Article Review: ‘Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial’

Published: October 24th, 2016

Category: Blog

Welcome to the first FN3 blog post!  My goal is to provide you with a quick summary of an article or topic and to stimulate discussion.  The article this week is entitled “Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial” and appeared in the Lancet (http://thelancet.com/journals/laneur/article/PIIS1474-4422(15)00347-6/fulltext). It comes to us courtesy of our fellow neonatologist from England.

Brief Background:

  • Xenon is a noble gas that has been used as an anesthetic in Europe.
  • Xenon interferes with excitotoxicity by partially blocking NMDA receptors
  • Xenon has rapid reversibility following stoppage and little clinical side effects.
  • The goal of the study was to assess whether the combination of cooling with inhaled xenon—administered at a concentration and within a timeframe suitable for general clinical application—could further improve neurological outcomes after birth asphyxia and neonatal encephalopathy.

Materials and methods:

  • Neonates who were eligible for hypothermia were enrolled in the study (including aEEG screening).
  • Xenon was administered at a concentration of 30% for 24 hours
  • Outcomes examined were MRI based. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth.

Results:

  • No significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference −0·01, 95% CI −0·03 to 0·02) in the posterior limb of the internal capsule were noted between the two groups.

Discussion:

  • This was a well-designed study. The study subjects were mostly neonates with severe encephalopathies. This raises the question of applicability to our kids in the State of Florida. A majority of our kids are moderate. Would the therapy benefit this patient population?
  • The study did not reach the target enrollment to meet the power calculations for the primary outcome of lactate to N-acetyl aspartate. It is interesting that the group used MRI as a surrogate for outcomes. This may greatly improve our screening of potential neuroprotective therapies in the future before undertaking large follow-up studies. What do folks think? Are you using MRS at your center?
  • It was meant to be a practical study and the Xenon was administered at a median of 10 hours. This is the only potential drawback of this study. There is data to suggest that earlier treatment with Xenon may be necessary for neuroprotection. This may mean transporting from referring sites. The earlier administration is currently being examined (https://clinicaltrials.gov/ct2/show/NCT02071394). This study will examine a higher concentration of Xenon (50% for 18 hours).
  • Overall, I think the jury is still out on Xenon! What do you think?

 

~Mike Weiss