Is Xenon Really Neuroprotective after Cardiac Arrest?
Fries, Michael M.D.*; Weis, Joachim M.D., Ph.D.; Rossaint, Rolf M.D., Ph.D.
To the Editor:—
Xenon has recently been shown to act as a neuroprotective agent in several in vitro
and in vivo
models of acute neuronal injury, probably inhibiting the N
In the May issue of Anesthesiology, Schmidt et al.3
provided pioneering data on the effects of xenon on porcine brains assessed by hemodynamic, electrophysiologic, and metabolic measurements in a large animal model of cardiac arrest and subsequent cardiopulmonary resuscitation. Using a microdialysis technique, they documented that levels of glycerol, an integral part of the cell membrane, are significantly lower after 90 min of reperfusion in pigs that received xenon anesthesia before cardiac arrest was induced when compared with a control group that was anesthetized with a total intravenous regimen. No other parameter, including glutamate, lactate, lactate/pyruvate ratio, brain tissue partial pressure of oxygen, and intracranial pressure, showed significant differences between the groups.
In the Western hemisphere, approximately 800,000 people annually experience sudden cardiac death.4,5
Although survival rates are increasing, complete neurologic recovery is often far from certain, and by the time of hospital discharge, every second patient is neurologically severely disabled or comatose.6
Accordingly, there is urgent need to find strategies that ameliorate neuronal injury.
In this respect, the study by Schmidt et al.3
is of high clinical relevance. However, we believe that some major limitations in the study design and the interpretation of the results are not adequately discussed.
First, a major drawback of this study that detracts from its clinical significance is that the authors elected to use an extremely short duration of cardiac arrest that results in only minor brain damage, if at all.7
It is therefore not surprising that the authors failed to establish differences in extracellular glutamate values. In contrast, the evidence for glycerol as a surrogate for neuronal damage is weak because glycerol is a naturally occurring three-carbon alcohol that is ubiquitously present in considerable amounts in the human body and an integral part of the energy metabolism.8
Glycerol readily moves across the blood–brain barrier, and therefore, increases in dialysis fluid are not exclusively indicative of nerve cell damage but might reflect overall metabolic changes or changes due to exogenous sources.9,10
Second, animals received xenon before cardiac arrest was induced. In the overwhelming majority of cases, however, cardiac arrest occurs suddenly and unexpectedly. A possible indication for xenon pretreatment might be procedures that require short periods of circulatory standstill, such as insertion of implantable cardioverters/defibrillators, which is known to be associated with neurocognitive sequelae.11
Third, the authors should consider the possibility that the anesthetic regimen might have biased the results because they used an opioid for pain relief, which reportedly exerts neuroprotective properties.12
Finally, definitive parameters of neurologic injury, i.e.
, measurements of serum markers of nervous tissue damage and neurohistopathologic examinations of vulnerable brain regions, would have been of major benefit to the study. In conclusion, the authors did not demonstrate that xenon is really neuroprotective in the setting of global ischemia and reperfusion, and accordingly, we believe that the title of the article, “Xenon Attenuates Cerebral Damage after Ischemia in Pigs,” overstates the data presented. Notwithstanding these important limitations, we acknowledge and appreciate that the authors have applied xenon for the first time in this clinically highly relevant model, and we hope that the article will stimulate further research in this area.
Michael Fries, M.D., *
Joachim Weis, M.D., Ph.D.
Rolf Rossaint, M.D., Ph.D.
*University Hospital RWTH Aachen, Aachen, Germany. firstname.lastname@example.org
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Xenon: recent developments and future perspectives
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