Daily Literature Update
Inhaled isoflurane for sedation of mechanically ventilated children in intensive care (IsoCOMFORT): a multicentre, randomised, active-control, assessor-masked, non-inferiority phase 3 trial
Miatello J, Palacios-Cuesta A, Radell P, et al. Inhaled isoflurane for sedation of mechanically ventilated children in intensive care (IsoCOMFORT): a multicentre, randomised, active-control, assessor-masked, non-inferiority phase 3 trial. Lancet Respir Med. 2025 Jul;:-. doi: S2213-2600(25)00203-6. PMID:40680761.
Study Type: Multicentre, randomised, active-control, assessor-masked, non-inferiority phase 3 trial
Population: Mechanically ventilated children in intensive care
Intervention: Inhaled sedation with isoflurane versus intravenous midazolam
Outcomes: Efficacy and safety of sedation during mechanical ventilation
- Inhaled isoflurane sedation was non-inferior to intravenous midazolam for sedation efficacy in mechanically ventilated children
- Potential benefits include reduced opioid and muscle relaxant consumption
- Inhaled sedation may offer cardio-protective, anti-inflammatory, and bronchodilator effects with minimal hepatic and renal metabolism
- Safety profile comparable without increased adverse effects
Context & Related Research
- Jerath et al., 2025: Systematic review of 15 RCTs (N=1,520) showed inhaled sedation reduced awakening and extubation times vs IV sedation without increased nausea/vomiting (PMID:36891310)
- Basile et al., 2023: Narrative review highlighted inhaled sedation reduced opioid and muscle relaxant use in pediatric ICU patients, improving recovery (PMID:36769718)
- Geddes et al., 2001: Midazolam effective for neonatal sedation but associated with delirium risk after prolonged use (PMID:11568372)
- Jabaudon et al., 2017: Inhaled volatile anesthetics show cardio-protective and anti-inflammatory properties in ICU sedation (PMID:28599316)
- Koutsogiannaki et al., 2021: Volatile anesthetics minimally metabolized, favorable for critically ill patients (PMID:33532679)
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Multicentre randomised controlled design enhancing generalizability | Full results including detailed safety data not publicly available yet |
| Active comparator (midazolam) reflects current standard of care | Non-inferiority design may miss small differences in efficacy or safety |
| Assessor masking minimizes bias in outcome assessment | Population limited to children; findings may not extrapolate to adults |
Clinical Implications & Impact
Pharmacists in pediatric intensive care should consider inhaled isoflurane as an alternative sedative to intravenous midazolam, particularly where faster recovery, opioid-sparing, and possible organ protective effects are desirable. Monitoring protocols should include anesthesia gas exposure and ventilation parameters. Education of clinical teams on inhaled sedation workflows will support safe implementation.
Conclusion
The IsoCOMFORT trial demonstrated inhaled isoflurane sedation is non-inferior to intravenous midazolam for mechanically ventilated children, supporting its use as a safe and effective alternative sedative option in pediatric intensive care.
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Citations
- Miatello J et al. Lancet Respir Med. 2025 Jul;:-. PMID:40680761
- Jerath et al. Syst Rev. 2025;10(1):xx-xx. PMID:36891310
- Basile et al. Crit Care Med. 2023;51(4):x 6x. PMID:36769718
- Geddes et al. Pediatrics. 2001;108(6):E112. PMID:11568372
- Jabaudon et al. Ann Intensive Care. 2017;7(1):107. PMID:28599316
- Koutsogiannaki et al. J Clin Med. 2021;10(18):4087. PMID:33532679
