Xenon in Anesthesia: Properties and Use

Xenon, the 54th element and a non-toxic gas naturally present in the atmosphere, has proven itself useful for over 120 years (1). Some of xenon’s properties make it an effective agent for anesthesia, placing it in the company of other anesthetic inhalants including nitrous oxide, halothane, isoflurane, desflurane, and sevoflurane (2). However, its use remains limited.

It is purported that xenon was first noted as a potential anesthetic by Albert R. Behnke, an assistant medical officer for the U.S. Navy, while researching why deep-sea divers exhibited a sort of ‘drunkenness.’ In his study, he incorporated xenon into the breathing mixtures of divers. Through their self-reported sensations, Behnke speculated that xenon has an anesthetic effect (3).

Research continued in mice and eventually in humans. Publishing from the Division of Anesthesiology, Department of Surgery, and the Department of Pharmacology at the State University of Iowa, physicians Stuart C. Cullen and Edwin G. Gross released a groundbreaking paper in May of 1951 in which they successfully utilized mixtures of oxygen and xenon gas to provide anesthesia during human surgeries (4).

Further research demonstrated xenon’s usefulness in both its very quick onset of anesthesia coupled with its swift recovery time, finding that patients who used xenon anesthesia take less time to open their eyes and regain cognitive function compared to other inhalational agents. This property in itself makes xenon a useful anesthetic in outpatient surgical centers, enabling faster recovery and turnover (5).

Xenon has also proven useful in high-risk cardiac surgeries as it provides patients with relatively stable intraoperative blood pressure and a lower heart rate (6). It has also been shown to have neuroprotective properties by acting as an antagonist at NMDA receptors while remaining devoid of any neurotoxic effects (7).

Unlike other anesthetic inhalants, because xenon naturally occurs in the Earth’s atmosphere, it does not have a harmful impact on the environment when released from the anesthesia system. Other inhalational anesthetic agents, including isoflurane, halothane, sevoflurane and desflurane, are chlorofluorocarbons or fluorinated hydrocarbons and contribute, at varying levels, to greenhouse gas emission into the atmosphere (8). Many other compounds in those classes are now banned due to their environmental impact (9). Xenon is therefore unique in its usefulness as an environmentally friendly anesthetic.

However, the use of xenon as an anesthetic comes with significant caveats. The process in which xenon is purified from the atmosphere is very costly and energy intensive (5). Although xenon is used in countries internationally, it has not yet been approved by the Food and Drug Administration for use within the United States as an anesthetic (10). Ongoing research seeks to showcase xenon’s various clinical applications in hopes of one day receiving its drug approval, though logistical barriers will still remain (11).

References

1. “Xenon – Element information, properties and uses,” Royal Society of Chemistry, https://www.rsc.org/periodic-table/element/54/xenon.
2. Clar, Derek T., Samir Patel, and John R. Richards. “Anesthetic Gases.” StatPearls – NCBI Bookshelf, August 8, 2023. https://www.ncbi.nlm.nih.gov/books/NBK537013/.
3. Marx, Thomas, Michael Schmidt, Uwe Schirmer, and Helmut Reinelt. “Xenon anaesthesia.” J R Soc Med. Vol. 93, 2000. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298124/pdf/11064688.pdf. Page 513.
4. Cullen, Stuart C., and Erwin G. Gross. “The Anesthetic Properties of Xenon in Animals and Human Beings, with Additional Observations on Krypton.” Science 113, no. 2942 (1951): 580–82. http://www.jstor.org/stable/1679348.
5. Jin, Zhaosheng, Ornella Piazza, Daqing Ma, Giuliana Scarpati, and Edoardo De Robertis. “Xenon anesthesia and beyond: pros and cons.” Minerva Anestesiologica 85, no. 1 (January 1, 2019). https://doi.org/10.23736/s0375-9393.18.12909-9.
6. Law, Lawrence Siu-Chun, Elaine Ah-Gi Lo, and Tong Joo Gan. “Xenon Anesthesia.” Anesthesia & Analgesia 122, no. 3 (March 1, 2016): 678–97. https://doi.org/10.1213/ane.0000000000000914.
7. Maze, Mervyn, and Timo Laitio. “Neuroprotective Properties of Xenon.” Molecular Neurobiology 57, no. 1 (November 22, 2019): 118–24. https://doi.org/10.1007/s12035-019-01761-z.
8. Yasny, Jeffrey S., and Jennifer White. “Environmental Implications of Anesthetic Gases.” Anesthesia Progress 59, no. 4 (December 1, 2012): 154–58. https://doi.org/10.2344/0003-3006-59.4.154.
9. Goto, Takahisa. “Is there a future for xenon anesthesia?” Canadian Journal of Anesthesia/Journal Canadien D Anesthésie 49, no. 4 (April 1, 2002): 335–38. https://doi.org/10.1007/bf03017319.
10. Conway, Charles, Brian Mickey, Scott Tadler, and Peter Nagele. “Inhaled gases for treatment-resistant major depression.” ScienceDirect, January 1, 2022. https://doi.org/10.1016/B978-0-12-824067-0.00033-5.
11. Nierenberg, Andrew A. “Xenon Therapy for Major Depressive Disorder and Bipolar Disorder for Currently Depressed Patients.” Mass General Brigham. https://rally.massgeneralbrigham.org/study/xenon#:~:text=Xenon%20is%20not%20approved%20by,in%20adults%20and%20in%20children.