Xenon anaesthesia

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)