mL/minute 1
• Advantages: Rapid onset, can be co-administered with morphine or haloperidol 1

Alternative: Subcutaneous Haloperidol for Delirium

• Haloperidol 1-2 mg subcutaneously every 2-4 hours as required 1
• If needed frequently, consider subcutaneous infusion of 2.5-10 mg over 24 hours 1
• Monitoring required: ECG for QTc prolongation, especially in elderly patients 2, 5

Second-Line Options for Refractory Agitation

Levomepromazine (if available) 1:

• Start 12.5-25 mg, with 50-75 mg continuous infusion
• Can be administered subcutaneously or intravenously
• Caution: Risk of orthostatic hypotension, especially in debilitated patients 1

Phenobarbital for severe refractory agitation 1:

• 1-3 mg/kg subcutaneous or IV bolus, followed by 0.5 mg/kg/hour infusion
• Usual maintenance: 50-100 mg/hour
• Advantage: Anticonvulsant properties, useful if extreme tolerance to opioids/benzodiazepines 1

Critical Safety Considerations

Benzodiazepine Risks in Elderly Hospice Patients

• Increased delirium incidence and duration 2, 3
• Paradoxical agitation in ~10% of elderly patients 2, 3
• Respiratory depression risk, especially when combined with opioids 1
• Tolerance and withdrawal if dose rapidly reduced after continuous infusion 1

Antipsychotic Risks

• All antipsychotics increase mortality risk 1.6-1.7 times higher than placebo in elderly patients 2
• QT prolongation, dysrhythmias, sudden death 2, 5
• Extrapyramidal symptoms (tremor, rigidity, bradykinesia) 5
• However: In hospice settings with imminent death, the mortality risk may be less relevant than symptom control 2

Practical Algorithm for Your Patient

Step 1: Address reversible causes (pain, infection, constipation, urinary retention) 1, 2

Step 2: While still able to swallow:

• Start lorazepam 0.25-0.5 mg orally/sublingually PRN for anxiety-driven agitation 1, 3
• OR haloperidol 0.5 mg orally PRN if delirium is present 1, 2

Step 3: When NPO or unable to swallow:

• Transition to midazolam 2.5-5 mg subcutaneously every 2-4 hours PRN 1
• If needed >2 times daily, start continuous subcutaneous infusion midazolam 10 mg/24 hours 1

Step 4: For refractory agitation despite midazolam:

• Add haloperidol 1-2 mg subcutaneously PRN (can be co-administered with midazolam) 1
• OR consider phenobarbital for extreme cases 1

Common Pitfalls to Avoid

• Don't use benzodiazepines as first-line for delirium-related agitation - They may worsen confusion 1, 2
• Don't combine high-dose benzodiazepines with olanzapine - Fatalities from oversedation and respiratory depression have been reported 1, 2
• Don't use initial haloperidol doses >1 mg - No evidence of greater effectiveness, significantly higher risk of sedation 4
• Don't forget to reduce midazolam dose by 50% if eGFR <30 1
• Don't overlook pain as a driver of agitation - This is the most common reversible cause in hospice patients 2

Documentation for Goals of Care Discussion

Given the hospice setting, discuss with the patient (if able) and family 2:

• The goal is comfort and symptom control, not prolonging life
• Sedation may be necessary to achieve comfort
• Risk of respiratory depression is acceptable in the context of terminal illness
• The plan to escalate medications as needed for symptom control