xenon anaesthesia

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  • Xenon anaesthesiaNick Harper

  • ContentsHistoryAnaesthetic propertiesEnvironmental impactCostAdvantages & potential for clinical useCardiovascular stabilityNeuroprotectionRenal transplantSummary

  • Rectification of liquid airRamsay & Travers-108.13C new gas discovered0.0000087%Xenon stranger

    To start off with, what is Xenon?Cool air down until it is a liquid, then warm it up slowly, individual gasses that make up air will boil off at different temperatures.In 1890, when Ramsay and Travers were doing this experiment, at -108. Degrees, they discovered a new gas.Very small % composition, that equates to about 1 part in 10 million, or in a room about this size about 4ml.Greek for stranger xenon*

  • Place on periodic tableNoble gas, very denseOne its of main uses is by NASA in thrusters used to give propulsion in space. Also very bright car headlights.So, whats xenon doing in an anaesthetic presentation?*

  • Xenon anaesthesia

    1939 Anaesthetic properties discovered

    Xenons anaesthetic properties first discovered during experiments on US navy divers in the late 30s*

  • Xenon anaesthesia

    1946 LawrenceMice1939 Anaesthetic properties discovered

    1946, mice were given the first ever xenon anaesthetic*

  • Xenon anaesthesia

    1946 LawrenceMice1951 CullenHumans1939 Anaesthetic properties discovered

    In 1951, Cullen gave the first human anaesthetics, reporting great success.*

  • Gas at room tempNon volatileNon teratogenicOdourless

    MAC 63.1% (Nakata et al, 2001)Blood/gas partition coefficient 0.115Rapid emergence = 5mins (2X faster than Desflurane)

    NMDA (N2O, Ketamine)Analgesia (1.5X potency N2O)

    (Petersen-Felix, S. et al., 1998)

    Properties of xenonLowest blood/gas partition coefficient of any inhalational anaesthetic agent.Gives very rapid inflow and washout, with an emergence time of about 5 mins, which is 2 X faster than Desflurane.Most inhalational agents work by increasing the activity of the GABA system. Xenon works by inhibiting NMDA receptors, like nitrous oxide and ketamine.As such, xenon also has analgesic properties, with a potency of about 1 and a half times that of nitrous oxide.*

  • Anaesthetic agentEnvironmental impactIsofluraneEnfluraneHalothaneChlorinated hydrocarbonsOzone depletingEmission banned from 2030DesfluraneSevofluraneFluorinated hydrocarbonsGreenhouse gas capacity 10X Co2Nitrous oxideGreenhouse gas capacity 230X Co2XenonNone

    At the moment there is also strong legal pressure to restrict the use of current inhalational anaesthetic agentsChlorinated hydrocarbons such as isoflurane are ozone depleting and as such their emission is been banned by international agreement from 2030. The montreal summit of 2007 accelerated this date for developed nations to 2020Desflurane and sevoflurane are fluorinated hydrocarbons. Regulations to reduce the emission were put in place at the Kyoto conference. Nitrous oxide has a green house gas capacity 230X that of Co2Xenon has certain environmental and legal advantages.*

  • CostXenon 10X cost of sevoflurane

    6 - 12 per litreXe uptake 3L/hour30 theoretical cost for 60mins100 actual cost

    Closed circuitLow flowRecycling

    So, whats the downside of xenon? Costs 10X that of SevofluraneThere are lots of methods of reducing the amount of xenon required during an anaesthetic, but as many of these principles can also be used with the other inhalational agents, xenon is still very expensive relative to the others.So, just how expensive is it?Amount of Xenon that is actually taken up by the body during an anaesthetic is about 3L an hour.Theoretical cost 30. Including the initial inflow stage and inefficiencies in the machine, actual cost is 100*

  • Advantages?

    Given the high cost, does xenon offer any advantages that would allow for clinical use.Concentrate on 3 systems, cardiovascular, central nervous system and renal.*

  • Cardiovascular stabilityXenon Vs Isoflurane (n=252) HR stability (P

  • IschaemiaGlutamate releaseNMDA receptor activationApoptotic cascadeexcitotoxicity

    Neuroprotection

    Moving onto the nervous system and the world of neuroprotection.It is currently thought that when an area of the brain becomes ischaemic, it sets up a self sustaining apoptotic cascade medicated by excess glutamate release. This results in a much larger area of neuronal damage. So called excitotoxicity.As xenon works by inhibiting these NMDA receptors, it was thought that perhaps it could be used to break the cycle and reduce neuronal damage.*

  • NeuroprotectionMouse neuronal-glial cell cultureLDH as index of damage

    Wilhelm, S. et al., 2002

    Hippocampal brain slicesPropidium Iodide

    Banks, P. et al., 2010

    Xenon dose dependent neuroprotection

    To test this idea, one group got a mouse neuronal-glial cell culture and deprived it of oxygen. They then measured LDH release as a marker of neuronal damage. They found that by adding different concentrations of xenon to the mix, they could reduce the amount of LDH release in a dose dependent manner.Taking this further, another group used hippocampal brain slices as a more accurate model of real brain. They then exposed these tissues to oxygen and glucose deprivation and used a fluorescent dye, propidium Iodide as a marker of neuronal damage. These pictures show that in oxygen, glucose deprivation, there is a lot of neuronal damage, but this can be significantly reduced by adding xenon.So xenon does show neuroprotection in vitro, but does it work in vivo and does it lead to an improvement in functional outcome?*

  • NeuroprotectionHypoxic/ischaemic brain injury1-6 per 1000 live birthsMortality 15-20%25% of survivors are severely disabled

    One particular area in which this is being studied is in relation to hypoxic/ischaemic brain injury of the newborn. This occurs in 1-6 per 1000 births and carries a very high mortality.Even if the child survives, there is a 1 in 4 chance of being left severely disabled. So there is obviously great potential for neuroprotection.The work behind this is being carried out in St Michaels Hill by Prof Thorensen. The same group that showed that therapeutic hypothermia can also help this group of patients*

  • NeuroprotectionNeonatal ratsUnilateral carotid ligation & 8% O250% Xenon +/- cooling

    Hobbs, C. et al., 2008

    Humans:80% neurological disability1st baby treated April 2010

    In one of their studies they got neonatal rats and ligated one of their carotid arteries and gave them 8% oxygen to breathe, mimicking hypoxic/ischaemic injury.They then treated half of the rats with 50% xenon, with and without the addition of cooling to 32 degrees.This is a graph of their results, showing a measure of neurological functional outcome at different weeks post-natally. You can see that the totally untreated rats had the worst functional outcome, whereas those treated with xenon and cooling performed identically to normal control rats who didnt have the initial ischaemic injury.In humans with hypoxic ischaemic brain injury, 80% show some neurological disability. Treating with xenon therefore offers a huge opportunity for helping to prevent this disability and reduce the need for long-term rehab. So in this case xenon may well be cost effective.Trials in humans to test this have started recently, with the first baby treated in April 2010 in St Michaels.*

  • Renal protectionRenal transplantIschaemia reperfusion injuryDelayed graft function, rejection, chronic nephropathy

    Rat renal transplant modelGraft harvested 1-28 days for analysis17 dayscontrol28 days (max)Xenon preconditioning (2hrs)

    Zhao, H. & Ma, D., 2011

    Finally, moving onto Renal protection.During renal transplant, ischaemia reperfusion injury of the donor kidney is a major cause of delayed graft function, rejection and chronic nephropathy.A study published a few months ago showed that in a rat model of renal transplant, if you examine the grafted kidney, the mean survival of that graft was about 17 days. This could be dramatically increased by pre-treating the donor rat with 2 hours of xenon. This study shows another example where xenon could be used in a high stakes procedure to reduce long term complications. It was only published a few months ago but will undoubtedly lead to more research into the use of xenon in organ transplantation.*

  • SummaryFast, analgesic, non toxic, odourless, environmentally friendly

    High cardiovascular riskNeuroprotectionOrgan transplantation

    Expensive!the perfect anaesthetic

  • References (1)Banks, P., Franks, N.P. & Dickinson, R. (2010)Competitive Inhibition at the Glycine Site of the N-Methyl-D-Aspartate Receptor Mediates Xenon Neuroprotection against HypoxiaIschemia. Anesthesiology 112: 614 622

    Baumert, J.H., Hein, M., Hecker, K.E., Satlow, S., Neef, P. & Rossaint, R. (2008) Xenon or propofol anaesthesia for patients at cardiovascular risk in non-cardiac surgery. British Journal of Anaesthesia 100 (5): 605611

    Bein, B., Turowski, P., Renner, J., Hanss, R., Steinfath, M., Scholz, J. & Tonner, P.H. (2005) Comparison of xenon-based anaesthesia compared with total intravenous anaesthesia in high risk surgical patients. Anaesthesia 60: 960967

    Hobbs, C,. Thoresen, M., Tucker, A., Aquilina, K., Chakkarapani, E. & Dingley, J. (2008) Xenon and Hypothermia Combine Additively, Offering Long-Term Functional and Histopathologic Neuroprotection After Neonatal Hypoxia/Ischemia. Stroke. 39(4): 1307-1313

    Homi, H.M., Yokoo, N., M.D., Ma, D., M.D., Warner, D.S., Franks, N.P., Maze, M. & Grocott, H.P. (2003) The Neuroprotective Effect of Xenon Administration during Transient Middle Cerebral Artery Occlusion in Mi

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