PACULit 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

Lesson Progress

0% Complete

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

Key Findings

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.

Listen to the Podcast

A short discussion of today's highlight.

Open the episode in a new tab

Read Full Study

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

PACULit Literature Updates September 2025: Emergency Medicine & Critical Care

Quizzes

Participants 440