Author: Barros M, et al.
Anesthesia & Analgesia 141(2):327-342, August 2025. doi:10.1213/ANE.0000000000007223
This preclinical systematic review and meta-analysis compared xenon and argon as neuroprotective treatments in animal models of perinatal hypoxic-ischemic encephalopathy (HIE). Twenty-one studies (data from 1591 animals across mice, rats, and piglets) met inclusion criteria. Using random-effects pairwise meta-analyses, both gases significantly improved neurological outcomes (histologic and/or behavioral) versus controls. The pooled effect for xenon was 39.7% (95% CI, 28.3%–51.1%), while argon showed a larger pooled effect of 70.3% (95% CI, 59.0%–81.7%), and the argon effect was significantly greater than xenon’s.
Heterogeneity was high among xenon studies, driven by species, dose, timing, duration, and study quality. Higher xenon concentration (≥70%) and earlier initiation (before or within 1 hour after injury) were associated with larger effects; longer treatment durations and higher study quality tended to yield smaller effects. Funnel-plot trim-and-fill suggested possible publication bias for xenon, though Egger’s test was negative. Argon’s pooled estimate showed low observed heterogeneity, but the small number of studies (n=4) limits certainty.
Clinically, xenon trials in neonatal HIE to date have been inconclusive, likely in part due to delayed treatment initiation beyond the preclinically suggested window (roughly within 3–6 hours). No clinical HIE trials of argon have been reported. The authors conclude that both gases warrant further study, with particular need for additional high-quality argon studies and time-to-treatment optimization before advancing to large clinical trials.
Key Takeaways
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Both xenon and argon demonstrated significant neuroprotection in preclinical perinatal HIE models.
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Argon’s pooled effect (~70%) was significantly greater than xenon’s (~40%) in this meta-analysis.
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For xenon, higher concentration (≥70%) and earlier start times (≤1 hour after injury) correlated with stronger effects.
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Xenon studies showed high heterogeneity and possible publication bias; argon evidence is promising but based on few studies.
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Translation hinges on rapid initiation in clinical settings and more rigorous, adequately powered trials—especially for argon.
Thank you to Anesthesia & Analgesia for publishing this comprehensive review on noble gas neuroprotection in perinatal HIE.