From the Guidelines
For end-of-life care (EOLC) agitation, midazolam should be administered at a dose of 2.5-5 mg subcutaneously every 2-4 hours as required. This recommendation is based on the most recent and highest quality study available, which provides guidance on managing COVID-19 symptoms, including at the end of life, in the community 1. The study suggests that if midazolam is needed frequently, a subcutaneous infusion via a syringe driver may be considered, starting with midazolam 10 mg over 24 hours. However, the dose should be reduced to 5 mg over 24 hours if the estimated glomerular filtration rate (eGFR) is <30 mL per minute.
Key considerations for midazolam dosing in EOLC agitation include:
- Starting dose: 2.5-5 mg subcutaneously every 2-4 hours as required
- Continuous infusion: 10 mg over 24 hours, with potential reduction to 5 mg over 24 hours for patients with renal impairment
- Dose adjustment: based on patient response and goals of care
- Regular reassessment: essential to balance symptom control with avoiding excessive sedation
It is also important to note that midazolam works by enhancing GABA effects in the brain, producing anxiolysis, sedation, and amnesia. While other studies provide guidance on sedative use in intensive care settings 1, the most recent and relevant study for EOLC agitation is the one published in the BMJ in 2020 1. Therefore, this study's recommendations should be prioritized when determining midazolam dosing for EOLC agitation.
From the Research
Midazolam Doses for EOLC Agitation
- The optimal dose of midazolam for agitation in end-of-life care (EOLC) is not explicitly stated in the provided studies, but the combination of haloperidol and midazolam is shown to be effective and safe for controlling agitation in palliative care 2, 3.
- A study published in 2012 reported the use of midazolam and haloperidol in cancer patients at the end of life, with a median dose of midazolam of 5 mg/day 4.
- Another study published in 2016 compared the combination of haloperidol and midazolam with haloperidol alone for the treatment of acute agitation in an inpatient palliative care service, and found that the combination protocol controlled 84% of episodes of agitation with only the first dose, with a median time to control of 15 minutes 2.
- The safety of midazolam use in palliative care has been reviewed, highlighting the importance of considering pharmacokinetics, adverse effects, and drug-drug interactions 5.
- Midazolam is considered an essential palliative care drug, with a faster onset and shorter duration of action than other benzodiazepines, making it suitable for use in EOLC 6.
Key Findings
- Combination of haloperidol and midazolam is effective and safe for controlling agitation in palliative care 2, 3.
- Median dose of midazolam used in cancer patients at the end of life is 5 mg/day 4.
- Midazolam has a faster onset and shorter duration of action than other benzodiazepines, making it suitable for use in EOLC 6.