TOPLINE:
Inhaled isoflurane demonstrated noninferior sedation efficacy compared with intravenous midazolam in critically ill children aged 3-17 years on mechanical ventilation, while also lowering opioid requirements and time to extubation along with maintaining an acceptable safety profile.
METHODOLOGY:
- Amid safety concerns over intravenous midazolam, inhaled isoflurane has emerged as an alternative sedative for critically ill patients requiring mechanical ventilation. However, supporting evidence remains limited.
- Researchers conducted a randomized phase 3 trial (IsoCOMFORT) across multiple pediatric ICUs to assess whether inhaled isoflurane was noninferior to intravenous midazolam as an alternate sedative strategy.
- They included 92 children who were critically ill and required invasive mechanical ventilation and sedation for ≥ 12 hours. They were randomly assigned to either inhaled isoflurane (n = 59; mean age, 8.1 years; 63% boys) or intravenous midazolam (n = 33; mean age, 7 years; 61% boys).
- At baseline after randomization, depth of sedation was assessed using the COMFORT Behavior scale, and children were assigned to light (score, 17-22), moderate (score, 11-16), or deep (score, 6-10) sedation target. Sedatives were titrated accordingly for up to 48 ± 6 hours during the treatment period.
- The primary outcome was the percentage of time maintaining adequate sedation within prescribed COMFORT Behavior scale target range — without rescue sedation, assessed every 2 hours over 12-48 hours.
TAKEAWAY:
- Isoflurane maintained sedation within the COMFORT Behavior target range for a greater proportion of time (68.94%) than midazolam (62.37%), with a mean difference of 6.57 percentage points (95% CI, -8.99 to 22.13), confirming isoflurane’s noninferiority to midazolam.
- The opioid requirements were lower in the isoflurane group (least squares mean dose, 2.1 μg/kg/h) than in the midazolam group (least squares mean dose, 4.6 μg/kg/h; P = .0004).
- Additionally, the time for extubation was significantly shorter with isoflurane (median, 0.75 hours) than with midazolam group (median, 1.09 hours).
- One child in each arm experienced treatment-related severe hypotension; three children receiving isoflurane discontinued due to adverse events, however, there were no treatment-related deaths.
IN PRACTICE:
“Based on [the study] results and on the regulatory support from the EMA [European Medicines Agency], inhaled sedation can be regarded as a therapeutic option for sedation during mechanical ventilation in pediatric intensive care,” the authors of the study wrote.
SOURCE:
This study was led by Jordi Miatello, PhD, from the IHU-SEPSIS Comprehensive Sepsis Centre and Paediatric Intensive Care in Le Kremlin-Bicêtre, France, and Alba Palacios-Cuesta, MD, from the 12 de Octubre University Hospital in Madrid, Spain. It was published online on July 15, 2025, in The Lancet Respiratory Medicine.
LIMITATIONS:
This study excluded children younger than 3 years, limiting the generalizability of the findings to younger pediatric ICU patients. The choice of inhaled sedative, as sevoflurane has replaced isoflurane for general anesthesia in many countries. Lastly, masking only the COMFORT Behavior assessor, rather than the entire clinical team, could lead to bias in outcome assessment.
DISCLOSURES:
This study was funded by Sedana Medical, Stockholm, Sweden. Few authors received honoraria from the funding organization for participation in the IsoCOMFORT Study Steering Committee. Two authors were employees of the funding organization. Two authors also reported being consultant with other pharmaceutical organizations.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.