X-Message-Number: 22774
Date: Wed, 5 Nov 2003 18:30:36 -0800
Subject: Xenon as sedative/neuroprotectant
From: Kennita Watson <>

It's the comment about neuroprotective effects that caught my eye.


----- from http://www.medscape.com/viewarticle/463368?mpid=20655 :
Xenon Effective, Well-Tolerated as Sedative for Critically Ill Patients

Mindy Hung

Oct. 24, 2003   Xenon is effective and well-tolerated as a sedative for 
critically ill patients, according to results of a randomized crossover 
trial published in the October issue of Critical Care Medicine.

"Xenon's reported lack of effect on the myocardium, cardiac index, 
arterial blood pressure, and vascular resistance makes it theoretically 
attractive for the sedation of the critically ill. This contrasts with 
the well-known myocardial depressive effects of propofol," write Amit 
Bedi, MD, and colleagues, from the Royal Group of Hospitals in Belfast, 
Northern Ireland.

Investigators studied 21 patients (15 men and 6 women; median age, 63 
years) capable of giving written informed consent who required 
mechanical ventilation after elective thoracic surgery. They excluded 
patients with a history of epilepsy or evidence of hepatic or renal 
dysfunction. Subjects also had Acute Physiology and Chronic Health 
Evaluation II scores evaluated at admission.

Thirty minutes before the anticipated end of surgery, anesthesia was 
maintained with isoflurane in oxygen for 10 subjects randomized to 
group A and 11 subjects randomized to group B. One unblinded clinician 
administered all sedatives and analgesics.

Group A received a standard sedation and analgesia regimen of 
intravenous propofol (2%) at 0 to 5 mg/kg-1/hr-1 and alfentanil 30 
 g/kg-1/hr-1 for eight hours. Investigators then stopped the drugs and 
noted the time when patients began to appear restless, at which point 
they began sedation using variable concentrations of xenon in 
oxygen-enriched air as required.

Group B received eight hours of xenon in oxygen-enriched air as the 
initial form of sedation. Medication was then stopped and investigators 
initiated the propofol-alfentanil regimen for eight hours when the 
subjects' consciousness level increased.

At the request of the blinded attending nurse or physician, 
investigators provided additional analgesia as needed, using boluses of 
alfentanil 250  g. If patients required more than six boluses in an 
hour, physicians began an infusion of alfentanil at a rate equivalent 
to the previous hour's requirement.

Nurses were instructed to increase medication to ensure that patients 
had a Ramsay sedation score of either 2 or 3. Nurses also requested the 
unblinded operator to provide additional analgesia if subjects seemed 
to be in pain or sore. A physician, unaware of ongoing sedation, 
administered inotropes, fluids, blood, and other drugs according to the 
patients' requirements.

Xenon was delivered using a novel bellows-in-bottle breathing interface 
driven by a conventional intensive care ventilator. It was not visible 
to caregivers and allowed routine tracheal suctioning and physiotherapy 
procedures to be performed.

Investigators successfully sedated all patients during the xenon 
regimen. The mean (SD) end-tidal xenon concentration required to 
provide sedation throughout the duration of the study was 28%   9.0% 
(range, 9%-62%). In patients receiving the propofol regimen, arterial 
systolic, diastolic, and mean pressures showed a greater tendency for 
negative gradients (P < .05, P < .10, and P < .01, respectively).

Patients receiving the xenon sedative regimen achieved a Ramsay 
sedation score of 1 in a significantly shorter time than those 
receiving the standard regimen (P < .0001). Hematologic and biochemical 
laboratory markers fell within normal clinical limits for both groups.

Dr. Bedi and colleagues acknowledge that clinically used sedatives have 
been subjected to more rigorous preclinical safety testing than xenon. 
They also note that changes in Ramsay sedation scores are a crude 
assessment of offset of sedative effect; but they counter that there 
were marked differences between emergence times for the regimens.

"We have shown that it is feasible to use xenon for intensive care unit 
[ICU] sedation and propose that it may have advantages over standard 
drugs in the sedation of hemodynamically unstable patients such as 
those recovering from myocardial infarction, endotoxemia, 
cardiomyopathy, or closed head injury," they write.

"The use of a specially designed close-circuit ventilation system 
minimized the cost while allowing routine tracheal suctioning and 
physiotherapy procedures to be performed."

In a related editorial, Thomas Marx, MD, from the University of Ulm in 
Germany, wrote that xenon's neuroprotective effects may reduce the 
length of ICU stay, which might offset its high price. "Prolonged ICU 
stay due to neuronal damage after cardiac bypass surgery alone is 
regarded to cost $2-4 billion in the United States annually," he notes.

He adds, "It is an important milestone for xenon's future to 
demonstrate how xenon could be administered during ICU therapy. I 
regret that the authors did not measure the real xenon usage to give a 
rough estimation of the expected costs."

Crit Care Med. 2003;31:2470-2477, 2556-2557

Reviewed by Gary D. Vogin, MD

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