Evaluation of Handheld-Multimedia Versus Midazolam Premedication on Perioperative Anxiety in Pediatric Day-Care Patients: A Randomized Controlled Trial

The primary objective of this study is to evaluate the necessity of **midazolam** premedication in pediatric day-care patients undergoing inhalational anesthesia. The study aims to compare the efficacy and safety of anxiolysis using multimedia devices, such as an iPad, against no anxiolysis and against premedication with midazolam prior to anesthetic induction. The primary endpoint is the reduction in the level of perioperative anxiety, particularly during induction, in children aged one to eight years undergoing day-care surgery. This is clinically relevant as managing perioperative anxiety can improve surgical outcomes and patient experience.

Secondary objectives include:

• Reduction of anxiety perioperatively in daycare, holding, and recovery areas.
• Incidence of stressful anesthetic mask inductions.
• Incidence of laryngeal spasms or bronchospasm.
• Parental satisfaction and stress/anxiety levels.
• Postoperative anxiety and POCIS (Postoperative Comfort Index Score).
• RASS-score evaluation of sedation or possible negative behavior preoperatively after midazolam administration.

The clinical trial involves **children** aged between one and eight years who are scheduled for elective procedures such as circumcision, dental care, or tonsillectomy/adenoidectomy in a day-care setting. The study population includes both male and female participants, with a general health status classified as ASA 1 or 2, indicating that they are either healthy or have mild systemic disease. The trial does not involve a vulnerable population. Participants were selected based on specific inclusion criteria, including the requirement for written informed consent from legal parents or caretakers. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy and safety of **midazolam** premedication compared to handheld-multimedia devices in managing perioperative anxiety in pediatric patients undergoing elective procedures such as circumcision, dental care, or tonsillectomy/adenoidectomy in a day-care setting. This is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to run from January 28, 2020, to December 1, 2027, with participant involvement lasting for the duration of their surgical procedure and immediate recovery period.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (1 to 8 years), ASA classification (1 or 2), and the provision of written informed consent by a legal guardian. The primary endpoint is the reduction in perioperative anxiety, measured using the mYPAS score and a parental 5-point anxiety scale. Secondary endpoints include the assessment of anesthetic satisfaction, parental satisfaction, and the occurrence of respiratory complications postoperatively.

Follow-up visits will occur preoperatively, during the procedure, and postoperatively to monitor anxiety levels and any adverse events. The end-of-study visit will coincide with the patient's discharge from the day-care unit. Participants may be withdrawn from the study if they experience significant adverse reactions or if they no longer meet the inclusion criteria. The trial aims to provide insights into whether multimedia distraction can offer comparable or superior anxiety control compared to standard care with **midazolam** premedication.

The clinical trial involves the administration of **BUCCOLAM 2.5 mg oromucosal solution**, which contains the active substance **midazolam**. This medication is provided in the form of an oromucosal solution and is intended for oral administration. The dosage is calculated based on the patient's weight, with a maximum daily dose of 1 mg/kg. The treatment period is limited to a maximum of one day. The solution is manufactured by Neuraxpharm Pharmaceuticals S.L. and is authorized for use in the European Union. The active substance, midazolam, is of chemical origin and classified under the ATC code N05CD08.

Another experimental medication used in the trial is **Midazolam Rowa 2.5 mg oromucosal solution**, also containing the active substance midazolam. This formulation is specifically designed for pediatric use and is produced by Rowa Pharmaceuticals Limited. Similar to BUCCOLAM, it is administered orally as an oromucosal solution, with the dosage also determined by the patient's weight, not exceeding 1 mg/kg per day. The treatment duration is restricted to one day. This product is authorized in Ireland and shares the same ATC classification as BUCCOLAM.

In addition to the experimental medications, the study includes a non-experimental treatment arm involving the use of handheld multimedia devices, such as tablets or iPads, as a form of anxiolysis. This approach is compared against the standard care involving midazolam premedication to assess its efficacy and safety in reducing perioperative anxiety in pediatric patients undergoing day-care surgery. The trial aims to determine whether multimedia distraction can provide anxiety control comparable to or better than midazolam premedication.

Efficacy in this clinical trial will be assessed by evaluating the reduction in the level of **perioperative anxiety** in pediatric patients undergoing day-care surgery. The primary endpoint is the difference in perioperative anxiety between two groups: one receiving midazolam premedication and the other using handheld multimedia devices such as an iPad for anxiolysis. Anxiety levels will be measured using the modified Yale Preoperative Anxiety Scale (mYPAS) and a parental scoring system based on a 5-point anxiety scale. These assessments will be conducted primarily during the induction phase of anesthesia in children aged between one and eight years.

Secondary endpoints include the evaluation of stressful anesthetic inductions, which will be categorized by the anesthesiologist post-induction into cooperative smooth induction, passive induction, anxious induction, and combative induction. Parental scoring for anxiety will also be conducted preoperatively, on holding, postoperatively in the recovery, and in the daycare unit. Additional secondary endpoints involve assessing respiratory postoperative complications, such as laryngospasm and bronchospasm, using specific scales. Parental satisfaction with anxiety management will be measured at various stages, including holding, after induction, recovery, and in the postoperative daycare unit. The Postoperative Comfort in Infants and Children (POCIS) score will be used upon leaving the recovery area, and preoperative sedation or negative behavior will be evaluated using the Richmond Agitation-Sedation Scale (RASS).