Midazolam

Midazolam, commonly known by the brand name Versed, is a benzodiazepine used for sedation before and during surgery, to calm severe agitation, and to treat seizures that last longer than five minutes. It makes people sleepy, reduces anxiety, and causes temporary memory loss for events that happen while under its influence. The drug does not render a person unconscious—it only sedates them.

It can be given by mouth, into a vein, into a muscle, sprayed up the nose, or absorbed through the cheek. When injected into a vein, it typically starts working within five minutes; an injection into a muscle takes about fifteen minutes; taken orally, it takes ten to twenty minutes to take effect.

Possible side effects include slowed breathing, low blood pressure, and drowsiness. With long-term use, the body can build tolerance, and withdrawal symptoms may occur. Some people, especially children and older adults, experience paradoxical reactions like increased activity. While there is evidence of risk during pregnancy, a single dose while breastfeeding appears safe. Midazolam was patented in 1974 and entered medical use in 1982. It is on the World Health Organization's List of Essential Medicines, is available as a generic, and is a controlled substance in many countries.

For seizures, midazolam is used for acute, prolonged episodes. Long-term use for epilepsy is not recommended because tolerance makes it ineffective and sedation is a significant problem. In children, it can be given in the cheek or nose for acute seizures, including status epilepticus. Drawbacks include a high rate of breakthrough seizures—over 50% of treated people—due to its short half-life, and treatment failure in 14–18% of those with refractory status epilepticus. Tolerance to its anticonvulsant effect develops quickly, sometimes requiring several times the initial dose. With prolonged use, tolerance and tachyphylaxis can occur, and the elimination half-life may lengthen to days. Buccal and intranasal midazolam are often easier to give and more effective than rectal diazepam for emergency seizure control.

For procedural sedation, intravenous midazolam is used, often with an opioid like fentanyl, for sedation before procedures, to induce general anesthesia, and for ventilated patients in critical care. It impairs memory of endoscopy better than diazepam, but propofol allows quicker recovery and better memory loss. It is the most popular benzodiazepine in intensive care units due to its short half-life, water solubility, and suitability for continuous infusion. For long-term sedation, lorazepam is preferred because it lasts longer, and propofol has advantages like shorter weaning time and earlier removal of breathing tubes. In neonatal intensive care, midazolam requires extra caution; it should not be used for more than 72 hours due to risks of tachyphylaxis, withdrawal, and neurological problems. Bolus injections are avoided because they can cause cardiovascular depression and neurological issues. Midazolam sedation is also used to manage anxiety and behavior in children during dental treatment.

For agitation, midazolam is given with an antipsychotic drug for acute management of schizophrenia when aggressive or out-of-control behavior occurs. In end-of-life care, it is routinely used at low doses via subcutaneous injection to help with agitation, restlessness, or anxiety in the final hours or days. It is a first-line agent for palliative continuous deep sedation when intolerable suffering cannot be relieved otherwise, though higher doses are rarely needed.

Special precautions are required in the elderly, during pregnancy, in children, in those with alcohol or drug dependence, or with psychiatric disorders. Critically ill patients need extra caution because midazolam and its active metabolites can accumulate. Kidney or liver problems can slow elimination, leading to prolonged or stronger effects.

Side effects in the elderly are noted. People who experience amnesia from midazolam are usually unaware of the memory loss unless they knew it was a possible side effect. Long-term benzodiazepine use is linked to lasting memory deficits, with only partial recovery six months after stopping; full recovery after longer abstinence is unclear. Benzodiazepines can cause or worsen depression. Paradoxical excitement, including worsening of seizures, occasionally occurs. Children, the elderly, those with a history of heavy alcohol use, or a history of aggression are at higher risk for paradoxical reactions, which are especially linked to intravenous use. After nighttime use, residual "hangover" effects like sleepiness can persist.