Starting Dose for Midazolam Subcutaneous Infusion
The recommended starting dose for midazolam subcutaneous infusion is 10 mg over 24 hours, with a reduced dose of 5 mg over 24 hours for patients with renal impairment (eGFR <30 mL/minute). 1
Dosing Algorithm
Initial Assessment
- Determine the indication for midazolam (anxiety, agitation, terminal restlessness)
- Check renal function (eGFR)
- Review patient's current medications for potential interactions
- Assess patient's age and frailty status
Standard Starting Dose
- Standard starting dose: 10 mg over 24 hours via subcutaneous infusion 1
- For patients with renal impairment (eGFR <30 mL/minute): 5 mg over 24 hours 1
- For elderly or debilitated patients: Consider starting at 5 mg over 24 hours
PRN Dosing Before Starting Infusion
- If immediate symptom control is needed before establishing the infusion:
- Give midazolam 2.5-5 mg subcutaneously every 2-4 hours as required 1
- If PRN doses are needed more than twice daily, initiate the continuous infusion
Titration Protocol
- Monitor patient response every 4-6 hours after starting infusion
- If symptoms persist:
- Maximum dose: No specified upper limit during end-of-life care, but titrate to symptom control 1
Clinical Pearls and Caveats
Pharmacokinetic Considerations
- Midazolam has excellent bioavailability (96%) when administered subcutaneously 2
- Half-life is approximately 3.2 hours after subcutaneous administration 2
- Metabolized in the liver by cytochrome P450 system to 1-hydroxymethyl midazolam
Practical Administration Tips
- Midazolam can be mixed in the same syringe as morphine/diamorphine for subcutaneous infusion 3
- Monitor injection sites for signs of irritation
- At higher doses, the volume required may present practical difficulties 3
Monitoring
- Assess for:
- Respiratory depression (particularly when combined with opioids)
- Excessive sedation
- Paradoxical agitation (rare)
- Hypotension
Special Populations
- Elderly: More sensitive to benzodiazepines; consider lower starting doses
- Renal impairment: Use reduced dose (5 mg/24 hours) 1
- Hepatic impairment: Consider dose reduction due to decreased metabolism
Combination Therapy
- When used for anxiety or agitation, ensure pain is adequately controlled first with opioids 1
- For delirium with agitation, consider combining with an antipsychotic like haloperidol 1
Remember that midazolam subcutaneous infusion has been shown to be effective in controlling terminal restlessness and agitation in palliative care settings, with studies demonstrating good symptom control in the majority of patients 3.