« Effect of sedative and anxiolytic sedation on children experience after general anesthesia » PEDIA_prem study.

The primary objective of this study is to evaluate the impact of **pharmacologic premedication** on the perioperative experience of children undergoing general anesthesia. This is clinically relevant as it aims to improve the overall experience and outcomes for pediatric patients by potentially reducing anxiety and improving cooperation during the perioperative period.

Secondary objectives include:

• Comparing the perioperative experience of three groups using the EVANpédia questionnaire at 24 hours postoperatively.
• Assessing child cooperation before anesthesia induction and the need for rescue sedation in cases of extreme agitation.
• Evaluating intraoperative hemodynamic effects, such as blood pressure and heart rate, and comparing incidences of hypotension or bradycardia.
• Measuring perioperative anxiety evolution using the EVA-anxiety scale from inclusion to 24 hours postoperatively.
• Assessing postoperative pain using the FPS-R scale and the amount of rescue analgesics administered.
• Evaluating postoperative cognitive status through recovery time, agitation, and amnesia using an adapted Brice questionnaire.
• Comparing premedication effects based on anxiety subgroups determined by the STAIC score.
• Identifying factors influencing the child's experience, including anxiousness, parental anxiety, medical history, and surgical invasiveness.

The clinical trial focuses on evaluating the impact of pharmacologic premedication on the perioperative experience of children undergoing surgery under **general anesthesia**. The study population comprises both male and female participants, specifically children older than 7 years and younger than 18 years. Participants are required to be capable of completing a self-questionnaire and must be scheduled for surgical intervention under general anesthesia. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria ensure that the study population is representative of the pediatric demographic undergoing surgical procedures requiring anesthesia.

The clinical trial is a **randomized**, double-blind, controlled study designed to evaluate the impact of pharmacologic premedication on the perioperative experience of children undergoing **general anesthesia**. The trial will involve the administration of **dexmedetomidine** and **midazolam**, with a placebo group receiving grenadine syrup. The study aims to assess the primary endpoint, which is the EVANpedia perioperative experience score, completed by the children 24 hours postoperatively or before hospital discharge for outpatients. Secondary endpoints include perioperative anxiety, hemodynamic changes, postoperative pain, sedation, time to extubation, rate of recovery, amnesia, cognitive impairment, behavioral changes, perioperative complications, and quality of life.

The trial is expected to run from April 18, 2023, to April 18, 2027, with participant involvement lasting up to 24 hours postoperatively. The study will include children aged 7 to 18 years who are scheduled for surgery under general anesthesia and are capable of completing a self-questionnaire. The trial will exclude any participants who do not meet these criteria. The sequence of study visits begins with a screening visit to confirm eligibility, followed by the intervention visit where the study drug or placebo is administered. Follow-up visits will occur at 24 hours postoperatively to collect data on the primary and secondary endpoints. The end-of-study visit will conclude the participant's involvement in the trial.

Participants may be withdrawn from the study if they experience adverse events that compromise their safety, if they withdraw consent, or if they fail to comply with the study protocol. The trial is categorized as a low-intervention study, as it involves experimental treatments that already have marketing authorization. The study is conducted in accordance with ethical guidelines and regulatory requirements to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **DEXMEDETOMIDINE EVER PHARMA 100 microgrammes/mL**, a **solution for infusion**. This experimental medication is provided in a pharmaceutical form suitable for infusion and is manufactured by EVER VALINJECT GMBH. The maximum daily dose is 2 µg/kg, with a total maximum dose of 2 µg/kg, administered orally. The treatment period is limited to one day. The medication is not formulated specifically for pediatric use, and its role in the trial is as a test substance.

Another experimental treatment used in the trial is **MIDAZOLAM VIATRIS 5 mg/ml**, which is available as a **solution for injection/infusion**. This medication contains the active substance **midazolam**, a chemical compound, and is produced by VIATRIS SANTE. The maximum daily and total dose is 2 ml, administered orally, with a treatment period of one day. Similar to dexmedetomidine, midazolam is not a pediatric formulation and serves as a test substance in the study.

The trial also includes a **placebo**, which is the grenadine syrup commonly used in anesthesia and resuscitation departments. This placebo does not have a specific pharmaceutical form or active substance and is not associated with any particular manufacturer. It is utilized to provide a control for comparison with the experimental treatments.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the EVANpedia perioperative experience score, which will be completed by children as a self-report at 24 hours postoperatively or before hospital discharge for those managed as outpatients. This score evaluates the children's experience during the perioperative period.

Secondary endpoints include a range of parameters such as perioperative anxiety, **haemodynamic** changes (including tachycardia, bradycardia, and hypotension) during the intervention, postoperative pain, sedation levels, and time to extubation. Additionally, the rate of recovery, amnesia, cognitive impairment, changes in behavior, and all perioperative complications across the three groups will be monitored. Quality of life assessments will also be conducted to provide a comprehensive evaluation of the treatment's impact.

The collection and analysis of these efficacy parameters will be conducted at specified timepoints, ensuring a thorough assessment of the pharmacologic premedication's impact on the perioperative experience of children undergoing surgery under general anesthesia. The trial is designed to provide insights into the effectiveness of the treatments, with a focus on improving the overall perioperative experience for pediatric patients.