Comparative Evaluation of Intranasal Atomized Midazalom Combined With Nitrous Oxide Versus Nitrous Oxide Monotherapy

Research Question What is the effect of intranasal atomized midazolam combined with nitrous oxide compared with nitrous oxide alone on treatment success in anxious pediatric dental patients? Population: Anxious children aged 4-8 years requiring dental treatment under sedation.

Intervention: Intranasal atomized midazolam combined N2O sedation. Comparator: N2O sedation alone. Outcome: Treatment success, nasal-mask acceptance, intra-operative behavior, recovery time, and adverse events.

OBJECTIVES

Primary Objective:

• To evaluate and compare the treatment success rates between a combined regimen of intranasal atomized midazolam with nitrous oxide versus nitrous oxide alone in anxious pediatric dental patients.

Secondary Objectives:

• To measure and compare inhalation mask acceptance between both interventional groups.
• To evaluate the quality of intra-operative clinical behavior of child using the Houpt Behavior Scale.
• To measure post-operative recovery timelines using the Modified Aldrete Recovery Score.

STUDY DESIGN:

Prospective, Parallel-Group, Double-Blind, Randomized Controlled Trial (RCT).

SETTING:

The study will be conducted at the Department of Pediatric Dentistry, Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU) Islamabad.

DURATION OF STUDY:

Three months following the approval from the Institutional Review Board (IRB) and clinical trials registry database registration.

All eligible children will be screened during the initial dental visit. After obtaining informed consent, baseline anxiety will be recorded using the Frankl Behavior Rating Scale. Participants will then be randomly allocated to one of two groups using a computer-generated randomization sequence prepared by an independent evaluator not involved in clinical assessments.

To minimize parental separation anxiety as a confounding behavioral variable, one parent or legal guardian will remain physically present beside the dental chair during the intranasal MAD mist administration and the initial inhalation mask placement. The parent will only be guided to the adjacent waiting area once the child achieves a stable, cooperative sedation level and before active clinical instrumentation begins.

• Group A (Test Group): Each child will receive intranasal midazolam at an initial dose of 0.2 mg/kg through a Mucosal Atomization Device (MAD). After intranasal midazolam administration, 10 min waiting window will be given. Within this window, the child's anxiety and cooperation will be assessed, after an initial 5-minute latency period, If the child remains inadequately calm or uncooperative, a supplemental dose of 0.1 mg/kg will be administered, and the remaining 5 minutes of the waiting window will be observed. Children showing an adequate response will not receive a supplemental dose. Following the completion of the 10-minute period, the nasal hood will be positioned and inhalational sedation will be initiated. Nitrous oxide will be titrated gradually with oxygen to a maximum effective concentration.
• Group B (Control Group): Each child will receive an equivalent volume of normal saline solution intranasally via the MAD. Following an identical 10-minute waiting window, the nasal hood will be positioned and inhalational sedation will be initiated. Nitrous oxide will be titrated gradually with oxygen to a maximum effective concentration.

The independent investigator will evaluate and record Mask Acceptance upon inhalation hood placement. Blinded investigator will monitor and record behavioral scores utilizing the Houpt Behavior Scale. Treatment status will be recorded as Successfully Completed or Aborted. Additionally, any incidence of hemodynamic or respiratory instability will be noted.

Following the procedure, the child will be shifted to the recovery area. The independent investigator will assess the Modified Aldrete Score every 5 minutes until a score of ≥9 is reached, and the total Recovery Time will be recorded in minutes. Immediate clinical complications (nausea, vomiting, desaturation, or paradoxical hyperactivity) will be documented.

Monitoring: Throughout the procedure, the following parameters will be continuously monitored:

• Oxygen saturation (SpO₂) via pulse oximetry.
• Heart rate.
• Respiratory rate.
• Level of consciousness and responsiveness. Safety and Rescue Protocol: Children will be appropriately screened, dosages will be weight-based, and trained personnel including Anesthesiologist will continuously monitor oxygen saturation, heart rate, respiration, and consciousness. Oxygen, suction, airway equipment, emergency drugs, and flumazenil will be available. Treatment will be stopped and the emergency protocol initiated if complications occur. Pediatric sedation requires continuous observation and appropriate rescue equipment. If any adverse physiological event occurs (e.g., SpO₂ \<92%, respiratory depression, paradoxical hyperactivity), nitrous oxide will be immediately discontinued, 100% oxygen will be administered, and appropriate medical intervention will be initiated.