Midazolam is a versatile benzodiazepine commonly used in clinical settings for anesthesia induction. It is water-soluble in its acid formulation but highly lipid soluble in vivo. The drug also has a relatively rapid onset of action and high metabolic clearance compared to other benzodiazepines, which is highly practical for more urgent cases.1,2 Though midazolam can be administered via multiple routes, intravenous delivery is most common.
Since midazolam is not easily absorbed following oral administration, the benzodiazepine is typically administered in its intravenous (IV) form. After IV administration, midazolam is partially metabolized by the CYP450 enzymes, a family of liver enzymes that plays a key role in the metabolism of drugs and other xenobiotics.3 Midazolam may also be metabolized through glucuronide conjugation, where it is converted into its active metabolite: alpha-1 hydroxy midazolam. Midazolam’s mechanism of action is indirect: it binds to benzodiazepine and GABA receptors, which increases the frequency of chloride channel openings, membrane hyperpolarization, and neuronal inhibition. The drug’s anticonvulsant properties and muscle-relaxing effects are tied to the increased GABA-mediated inhibition of specific neural circuitry and midazolam’s interaction with glycine receptors, respectively.1,4
In the context of anesthesia, intravenous midazolam is not as rapid acting nor as predictable in its hypnotic effects. However, its advantages during the maintenance period, such as anxiolysis, high tolerance, and dose flexibility, make it a useful addition to many anesthesia regimes. Midazolam’s ability to increase glycine inhibitory neurotransmitters in the brain stem and spinal cord is thought to contribute to its anxiolytic properties.2 Compared to other anesthesia adjuncts, midazolam enhances patient satisfaction and comfort, increasing the use of the drug in regional and local anesthesia. Due to its rapid, non-painful administration, midazolam is beneficial in pediatric patients.1 In terms of seizure management, midazolam is commonly used in treating immediate seizure cases, such as status epilepticus. It has a 75% success rate for preventing further seizures and is applicable as a continuous infusion for refractory status epilepticus.5 Midazolam’s anticonvulsant effects are thought to be caused by the increased action of GABA on motor circuits.
Common adverse effects of midazolam include coughing, nausea, and vomiting. Injection-related complications, such as thrombophlebitis, thrombosis, and injection site pain are also commonly reported for intravenous midazolam, although less frequently than with other IV benzodiazepines. Like other benzodiazepines, midazolam can cause retrograde amnesia, ataxia, confusion, and drowsiness. The agent can also increase the likelihood of falls or impaired coordination in elderly or sick patients. Rapid intravenous administration of midazolam can have more severe impacts, like hypotension or tachycardia, and high dosages may result in respiratory depression and paradoxical reactions, such as involuntary movements or speech, uncontrollable emotions, and uncharacteristically aggressive behavior. The risk of respiratory depression increases when midazolam is administered in conjunction with other CNS depressants, like fentanyl.1
Midazolam is a highly versatile and effective benzodiazepine with a large range of clinical applications, particularly in anesthesia and seizure management. Its rapid onset, high metabolic clearance, and anxiolytic properties make it very useful in both emergency and routine medical procedures. While it offers significant benefits, such as ease of administration and patient comfort, it comes with its own set of risks. Adverse effects like respiratory distress, amnesia, and injection-related complications must all be carefully managed. Despite these challenges, midazolam remains an important tool in anesthesia and acute seizure treatment.
References
- Karunarathna, I., Hapuarachchi, T., Gunasena, P., & Gunathilake, S. (2024). Intravenous Midazolam: Applications in Anesthesia and Seizure Management.
- Reves, J. G., et al. “Midazolam: Pharmacology and Uses.” Anesthesiology, vol. 62, no. 3, Mar. 1985, pp. 310–24. 10.1097/00000542-198503000-00017
- McDonnell, Anne M., and Cathyyen H. Dang. “Basic Review of the Cytochrome P450 System.” Journal of the Advanced Practitioner in Oncology, vol. 4, no. 4, 2013, pp. 263–68. PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093435/
- Richter, James J. “Current Theories about the Mechanisms of Benzodiazepines and Neuroleptic Drugs.” Anesthesiology, vol. 54, no. 1, Jan. 1981, pp. 66–72. https://doi.org/10.1097/00000542-198101000-00013
- Walker, Matthew. “Status Epilepticus: An Evidence Based Guide.” BMJ : British Medical Journal, vol. 331, no. 7518, Sept. 2005, pp. 673–77. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226249/