Xenon Critical Care.docx

1、Xenon Critical CareUse of Xenon as a Sedative for Patients Receiving Critical CareAmit Bedi, MD, James M. Murray, MD, John Dingley, FRCA, Michael A. Stevenson, BSc (Hons), J. P. Howard Fee, PhDCrit Care Med. 2003;31(10) Objective: Many sedative regimens are used in the intensive care setting, but no

2、ne are wholly without adverse effect. Xenon is a noble gas with sedative and analgesic properties. It has been used successfully as a general anesthetic and has many desirable properties, not least of which is a minimal effect on the myocardium. In theory, xenon may provide sedation without adverse

3、effect for certain groups of critically ill patients. The objective of this study was to assess the feasibility of using xenon as an intensive care sedative.Design: Double-blind, randomized study.Setting: Tertiary-level intensive care unit.Subjects: Twenty-one patients admitted to an intensive care

4、unit following elective thoracic surgery.Interventions: A standard intensive care sedation regimen (intravenous propofol at 0-5 mgkg-1hr-1 and alfentanil 30 gkg-1hr-1) was compared with a xenon sedation regimen delivered using a novel bellows-in-bottle delivery system.Measurements and Main Results:

5、Each sedative regimen was continued for 8 hrs. The hemodynamic effects, additional analgesic requirements, recovery from sedation, and effect on hematological and biochemical variables were compared for the two sedation regimens. All patients were successfully sedated during the xenon regimen. The m

6、ean SD end-tidal xenon concentration required to provide sedation throughout the duration of the study was 28 9.0% (range, 9-62%). Arterial systolic, diastolic, and mean pressures showed a greater tendency for negative gradients in patients receiving the propofol regimen (p .05, p .1, and p .01, res

7、pectively). Recovery following xenon was significantly faster than from the standard sedation regimen (p .0001). Hematological and biochemical laboratory markers were within normal clinical limits in both groups.Conclusions: Xenon provided satisfactory sedation in our group of patients. It was well

8、tolerated with minimal hemodynamic effect. Recovery from this agent is extremely rapid. We have demonstrated the feasibility of using xenon within the critical care setting, without adverse effect.Modern intensive care units have changed significantly since their inception during the polio epidemics

9、 of the 1950s. It was during this period that anesthetic agents were used as sedatives, initially to facilitate the removal of tracheal secretions. It was immediately apparent that when these agents were used in critically ill patients, the adverse effects of the agents would be greatly increased. A

10、lthough many sedative regimens presently are used, intensive care still remains an unpleasant experience for many patients.1 No currently used regimen is totally free from adverse effects. Midazolam, alfentanil, and propofol, given by intravenous infusion, form the mainstay of current clinical pract

11、ice in the United Kingdom.2 Inhaled anesthetics have been used successfully in the critical care setting,3 but their use is not common. Isoflurane, a methyl ethyl ether, is advocated for a number of applications, most importantly, the sedation of brittle asthmatics,4 but this remains a niche applica

12、tion.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 prolonge

13、d, high-dose infusions of propofol has been questioned in both children5 and adults.6Xenon 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

14、which is a minimal effect on the myocardium.7 It has been shown to provide pleasant, well-tolerated sedation in volunteers.8 Xenon has not become established in modern anesthetic practice due to its relatively low potency and its expense.9 Its pharmacokinetic and pharmacodynamic properties are close

15、 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 gas10 means that its effect and recovery profile are both rapid.11 In theory, xenon may prov

16、ide 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 breat

17、hing 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

18、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 h

19、epatic 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: gro

20、up 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 an

21、d analgesia regimen using intravenous propofol (2%) at 0-5 mgkg-1hr-1 and alfentanil 30 gkg-1hr-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.12 Sedation then was recommenced using variable

22、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 patients conscious level allowed

23、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, us

24、ing boluses of alfentanil 250 g. 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 hours requirement.An unblinded clinician-at the request of a nurse who was blinded to both sedative regimens-administered all sedati

25、ves 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 score12 of either 2 or 3. If the nurse believed that the patient was in pain, despite adequate sedation, if pain was preventing adequate sedati

26、on, or if the patient communicated to the nurse that he or she was sore, the nurse instructed additional analgesia to be administered by the unblinded operator. A physician, unaware of the ongoing sedation regimen, administered inotropes, fluids, blood, and other drugs according to the patients requ

27、irements. To ensure blinding of the observers, the xenon delivery system remained unchanged in appearance throughout the study. The addition of xenon to the closed-circuit breathing system was not visible to the caregivers. The concentration of xenon delivered was monitored using a calibrated therma

28、l conductivity meter that was only seen by the operator and not the attending physician or the nursing staff. The alternate sedation regimen (the propofol/alfentanil regimen) was replaced by a placebo infusion of Intralipid and saline to ensure that the appearance of both sedation regimens (to all e

29、xcept the sedation operator) was identical.The patients lungs were ventilated using a Bennett Puritan ventilator and a bellows-in-bottle breathing interface.13 This system operated as a balanced, closed-circuit breathing system driven by a conventional intensive care ventilator. The ventilatory mode

30、s of positive end-expiratory pressure, continuous positive airway pressure, and synchronized intermittent mandatory ventilation were applied as deemed clinically necessary. All measurements of both airway pressure and changes in inspiratory pressure required to initiate ventilation were made by the

31、Puritan Bennett 7200A ventilator as normal. The bellows-in-bottle interface did not alter the performance of the ventilator. Once balanced, the system automatically replaced oxygen uptake from the circle with oxygen from the driving ventilator (Figure 1). Aliquots of xenon were added through a one-w

32、ay valve by an unblinded operator to achieve the level of sedation directed by the blinded observer. The end-tidal concentrations of carbon dioxide and oxygen concentration were monitored continuously using an infrared gas analyzer (Datex Capnomac, Datex) and the ventilatory rate and tidal volume adjusted as appropriate to maintain an end-tidal carbon dioxide concentration between 4% and 6%. The end-tidal concentration of xenon was monitored using a calibrated thermal conductivity monitor (Bedfont Scientific, UK). Patients were monitored noninvasively using a pulse oximeter and electroc