A Comparison of Midazolam with Other Benzodiazepines 

Benzodiazepines are depressants that have various effects, including hypnosis, anti-convulsant activity, sedation, decreased anxiety, mediated muscle relaxation, and anterograde amnesia [1]. Some of the most commonly used benzodiazepines, particularly in the clinical anesthesia setting, are midazolam, flumazenil, lorazepam, and diazepam [1]. Because of its rapid onset of action but short duration, midazolam is widely favored among benzodiazepines [1]. This article will explore how midazolam compares to other benzodiazepines in three contexts: sedating patients, treating status epilepticus, and reducing premedication anxiety. 

To begin, midazolam is widely used as a sedative [1]. It is “mainly used for sedation in minor investigative or surgical procedures, premedication, induction of general anaesthesia, and sedation in intensive care unit (ICU) patients” [1]. Compared to diazepam, research indicates that midazolam is more potent, has a quicker half-life (1.5 to 3.5 hours compared to approximately 20 hours), and, generally, provides a superior pre-operative sedative effect [2]. However, previous studies indicate that this may not hold in all cases. For instance, Sanatkar and colleagues reported that, in the context of cataract surgery, diazepam outscored midazolam in terms of the level of sedation, surgeon satisfaction, perioperative hemodynamic profile, and occurrence of apnea [3]. Another study indicates that, in terms of sedative effect, lorazepam has a longer duration of action and higher potency than midazolam [4]. Though it may not be universally better than other benzodiazepines, the consensus appears to be that midazolam is an effective and safe sedative and, when paired with flumazenil, can enhance its safety profile in cases of overdose [5]. 

As for the treatment of status epilepticus, midazolam appears to be superior or, at the very least, comparable to other benzodiazepines. McMullan and colleagues conducted a meta-analysis of six studies, concerning 774 total subjects, and concluded that, compared to diazepam, midazolam was superior in terms of seizure cessation by any route [6]. While both depressants produced similar times between administration and seizure cessation, midazolam administered faster than diazepam [6]. In the pediatric context, compared to lorazepam and diazepam, Zhao et al. reported that midazolam was more likely to achieve seizure cessation, but lorazepam was better in terms of reducing respiratory depression [7]. Lorazepam may also be preferable because of its longer half-life [8]. Still, both drugs are generally considered efficacious [8]. 

Conversely, as a treatment for premedication anxiety, midazolam may not be the optimal choice compared to other benzodiazepines. In ambulatory settings, intravenous midazolam is the most widely-used benzodiazepine for premedication purposes, but research indicates that other benzodiazepines are preferable on some metrics [9]. For instance, Ali et al. noted that diazepam was better at reducing anxiety, although it also contributed to amnesiac episodes [9]. This observation led the researchers to conclude that, at least in moderate doses, midazolam may be a safer option [9]. Another study comparing lorazepam, diazepam, and midazolam, found that midazolam alone produced certain side effects, such as drowsiness, physical agitation, and low peripheral capillary oxygen saturation [10]. While these studies do not suggest that the premedication use of midazolam should be avoided, medical professionals should exercise caution when administering it. 

Altogether, research supports the use of midazolam as a versatile drug. Of course, it is not perfect, producing considerable side effects and limited by its short half-life, but compared to other benzodiazepines, midazolam has several advantages. 

Sources 

[1] K.T. Olkkola and J. Ahonen. “Midazolam and Other Benzodiazepines,” in Modern Anesthetics, 1st ed. Berlin, Germany: Springer Berlin, 2007, pp. 335-360. Accessed: February 11, 2023. [Online]. Available: https://link.springer.com/chapter/10.1007/978-3-540-74806-9_16. 

[2] Y. Suri, “Evaluation of Midazolam and Diazepam for Pre-Operative Sedation,” Medical Journal Armed Forces India, vol. 56, no. 4, pp. 287-292, March 2016. [Online]. Available: https://doi.org/10.1016%2FS0377-1237(17)30209-5.  

[3] M. Sanatkar, M. Shorooghi, and M. S. Sanie, “Comparison of Effectiveness and Side Effects of Diazepam versus Midazolam Administration for Conscious Sedation in Patients Who Underwent Cataract Surgery,” Archives of Anesthesiology and Critical Care, vol. 5, no. 3, pp. 81-85, Summer 2019. [Online]. Available: https://doi.org/10.18502/aacc.v5i3.1204.  

[4] J. Barr et al., “A Double-blind, Randomized Comparison of IV Lorazepam versus Midazolam for Sedation of ICU Patients via  a Pharmacologic Model,” Anesthesiology, vol. 95, pp. 286-298, August 2001. [Online]. Available: https://doi.org/10.1097/00000542-200108000-00007.  

[5] J. C. Hong. “Midazolam: Mechanism and perioperative applications,” in Treatment, Mechanisms, and Adverse Reactions of Anesthetics and Analgesics, 1st ed. Cambridge, Massachusetts: Academic Press, 2021, pp. 131-138. Accessed: February 11, 2023. [Online]. Available: https://doi.org/10.1016/B978-0-12-820237-1.00014-4.  

[6] J. McMullan et al., “Midazolam Versus Diazepam for the Treatment of Status Epilepticus in Children and Young Adults: A Meta-Analysis,” Academic Emergency Medicine, vol. 17, no. 6, pp. 575-582, August 2014. [Online]. Available: https://doi.org/10.1111%2Fj.1553-2712.2010.00751.x.  

[7] Z. Zhao et al., “A Comparison of Midazolam, Lorazepam, and Diazepam for the Treatment of Status Epilepticus in Children: A Network Meta-analysis,” Journal of Child Neurology, vol. 31, no. 9, pp. 1093-1107, March 2016. [Online]. Available: https://doi.org/10.1177/0883073816638757.  

[8] E. Prommer, “Midazolam: an essential palliative care drug,” Palliative Care & Social Practice, vol. 14, pp. 1-12, January 2020. [Online]. Available: https://doi.org/10.1177/2632352419895527.  

[9] E. Ali et al., “Effectiveness of Midazolam Compared to Diazepam and Placebo For Reducing Anxiety after premedication at Sylhet Women’s Medical College,” International Journal of Medical Research Professionals, vol. 6, no. 2, pp. 78-81, March 2020. [Online]. Available: https://doi.org/10.21276/ijmrp.2020.6.2.017.  

[10] W. Vlastra et al., “Premedication to reduce anxiety in patients undergoing coronary angiography and percutaneous coronary intervention,” Open Heart, vol. 5, no. 2, pp. 1-8, August 2018. [Online]. Available: https://doi.org/10.1136/openhrt-2018-000833.