Preoperative anxiety is common amongst patients undergoing surgery, with one meta-analysis estimating a global pooled prevalence of 48%.1 Preoperative anxiety has been associated with numerous postoperative complications including insomnia, pain, nausea, vomiting, and neurocognitive dysfunction, while running additional risks of increased preoperative cardiac demand due to sympathetic activation, delays in wound healing, and extended hospital time.2 As a result, preoperative sedation is a cornerstone of anesthetic practice and is beneficial in many cases. Ongoing research seeks to better understand the effects of available medications and develop improved medications for preoperative sedation.
Benzodiazepines are the predominant class of sedative medications used preoperatively, as reflected in a 2023 review paper on pharmacologic interventions for preoperative anxiety in patients undergoing major surgery.3 However, there is mixed data for its efficacy. In the PremedX study, a randomized controlled trial assessing the efficacy of lorazepam as a sedative premedication for perioperative patients, patients premedicated with lorazepam did not report increased levels of satisfaction (p = 0.38) compared to those given either placebo or no premedication.4 Additionally, use of lorazepam was associated with increased time to extubation (p <0.001).4
More recently, there has been discussion surrounding the efficacy in co-administering ketamine along with midazolam for preoperative sedation. The pharmacodynamic rationale for this co-administration is preoperative and postoperative optimization through the anxiolytic effects of midazolam paired with the sedative and analgesic effects of ketamine, respectively, without the compounding of adverse side effects.5 A meta-analysis focusing on pediatric patients did not find that co-administration resulted in reduced preoperative anxiety; however, co-administration was associated with success in secondary outcomes such as accepted separation from parents, lower levels of fear during face mask administration, and cooperative behavior during peripheral venous cannulation.5
Similarly, additional scientists have studied and compared the efficacy of other preoperative sedative medications with midazolam. A 2016 randomized controlled trial assessed the utility of propofol versus midazolam as a premedication drug.6 When compared to saline, both propofol and midazolam groups resulted in statistically significant increases in patient sedation (p <0.001). 20 mg of intravenous (IV) propofol administered 5 minutes prior to entering the operating room (OR) was found to be as effective in reducing patient anxiety as 2 mg of IV midazolam also administered 5 minutes prior to OR entry. Major differences were increased injection site pain with propofol and reduced recall with midazolam.6
Dexmedetomidine has also been studied in comparison with midazolam.7 A 2011 study found statistically significant sedation and decrease in anxiety associated with the preoperative administration of 1 ug/kg of IV dexmedetomidine as well as the 0.04 mg/kg IV administration of midazolam, suggesting 1ug/kg of IV dexmedetomidine is just as effective as higher doses (i.e., 0.04 mg/kg) of IV midazolam for preoperative sedation.7 Major physiologic differences associated with the administration of dexmedetomidine were the statistically significant drop in mean arterial pressure (MAP) (p <0.01) and heart rate (HR) (p <0.05), though the authors note these physiologic changes likely normalized the already increased MAP and HR attributed to the sympathetic surge from preoperative anxiety – effectively, normalizing MAP and HR.7
By virtue of literature representation, midazolam appears to be the most commonly administered preoperative sedative medication. There is ongoing research into alterative and adjunctive sedatives including ketamine, propofol, and dexmedetomidine. Each comes with their own pharmacodynamic, physiologic, and side effect profiles. When adjudicating which preoperative sedative or sedatives to administer, it is important to consider drug differences and patient physiology.
References
1. Abate SM, Chekol YA, Basu B. Global prevalence and determinants of preoperative anxiety among surgical patients: A systematic review and meta-analysis. Int J Surg Open. 2020;25:6-16. doi:10.1016/j.ijso.2020.05.010
2. Ni K, Zhu J, Ma Z. Preoperative anxiety and postoperative adverse events: a narrative overview. Anesthesiol Perioper Sci. 2023;1(3):23. doi:10.1007/s44254-023-00019-1
3. Abdullah Alalhareth KA, Al Alshahi AH, Hamad Alyami MS, et al. Pharmacological interventions to reduce preoperative anxiety among patients with major surgery. Published online April 11, 2022.
4. Maurice-Szamburski A, Auquier P, Viarre-Oreal V, et al. Effect of Sedative Premedication on Patient Experience After General Anesthesia: A Randomized Clinical Trial. JAMA. 2015;313(9):916. doi:10.1001/jama.2015.1108
5. Oliveira Filho Get. lio RD, Castilhos CM, Kriegl JP, Bianchi GN. Oral preanesthetic medication in children … comparison between midazolam alone and in combination with ketamine: a systematic review and meta-analysis. Braz J Anesthesiol Engl Ed. 2023;73(4):477-490. doi:10.1016/j.bjane.2021.07.026
6. Elvir Lazo OL, White PF, Tang J, et al. Propofol versus midazolam for premedication: a placebo‑controlled, randomized double‑blinded study. Minerva Anestesiol. 2016;82(11):1170-1179.
7. Eren G, Cukurova Z, Demir G, Hergunsel O, Kozanhan B, Emir NS. Comparison of dexmedetomidine and three different doses of midazolam in preoperative sedation. J Anaesthesiol Clin Pharmacol. 2011;27(3):367-372. doi:10.4103/0970-9185.83684
