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Intravenous midazolam is indicated for procedural sedation (often in combination with an opioid, such as fentanyl), for preoperative sedation, for the induction of general anesthesia, and for sedation of people who are ventilated in critical care units.

It is the most popular benzodiazepine in the intensive care unit (ICU) because of its short elimination half-life, combined with its water solubility and its suitability for continuous infusion.

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Tolerance and the resultant withdrawal syndrome may be due to receptor down-regulation and GABA Prolonged infusions with midazolam results in the development of tolerance; if midazolam is given for a few days or more a withdrawal syndrome can occur.

Therefore, preventing a withdrawal syndrome requires that a prolonged infusion be gradually withdrawn, and sometimes, continued tapering of dose with an oral long-acting benzodiazepine such as clorazepate dipotassium.

Midazolam is effective for status epilepticus that has not improved following other treatments or when intravenous access cannot be obtained, and has advantages of being water-soluble, having a rapid onset of action and not causing metabolic acidosis from the propylene glycol vehicle, which occurs with other benzodiazepines.

Drawbacks include a high degree of breakthrough seizures—due to the short half-life of midazolam—in over 50% of people treated, as well as treatment failure in 14–18% of people with refractory status epilepticus.

When signs of tolerance to midazolam occur during intensive care unit sedation the addition of an opioid or propofol is recommended.

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