Iran J Pediatr. 2020 June; 30(3):e102183. Published online 2020 May 4. doi: 10.5812/ijp.102183. Research Article A Double-Blind Clinical Trial to Determine the Effect of Oral Zolpidem and Midazolam on the Level of Preoperative Anxiety in Children Undergoing Eye Examination Under General Anesthesia Pooya Derakhshan 1, * , Seyed Hamid Reza Faiz 1 , Azadeh Emami 1 , Masood Mohseni 1 and Mohsen Shirani 1 1 Anesthesiology Department, Iran University of Medical Sciences, Tehran, Iran * Corresponding author: Anesthesiology Department, Iran University of Medical Sciences, Tehran, Iran. Email: pooyaderakh@yahoo.com Received 2020 February 25; Revised 2020 March 29; Accepted 2020 April 01. Abstract Background: Preoperative anxiety is a very important factor in pediatric surgery; 40% - 60% of children experience a high level of anxiety in the preoperative period. Objectives: Given the need for anxiety control in children and considering that limited studies have been conducted in this regard, this research was performed to compare the effect of oral zolpidem and midazolam on level of preoperative anxiety in children. Methods: In a prospective double-blind randomized controlled trial, 56 cases were randomly divided into two groups of 28 partici- pants. A group underwent zolpidem premedication and the other underwent midazolam premedication. The level of preoperative and postoperative anxiety was measured by MYPAS SCORE checklist and compared. Results: The study comprised 56 patients (19 girls and 37 boys) aged between 3 - 9 years. The mean score of anxiety in the group receiving midazolam was 63.80 in pre-test and 32.61 in post-test (P < 0.001). The mean score of anxiety in the group receiving zolpi- dem was 62.49 in pre-test and 30.94 in post-test (P < 0.001). Mean anxiety in the patients of zolpidem group was lower than that in midazolam group (P < 0.001). Conclusions: Our results show that both zolpidem and midazolam reduce preoperative anxiety, however, the preoperative anxiety was significantly decreased after taking zolpidem in comparison with midazolam. Zolpidem is a hypnotic drug with rapid onset and short duration of action, which might be an alternative premedication for midazolam in pediatric anesthesia, particularly when the reduced anxiety and child cooperation are needed. Keywords: Zolpidem, Midazolam, Anxiety, General Anesthesia, Children 1. Background Surgery and anesthesia are stressful for children. 40% - 60% of children experience a high level of anxiety in the preoperative period. An increase in preoperative anxiety not only causes discomfort for the child and parents, but also leads to delay of induction and recovery after anes- thesia. This anxiety causes more pain in the patient and also increases the likelihood of delirium and maladaptive behaviors (1-3). Drug sedation is used for reduction or re- moval of negative behavior, fear and negative psycholog- ical response to treatment, and maximizing amnesia to control behavior during the procedure. Sedative drugs can be administered by oral, inhalation, rectal, submucosal, intramuscular or intravenous meth- ods. The oral sedation is the simplest and easiest method to manage a sick child who does not cooperate, because there is no need for masking and injection (4). The oral midazo- lam is the most common pre-anesthetic medicine for chil- dren (5). Midazolam is rapidly absorbed from the gastroin- testinal tract with peak of action about 30 min and short half-life (1.5 hours) (6). The oral midazolam at a dose of 0.25 to 0.33 mg/kg usu- ally leads to separation of children from their parents with- out crying. As an oral pre-med, zolpidem has a short elimi- nation half-life which is on average 2.4 hours in adults com- pared to diazepam that is 24 - 57 hours (7). Zolpidem is not associated with benzodiazepines in terms of structure, but it seems that its activity, which is associated with activation of GABAergic system, is similar to benzodiazepines (2, 8). Zolpidem is well tolerated in children and is suggested at a dose of 0.25 mg/kg and a maximum dose of 20 mg (9, 10). Copyright © 2020, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.