Using inhaled sedatives to improve outcomes in critically ill children

Advancing Brain Outcomes in Pediatric Critically Ill Patients Sedated With Volatile AnEsthestic Agents: A Pilot Multicentre Randomized Controlled Trial

This study is testing if using inhaled sedatives can help critically ill children on ventilators feel less confused and improve their recovery compared to regular IV sedation.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 1 Month to 18 Years
• Sex: All
• Sponsor: Sunnybrook Health Sciences Centre (other)
• Locations: 3 sites (Hamilton, Ontario and 2 other locations)
• Trial ID: NCT05867472 on ClinicalTrials.gov

What this trial studies

This pilot study aims to evaluate the effectiveness of inhaled sedatives, specifically isoflurane and sevoflurane, in reducing delirium in pediatric patients who require mechanical ventilation. Participants will be randomly assigned to receive either inhaled sedation or standard intravenous sedation and will be monitored for up to 28 days. The study will also assess recruitment feasibility, participant retention, and acceptance of the study procedures by healthcare teams. After 9-12 months, participants will undergo assessments of memory, thinking, and behavior.

Who should consider this trial

Good fit: Ideal candidates are pediatric patients aged 1 month to less than 18 years who need sedation for mechanical ventilation lasting 24 hours or more.

Not a fit: Patients with a history of malignant hyperthermia, certain metabolic diseases, or those expected to survive less than 24 hours may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved cognitive outcomes and reduced delirium in critically ill children requiring sedation.

How similar studies have performed: While this approach is novel in the pediatric population, similar studies in adults have shown promising results with inhaled sedatives.

Eligibility criteria

Inclusion Criteria:

1. Pediatric patients age from 1 month to less than 18 years who need sedation to tolerate mechanical ventilation and will remain ventilated for ≥ 24 hours
2. Receiving IV sedation by infusion or bolus for ≤72h to aid mechanical ventilation (but will be recruited as early as possible)

Exclusion Criteria:

1. Current use of inhaled prostacyclin (high viscosity of prostacyclin impairs vaporizer device) or continuous salbutamol nebulization (impairs gas analyzer function)
2. Family history or personal history of malignant hyperthermia (MH)
3. Allergy to isoflurane, sevoflurane or other volatile inhaled anesthetic gas
4. Metabolic, mitochondrial or myopathy disease e.g., Duchenne muscular dystrophy (volatiles may trigger malignant hyperthermia like reaction)
5. Moribund with expected survival \< 24h
6. Known pregnancy or lactation
7. Suspected or evidence of high intracranial pressure (ICP)
8. Not a 'closed ventilator circuit' with potential for gas leak (e.g. uncuffed ETT, bronchopleural fistula, tracheal/trachea-esophageal fistulas, or other sources of "gas leak" from patient circuit that cannot be removed)
9. Prior enrollment in the ABOVE trial

Where this trial is running

Hamilton, Ontario and 2 other locations

• McMaster Children's Hospital — Hamilton, Ontario, Canada (RECRUITING)
• Children's Hospital - London Health Sciences Centre — London, Ontario, Canada (RECRUITING)
• The Hospital for Sick Children (SickKids) — Toronto, Ontario, Canada (RECRUITING)

Study contacts

• Principal investigator: Angela Jerath, MD — Sunnybrook Health Sciences Centre
• Study coordinator: Sunnybrook Research Institute, Program Manager - Centre for Clinical Trials Services

Conditions: Intensive Care Units, Pediatric, Anesthetics, Inhalation, Mechanically Ventilated, Critically Ill Children