What are the recommended approaches for managing terminal restlessness?

Management of Terminal Restlessness

Midazolam is the first-line medication for managing terminal restlessness, with a starting dose of 0.5-1 mg/h subcutaneously or 1-5 mg as needed, due to its rapid onset and effectiveness in providing symptom relief. 1

First-Line Pharmacological Management

• Midazolam is the preferred benzodiazepine for terminal restlessness with a usual effective dose range of 1-20 mg/h 2, 1
• For continuous infusion, start with 0.5-1 mg/h subcutaneously, which can be increased to 10 mg over 24 hours via syringe driver for more severe cases 1
• Midazolam can be co-administered with morphine or haloperidol when multiple symptoms are present 2
• For breakthrough restlessness, bolus doses of 1-5 mg can be administered as needed 2

Second-Line Pharmacological Options

• Neuroleptics/antipsychotics are recommended when delirium is contributing to terminal restlessness 2, 3
• Levomepromazine (methotrimeprazine) is effective with a starting dose of 12.5-25 mg subcutaneously or 50-75 mg continuous infusion 2
• Chlorpromazine can be administered intravenously (12.5 mg every 4-12 hours), intramuscularly, or rectally (25-100 mg every 4-12 hours) 2, 4
• Haloperidol can be administered subcutaneously as required or as infusion of 2.5-10 mg over 24 hours 1

Third-Line Pharmacological Options

• For patients who have developed tolerance to benzodiazepines and neuroleptics, phenobarbital can be used with a starting dose of 1-3 mg/kg subcutaneously or IV bolus, followed by infusion of 0.5 mg/kg/h 2, 1
• Propofol is an alternative with rapid onset and short duration, administered with a loading dose of 20 mg followed by infusion of 50-70 mg/h, but requires careful monitoring due to potential respiratory depression 2, 1

Clinical Assessment and Decision Algorithm

1. Assess for reversible causes of restlessness:

   • Rule out pain, urinary retention, constipation, medication side effects, and hypoxia 1, 5
   • Distinguish between anxiety and delirium, as benzodiazepines can worsen delirium 6

2. Select medication based on clinical presentation:

   • For anxiety-predominant restlessness: midazolam 1
   • For delirium-predominant restlessness: haloperidol, levomepromazine, or chlorpromazine 1
   • For mixed presentation: combination therapy may be appropriate 3

3. Monitoring and dose adjustment:

   • For imminently dying patients: monitor for comfort only, not vital signs 2
   • For non-imminently dying patients: monitor sedation level and physiological parameters 2
   • If respiratory depression occurs in non-imminently dying patients, consider dose reduction or flumazenil administration 2

Important Considerations

• Medications for symptom palliation used before sedation should be continued unless ineffective or causing distressing side effects 2
• Medications inconsistent with comfort goals can be discontinued 6
• Provision for breakthrough symptom management should always be included 6
• Terminal restlessness affects between 25% and 88% of dying patients, making it a common end-of-life symptom requiring prompt management 3
• Combination therapy with benzodiazepines and neuroleptics may be more effective than monotherapy in refractory cases 3

Family Support and Communication

• Allow and encourage family members to be with the patient 2
• Provide reassurance that sedation is unlikely to shorten the patient's life 2
• Keep family informed about the patient's well-being and what to expect 2
• Offer support to family members, including listening to concerns and providing guidance on how they can help the patient 2
• Consider offering a post-death meeting with family to address any concerns about end-of-life care 2