Criticare - A special feature on Anaesthesiology

Xenon: A modern anaesthetic

Dr Sanjay Singh

Xenon is well known as an inert gas filled inside incandescent lamps. Although, named after a Greek word ‘stranger’, Xenon is becoming less and less of a stranger for anesthesiologist. Knowledge of the anesthetic properties of xenon goes back to 1939, where Behnke and Yarborough investigated for the US Navy, the reason for mental effects in deep sea diving. Lawrence published initial experiments with xenon anesthesia in 1946. With a minimum alveolar concentration of 0.63, it is more potent than N2O. However, the extremely high cost (approx USD 10.00 per liter) has hindered its wide clinical application. Xenon was completely forgotten for more than 30 years since the early clinical trials in 1950’s, until Lachmann, Erdmannand their colleagues at Rotterdam rediscovered it in 1990. Since then, there has been a growing interest in xenon, especially in Europe and Japan, and two multi-centre clinical trials have been completed in the European Union.

Xenon belongs to the group of noble gases and is found in very small concentration in the air (0.0000087 per cent). It is manufactured by fractional distillation of liquefied air, which is obtained as a by-product during the process of pure oxygen production. After several separation processes, a purity of 99.995 per cent can be obtained; only impurity being O2 and N2. The production of one liter of Xenon consumes 220-Watt hours of energy. Corresponding to its rarity, xenon is expensive. The current world production of xenon is approximately 10 million liters per year.

Only 1.5 million liter per year is utilised for medical purposes, with half of this amount being used for anesthetic purposes. Xenon has been used for decades to study blood flow and gas distribution in lung although recent technical developments have expanded its use in magnetic resonance imaging. The resurgence of xenon as anesthetic despite its rarity and high cost may invite natural wonder in this era of cost containment.

There are three major reasons for Xenon’s popularity:

• Pharmacological and clinical advantage
• Its usefulness as scientific tool
  
• Environment friendliness.

Pharmaco clinical advantage –Xenon exists as a monatomic gas under normothermic and normobaric conditions. Although virtually inert, the very large outer electron shell of xenon may get polarised and distorted by nearby molecules and permits xenon to interact with and bind to proteins such as myoglobin as well as bi-layer lipids. Xenon’s ability to interact with cell proteins and cell membrane constituents is presumably responsible for its anesthetic potency.

Xenon also inhibits plasma membrane Ca++ pump, an action similar to that of volatile anesthetics, which may be responsible for an increase in neuronal Ca++ concentration and altered excitability.

Franks et al found that xenon despite a relatively simple atomic structure, acts selectively by blocking the N-methyl-d-aspartate receptor. This NMDA receptor inhibitor is responsible for inhibition of nociceptive responsiveness of spinal dorsal horn neurons.

Xenon has been shown not to alter voltage gated ion channels in the myocardium, nor does it sensitises the myocardium to the dysrhythmogenic effects of epinephrine. Xenon has many properties of an ideal anesthetic gas. These include:

1. Non-inflammable and non explosive

2. Rapid induction and emergence due to its low blood gas partition coefficient (0.12), which is lowest of all known anesthetics.

3. Human minimum alveolar conc (MAC) value of 0.63 makes it suitable as an inhalation anesthetic in a mixture of 30 percent O2. It is 1.5 times more potent then N2O.

4. Sufficient analgesic and hypnotic effect in mixture with 30 per cent O2.

5. The absence of metabolism, low toxicity and devoid of teratogenicity.

6. Compared to another anesthetic regimen, xenon anesthesia produces highest regional blood flow in the brain, liver, kidney and intestine. Dangers of tissue hypoxia are greatly reduced. It therefore appears to be an interesting alternative for anesthesia in transplant surgery.

7. It may protect neural cells against ischemic injury. During cardiopulmonary surgery its neuro protective effect is confirmed.

8. Undisturbed ventilation and pulmonary function. Despite higher density than N2O it does not alter respiratory mechanics. Airway resistance is not increased.

9. Lack of cardiovascular depression is the most appealing characteristics of Xenon. Even with 80 per cent concentration of Xe, Ca++ flow in human cardiomyocytes remains unaffected. Myocardial performance Index (MPI) and contractility, as measured by measuring the velocity of circumferential fiber shortening (Vcfe) and left ventricular and systolic wall stress (LVESW) using Tran esophageal echocardiography did not show any depression. The unique combination of analgesia, hypnosis and lack of hemodynamic depression makes it a very attractive choice for patients. Though its limited cardiovascular reserve, makes it expensive.

10. Diffusion hypoxia is less than N2O.

Xenon as scientific tool

Xenon is an interesting scientific tool to investigate the mechanism of anesthesia. Although it has been shown that Xe inhibits the function of N-methyl-D-aspartate subtype of glutamate receptor and also of the nicotinic acetycholine receptor. How it does so remains a mystery. Being inert, it displays an extremely low chemical reactivity, therefore it alters the function of these receptors via physiochemical means or these receptors may not be as important as we would like to believe. Xe hardly affects the function of gamma- amino butyric acid receptor but produces hypnotic effect electrophysiologically similar to other volatile anesthetics. His provocative finding stimulates rethinking on the mode of action of anesthetics.

Xenon and the global environment

Environment friendliness of Xe strongly appeals to the increasing numbers of ecologically minded people in anesthesia community. Agents such as halogenated alkenes or alkyle-ether as well as N2O are involved in destruction of ozone layer and contribute to greenhouse effect. N2O is 230 times more potent as a green house gas than is CO2 on a molecular basis and N2O released as a waste anesthetic contributes roughly 0.1 per cent of the whole global warming. To make things worse the lifetime of N2O in the atmosphere is long – approximately 120 years. Xe being a part of atmosphere and manufactured from liquefied air, doesn’t add to atmospheric pollution when emitted from anesthetic circuit because it simply goes back to the atmosphere.

Xenon doesn’t contribute to the depletion of ozone layer. This conforms to the growing concerns that mankind may not be able to live through 21st century if global warming and other forms of atmospheric pollution continue at the present rate.

Future of anaesthesia

Because of its rarity and expensiveness, the use of this gas as an anesthetic agent can be justified only if its waste is reduced to absolute minimum. It must be applied via rebreathing system using the lowest possible gas flow. Close system anesthesia is the only economically acceptable technique for application of Xe anesthesia. An electronically controlled anesthesia delivery system that continuously monitors gas concentration inside the breathing circuit may be used for this purpose. A closed loop feedback control mechanism delivers Xe and oxygen into the system in the amount needed to maintain constant gas concentration and circulating gas volume.

Recycling of Xe contained in the gas escaping via the exhaust port rather than wasting it in to the atmosphere is the only way to guarantee the availability of a sufficient amount of Xe for routine use as an anesthetic gas. Because of considerable expense and the fact that it cannot be synthesised but rather must be extracted from the atmosphere, it is unlikely that Xe will gain wide spread use. However, should delivery system become available with appropriate technique of recycling the gas, Xe anesthesia may become more readily available. Over the next few years, it will be interesting to see better definition of its pharmacologic characteristic at the cellular level as well as its effects and cost benefit ratio in clinical trials.

The author is chief cardiac anaesthesiologist at Suraksha Hospital, Kolkata.