From the Guidelines
Midazolam is recommended for sedation at an initial intravenous dose of 1-2 mg in healthy adults younger than 60 years of age, with additional doses of 1 mg administered at 2-minute intervals until adequate sedation is achieved, not exceeding a total dose of 6 mg 1. The dosage and usage of midazolam for sedation vary by administration route, patient age, and clinical context.
Key Considerations
- For adults receiving IV midazolam, the typical initial dose is 1-2 mg given slowly over 1-2 minutes, with additional doses of 1 mg administered every 2 minutes until adequate sedation is achieved, generally not exceeding a total dose of 6 mg 1.
- Elderly or debilitated patients should receive lower doses, typically starting at 0.5-1 mg, with a dose reduction of 20% or more for patients older than 60 and those with ASA physical status 3 or above 1.
- When midazolam is used with an opioid, a synergistic interaction occurs, and a reduction in the dose of midazolam may be indicated 1.
Administration and Monitoring
- Midazolam works by enhancing the inhibitory effects of GABA in the central nervous system, producing anxiolysis, amnesia, and sedation.
- Patients should be monitored for respiratory depression, hypotension, and paradoxical reactions, particularly when midazolam is combined with other sedatives or opioids 1.
- Flumazenil should be available as a reversal agent.
Clinical Applications
- The major clinical applications of midazolam are procedural sedation and induction of general anesthesia 1.
- Midazolam has been shown to be more potent and faster acting than diazepam, with fewer adverse events, including respiratory depression 1.
From the FDA Drug Label
Patients who exhibit agitation, hypertension or tachycardia in response to noxious stimulation, but who are otherwise adequately sedated, may benefit from concurrent administration of an opioid analgesic. The initial dose of midazolam should be administered over 2 to 3 minutes For all pediatric patients, regardless of the indications for sedation/anxiolysis, it is vital to titrate midazolam and other concomitant medications slowly to the desired clinical effect. Pediatric patients less than 6 months of age: Limited information is available in non-intubated pediatric patients less than 6 months of age Pediatric patients 6 months to 5 years of age: Initial dose 0. 05 to 0.1 mg/kg. Pediatric patients 6 to 12 years of age: Initial dose 0.025 to 0.05 mg/kg; Pediatric patients 12 to 16 years of age: Should be dosed as adults Healthy Adults Below the Age of 60: Titrate slowly to the desired effect, e.g., the initiation of slurred speech. Some patients may respond to as little as 1 mg. Patients Age 60 or Older, and Debilitated or Chronically Ill Patients: Because the danger of hypoventilation, airway obstruction, or apnea is greater in elderly patients and those with chronic disease states or decreased pulmonary reserve, and because the peak effect may take longer in these patients, increments should be smaller and the rate of injection slower.
The recommended dosage and usage of midazolam for sedation vary based on age and patient status.
- For pediatric patients:
- Less than 6 months: Limited information available
- 6 months to 5 years: Initial dose 0.05 to 0.1 mg/kg
- 6 to 12 years: Initial dose 0.025 to 0.05 mg/kg
- 12 to 16 years: Dosed as adults
- For adults:
- Healthy adults below 60: Titrate slowly to desired effect, starting with 1 mg
- Patients 60 or older, debilitated, or chronically ill: Smaller increments and slower rate of injection, starting with 1 mg It is essential to titrate midazolam slowly and monitor patients closely to avoid adverse effects, especially in vulnerable populations 2 2.
From the Research
Recommended Dosage and Usage of Midazolam for Sedation
- The recommended dose of midazolam for preoperative sedation is 0.07-0.1 mg/kg given by intramuscular injection one hour before surgery 3.
- For conscious sedation, 0.1-0.15 mg/kg intravenously in divided doses is usually adequate 3.
- Lower doses of midazolam are recommended for elderly or debilitated patients and patients who have severe liver disease 3.
- Midazolam can be administered by several routes including oral, intravenous, intranasal, and intramuscular 4, 5.
Effectiveness of Midazolam for Sedation
- There is low-quality evidence that intravenous midazolam reduces anxiety when compared with placebo 4, 5.
- Midazolam produced greater anterograde amnesia compared to diazepam 4.
- Oral midazolam versus chloral hydrate: midazolam increased the risk of incomplete procedures, but there was no difference in ratings of anxiety 4, 5.
- Oral midazolam versus placebo: midazolam reduced ratings of anxiety and pain, but the effect estimates are uncertain due to concerns about risk of bias and imprecision 5.
Pharmacokinetics and Interactions
- Midazolam is metabolized by cytochrome P450 (CYP) enzymes and by glucuronide conjugation 6.
- CYP3A4 is important in the biotransformation of both midazolam and diazepam 6.
- Midazolam has many clinically significant interactions with inhibitors and inducers of CYP3A4 and 2C19 6.
- Midazolam has synergistic interactions with other hypnotics and opioids 6.