Inert gases as the future inhalational anaesthetics?

Of all the inert gases, only xenon has considerable anaesthetic properties under normobaric conditions. Its very low blood/gas partition coefficient makes induction of and emergence from anaesthesia more rapid compared with other inhalational anaesthetics. In experimental and clinical studies the safety and efficiency of xenon as an anaesthetic has been demonstrated. Xenon causes several physiological changes, which mediate protection of the brain or myocardium. The use of xenon might therefore be beneficial in certain clinical situations, as in patients at high risk for neurological or cardiac damage.     

Xenon - noble gas with organprotective properties

Besides it's anaesthetic properties, xenon may induce biological effects that may protect various organs from ischaemia-reperfusion injury. Xenon is an antagonist of the NMDA-receptor and reduces the neuronal injury mediated via these receptors. In contrast to other NMDA-receptor antagonists, xenon has no neurotoxic side effects. Xenon also protects the heart in ischaemia-reperfusion situations. Xenon reduces the post-ischaemic reperfusion injury and offers cardioprotection by inducing pharmacological preconditioning. These organ protective properties of xenon might be useful in special clinical situations.     

Xenon does not induce contracture in human malignant hyperthermia muscle

Xenon has many characteristics of an ideal anaesthetic agent. It is not known whether xenon is a safe alternative to the potent inhalational anaesthetics in patients susceptible to malignant hyperthermia (MH). We investigated the effect of xenon, halothane and caffeine on muscle specimens of 31 individuals, referred to the MH Unit of the University of Ulm, and performed genetic epidemiology. Thirteen individuals were classified as MH susceptible and 18 as MH negative. Xenon 70% did not cause an increase in baseline tension of any MH-susceptible muscle specimen in contrast to halothane and caffeine. The evoked twitch response increased transiently in MH-susceptible and normal specimens indicating a mechanism independent of MH susceptibility. These results suggest that xenon, in concentrations up to 70% may be a safe anaesthetic for MH-susceptible patients.     

Xenon – ein neues Anästhetikum

Today, xenon anaesthesia becomes an interesting object due to xenon's positive ecological aspects as well as its nearly ideal properties as an anaesthetic gas. The application of xenon provides advantages regarding intraoperative hemodynamic stability and the recovery period. Xenon increases tissue perfusion in most organ systems. This increase of tissue perfusion during an operation can be important during some surgical procedures and may improve postoperative outcome. In anaesthetic concentrations xenon leads to an increase in cerebral perfusion. For that reason, xenon should be avoided in patients with increased cerebral pressure or cerebral perfusion disorders. Therefore, further clinical investigations are necessary to improve these clinical findings. The development of accepted indications of xenon anaesthesia becomes necessary regarding a limited availability and high costs of the gas. Focussing this target, more clinical and experimental investigations will become necessary in the next years.     

Xenon anesthesia: from myth to reality

OBJECTIVE: To analyze the current knowledge concerning xenon anaesthesia. DATA SOURCES: References were obtained from computerized bibliographic research (Medline), recent review articles, the library of the service and personal files. STUDY SELECTION: All categories of articles on this topic have been selected. DATA EXTRACTION: Articles have been analysed for history, biophysics, pharmacology, toxicity and environmental effects and using prospect. DATA SYNTHESIS: The noble gas xenon has anaesthetic properties that have been recognized 50 years ago. Xenon is receiving renewed interest because it has many characteristics of an ideal anaesthetic. In addition to its lack of effects on cardiovascular system, xenon has a low solubility enabling faster induction of and emergence from anaesthesia than with other inhalational agents. Nevertheless, at present, the cost and arety of xenon limit its widespread use in clinical practice. The developement of closed rebreathing system that allowed recycling of xenon and therefore reducing its waste has led to a recent interest in this gas. Reducing its cost will help xenon to find its place among anaesthetic agents. An European multicentric clinical trial under submission will contribute to the discussion of the opportunity for xenon introduction in anaesthesia.     

Avantages décisifs,indications et limites de l’anesthésie au xénon

Objective

To analyze the current knowledge related to xenon anaesthesia.

Data sources

References were obtained from computerized bibliographic research (Medline^®), recent review articles, the library of the service and personal files.

Study selection

All categories of articles on this topic have been selected.

Data extraction

Articles have been analyzed for biophysics, pharmacology, toxicity and environmental effects, clinical effects and using prospect.

Data synthesis

The noble gas xenon has anaesthetic properties that have been recognized 50 years ago. Xenon is receiving renewed interest because it has many characteristics of an ideal anaesthetic. In addition to its lack of effects on cardiovascular system, xenon has a low solubility enabling faster induction of and emergence from anaesthesia than with other inhalational agents. Nevertheless, at present, the cost and rarity of xenon limits widespread use in clinical practice. The development of closed rebreathing system that allowed recycling of xenon and therefore reducing its waste has led to a recent interest in this gas.

Conclusion

Reducing its cost will help xenon to find its place among anaesthetic agents and extend its use to severe patients with specific pathologies.     

Comparison of xenon-based anaesthesia compared with total intravenous anaesthesia in high risk surgical patients

Xenon, a noble gas with anaesthetic and analgesic properties, has gained renewed interest due to its favourable physical properties which allow a rapid emergence from anaesthesia. However, high costs limit its use to a subset of patients who may benefit from xenon, thereby offsetting its costs. To date, there are only limited data available on the performance of xenon in high risk patients. We studied 39 patients with ASA physical status III undergoing aortic surgery. The patients were randomly assigned to either a xenon (Xe, n = 20) or a TIVA (T, n = 19) group. Global cardiac performance and myocardial contractility were assessed using transoesophageal echocardiography, and myocardial cell damage with troponin T and CK-MB. Echocardiographic measurements were made prior to xenon administration, following xenon administration, and after clamping of the abdominal aorta, after declamping and at corresponding time points in the TIVA group. Laboratory values were determined repeatedly for up to 72 h. Data were analysed using two-way anova factoring for time and anaesthetic agent or with ancova comparing linear regression lines. No significant differences were found in global myocardial performance, myocardial contractility or laboratory values at any time during the study period. Mean (SEM) duration of stay on the ICU (xenon: 38 +/- 46 vs. TIVA 25 +/- 15 h) or in hospital (xenon: 14 +/- 12 vs. TIVA 10 +/- 6 days) did not differ significantly between the groups. Although xenon has previously been shown to exert superior haemodynamic stability, we were unable to demonstrate an advantage of xenon-based anaesthesia compared to TIVA in high risk surgical patients.     

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.     

Xenon as a replacement for nitrous oxide?

Although nitrous oxide (N₂O) has been used routinely since the beginning of the modern era of anaesthesia, some of its adverse effects have only been discovered during the last decades. Thus there are some who advocate abandoning the use of N₂O for anaesthesia. However, if the use of N₂O is stopped, the anaesthetic regimen will have to be changed in order to substitute for a loss in potency. Thus, xenon has been suggested as a replacement for N₂O. N₂O and xenon share some clinical and physicochemical properties. For example, both of them are only weak anaesthetics but are potent analgesics. However, in many respects xenon appears to be advantageous compared to N₂O. Xenon exerts a high degree of cardiovascular stability and does not have teratogenic or fetotoxic effects. In contrast to N₂O it does not support the greenhouse effect. The costs of xenon are prohibitively high at the moment. Advanced anaesthesia machines and recycling equipment have necessary in order use xenon in an economically feasible way.     

Xenon measurement in breathing systems: a comparison of ultrasonic and thermal conductivity methods

Xenon is an anaesthetic and possibly neuroprotective gas that is impossible to measure using conventional anaesthetic gas analysers. We compared the performance of two commissioned xenon analysers using ultrasonic and thermal conductivity principles against a reference method of laser refractometry. An experimental gas circuit was constructed and xenon concentrations compared over a range of 0-100% in oxygen. Eighty-two paired measurements were made comparing the experimental methods with laser refractometry. The ultrasonic method displayed good agreement with laser refractometry, with a mean difference of - 0.74% and two standard deviation limits of agreement of + 1.08% to - 2.56%. The agreement between laser refractometry and thermal conductivity was poor, the mean difference being - 5.37%, with two standard deviation limits of agreement of + 0.6% to - 11.3%. The ultrasonic method for measuring xenon concentrations can be used in breathing circuits. The thermal conductivity instrument may need further development.     

Haemodynamic and neurohumoral effects of xenon anaesthesia A comparison with nitrous oxide

Thirty-two patients were randomly allocated to be anaesthetised either with nitrous oxide or xenon. Those who received nitrous oxide required significantly more fentanyl peroperatively. Arterial blood pressure and heart rate were adequately controlled during surgery in both groups. Plasma noradrenaline and prolactin increased peroperatively in both groups, but plasma adrenaline and cortisol, which increased in the nitrous oxide group, did not change in the xenon group. Growth hormone was below control in those given xenon, but not in the nitrous oxide group, while dopamine remained unchanged in both groups. Postoperative plasma concentrations of noradrenaline, adrenaline, cortisol and prolactin (in both groups) and dopamine (in the nitrous oxide group) were elevated, and slowly returned to control. No differences were seen between the two gases in effects on plasma sodium and potassium. Xenon, because of its favourable haemodynamic, neurohumoral and antinociceptive properties, deserves a more prominent place in anaesthetic practice than it has so far occupied.     

Effects of xenon on in vitro and in vivo models of neuronal injury

BACKGROUND: Xenon, the "inert" gaseous anesthetic, is an antagonist at the N-methyl-D-aspartate (NMDA)-type glutamate receptor. Because of the pivotal role that NMDA receptors play in neuronal injury, the authors investigated the efficacy of xenon as a neuroprotectant in both in vitro and in vivo paradigms. METHODS: In a mouse neuronal-glial cell coculture, injury was provoked either by NMDA, glutamate, or oxygen deprivation and assessed by the release of lactate dehydrogenase into the culture medium. Increasing concentrations of either xenon or nitrogen (10-75% of an atmosphere) were coadministered and maintained until injury was assessed. In separate in vivo experiments, rats were administered N-methyl-dl-aspartate and killed 3 h later. Injury was quantified by histologic assessment of neuronal degeneration in the arcuate nucleus of the hypothalamus. RESULTS: Xenon exerted a concentration-dependent protection against neuronal injury provoked by NMDA (IC(50) = 19 +/- 6% atm), glutamate (IC(50) = 28 +/- 8% atm), and oxygen deprivation (IC(50) = 10 +/- 4% atm). Xenon (60% atm) reduced lactate dehydrogenase release to baseline concentrations with oxygen deprivation, whereas xenon (75% atm) reduced lactate dehydrogenase release by 80% with either NMDA- or glutamate-induced injury. In an in vivo brain injury model in rats, xenon exerted a concentration-dependent protective effect (IC(50) = 78 +/- 8% atm) and reduced the injury by 45% at the highest xenon concentration tested (75% atm). CONCLUSIONS: Xenon, when coadministered with the injurious agent, exerts a concentration-dependent neuroprotective effect at concentrations below which anesthesia is produced in rodents. Unlike either nitrous oxide or ketamine (other anesthetics with NMDA antagonist properties), xenon is devoid of both neurotoxicity and clinically significant adverse hemodynamic properties. Studies are proposed to determine whether xenon can be used as a neuroprotectant in certain clinical settings.     

Xenon inhalation increases airway pressure in ventilated patients

BACKGROUND: The inert gas xenon, known as an anaesthetic for nearly 50 years, is also used as a contrast agent during computerised tomography (CT)-scanning. As xenon has a higher density and viscosity than air, xenon inhalation may increase airway resistance. METHODS: In a retrospective study we investigated the effects of 33% xenon/67% oxygen on airway pressure and cardio-respiratory parameters in 37 long-term mechanically ventilated patients undergoing cerebral blood flow (rCBF) measurements by means of stable xenon-enhanced CT. RESULTS: Xenon administration caused a significant increase in peak airway pressure from 31.6+/-8.0 cm H2O to 42.7+/-16.9 cm H2O. This effect was reproducible, did not occur after reduction of inspiratory flow rate by 50% from 0.56+/-0.15 L x s(-1) to 0.28+/-0.08 L x s(-1), and vanished immediately after termination of xenon delivery. CONCLUSION: Due to the higher density and viscosity of this gas mixture, ventilation with xenon/oxygen produces a higher Reynolds' number than oxygen/air when given at the same flow rate. This means that during xenon ventilation the zone of transition from turbulent to laminar gas flow may be located more peripherally (in smaller airways) than during oxygen/air ventilation with a subsequent increase in airway resistance. Our results indicate that xenon inhalation may cause a clinically relevant increase of peak airway pressure in mechanically ventilated patients.     

Xenon anesthesia for liver transplant surgery: a report of four cases

It is well established that patients presenting for orthotopic liver transplantation pose challenging surgical and anesthesiological problems. Intraoperatively, severe hemodynamic instability due to profuse bleeding and acute cardiomyopathy during reperfusion are major concerns. In addition, ischemia-reperfusion injury can compromise postoperative graft function. Xenon, with its potential to maintain hemodynamic stability, preserve cardiac function, and protect the liver graft of the recipient, seems to be a promising anesthetic agent for liver transplant surgery. To date, xenon has not been used as an anesthetic in liver transplantations. We therefore have reported our initial experience with four patients who underwent orthotopic deceased donor liver transplantation under xenon anesthesia. Although all patients had advanced liver disease and experienced significant intraoperative bleeding, their intraoperative courses, including reperfusion, under xenon anesthesia were remarkably stable. The patients required only moderate, temporary catecholamine support, which was withdrawn at the end of the surgery. Xenon anesthesia for liver transplant procedures proved to be feasible. Immediate postoperative organ function was satisfactory in all patients.     

Xenon Does Not Trigger Malignant Hyperthermia in Susceptible Swine

Background: Xenon is a noble gas with anesthetic properties currently under investigation for use in humans. This study was performed to evaluate whether xenon may trigger malignant hyperthermia in susceptible swine.

Methods: Nine malignant hyperthermia-sensitive swine (Pietrain) were initially anesthetized with pentobarbital and then ventilated with 70% xenon in oxygen for 2 h. Heart rate, mean arterial pressure, cardiac output, body temperature, arterial and mixed-venous blood gases, and plasma catecholamine and lactate levels were measured every 10 min both during xenon-oxygen ventilation and after a 30-min xenon washout phase followed by subsequent administration of halothane (1% inspired) and succinylcholine (3 mg/kg intravenous). During the investigation, no malignant hyperthermia-specific therapy was instituted.

Results: Xenon exposure did not induce any changes in metabolic and hemodynamic parameters nor elevations of the plasma catecholamine levels indicative for an episode of malignant hyperthermia. By contrast, in all animals, within 20 min after the administration of halothane and succinylcholine, fulminant and fatal malignant hyperthermia episodes were initiated.     

氙气麻醉的临床药理新进展

背景氙气麻醉在同际上已有大量的基础和临床的研究,逐步应用于临床后,显示出了许多优点,但国内还未有研究氙气麻醉的报道.目的 通过对氙气麻醉的临床药理进行综述,总结了氙气在临床麻醉中应用的优点和缺点,以增进临床麻醉医生对氙气药理学特性的了解,为促进国内氙气麻醉的基础与临床的研究提供帮助.内容该综述系统地总结了氙气麻醉作用机...     

Feasibility and safety of delivering xenon to patients undergoing coronary artery bypass graft surgery while on cardiopulmonary bypass: phase I study

BACKGROUND: Postoperative neurocognitive deficit is prevalent after cardiac surgery. Xenon may prevent or ameliorate acute neuronal injury, but it also may aggravate injury during cardiac surgery by increasing bubble embolism. Before embarking on a randomized clinical trial to test the safety and efficacy of xenon for postoperative neurocognitive deficit, we undertook a phase I study to investigate the safety of administering xenon to patients undergoing coronary artery bypass grafting while on cardiopulmonary bypass and to assess the practicability of our xenon delivery system. METHODS: Sixteen patients scheduled for coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass gave their informed consent to participate in an open-label dose-escalation study (0, 20, 35, 50% xenon in oxygen and air). Xenon was delivered throughout surgery using both a standard anesthetic breathing circuit and the oxygenator. Gaseous and blood xenon partial pressures were measured five times before, during, and after cardiopulmonary bypass. Middle cerebral artery Doppler was used to assess embolic load, and major organ system function was assessed before and after surgery. RESULTS: Middle cerebral artery Doppler showed no evidence of increased emboli with xenon. Patients receiving xenon had no major organ dysfunction: Troponin I and S100beta levels tended to be lower in patients receiving xenon. Up to 25 l xenon was used per patient. Xenon partial pressure in the blood tracked the delivered concentration throughout. CONCLUSIONS: Xenon was safely and efficiently delivered to coronary artery bypass grafting patients while on cardiopulmonary bypass. Prevention of nervous system injury by xenon should be tested in a large placebo-controlled, randomized clinical trial.     

Clinical experience with minimal flow xenon anesthesia

Xenon is a more potent anesthetic than nitrous oxide, and gives more profound analgesia. This investigation was performed to assess the potential of xenon for becoming an anesthetic inspite of its high manufacturing cost. Seven ASA I—-II patients undergoing cholecystectomy (n = 4), hernia repair (n = 2), or mammoplasty (n=l) were studied. Denitrogenation by 15–20 min of oxygen breathing under propofol anesthesia was followed by fentanyl–supplemented xenon anesthesia administered via an automatic minimal flow system which held the oxygen concentration at 30%. Xenon anesthesia lasted 76–228 min and 8–14 1 of xenon (ATPD) was used, of which 5.6–8.1 1 was expended during the first 15 min. Anesthesia appeared to be satisfactory, and the patients woke up rapidly after xenon was discontinued. The automatic system made minimal flow xenon anesthesia easy to administer, but nitrogen accumulation is still a problem. Assuming a xenon price of 10 US $ per litre, the average cost for xenon was about 65 US $ for the first 15 min and then about 25 USS for each subsequent hour of anesthesia.     

Xenon administration during early reperfusion reduces infarct size after regional ischemia in the rabbit heart in vivo

The noble gas xenon can be used as an anesthetic gas with many of the properties of the ideal anesthetic. Other volatile anesthetics protect myocardial tissue against reperfusion injury. We investigated the effects of xenon on reperfusion injury after regional myocardial ischemia in the rabbit. Chloralose-anesthetized rabbits were instrumented for measurement of aortic pressure, left ventricular pressure, and cardiac output. Twenty-eight rabbits were subjected to 30 min of occlusion of a major coronary artery followed by 120 min of reperfusion. During the first 15 min of reperfusion, 14 rabbits inhaled 70% xenon/30% oxygen (Xenon), and 14 rabbits inhaled air containing 30% oxygen (Control). Infarct size was determined at the end of the reperfusion period by using triphenyltetrazolium chloride staining. Xenon reduced infarct size from 51%+/-3% of the area at risk in controls to 39%+/-5% (P<0.05). Infarct size in relation to the area at risk size was smaller in the xenon-treated animals, indicated by a reduced slope of the regression line relating infarct size to the area at risk size (Control: 0.70+/-0.08, r = 0.93; Xenon: 0.19+/-0.09, r = 0.49, P<0.001). In conclusion, inhaled xenon during early reperfusion reduced infarct size after regional ischemia in the rabbit heart in vivo.     

Expansion of gas bubbles by nitrous oxide and xenon

BACKGROUND: Nitrous oxide is well known to expand gas bubbles trapped in enclosed spaces and is contraindicated in situations where this may occur. Xenon, an anesthetic gas with similar physical properties to nitrous oxide, is also likely to expand gas bubbles, and it has been predicted that microbubbles in the circulation may expand dramatically when exposed to xenon. Because of the possibility that xenon will be used during cardiopulmonary bypass surgery, a procedure that is likely to introduce microbubbles into the circulation, the authors reinvestigated the extent to which xenon expands gas bubbles in aqueous solution. METHODS: Gas bubbles of either air or oxygen were formed in an aqueous solution, and their size was monitored using optical microscopy when they were exposed to a rapidly flowing solution of xenon, nitrous oxide, or a xenon-oxygen mixture. RESULTS: Both nitrous oxide and xenon rapidly expanded air bubbles, although nitrous oxide caused a much larger expansion. The observed expansion was not greatly dependent on the initial size of the bubble but was significantly greater at lower temperatures. Under conditions relevant to cardiopulmonary bypass surgery (50% xenon-50% oxygen, 30 degrees C), the increase in diameter was modest (9.7 +/- 0.8%). CONCLUSIONS: Although xenon does expand small air and oxygen bubbles, the extent to which this occurs under clinically relevant conditions of concentration and temperature is modest.