Xenon anaesthesiaNick Harper
Contents• History
• Anaesthetic properties
• Environmental impact
• Cost
• Advantages & potential for clinical use– Cardiovascular stability– Neuroprotection– Renal transplant
• Summary
1898
1939
1946
1951
Rectification of liquid air
•Ramsay & Travers
•-108.13C new gas discovered
•0.0000087%
•Xenon “stranger”
Xenon anaesthesia
1898
1939
1946
1951
1939 Anaesthetic properties discovered
Xenon anaesthesia
1946 Lawrence
Mice
1898
1939
1946
1951
1939 Anaesthetic properties discovered
Xenon anaesthesia
1946 Lawrence
Mice
1951 Cullen
Humans
1898
1939
1946
1951
1939 Anaesthetic properties discovered
• Gas at room temp
• Non volatile
• Non teratogenic
• Odourless
• MAC 63.1% (Nakata et al, 2001)
• Blood/gas partition coefficient 0.115
• Rapid emergence = 5mins (2X faster than Desflurane)
• NMDA (N2O, Ketamine)
• Analgesia (1.5X potency N2O)(Petersen-Felix, S. et al., 1998)
Anaesthetic agent Environmental impact
IsofluraneEnfluraneHalothane
Chlorinated hydrocarbonsOzone depleting
Emission banned from 2030
DesfluraneSevoflurane
Fluorinated hydrocarbonsGreenhouse gas capacity 10X Co2
Nitrous oxide Greenhouse gas capacity 230X Co2
Xenon None
CostXenon 10X cost of sevoflurane
• £6 - £12 per litre
• Xe uptake 3L/hour
• £30 theoretical cost for 60mins
• £100 actual cost
• Closed circuit• Low flow• Recycling
Advantages?
Cardiovascular stability• Xenon Vs Isoflurane (n=252)
• HR stability (P<0.05)
• arterial pressure stability (P<0.05)Wappler, F. et al., 2007
• Xenon vs Propofol (n=40 )
• ASA III/IV, known CAD
• Elective non-cardiac
• Improved myocardial performanceBaumert, J.H. et al., 2008
Ischaemia
Glutamate release
NMDA receptor activation
Apoptotic cascade
“excitotoxicity”
Neuroprotection
Neuroprotection
• Mouse neuronal-glial cell culture• LDH as index of damage
Wilhelm, S. et al., 2002
• Hippocampal brain slices• Propidium Iodide
Banks, P. et al., 2010
• Xenon – dose dependent neuroprotection
Neuroprotection
Hypoxic/ischaemic brain injury
1-6 per 1000 live births
Mortality 15-20%
25% of survivors are severely disabled
Neuroprotection
•Neonatal rats•Unilateral carotid ligation & 8% O2•50% Xenon +/- coolingHobbs, C. et al., 2008
Humans:80% neurological disability
1st baby treated April 2010
Renal protection
Renal transplant• Ischaemia reperfusion injury
• Delayed graft function, rejection, chronic nephropathy
Rat renal transplant model• Graft harvested 1-28 days for analysis
• 17 days control• 28 days (max) Xenon preconditioning (2hrs)
Zhao, H. & Ma, D., 2011
Summary• Fast, analgesic, non toxic, odourless, environmentally friendly
• High cardiovascular risk
• Neuroprotection
• Organ 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 Hypoxia–Ischemia. 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): 605–611
• 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: 960–967
• 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 Mice. Anesthesiology. 99: 876 – 881
• Petersen-Felix, S., Luginbühl, M., Schnider, T.W., Curatolo, M., Arendt-Nielsen, L. & Zbinden, A.M. (1998) Comparison of the analgesic potency of xenon and nitrous oxide in humans evaluated by experimental pain. British Journal of Anaesthesia . 81(5): 742-747
• Wappler, F., Rossaint, R., Baumert, J., Scholz, J., Tonner, P.H., van Aken, H., Berendes, E., Klein, J,. Gommers, D., Hammerle, A., Franke, A., Hofmann, T. & Schulte Esch, J. Xenon Multicenter Study Research Group. (2007) Multicenter Randomized Comparison of Xenon andIsoflurane on Left Ventricular Function in PatientsUndergoing Elective Surgery. Anesthesiology. 106(3):463-471
• Wilhelm,S., Ma, D., M.D., Maze, M.& Franks, N.P. (2002) Effects of Xenon on In Vitro and In
Vivo Models of Neuronal Injury. Anesthesiology. 96: 1485–1491 • Zhao, H. & Ma, D. (2011) Xenon preconditioning protects renal graft against ischaemia –
reperfusion injury in rats. British Journal of Anaesthesia. 106(3): 428–446P
References (2)