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Assessing the suitability of Xenon treatment for mass use in cases of Neonatal Hypoxic Ischemic Encephalopathy

This essay was written by lower-sixth former Jack Doyle, and shortlisted for the 2020 Fifth Form Transitional Research Project. The following provides a short abstract to the full essay.

Estimated read time of abstract: 3 minutes

Estimated read time of essay: 15 minutes


This essay was written by lower-sixth former Jack Doyle, and shortlisted for the 2020 Fifth Form Transitional Research Project. The following provides a short abstract to the full essay, which can be found at the bottom.

Estimated read time of abstract: 3 minutes
Estimated read time of essay: 15 minutes

In 2019 the University of Liverpool published their findings, in the British medical journal, on the unusual and unprecedented rise in infant mortalities within the UK. [1]This conclusion made goes entirely against the tide of lowering infant mortality rates in high income countries. In contraray to common belief, we are not yet at the stage where every child born will be healthy or even survive, and this is amplified across lower income countries around the world. There are many causes to new-born death and disability, with one of them being the lack of blood flow to brain leading to brain tissue being damaged, this is called neonatal hypoxic encephalopathy (HIE’s) [2]. There are numerous research groups worldwide that are looking into ways of treating and preventing this condition, minimising its impact on babies globally. One of the exciting and promising treatments that has shown potential in early trials is Xenon, an inert gas found in our atmosphere.

Xenon is easy to administer which means can be used in pre-existing and low cost delivery settings, with the onset of effects on the baby being rapid and controllable [3]. Xenon has a high tendency to combine with lipids, meaning that it can cross across the placenta to the baby. This tendency to combine with lipids also leads it to it being able to bypass some of the hurdles the brain puts up to prevent substances getting into it [4]. Side effects to the mother, due to delivery occurring through the mother by inhalation, seem to be minimal with the effects on the baby also being similarly minute [5]. The gas itself is expensive, caused by the arduous extraction of this gas, however multiple systems are being developed that could recycle this gas from patients. This would make Xenon treatment much more feasible and economically viable, even for use in lower income countries [6]. More work has to be done to rule out harmful interactions with other treatments, however current understanding suggests there aren’t significant interactions known.

Most importantly there have been numerous studies shown that suggest that it has beneficial effects on the outcomes of new-borns in treatment pre and post delivery. Furthermore, it has been shown that not only does it halt the progression of damage but it also potentially reverses tissue damage to a certain degree, however the way in which it does this nor the reliability of these findings are known. [7] [8] [9]

Currently the treatments for this HIE’s in newborns are very limited with the only widespread treatment is cooling. This has been shown to have an effect on limiting damage, but does not have that high of a success rate nor the ability to reverse damage. Therefore new treatments need to be developed, and the use of treatments alongside cooling could be an effective method of treatment. Studies showing Xenon in conjunction with cooling have also shown a potential benefit above Xenon solely. [10]

Despite all this there have also been a number of studies that show it does not have a noteworthy beneficial effect, therefore the evidence for it working is conflicting. Theoretically and on paper it should work effectively with a number of academics and researchers that I have talked to suggesting that it could have some benefit. More research would need to be done on this and its effects before Xenon could be used in confidence, but it is a promising drug for a fatal condition that desperately needs effective treatments.

With thanks to Dr Richard Daneman (Department of Neurosciences and Pharmacology at University of California, San Diego) and to Dr Robert Dickinson (Department of Surgery and Cancer at Imperial College, London)

To view Jack’s full article, follow this link below.

Works Cited

1U. o. Liverpool, “An ‘unprecedented’ rise in infant mortality in England linked to poverty,” Science Daily, 5 October 2019. [Online]. Available: https://www.sciencedaily.com/releases/2019/10/191005134007.htm. [Accessed 28 October 2020].
2ucsfbenioffchildrens, “Neonatal Hypoxic Ischemic Encephalopathy,” [Online]. Available: https://www.ucsfbenioffchildrens.org/conditions/neonatal_hypoxic_ischemic_encephalopathy/. [Accessed 8 6 2020].
3E. Ferrari, G. Natale, F. Giunta and A. Paparelli, “Usefulness of i.v. administration of gas during xenon anaesthesia,” European Journal of Anaesthesiology, 2000. [Online]. Available: https://journals.lww.com/ejanaesthesiology/Fulltext/2000/00003/Usefulness_of_i_v__administration_of_gas_during.6.aspx. [Accessed 28 October 2020].
4H. S. M. S. Y. N. F. I. S. M. T Goto 1, “Xenon provides faster emergence from anesthesia than does nitrous oxide-sevoflurane or nitrous oxide-isoflurane,” June 1997. [Online]. Available: https://pubmed.ncbi.nlm.nih.gov/9197295/. [Accessed 28 October 2020].
5D. Chakkarapani, “Can xenon help protect against neonatal brain damage?,” 8 January 2020. [Online]. Available: http://www.bristol.ac.uk/blackwell/funding/case-studies/2020/xenon-and-neonatal-brain-damage.html. [Accessed 28 October 2020].
6F. John Dingley, F. George P. Findlay, F. Bernard A. Foëx, P. John Mecklenburgh, F. Mohammed Esmail and P. F. Roderick A. Little, “A Closed Xenon Anesthesia Delivery System,” Anesthesiology , January 2001. [Online]. Available: https://anesthesiology.pubs.asahq.org/article.aspx?articleid=1945203. [Accessed 28 October 2020].
7*. T. L. J. X. H. T. Y. W. H. Z. M. H. P. H. M. a. M. M. Daqing Ma, “Xenon Preconditioning Protects against Renal Ischemic-Reperfusion Injury via HIF-1α Activation,” April 2009. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663824/. [Accessed 28 October 2020].
8M. P. a. D. M. F. M. Sandra E. Juul, “Pharmacological neuroprotective strategies in neonatal brain injury,” 1 March 2015. [Online]. Available: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929237/. [Accessed 28 October 2020].
 9Y. Zhang, “Xenon exerts anti-seizure and neuroprotective effects in kainic acid-induced status epilepticus and neonatal hypoxia-induced seizure,” September 2019. [Online]. Available: https://www.researchgate.net/publication/335672856_Xenon_exerts_anti-seizure_and_neuroprotective_effects_in_kainic_acid-induced_status_epilepticus_and_neonatal_hypoxia-induced_seizure. [Accessed 28 October 2020].
10p. R. E.Oorschot, “Xenon Combined With Hypothermia in Perinatal Hypoxic-Ischemic Encephalopathy: A Noble Gas, a Noble Mission,” July 2018. [Online]. Available: https://www.sciencedirect.com/science/article/abs/pii/S0887899417312389#:~:text=Combining%20both%20hypothermia%20and%20xenon,another%20NMDA%20glutamate%20receptor%20antagonist.&text=Xenon%20at%2050%25%20in%20conjunction,three%20hours%20after%20severe%20HI. [Accessed 28 October 2020].

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