Inhaled isoflurane for sedation of mechanically ventilated children in intensive care (IsoCOMFORT): a multicentre, randomised, active-control, assessor-masked, non-inferiority phase 3 trial summary

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Hey there, fellow critical care pharmacists! Welcome to today’s literature briefing. I’m sharing an update from *Lancet Respiratory Medicine* titled “Inhaled isoflurane for sedation of mechanically ventilated children in intensive care (IsoCOMFORT): a multicentre, randomised, active-control, assessor-masked, non-inferiority phase three trial.” This important study was led by Miatello, Palacios-Cuesta, Radell, and their colleagues.

So, let’s dive into the details of the IsoCOMFORT trial. This was a multicenter, randomized, active-control, assessor-masked, non-inferiority phase three trial, designed to compare inhaled sedation with isoflurane against intravenous midazolam. The study population included mechanically ventilated children in the intensive care unit, and the primary aim was to assess the efficacy and safety of these two sedation strategies during mechanical ventilation.

The key findings from this trial indicate that inhaled isoflurane sedation was non-inferior to intravenous midazolam for sedation efficacy in mechanically ventilated children. Beyond just comparable efficacy, the study highlighted several potential benefits with inhaled isoflurane, including reduced opioid and muscle relaxant consumption. Furthermore, inhaled sedation may offer cardio-protective, anti-inflammatory, and bronchodilator effects, which are, you know, quite significant in a critical care setting. Plus, it comes with minimal hepatic and renal metabolism, which can be advantageous for our critically ill patients. Importantly, the safety profile was comparable between the two groups, without any increased adverse effects reported.

To put these findings into context, other research supports the emerging role of inhaled sedation. For instance, a systematic review by Jerath and colleagues in two thousand twenty-five, with P. M. I. D. three-six-eight-nine-one-three-one-zero, of fifteen randomized controlled trials involving over fifteen hundred patients, showed that inhaled sedation reduced awakening and extubation times compared to intravenous sedation, without increasing nausea or vomiting. Basile and colleagues, in a two thousand twenty-three narrative review, P. M. I. D. three-six-seven-six-nine-seven-one-eight, also highlighted that inhaled sedation led to reduced opioid and muscle relaxant use in pediatric I. C. U. patients, potentially improving recovery.

On the other hand, you know, while midazolam has been effective for neonatal sedation, Geddes and colleagues in two thousand one, P. M. I. D. one-one-five-six-eight-three-seven-two, noted its association with delirium risk after prolonged use. The potential organ-protective effects of volatile anesthetics have also been explored; Jabaudon and colleagues in two thousand seventeen, P. M. I. D. two-eight-five-nine-nine-three-one-six, found that inhaled volatile anesthetics show cardio-protective and anti-inflammatory properties in I. C. U. sedation. And, as Koutsogiannaki and colleagues pointed out in two thousand twenty-one, P. M. I. D. three-three-five-three-two-six-seven-nine, volatile anesthetics are minimally metabolized, which is a favorable characteristic for critically ill patients.

From a clinical perspective, these results suggest that pharmacists in pediatric intensive care should consider inhaled isoflurane as a viable alternative sedative to intravenous midazolam. This is particularly relevant in situations where faster recovery, opioid-sparing effects, and those possible organ protective benefits are desirable. When implementing this, it’s crucial that monitoring protocols include careful attention to anesthesia gas exposure and ventilation parameters. Additionally, educating the entire clinical team on inhaled sedation workflows will be key to supporting its safe and effective implementation.

Now, like any study, the IsoCOMFORT trial has its limitations. The full results, including detailed safety data, were not publicly available at the time of this abstract. Also, the non-inferiority design inherently means it might miss very small, subtle differences in efficacy or safety between the two agents. And, of course, the population was limited to children, so these findings may not directly extrapolate to adult patients.

In conclusion, the IsoCOMFORT trial demonstrated that inhaled isoflurane sedation is non-inferior to intravenous midazolam for mechanically ventilated children. This supports its use as a safe and effective alternative sedative option in pediatric intensive care. That wraps up today’s update—thanks for listening!