1、31(10) Objective: Many sedative regimens are used in the intensive care setting, but none 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 m
2、inimal effect on the myocardium. In theory, xenon may provide sedation without adverse 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
3、-level intensive care unit.Subjects: Twenty-one patients admitted to an intensive care unit following elective thoracic surgery.Interventions: A standard intensive care sedation regimen (intravenous propofol at 0-5 mgkg-1hr-1 and alfentanil 30 ghr-1) was compared with a xenon sedation regimen delive
4、red using a novel bellows-in-bottle delivery system.Measurements and Main Results: 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 sedati
5、on regimens. All patients were successfully sedated 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%). Arterial systolic, diastolic, and mean pressures showed a greater tendency for negativ
6、e gradients in patients receiving the propofol regimen (p .05, p .1, and p .01, respectively). 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.Concl
7、usions: Xenon provided satisfactory sedation in our group of patients. It was well 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 car
8、e units have changed significantly since their inception during the polio epidemics 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 criti
9、cally ill patients, the adverse effects of the agents would be greatly increased. Although 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 p
10、ropofol, given by intravenous infusion, form the mainstay of current clinical practice 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
11、 importantly, the sedation of brittle asthmatics,4 but this remains a niche application.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, espec
12、ially in patients with multiple organ dysfunction. Recently, the safety of prolonged, 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 succes
13、sfully used as a general anesthetic. It has many desirable properties not least of 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 pot
14、ency and its expense.9 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 gas10 mea
15、ns that its effect and recovery profile are both rapid.11 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 ass
16、ess 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.F
17、ollowing 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 in
18、formed 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, th
19、e 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
20、 allocated to one of two sedative regimens. Group A received a standard sedation and analgesia regimen using intravenous propofol (2%) at 0-5 mghr-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 not
21、ed.12 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
22、as in group A the patients 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
23、 regimen, according to normal clinical practice, using 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 blinde
24、d 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 score12 of either 2 or 3. If the nurse believed that the patient was in pain, despite adequa
25、te sedation, if pain was preventing adequate sedation, 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, bl
26、ood, and other drugs according to the patients requirements. 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 xeno
27、n delivered was monitored using a calibrated thermal 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
28、 the appearance of both sedation regimens (to all except 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 conventio
29、nal intensive care ventilator. The ventilatory modes 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
30、 required to initiate ventilation were made by the 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 (Figu
31、re 1). Aliquots of xenon were added through a one-way 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,
32、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
copyright@ 2008-2022 冰豆网网站版权所有
经营许可证编号:鄂ICP备2022015515号-1