What causes agitation in hospice patients?

From the Guidelines

Agitation in hospice patients should be managed with a combination of non-pharmacological approaches and medications when necessary, prioritizing haloperidol (0.5-2mg orally, subcutaneously, or intravenously every 4-6 hours) as the first-line treatment for acute agitation, as supported by the most recent and highest quality study 1.

Non-Pharmacological Interventions

Non-pharmacological interventions are crucial in managing agitation in hospice patients. These include:

• Maintaining a calm environment
• Ensuring familiar caregivers are present
• Providing gentle reassurance and comfort measures
• Identifying and addressing underlying causes such as pain, urinary retention, constipation, or medication side effects

Pharmacological Interventions

When medications are necessary, the following options are considered:

• Haloperidol (0.5-2mg orally, subcutaneously, or intravenously every 4-6 hours) as the first-line treatment for acute agitation 1
• Alternatives include lorazepam (0.5-2mg every 4-6 hours), risperidone (0.25-1mg twice daily), or quetiapine (25-100mg daily to twice daily) 1
• For severe agitation, midazolam (2.5-5mg subcutaneously) may be used, with potential for continuous infusion (0.5-1mg/hour) in refractory cases

Considerations

Medications should be titrated to the lowest effective dose to minimize side effects. Regular reassessment is crucial as agitation may fluctuate with disease progression. This approach balances symptom control with quality of life, recognizing that agitation often stems from the body's response to advancing disease, unmet needs, or existential distress in the dying process. The use of standardized assessment tools, such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) or Intensive Care Delirium Screening Checklist (ICDSC), is recommended for evaluating delirium in critically ill patients 1.

From the FDA Drug Label

In patients with depression, a possibility for suicide should be borne in mind; benzodiazepines should not be used in such patients without adequate anti-depressant therapy. The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Lorazepam should be used with caution in patients with compromised respiratory function (e. g. COPD, sleep apnea syndrome). Paradoxical reactions have been occasionally reported during benzodiazepine use Such reactions may be more likely to occur in children and the elderly. Psychiatric Disorders: Agitation, Confusional state, Depression, Insomnia

Agitation in Hospice Patients:

• Lorazepam may be used to treat agitation in hospice patients, but it should be used with caution due to the risk of respiratory depression, especially when combined with opioids.
• The use of lorazepam in hospice patients requires careful monitoring and dosage adjustment to minimize the risk of adverse effects.
• Haloperidol may also be used to treat agitation in hospice patients, but it carries a risk of extrapyramidal symptoms and other adverse effects.
• The choice of medication for agitation in hospice patients should be based on the individual patient's needs and medical history, and should be made in consultation with a healthcare provider. 2 3 4

From the Research

Agitation in Hospice Patients

• Agitation in hospice patients is a significant concern, and various studies have investigated the effectiveness of different pharmacological treatments for managing agitated delirium in the last days of life 5, 6, 7, 8, 9.
• High-dose neuroleptics, such as haloperidol, may be ineffective at low doses or poorly tolerated at higher doses, and rotation to an alternate neuroleptic may be necessary to achieve control of agitation 5.
• The combination of haloperidol with as-needed benzodiazepines, chlorpromazine, or levomepromazine may be effective and safe for terminal agitation, with chlorpromazine and levomepromazine potentially having an advantage in terms of not requiring medication changes 6.
• The addition of lorazepam to haloperidol has been shown to result in a significantly greater reduction in agitation at 8 hours compared to haloperidol alone in patients with agitated delirium in the setting of advanced cancer 7.
• Benzodiazepines, such as lorazepam, may be used in specific delirium settings, including persistent agitation in patients with terminal delirium and delirium tremens, but their use should be approached with caution due to the risks of precipitating or worsening delirium and over-sedation 8.
• The combination of haloperidol, lorazepam, and diphenhydramine (B52) has been compared to the combination of haloperidol and lorazepam (52) in the treatment of acute agitation, with no significant difference in administration frequency of additional agitation medication, but the 52 combination resulted in fewer adverse effects and a shorter length of stay 9.

Treatment Options

• Haloperidol with as-needed benzodiazepines 6
• Chlorpromazine 5, 6
• Levomepromazine 6
• Lorazepam with haloperidol 7, 8
• Combination haloperidol, lorazepam, and diphenhydramine (B52) 9
• Combination haloperidol and lorazepam (52) 9

Considerations

• The goal of care for patients with terminal delirium is to maximize comfort, recognizing that patients are unlikely to recover from their delirium 8.
• Clinicians should exercise caution when prescribing benzodiazepines due to the risks of precipitating or worsening delirium and over-sedation 8.
• The selection of the right medication, dose, and indication for the right patient at the right time is crucial for effective and safe treatment of agitation in hospice patients 8.