From the Guidelines
Intravenous (IV) midazolam and subcutaneous (sub-Q) midazolam are considered to have a 1:1 dose equivalence, meaning the same dose can be used when converting between these two routes of administration. For example, if a patient is receiving 2 mg of IV midazolam, they would receive 2 mg when switched to sub-Q administration. This equivalent dosing is possible because midazolam has excellent bioavailability when administered subcutaneously, with absorption rates similar to IV administration, though the onset of action may be slightly delayed with sub-Q (typically 5-10 minutes versus 1-5 minutes for IV) 1. When converting between these routes, no dose adjustment is typically necessary, but clinicians should monitor patients for clinical effect, especially when initiating therapy or changing routes. The subcutaneous route is often preferred in palliative care settings or when IV access is difficult to maintain. Both routes should be used cautiously in elderly patients or those with respiratory compromise, as midazolam can cause respiratory depression regardless of administration route 1. Some key considerations when using midazolam include:
- Initial intravenous dose in healthy adults younger than 60 years of age is 1 mg (or no more than 0.03 mg/kg) injected over 1-2 minutes 1
- Patients older than 60 and those with ASA physical status III or greater require a dose reduction of 20% or more 1
- Midazolam clearance is reduced in the elderly, obese, and those with hepatic or renal impairment 1 It's essential to note that while the provided studies do not directly address the subcutaneous administration of midazolam, the equivalent dosing is based on the drug's pharmacokinetic properties and clinical experience. However, the most recent and highest quality study available is from 2012 1, which provides guidance on the use of midazolam in gastrointestinal endoscopy, but does not specifically address subcutaneous administration. Therefore, the recommendation is based on the available evidence and clinical expertise, prioritizing patient safety and monitoring for clinical effect.
From the Research
Equivalent Dose of Intravenous (IV) Midazolam to Subcutaneous (Sub-Q) Midazolam
There are no direct studies comparing the equivalent dose of IV midazolam to sub-Q midazolam. However, some studies provide information on the pharmacokinetics and pharmacodynamics of midazolam after different routes of administration.
- The bioavailability of midazolam after intramuscular (IM) administration is 92% 2, but there is no information on the bioavailability after sub-Q administration.
- The study on alpacas found that the maximum concentration of midazolam after IM administration was 411 ng/mL, which is lower than the maximum concentration after IV administration (1,394 ng/mL) 2.
- Another study found that midazolam is well absorbed after IM administration, with a short duration of action and moderate levels of sedation 2.
- There is no information on the equivalent dose of IV midazolam to sub-Q midazolam in the provided studies.
Pharmacokinetics and Pharmacodynamics of Midazolam
The pharmacokinetics and pharmacodynamics of midazolam vary depending on the route of administration.
- After IV administration, midazolam has a rapid onset of action and a short duration of action 3, 4.
- After IM administration, midazolam has a slower onset of action and a longer duration of action compared to IV administration 2.
- The elimination half-life of midazolam after IV administration is approximately 1 hour, but this can be prolonged in patients with renal or hepatic dysfunction 3.
Clinical Use of Midazolam
Midazolam is commonly used for sedation, anxiolysis, and amnesia in various clinical settings.
- The recommended dose of midazolam for children varies depending on the age and weight of the child, with a typical initial dose of 0.05 to 0.1 mg/kg for children 6 months to 5 years of age 5.
- Midazolam can cause respiratory depression, particularly when used in combination with other sedatives or in elderly patients 6.