What is Midazolam (Benzodiazepine)?

From the Guidelines

Midazolam is the preferred benzodiazepine for sedation due to its rapid onset and short duration of action, with a recommended initial dose of 1-2 mg intravenously for healthy adults younger than 60 years of age 1.

Key Characteristics of Midazolam

• Midazolam has a rapid onset of action, with effects beginning within 1-2 minutes after intravenous administration, and a peak effect achieved within 3-4 minutes 1.
• Its duration of effect is 15-80 minutes, making it suitable for brief procedures 1.
• Midazolam clearance is reduced in the elderly, obese, and those with hepatic or renal impairment, necessitating dose adjustments in these populations 1.

Clinical Applications and Dosing

• The initial intravenous dose for healthy adults younger than 60 years of age is 1-2 mg (or no more than 0.03 mg/kg) injected over 1-2 minutes, with additional doses of 1 mg (or 0.02-0.03 mg/kg) administered at 2-minute intervals as needed 1.
• Patients older than 60 and those with ASA physical status III or greater require a dose reduction of 20% or more 1.
• A total intravenous dose greater than 6 mg is usually not required for routine endoscopic procedures 1.

Safety and Side Effects

• The major side effect of midazolam is respiratory depression, which can be fatal when combined with opioids 1.
• Monitoring is essential during administration to promptly identify and manage adverse effects, including respiratory depression, hypotension, and paradoxical reactions 1.
• Midazolam should be used cautiously in elderly patients, those with respiratory conditions, and when combined with other central nervous system depressants 1.

From the FDA Drug Label

Midazolam is a short-acting benzodiazepine central nervous system (CNS) depressant. The effects of midazolam on the CNS are dependent on the dose administered, the route of administration, and the presence or absence of other medications Onset time of sedative effects after intramuscular (IM) administration in adults is 15 minutes, with peak sedation occurring 30 to 60 minutes following injection In one adult study, when tested the following day, 73% of the patients who received midazolam intramuscularly had no recall of memory cards shown 30 minutes following drug administration; 40% had no recall of the memory cards shown 60 minutes following drug administration Onset time of sedative effects in the pediatric population begins within 5 minutes and peaks at 15 to 30 minutes depending upon the dose administered. In pediatric patients, up to 85% had no recall of pictures shown after receiving intramuscular midazolam compared with 5% of the placebo controls Sedation in adult and pediatric patients is achieved within 3 to 5 minutes after intravenous (IV) injection; the time of onset is affected by total dose administered and the concurrent administration of narcotic premedication Seventy-one percent of the adult patients in endoscopy studies had no recall of introduction of the endoscope; 82% of the patients had no recall of withdrawal of the endoscope. In one study of pediatric patients undergoing lumbar puncture or bone marrow aspiration, 88% of patients had impaired recall vs 9% of the placebo controls In another pediatric oncology study, 91% of midazolam treated patients were amnestic compared with 35% of patients who had received fentanyl alone. When midazolam is given intravenous as an anesthetic induction agent, induction of anesthesia occurs in approximately 1.5 minutes when narcotic premedication has been administered and in 2 to 2. 5 minutes without narcotic premedication or other sedative premedication. Some impairment in a test of memory was noted in 90% of the patients studied. A dose response study of pediatric patients premedicated with 1 mg/kg intramuscular meperidine found that only 4 out of 6 pediatric patients who received 600 mcg/kg intravenous midazolam lost consciousness, with eye closing at 108 ± 140 seconds This group was compared with pediatric patients who were given thiopental 5 mg/kg intravenous; 6 out of 6 closed their eyes at 20 ± 3. 2 seconds. Midazolam did not dependably induce anesthesia at this dose despite concomitant opioid administration in pediatric patients. Midazolam, used as directed, does not delay awakening from general anesthesia in adults Gross tests of recovery after awakening (orientation, ability to stand and walk, suitability for discharge from the recovery room, return to baseline Trieger competency) usually indicate recovery within 2 hours but recovery may take up to 6 hours in some cases. When compared with patients who received thiopental, patients who received midazolam generally recovered at a slightly slower rate

Midazolam is a short-acting benzodiazepine with sedative and amnestic effects.

• The onset of sedation occurs within 15 minutes after intramuscular administration and within 3 to 5 minutes after intravenous administration.
• Amnesia is a common effect, with 73% of adult patients having no recall of events 30 minutes after administration and 85% of pediatric patients having no recall of pictures shown after receiving midazolam.
• Recovery from midazolam typically occurs within 2 hours, but may take up to 6 hours in some cases 2.

From the Research

Midazolam Overview

• Midazolam is used for sedation before diagnostic and therapeutic medical procedures 3, 4.
• It is an imidazole benzodiazepine that has depressant effects on the central nervous system (CNS) with rapid onset of action and few adverse effects 3.
• The drug can be administered by several routes including oral, intravenous, intranasal, and intramuscular 3, 4.

Efficacy of Midazolam

• There is low-quality evidence that intravenous midazolam reduces anxiety when compared with placebo 3, 4.
• Intravenous midazolam versus diazepam showed no difference in anxiety or discomfort/pain, but midazolam produced greater anterograde amnesia 3.
• Oral midazolam versus chloral hydrate resulted in midazolam increasing the risk of incomplete procedures, with moderate-quality evidence suggesting that oral midazolam produces less-effective sedation than chloral hydrate for completion of procedures for children undergoing non-invasive diagnostic procedures 3, 4.

Comparison with Other Sedatives

• Lorazepam is a useful alternative to midazolam for the long-term sedation of patients in the medical intensive care unit and provides easier management of the sedation level, with a significant cost-savings 5.
• Flumazenil effectively reverses the benzodiazepine component of ventilatory depression during combined administration of a benzodiazepine and an opioid 6.

Administration and Dosage

• The optimal intravenous dosing strategies for sedatives and analgesics in the intensive care unit involve understanding the clinical pharmacology of commonly used sedative agents, including midazolam 7.
• Midazolam and morphine both have active metabolites that can accumulate in critically ill patients receiving long-term infusions, adding to the sedative effects of the primary compound 7.