The pharmacokinetics of even the commonly used intravenous anesthetics remain uncertain in the critically ill, and all existing intravenous drugs carry the risks of cumulation and cardiovascular depression, especially in patients with multiple organ dysfunction. Recently, the safety of prolonged, high-dose infusions of propofol has been questioned in both children and adults.
Xenon is a noble gas with sedative and analgesic properties. It is for all intents and purposes chemically inert and has been successfully used as a general anesthetic. It has many desirable properties not least of which is a minimal effect on the myocardium. It has been shown to provide pleasant, well-tolerated sedation in
volunteers. Xenon has not become established in modern anesthetic practice due to its relatively low potency and its expense. Its pharmacokinetic and pharmacodynamic properties 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 anesthetic gas means that its effect and recovery profile are both rapid. In theory, xenon may provide sedation without adverse effect for certain groups of critically ill patients.
We report the first use of xenon as an intensive care sedative. The primary objective of this double-blind, randomized study was to assess the feasibility of using xenon for this purpose. We used a closed circuit
breathing system especially designed for use in the intensive care unit and studied a group of relatively low-risk patients who were capable of giving informed consent before elective admission to the intensive care unit. Following local Research Ethics Committee approval and written informed consent, 21 patients requiring mechanical ventilation after elective thoracic surgery were studied using a randomized, crossover design.
These patients, admitted electively to the intensive care unit, were able to give written informed consent before surgery. Patients with a history of epilepsy or evidence of hepatic or renal dysfunction were not studied. The Acute Physiology and Chronic Health Evaluation II score was measured at admission to the intensive care unit in accordance with standard practice.
Following consent, the subjects were randomized into one of two groups as part of a crossover study: group A (n = 10) and group B (n = 11). Thirty minutes before the anticipated end of surgery, anesthesia was maintained with isoflurane in oxygen. At admission to the intensive care unit, patients were stabilized and then allocated to one of two sedative regimens. Group A received a standard sedation and analgesia regimen using intravenous propofol (2%) at 0-5 mg·kg-1·hr-1 and alfentanil 30 µg·kg-1·hr-1 for 8 hrs. These drugs then were stopped, and the time taken for the patient to begin to appear restless (Ramsay score 1) to a blinded observer was noted. Sedation then was recommenced using variable concentrations of xenon in oxygen-enriched air as required. Patients in group B (the other limb of the crossover trial) initially were sedated using the xenon in oxygen-enriched air regimen for 8 hrs. After this period, the sedation was stopped and as in group A the patient's conscious level allowed to increase. The alternate regimen of propofol and alfentanil then was begun and continued for 8 hrs.
Additional analgesia was provided in both groups (when required) at the request of the attending nurse or physician, who was blinded to the sedation regimen, according to normal clinical practice, using boluses of alfentanil 250 µg. If more than six boluses were needed in any 1-hr period, then an infusion of alfentanil was begun at a rate equivalent to the previous hour's requirement.
An unblinded clinician-at the request of a nurse who was blinded to both sedative regimens-administered all sedatives and analgesics. The nurse providing care of the patient was instructed to order an increase in
sedation to ensure that the patient had a Ramsay sedation score of either 2 or 3. If the nurse believed that the patient was in pain, despite adequate sedation, if pain was preventing adequate sedation,