Management of Terminal Restlessness

First-Line Alternatives

The European Society for Medical Oncology recommends midazolam as the preferred alternative to lorazepam for terminal restlessness, with a starting dose of 0.5-1 mg/h subcutaneously or 1-5 mg as needed 1
Midazolam can be administered intravenously or subcutaneously, and can be co-administered with morphine or haloperidol, with a usual effective dose of 1-20 mg/h 1
For severe agitation, the British Medical Journal suggests 2.5-5 mg subcutaneously every 2-4 hours as needed, and for continuous infusion, start with 10 mg over 24 hours via syringe driver 2

The European Society for Medical Oncology recommends levomepromazine as an antipsychotic phenothiazine with some analgesic effect, with a starting dose of 12.5-25 mg subcutaneously or 50-75 mg continuous infusion 1
Chlorpromazine is a widely available antipsychotic with multiple administration routes, with a starting dose of 12.5 mg IV or IM every 4-12 hours, or 3-5 mg/h IV, or 25-100 mg every 4-12 hours rectally 1
Haloperidol can be administered subcutaneously as required or as infusion of 2.5-10 mg over 24 hours, with a consideration for higher starting dose for severe distress 2

Phenobarbital is useful when patients have developed tolerance to benzodiazepines, with a starting dose of 1-3 mg/kg subcutaneously or IV bolus, followed by infusion of 0.5 mg/kg/h 1
Propofol has a similar effect to short-acting barbiturates, with a loading dose of 20 mg, followed by infusion of 50-70 mg/h, requiring careful monitoring due to potential for respiratory depression 1

The British Medical Journal recommends assessing for reversible causes first, exploring patient's concerns and anxieties, and ensuring effective communication and orientation 2
The European Society for Medical Oncology suggests choosing medication based on clinical presentation, with midazolam preferred for anxiety, and haloperidol, levomepromazine, or chlorpromazine for delirium 1, 2

The British Medical Journal advises adjusting dosing for special populations, including elderly patients, patients on opioid medication, and patients with impaired liver or renal function 2
The European Society for Medical Oncology recommends monitoring sedation level and physiological parameters for non-imminently dying patients, and considering combining benzodiazepines with antipsychotics for refractory cases 1, 2