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San Sebastian 2004 Session 3-1 |
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Neuroprotective effects of Xenon: A new agent
for cardiac anaesthesia and intensive care medicine / Acción neuroprotectora del Xenon: Un nuevo agente para anestesia cardiaca
y medicina intensiva.
Dr. Schmidt M., Marx T., Schirmer U., Reinelt H. University of Ulm, Dept. Cardiac Anesthesia, Ulm Germany
A new
agent for for cardiac anaesthesia and intensive care medicine.
Although modern intensive
care medicine has changed a lot over the years, no currently used regimen for
analgosedation is totally free from adverse effects. Midazolam, fentanil, alfentanil,
and propofol, given by intravenous infusion, are mostly used in cardiac
anaesthesia and intensive care in current clinical practice. The
pharmacokinetics of even the commonly used intravenous anaesthetics remain
uncertain in critically ill patients, and all existing intravenous drugs carry
the risks of cumulation and cardiovascular depression, specially in elderly
patients with multiple organ dysfunction.
Xenon is a noble gas with
sedative and analgesic properties and shows promise in protecting the brain
from the neurological damage often associated with the use of cardiopulmonary
bypass 1. It is chemically inert, not cerebrotoxic and has
been successfully used as a general anaesthetic. It has many desirable
properties as almost no effect on plasma catecholamines 2 and a minimal effect on the myocardium 3 and left ventricular performance. Luttrop 4 investigated the effects of
xenon anaesthesia on myocardial function with transoesophageal
echocardiography. Seventeen ASA 1 patients were studied as anaesthesia with 65%
xenon in oxygen was performed. The echocardiographically obtained mean (SD)
fractional area change in a short axis view of the left ventricle at the level
of the papillary muscles was not changed during xenon inhalation. It was
concluded, that xenon anaesthesia had no adverse effect on left ventricular
myocardial function 4. Xenon has been
described by Bedi 5 to provide
pleasant, well-tolerated sedation in volunteers. In modern anaesthetic practice
xenon has not been used in larger scale due to its relatively low potency and
expensive costs 6. The
pharmacological properties of xenon are close to those of an "ideal"
sedative, and it is exhaled by the lungs unchanged, a highly desirable property
in the patient with hepatic or renal impairment. Having the lowest blood gas
solubility of any anaesthetic gas 7 means that it
shows a rapid onset and offset of anaesthesia 8. In theory, xenon
may provide sedation for critically ill patients without adverse effect for
multimorbide groups of patients as in cardiac surgery combined with a
neuroprotective effect.
As there are no published
data about right ventricular pump performance, goal of the presented study is
the evaluation of the right ventricular ejection fraction (RVEF) before and
after cardiac arrest during xenon inhalation in an animal model as compared to
TIVA.
After approval by the local
animal care committee we investigated 24 pigs (12-16 weeks) in a randomised
design. The TIVA anaesthetized and oxygen ventilated animals were randomly
assigned in two groups to receive either xenon or air in stepwise increased
concentration until either xenon (75%) in oxygen (25%) or TIVA combined with
air in oxygen (25%) ventilation was reached. Haemodynamic parameters, pulmonary
artery pressure and right ventricular ejection fraction were determined. After
15min, ventricular fibrillation with cardio-circulatory arrest of 4 min and CPR
for 1min ROSC was established and an investigation time of 240 min was
performed. For statistical data analysis ANOVA was performed.
Although PAP was
significantly increased during inhalation of xenon >40% (p<0,05), there was no significant difference in REF values for
xenon vs. control, neither before nor after cardiac arrest in a pig model.
As a
second point of interest we investigated the influence of cerebral ischemia
(imitating cerebral hypoxia during cardiopulmonary bypass caused by air,
atheromatous emboli etc.) on cerebral microdialysis results in pigs with xenon
inhalation vs. TIVA to evaluate a potential neuroprotective effect. Cerebral blood flow may be compromised in a variety of
anaesthetic procedures and ischemic cerebral complications represent the
leading cause of morbidity after cardiac operations. With the growing
importance of neuroprotective strategies, the current study was designed to
determine whether xenon would attenuate cardiac arrest induced brain injury in
pigs.
After approval by the local
animal care committee, 24 pigs (age 12-16 weeks) were investigated in a
randomized design. General haemodynamics, intracranial
pressure (ICP), brain-tissue oxygenation (ptiO2) and cerebral
microdialysis (CMD) parameters were investigated. The animals were assigned to
two groups to receive anaesthesia with either xenon (75%) in oxygen (25%) or
TIVA combined with air in oxygen (25%) ventilation 15 min prior to cardiac
arrest. After cardiac arrest of 4 min, CPR was performed for 1min and the
induced ventricular fibrillation was terminated by electrical defibrillation.
The investigation time was 240 min.
Approximately 60s after
cardiac arrest, brain ptiO2 dropped to a critical level of
<5mmHg, paralleled by a decrease in EEG activity. Glycerol as a damage
marker increased significantly (>200 Mol/ l; p<0,05),
with a peak 90 min after cardiac arrest in both groups. Also the lactate/
pyruvate ratio as a metabolic marker increased to a pathologic peak (>20)
after 90 min in both groups.
As a major finding of this
study, glycerol levels during reperfusion were significant lower and normalized
faster in the xenon group as compared to the TIVA group.
Cardiac arrest and
resuscitation in this animal model produced a transient cerebral ischemia
followed by pathologic changes in CMD damage and metabolic markers. Although
the primary ischemic lesion in this model was similar in both groups, the data
show a neuroprotective effect of xenon during reperfusion after cerebral
ischemia.
In conclusion, xenon is an
anaesthetic gas that appears to be both neuro- and cardio-protective and there
is an indication for patients undergoing cardiac surgery,
that are at risk both from neurological injury and myocardial
dysfunction. Clinical experience in cardiac anaesthesia with xenon is rare
however, being limited by the very high cost of xenon and the need of special
low flow administration and recycling systems. But as shown by Dingley 9 and Bedi 10 the sedative and analgesic effect combined with rapid
onset and offset times and stable haemodynamic profile presents xenon with a
new indication as an promising adjunct for use in postoperative intensive care
in patients with limited cardiac pump performance.
1. Ma D, Yang H, Lynch
J, Franks NP, Maze M, Grocott HP: Xenon attenuates
cardiopulmonary bypass-induced neurologic and neurocognitive dysfunction in the
rat. Anesthesiology 2003; 98: 690-8
2. Marx T, Wagner D,
Baeder S, Goertz A, Georgieff M, Froeba G: Haemodynamics and catecholamines in
anaesthesia with different concentrations of xenon. Appl.Cardiopulm.Pathophys.
1998; 7: 215-21
3. Boomsma F, Rupreht J,
Man-in-'t-Veld-AJ, de Jong FH, Dzoljic M, Lachmann B: Haemodynamic and
neurohumoral effects of xenon anaesthesia. A comparison with
nitrous oxide [see comments]. Anaesthesia 1990; 45: 273-8
4. Luttropp HH, Romner
B, Perhag L, Eskilsson J, Fredriksen S, Werner O: Left
ventricular performance and cerebral haemodynamics during xenon anaesthesia. A
transoesophageal echocardiography and transcranial Doppler sonography study.
Anaesthesia 1993; 48: 1045-9
5. Bedi A, McCarroll C,
Murray JM, Stevenson MA, Fee JP: The effects of subanaesthetic concentrations
of xenon in volunteers. Anaesthesia 2002; 57: 233-41
6. Lachmann B,
Armbruster S, Schairer W, Landstra M, Trouwborst A, Van Daal GJ, Kusuma A,
Erdmann W: Safety and efficacy of xenon in routine use as an inhalational
anaesthetic. Lancet 1990; 335: 1413-5
7. Goto, T., Suwa, K.,
Uezono, S., Ichinose, F., Uchiyama, M., and Morita, H. The blood gas partition
coefficient of xenon may be lower as expected. Br.J.Anaesth. 80, 255-256. 1998.
Ref Type: Generic
8. Goto T, Saito H,
Nakata Y, Uezono S, Ichinose F, Morita S: Emergence
times from xenon anaesthesia are independent of the duration of anaesthesia.
Br.J.Anaesth. 1997; 79: 595-9
9. Dingley J, King R,
Hughes L, Terblanche C, Mahon S, Hepp M, Youhana A, Watkins A: Exploration of
xenon as a potential cardiostable sedative: a comparison with propofol after
cardiac surgery. Anaesthesia 2001; 56: 829-35
10. Bedi A, Murray JM,
Dingley J, Stevenson MA, Fee JP: Use of xenon as a sedative for patients
receiving critical care. Crit Care Med. 2003; 31: 2470-7
