Sign in Subscribe

Xenon

Last updated on 
Xenon

Take home messages

  • Xenon is the closest to an ideal anaesthetic agent that we have
  • It's cardiostable and neuroprotective, and an analgesic
  • But it's very expensive

Xenon is seriously cool

A common FRCA Primary question is to describe the 'ideal' anaesthetic agent, triggering the candidate to begin joyfully spewing a pre-recorded list of coefficients, physicochemical and metabolic properties.

What are the characteristics of an ideal inhalational anaesthetic agent?

These characteristics can be divided into:

Physical

  • Easy and cheap to manufacture
  • Not damaging to the environment during its production or use
  • Non-flammable and non-explosive
  • Safe to store and transport at room temperature
  • Stable on exposure to light and at a range of temperatures
  • Compatible with existing anaesthetic equipment - non-reactive to metal, rubber and soda lime

Chemical

  • Inert in air, glass and plastic
  • Non-immunogenic

Clinical

  • Pleasant odour
  • High oil:gas partition coefficent - increased potency
  • Low blood:gas partition coeffient - fast onset and offset
  • Minimal metabolism - entirely excreted by the lungs
  • Non toxic
  • No effect on other body systems - e.g. minimal cardiovascular effects, non-epileptogenic (enflurane demonstrates epileptiform activity on EEG)
  • Predictable pharmacokinetics
  • Easily measurable in real-time using existing equipment, such as infrared spectrometry
  • Sufficient dose-dependent respiratory depression to prevent oversedation when patient is spontaneously breathing
  • Ideally an element of analgesia as well

Here's our post on inhalational anaesthetic agents

Of course, no single agent satisfies all of these parameters, but to be fair - Xenon gets pretty close.

A spot of history

Meet Sir William Ramsay (left) and Morris Travers (right)

In 1898 these clever lads discovered Xenon with no real purpose in mind other than 'for science'.

It wasn't until 1939 that Albert R. Behnke et colleagues realised that it made people wobbly, and in 1951 Cullen and Gross suggested it could be used for anaesthesia.

What is it good for?

Unlike war, xenon is pretty good for a lot of stuff:

  • Heart - cardiostable
  • Brain - neuroprotective
  • Kidneys - excreted unchanged by the lungs, zero metabolism
  • Environment - no greenhouse gas effects
  • Theatre coordinator - rapid emergence*
  • Pain relief - NMDA receptor antagonist
  • Non toxic - inert and doesn't trigger malignant hyperthemia
  • PONV - considerably less than other volatiles

*Blood gas partition coefficient of 0.14, (compared to desflurane's 0.42 and sevo's 0.65) making it very rapid onset and offset.

It also doesn't matter how long they've been asleep - if they've been asleep long enough for a propofol TIVA wake up to take 25 minutes, think 3 minutes for xenon.

Heart stuff

Xenon appears to be fabulously cardiostable, with minimal effects on:

  • Heart rate
  • Blood pressure
  • LV function and cardiac output

Brain stuff

  • If you assume that a culture of neuronal and glial cells from neonatal mice can be used as reasonable comparators to human brains
  • And you assume that measurable LDH release into the culture medium is a useful surrogate for 'amount of brain damage'
  • Then you can safely say that lots of NMDA can induce brain damage
  • Therefore NMDA antagonists are often considered 'neuroprotective'

Xenon is one of these such antagonists.

And these assumptions are also backed up by more robust in vivo experiments on rats.

In the first five minutes of exposure to xenon, cerebral blood flow increases. Then, blood flow seems to reduce to lower than initial levels, and it's not clear why.

You can, however, still alter cerebral blood flow by adjusting your patient's PaCO2.

It doesn't seem to have much effect on intracranial pressure, unless your patient already has severe head injury, in which case it increases substantially.

We also don't really know what effect it has on cerebral oxygen demand just yet.

How it works

It's kind of like a clean, inhaled version of ketamine without the K-hole and fisticuffs on emergence.

💡
Xenon is a glutamatergic NMDA receptor antagonist

It also has some antagonistic action at nicotinic acetylcholine receptors, but we're not totally sure whether this is clinically all that significant just yet.

What's the MAC?

This is weirdly tricky to figure out, and so we have an extrapolated value.

Because giving more than 70% xenon without hypoxia is tricky, the original researchers co-administered xenon with a known agent such as sevoflurane, and then gradually lowered how much sevo they were giving to figure out how hard the xenon was working.

They then presumed a linear extrapolation would be fine and so we now have the number of 63% to play with.

It also depends on the isotope of xenon and its nuclear spin, meaning that you can start using the phrase 'quantum anaesthesia' to impress people.

💡
Xenon's MAC is estimated at around 63%

Not quite as infeasibly high as nitrous oxide's 103%, but certainly a darn sight higher than our usual vapours of choice.

Clearly this makes an oxygen requirement of greater than 37% tricky to manage.

But hey, if you've got enough xenon hanging around to play about with, you've probably got the money for a hyperbaric chamber too.

It's a bit tricky to measure

Figuring out how deeply unconscious your patient is can prove rather challenging.

Normally we rely on the dose-dependent bradycardias and hypotensions (that we so lament when discussing how un-ideal our inhalational agents currently are) to show that there's no way a laparotomy patient could be aware with a heart rate of 56 and a systolic of 93.

But xenon doesn't seem to drop your respiratory rate, blood pressure or heart rate in quite the same way so we face a bit of an issue.

You also can't use BIS - which is validated for GABA blockers - for NMDA receptor antagonists (same as ketamine and nitrous) but mid-latency auditory evoked potentials (MLAEPs) might be useful.

I guess you just have to go on trends - if they don't flinch and there isn't a sudden jump in heart rate or blood pressure from whatever it was before knife to skin, they're probably asleep enough.

Pain relief

Xenon is similar to, or slightly better, than nitrous oxide in its analgesic activity depending on the type of pain you're testing.

It also blocks any tachycardic or hypertensive response to incision three times better than sevoflurane at comparable MAC values.

Like ketamine, we know nitrous oxide is an NMDA receptor antagonist, and xenon appears to do the same, so we think this is probably how it provides analgesia.

  • Nitrous induces release of endogenous opioid receptor ligands
  • These work in the periaqueductal grey
  • This activates descending inhibitory neurons in the spinal cord
  • If you give opioid receptor blockers or alpha 2 antagonists, the pain relief effect is ruined

However xenon's analgesia doesn't appear to be affected by these antagonists, so it must be doing something else.

Either way - it seems to work.

Show me the money

If you're wondering 'what's the catch?' well here it is.

Xenon is hideously expensive, largely due to its rarity and difficulty in production, because you have to fractionally distill it from the atmosphere.

It's name literally means stranger because it's only 0.00000875% of the atmosphere or 0.0875 ppm

💡
1 litre of 99.99% xenon is $10

This means anaesthetising an ASA 1 adult undergoing a laparoscopic appendix would cost in the region of hundreds of dollars, mostly because of the amount of flushing and priming the breathing circuit required before you can even start.

Because of this cost, it needs highly specialised equipment to ensure every last shred of xenon is reused as many times as possible before being lost to the atmosphere.

Ideally you'd scavenge every molecule, clean them (how?!) and give them to the next person.

What about the environment?

It's fairly well established how terrible our drugs and vapours are for the environment, so it would be lovely if we could just find something to use that didn't destroy everything around us.

Hello xenon.

While nitrous oxide is 230 times more greenhousey than CO2 and takes over 100 years to break down, xenon appears to do very little harm as far as we know.

It won't warm the planet up, doesn't anaesthetise the fish and will leave your conscience feeling fresh as a daisy.

Your wallet might disagree though.

The verdict

Like literally everything new in the world of anaesthesia, the overall verdict is,

"Sounds cool, we'll have to see how it goes"
  • Can we feasibly and sustainably manufacture it in meaningful quantities for mainstream anaesthesia?
  • Can we be sure it doesn't cause some horrendous malignancy 68 years down the line?
  • Would our attention, time and money be better spent on making current systems more efficient and cost-effective instead?

Big questions for a little blog post. We'd love to hear your thoughts and experiences - let us know in the comments or email us at anaestheasier@gmail.com

Useful stuff

References and Further Reading

Xenon or propofol anaesthesia for patients at cardiovascular risk in non-cardiac surgery - PubMed
Xenon anaesthesia provided a higher arterial pressure level than propofol, with no signs of cardiovascular compromise, in patients with CAD. Echocardiographic indices showed better LV function with xenon.
PubMedJ-H Baumert