Timing of Midazolam in Children Undergoing Adenotonsillectomy: Effects on Stress, Cortisol, and Recovery (TIMING-MIDAZOL)

This study is a prospective, randomized, controlled clinical trial designed to evaluate the effects of the timing of midazolam administration on physiological stress response, behavioral anxiety, postoperative pain, recovery quality, and parental satisfaction in pediatric patients undergoing elective adenotonsillectomy.

The primary objective is to compare the effect of midazolam administration timing on physiological stress response, assessed by serum cortisol levels. Secondary objectives include evaluating preoperative anxiety levels, postoperative pain scores, recovery quality, and parental satisfaction between groups receiving midazolam at different time points.

The study will include children aged 3-10 years, classified as ASA physical status I-II, scheduled for elective adenoidectomy, tonsillectomy, or adenotonsillectomy.

Eligible patients will be identified during preoperative anesthesia evaluation. Parents or legal guardians will be informed about the study, and written informed consent will be obtained prior to enrollment.

Participants will be randomly assigned to one of two groups using a computer-generated randomization sequence with sealed envelope allocation:

Group A (Preoperative Midazolam Group): Patients will receive oral midazolam (0.5 mg/kg) 30 minutes before surgery, administered with a small volume of apple juice under clinical supervision.

Group B (Intraoperative Midazolam Group): Patients will receive intravenous midazolam (0.05-0.1 mg/kg) during anesthesia induction.

Anesthesia Protocol

To ensure comparability between groups, all patients will undergo a standardized anesthesia protocol. Vascular access will be established after inhalational induction using sevoflurane in oxygen, minimizing stress associated with intravenous cannulation.

Lidocaine (0.5-1 mg/kg) will be administered prior to propofol injection to reduce injection pain Propofol (2-3 mg/kg) will be used for induction Rocuronium (0.6 mg/kg) will be administered for neuromuscular blockade Fentanyl (1-2 µg/kg) will be used for analgesia

Anesthesia maintenance will be achieved with sevoflurane (2-3%) in a mixture of oxygen and air, targeting an age-adjusted MAC ≥1.3. Mechanical ventilation will be standardized with volume-controlled settings appropriate for age.

Intraoperative fluid management will be based on body weight using standard pediatric maintenance formulas and isotonic saline solution.

Neuromuscular blockade will be reversed with sugammadex (2 mg/kg) Extubation will be performed based on clinical recovery criteria, including adequate spontaneous respiration and responsiveness

All patients will receive intravenous paracetamol (10-15 mg/kg) for postoperative analgesia and ondansetron (0.1 mg/kg) for prophylaxis of nausea and vomiting.

Serum cortisol levels will be measured at two time points:

Intraoperative period (10 minutes after anesthesia induction) Early postoperative period (15 minutes after admission to the post-anesthesia care unit)

Cortisol levels will be analyzed using an electrochemiluminescence immunoassay method.

Preoperative anxiety will be assessed using a modified observational anxiety scale. Postoperative pain will be evaluated using a validated behavioral pain scoring system, and recovery status will be assessed using standard recovery criteria.

Parental satisfaction will be evaluated within the first 30 minutes after surgery using a structured questionnaire assessing overall perioperative experience.

All perioperative data will be recorded by the anesthesia team and post-anesthesia care unit staff. Collected data will be analyzed statistically to compare outcomes between the two groups.