The Hip Fracture Surgery in Elderly Patients (HIPELD) study: protocol for a randomized, multicenter controlled trial evaluating the effect of xenon on postoperative delirium in older patients undergoing hip fracture surgery.

BACKGROUND: Strategies to protect the brain from postoperative delirium (POD) after hip fracture are urgently needed. The development of delirium often is associated with the loss of independence, poor functional recovery, and increased morbidity, as well as increases in length of hospital stay, discharges to nursing facilities, and healthcare costs. We hypothesize that xenon may reduce the burden of POD, (i) by avoiding the need to provide anesthesia with a drug that targets the γ-amino-butyric acid (GABA)A receptor and (ii) through beneficial anesthetic and organ-protective effects. METHODS AND DESIGN: An international, multicenter, phase 2, prospective, randomized, blinded, parallel group and controlled trial to evaluate the incidence of POD, diagnosed with the Confusion Assessment Method (CAM), in older patients undergoing hip fracture surgery under general anesthesia with xenon or sevoflurane, for a period of 4 days post surgery (primary outcome) is planned. Secondary objectives are to compare the incidence of POD between xenon and sevoflurane, to evaluate the incidence of POD from day 5 post surgery until discharge from hospital, to determine the time to first POD diagnosis, to evaluate the duration of POD, to evaluate the evolution of the physiological status of the patients in the postoperative period, to evaluate the recovery parameters, to collect preliminary data to evaluate the economical impact of POD in the postoperative period and to collect safety data. Patients are eligible if they are older aged (≥ 75 years) and assigned to a planned hip fracture surgery within 48 h after the hip fracture. Furthermore, patients need to be willing and able to complete the requirements of this study including the signature of the written informed consent. A total of 256 randomized patients in the 10 participating centers will be recruited, that is, 128 randomized patients in each of the 2 study groups (receiving either xenon or sevoflurane). TRIAL REGISTRATION: EudraCT Identifier: 2009-017153-35; ClinicalTrials.gov Identifier: NCT01199276.

[Xenon for postoperative analgesia: why not?].

Xenon is widely used for maintenance of anesthesia, however the analgesic effect of this noble gas brings to an idea of its use in analgesic schemes. The first time antinociceptive features of Xe were described by B. Lachman and colleagues in 1988. It is well known that Xe realises its analgesic potential through powerful non-competitive blockade of NMDA-glutamate receptors, by that suppressing the development of hyperalgesia process in neurons of posterior horns of spinal cord, which take part in the process of pain transmission and forming of central sensitization and becoming the actual "gates of pain". In the given review the literature data on mechanisms, effectiveness, safety and farmacoeconomic justification of the use of Xe as an analgesic in clinical practice are brought up.

Xenon as an anesthetic agent.

Discovered in 1898 by British chemists, xenon is a rare gas belonging to the noble gases of the periodic table. Xenon is used in many different ways, from high-intensity lamps to jet propellant, and in 1939, its anesthetic properties were discovered. Xenon exerts its anesthetic properties, in part, through the noncompetitive inhibition of N-methyl-D-aspartate receptors. Currently, xenon is being used primarily throughout Europe; however, the high price of manufacturing and scavenging the noble gas has discouraged more widespread use. As technology in anesthetic delivery improves, xenon is being investigated further as a possible replacement for nitrous oxide as an inhalational agent. This article reviews the anesthetic properties of xenon and current and potential research about the gas.

A cost-effective and versatile xenon gas dispenser.

OBJECTIVE: To modify a commercial xenon gas dispenser so that two xenon unit-dose vials could be combined with a modified dispenser to deliver a recommended dose. METHOD: To maintain the same operating mechanism, changes were made only to the vial shield and the needle port of the original gas dispenser. The modified gas dispenser consisted of two puncture needles and two vial holders shielded with the same thickness of lead as the commercial dispenser. RESULTS: Our evaluation showed that the modified gas dispenser operated the same way as the commercial unit, and the average 133Xe residual activity in either one or two xenon unit-dose vials of the modified gas dispenser was not significantly different from that in one vial of the commercial xenon gas dispenser. CONCLUSION: The modified xenon gas dispenser allows the stock of xenon gas vials to be managed cost-effectively. The modified unit can be used to dispense two low-activity xenon gas vials to deliver a standard dose to a patient. Also, the modified gas dispenser can be used to combine different amounts of xenon activity in two unit-dose vials in order to customize the dose delivered to patients with special needs (e.g., obese patients). Our modified device can also function as a single-dose dispenser by placing an empty vial alongside the unit-dose vial of radioactive xenon gas.

[The method of low-flow xenon anesthesia]. / Metodika nizkopotochnoi ksenonovoi anestezii.

Two variants of low-flow xenon (Xe) anesthesia was used in 150 patients operated on in general surgery, gynecology, urology, and vascular surgery; 116 patients received a combined endotracheal variant of Xe anesthesia and 34 patients received mask-type mono-narcosis. Limited possibilities of Russian-made apparatuses ("Polinarkon-2P") were shown in the process of minimizing the Xe consumption. An average Xe consumption reached, in a 2-hour anesthetic session, 42 l ($210). When foreign-made narcosis apparatuses ("Medimorph", "Anemat-8" etc.) were used, it was possible to minimize the Xe consumption during the same time period to 22 l ($110). When the endotracheal variant was in use, the Xe consumption was 15-16 l ($75-80) during 2 hours. When Xe was recycled by the desorption processor and fine cleaning at "Akela-N" Ltd. production facility, the cost of 2-hour anesthesia went down five-fold ($16-20). The article contains some recommendations made by authors to improve the method of low-flow Xe anesthesia as a method reducing the cost of Xe anesthesia in the routine medical practice.

Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery.

BACKGROUND: All general anesthetics used are known to have a negative inotropic side effect. Since xenon does not have a negative inotropic effect, it could be an interesting future general anesthetic. The aim of this clinical multicenter trial was to test the hypothesis of whether recovery after xenon anesthesia is faster compared with an accepted, standardized anesthetic regimen and that it is as effective and safe. METHOD: A total of 224 patients in six centers were included in the protocol. They were randomly assigned to receive either xenon (60 +/- 5%) in oxygen or isoflurane (end-tidal concentration, 0.5%) combined with nitrous oxide (60 +/- 5%). Sufentanil (10 mcirog) was intravenously injected if indicated by defined criteria. Hemodynamic, respiratory, and recovery parameters, the amount of sufentanil, and side effects were assessed. RESULTS: The recovery parameters demonstrated a statistically significant faster recovery from xenon anesthesia when compared with isoflurane-nitrous oxide. The additional amount of sufentanil did not differ between both anesthesia regimens. Hemodynamics and respiratory parameters remained stable throughout administration of both anesthesia regimens, with advantages for the xenon group. Side effects occurred to the same extent with xenon in oxygen and isoflurane-nitrous oxide. CONCLUSION: This first randomized controlled multicenter trial on the use of xenon as an inhalational anesthetic confirms, in a large group of patients, that xenon in oxygen provides effective and safe anesthesia, with the advantage of a more rapid recovery when compared with anesthesia using isoflurane-nitrous oxide.

Xenon expenditure and nitrogen accumulation in closed-circuit anaesthesia.

The high price of xenon has prevented its use in routine, clinic anaesthetic practice. Xenon therefore has to be delivered by closed-circuit anaesthesia. The accumulation of nitrogen is a significant problem within the closed circuit and necessitates flushing, which in turn increases gas expenditure and costs. In previous investigations, nitrogen concentrations between 12% and 16% have been reported in closed-circuit anaesthesia. In order to avoid such nitrogen accumulation, we denitrogenised seven pigs using a non-rebreathing system and connected the animals to a system primed with a xenon/oxygen mixture. In comparison, seven pigs were anaesthetised with xenon using a standard low-flow anaesthetic procedure. Anaesthesia time was 2 h. Nitrogen concentrations in the closed system ranged from 0.08 to 7.04% and were not significantly different from those observed during low-flow anaesthesia. Closed-circuit anaesthesia reduced the xenon expenditure 10-fold compared with low-flow anaesthesia.

Cost analysis of xenon anesthesia: a comparison with nitrous oxide-isoflurane and nitrous oxide-sevoflurane anesthesia.

STUDY OBJECTIVE: To determine the cost of xenon (Xe) anesthesia in relation to the anesthetic duration by conducting a cost analysis of this relatively expensive inhaled anesthetic. DESIGN: Cost analysis based on the literature on Xe anesthesia. SETTING: Anesthetic simulation based on data obtained in the operating rooms at a university hospital. PATIENTS: A 40-year-old, ASA physical status I adult patient model weighing 70 kg, undergoing elective minor surgery with endotracheal intubation and mechanical ventilation. INTERVENTIONS: Anesthesia was given in the following four techniques: 1) closed-circuit technique with Xe; 2) closed-circuit technique with nitrous oxide (N2O)-isoflurane; 3) semi-closed technique with N2O-isoflurane; and 4) semi-closed technique with N2O-sevoflurane. MEASUREMENTS AND MAIN RESULTS: Cost of each anesthetic technique was compared in U.S. dollars. The cost of Xe anesthesia was consistently higher than that of N2O-isoflurane or N2O-sevoflurane (for 240-min anesthesia; $356 with Xe, $52 with closed-circuit N2O-isoflurane, $94 with semi-closed N2O-isoflurane, and $84 with semi-closed N2O-sevoflurane). The major cost of Xe anesthesia was a result of the cost of priming and flushing; the cost of Xe used for its anesthetic effects was comparable with the other semi-closed techniques after 240 minutes. CONCLUSIONS: For Xe to be widely used in routine anesthesia, the methods of minimizing the amount of Xe necessary for priming and flushing must be developed.