How is terminal restlessness best managed?

Management of Terminal Restlessness

Terminal restlessness should be managed with a combination of non-pharmacological approaches and medications, with antipsychotic drugs such as haloperidol, olanzapine, or chlorpromazine as first-line pharmacological treatment, and benzodiazepines such as midazolam or lorazepam added for refractory agitation. 1

Assessment and Identification

• Terminal restlessness is a form of delirium that occurs in dying patients, affecting between 25% and 88% of patients at the end of life 2
• Assess using Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria to confirm delirium 1
• Identify and address reversible causes before initiating pharmacological management 1
• Evaluate for potential iatrogenic causes such as medications (steroids, anticholinergics) that should be reduced or eliminated when possible 1

Non-Pharmacological Interventions

• Maximize non-pharmacological interventions before starting medications 1:
  • Reorientation strategies
  • Cognitive stimulation
  • Sleep hygiene measures
  • Environmental modifications to reduce stimulation
• Support caregivers in coping with this distressing condition 1
• Consider use of assistive devices such as robotic pets for patients with dementia experiencing terminal restlessness 3

Pharmacological Management

First-Line Treatment

• For moderate delirium/restlessness, use oral antipsychotics 1:
  • Haloperidol
  • Risperidone
  • Olanzapine
  • Quetiapine fumarate

Severe Agitation/Restlessness

• For severe agitation, use antipsychotic/neuroleptic drugs 1:
  • Haloperidol (oral or parenteral)
  • Olanzapine
  • Chlorpromazine (IV only in bed-bound patients due to hypotensive effects) 1

Refractory Symptoms

• Add benzodiazepines for agitation refractory to high doses of neuroleptics 1:
  • Lorazepam can be added to neuroleptics 1
  • Midazolam by subcutaneous infusion (0.4-0.8 mg/hr initially, titrating up as needed) is highly effective for terminal restlessness 4, 5
  • Therapeutic levels of neuroleptics help prevent paradoxical excitation sometimes seen with benzodiazepines 1

Medication Titration and Administration

• Titrate medication doses to achieve optimal symptom relief 1
• For imminently dying patients, focus monitoring on comfort rather than vital signs 1
• Do not reduce sedation if respiratory rate gradually decreases, as this is expected with approaching death 1
• Administration routes may include 1:
  • Intravenous
  • Subcutaneous (particularly useful for midazolam infusions) 4, 5
  • Intramuscular
  • Rectal
  • Via stoma or gastrostomy when necessary

Special Considerations

• If delirium is believed to be caused by opioid neurotoxicity, consider opioid rotation 1
• For refractory delirium in dying patients, palliative sedation can be considered after consultation with palliative care specialists 1
• Remove unnecessary medications and tubes 1
• The level of sedation should be the least necessary to provide adequate relief of suffering 1
• Decisions about hydration and nutrition are separate from decisions about sedation 1

Monitoring and Follow-up

• For imminently dying patients, monitor only for comfort parameters 1
• For patients not imminently dying, consider monitoring sedation level and physiological parameters 1
• Provide emergency bolus therapy for breakthrough symptoms 1
• Consider downward titration of medication only if specifically requested by the patient before sedation was initiated 1

Terminal restlessness requires prompt recognition and intervention to ensure patient comfort at the end of life, with treatment approaches tailored to the severity of symptoms and the patient's proximity to death 1, 2, 6.