Xenon: Biological Mechanisms, Surgical Applications and Side Effects

Xenon is a nonflammable, colorless, odorless noble gas that has a variety of practical applications.¹ Most commonly, xenon is used in specialized light sources, such as electronic flash bulbs for photography, ruby lasers, sunbed lamps and bactericidal lamps for food preparation and processing.¹ Xenon is also present in the atmosphere, along with nitrogen, oxygen and trace gases, and can be found in some mineral springs or even the earth’s core.² Xenon was first discovered in 1898 by the Scottish chemist William Ramsay and the English chemist Morris Travers, after distillation of krypton and isolation of the heavier gas.¹ It was previously thought to be inert, but researchers in the 20^th and 21^st centuries have shown that it is capable of reacting and forming more than one hundred new compounds.¹ Recent studies have a newfound interest in xenon as an anesthetic.³ Because the clinical application of xenon is relatively new, anesthesia providers should have thorough knowledge of its biological mechanisms, surgical applications and side effects.

Action on neurotransmitters and their receptors is responsible for xenon’s anesthetic effect.⁴ Specifically, xenon is a potent, noncompetitive inhibitor of N‐methyl‐D‐aspartate (NMDA) receptors.⁴ Studies have also found that xenon can inhibit nicotinic acetylcholine receptors (nAChRs)⁵ or even specific serotonin receptors,⁶ though the latter has never been shown in humans.⁴ Some recent researchers have found that xenon activates particular potassium channels, which may contribute to its anesthetic actions.³ Xenon does not have an effect on gamma aminobutyric acid (GABA) receptors or non-NMDA glutamatergic receptors, such as the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor.⁴ Lack of action at GABA_A receptors is a common feature of xenon, nitrous oxide, cyclopropane and ketamine, while other inhaled anesthetics target these GABA_A receptors.³ Given all its actions in the nervous system, antagonism of the NMDA receptor is thought to be xenon’s primary site for anesthetic action.³

Xenon has advantages over many other general anesthetics in the surgical setting. For one, it provides relatively more stable intraoperative blood pressure, lower heart rate and faster emergence from anesthesia than volatile and propofol anesthesia.⁷ The hemodynamic stability of xenon makes it preferable for patients who have limited cardiovascular capabilities.⁸ Additionally, xenon is associated with the highest regional blood flow to the brain, liver, kidneys and intestines when compared to other inhaled anesthetics.⁸ Xenon is also associated with improved respiratory gas exchange when compared to sevoflurane, particularly in obese patients.⁹ Unlike other inhalational anesthetic drugs, xenon does not trigger malignant hyperthermia, has low potential for toxicity and has no teratogenic (i.e., fetus-harming) effects.⁴ In fact, xenon may even have neuroprotective effects¹⁰ that include protecting neural cells against ischemic injury from low blood flow.⁸ Furthermore, xenon exhibits more potent analgesic effects than nitrous oxide, which is the only other inhaled anesthetic with true analgesic efficacy.⁴ Its low solubility also allows for a quick induction and recovery period from anesthesia.¹¹ The use of xenon as a general anesthetic may reduce pain, improve hemodynamic stability and lower risk of organ injury when compared to other anesthetic drugs.

Unlike other inhaled anesthetics, xenon has virtually no side effects.¹² This is likely due to its extremely low chemical reactivity, which contrasts with other anesthetics that have complex molecular structures.¹² However, some researchers have found that xenon increases postoperative nausea and vomiting (PONV) compared to other general anesthetics. These findings were consistent in separate studies by Fahlenkamp et al.¹³ and Abramo et al.,⁹ as well as in a meta-analysis by Law et al.⁷ As Sanders et al. suggest, this increase in PONV may be associated with xenon’s action at serotonin receptors.⁴ However, more research is needed to clarify the cause of this unpleasant side effect.

Xenon, which has historically been used in specialized lights, is now being considered as a safe and efficacious anesthetic drug. Xenon acts on various neural receptors to cause anesthesia, and it is associated with better hemodynamic stability, lower toxicity and more potent analgesia than other anesthetics. The major disadvantage of xenon is an increase in PONV. Future research should focus on reducing the incidence of PONV; lowering costs,¹¹ which may involve changing priming and flushing practices;¹⁴ and evaluating the environmental impact of xenon when compared to greenhouse gases like nitrous oxide.⁴

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