Xenon: recent developments
1999; Wiley; Volume: 54; Issue: 4 Linguagem: Inglês
10.1046/j.1365-2044.1999.00807.x
ISSN1365-2044
AutoresJohn Dingley, T. M. Ivanova‐Stoilova, S. Grundler, Tracey J Wall,
Tópico(s)Anesthesia and Sedative Agents
ResumoXenon is the Greek word for stranger. The gas was discovered by Ramsay and Travers in 1898 in the residue left after evaporating liquid air components. It was originally labelled, with others, an inert gas but after discovery of some compounds this group was renamed the noble gases in 1962. It is the heaviest stable gas in this group and the only one which is anaesthetic under normobaric conditions [1]. Xenon constitutes 0.0000087% of the atmosphere, which is estimated to contain around 400 million tonnes. An average room contains about 4 ml. Based on the assumption that the relative distribution of all elements on all planets in the solar system is roughly the same, the earth's atmosphere contains about 2000 times less than expected. It is manufactured by fractional distillation of air, costing around 2000 times as much as nitrous oxide. Where possible it is recycled, e.g. from old computer displays. It is used in lasers, high-intensity lamps, flash bulbs, space applications, X-ray tubes and medicine (imaging, anaesthesia). As an anaesthetic it exhibits many of the features of the ideal agent. Xenon has been used for routine clinical anaesthesia in Russia, Germany, the Netherlands and Sweden. It is considered not to have any occupational and environmental disadvantages and with an MAC of 71% it is more potent than nitrous oxide (N2O) [234]. Xenon has minimal haemodynamic effects and has the lowest blood/gas partition coefficient of any known anaesthetic agent, with very rapid induction and recovery characteristics [567891011121314]. The realisation in recent years that nitrous oxide is a potent greenhouse gas with potentially toxic biochemical effects in the body has led to continued anaesthetic interest in xenon despite its high cost [151617181920]. Research into automated fully closed delivery systems and recovery devices continues in the quest to make xenon anaesthesia economically acceptable [212223242526272829303132]. Practicable very low flow and closed breathing systems are now becoming available. All these factors when combined make serious consideration of xenon anaesthesia possible. Much of the work described here is extremely current and in some areas very limited. By necessity the information has been obtained from many different sources. This review concentrates on the technical developments necessary for clinical use, physiological effects and the clinical experience gained so far. Xenon is a colourless, odourless, tasteless monatomic gas. It has an atomic number of 54 and a molecular weight of 131.3. It has nine stable isotopes and many artificial isotopes [12, 33]. It freezes at −111.9 °C and boils at −107.1 °C. Xenon is four times as dense as air and 3.4 times as dense as N2O. It is nonflammable and does not support combustion. Its oil/water solubility coefficient is 20.0 and it has the highest coefficient of any of the noble gases, being the only one with anaesthetic properties at atmospheric pressure. It has an extremely low blood/gas partition coefficient of 0.14, even compared to nitrous oxide (0.47) or sevoflurane (0.65). Xenon diffuses freely through rubber and there can be significant losses of gas by this route during anaesthesia. In one breathing system incorporating silicon rubber tubing, a loss rate of 750 ml.h−1 was observed by this route alone [9]. Pittenger et al. found that Rhesus monkeys stopped breathing when the partial pressure of xenon slightly exceeded atmospheric pressure [34]. They observed that the apnoea and muscular relaxation were in excess of what one might expect on the basis of the depth of anaesthesia (as shown on the animals' electroencephalograms) and from experience with other anaesthetic gases. It is very likely that the same central mechanism that causes apnoea at high xenon concentrations is responsible for the marked slowing of respiratory rate observed during 33% xenon inhalation in cerebral blood flow studies [35]. This respiratory slowing is accompanied by a compensatory increase in tidal volume, resulting in little change in minute ventilation. This is unlike other anaesthetic agents which increase respiratory rate and decrease tidal volume and minute ventilation [36, 37]. Airway resistance depends not only on airway geometry but also on flow rate, gas density and viscosity [38, 39]. Airway resistance has viscosity-dependent and density-dependent components: it is viscosity-dependent in the presence of laminar flow but is density-dependent with turbulent flow. In peripheral airways, flow is laminar but in more central airways, the resistance changes greatly with flow rate. At a flow of <1 l.s−1, flow is laminar but above this, turbulent flow is dominant [38]. Xenon has a higher density and viscosity than nitrous oxide (≈ 3 and 1.5 times, respectively). This might be expected to cause an increase in airway resistance during inhalation, especially in patients with obstructive pulmonary disease. The use of xenon in neuroradiology has an excellent safety record. It has been suggested, however, that patients with reduced pulmonary function may not be suitable for these procedures on safety grounds. In any case the data obtained from cerebral blood flow studies in these patients may be suspect if there is doubt as to whether the end-tidal xenon concentration reflects the arterial value [40]. In experiments by Zhang et al. the lungs of intubated dogs were mechanically ventilated with varying ratios of N2O in oxygen and varying ratios of xenon in oxygen, whilst the pulmonary resistance was measured. This was repeated after bronchoconstriction had been produced by a methacholine infusion. The results suggested that inhalation of a high concentration of xenon increases airway resistance, but only to a modest extent in animals with normal or methacholine treated airways. The PaO2, PaCO2 and peak airway pressures were unaffected by xenon inhalation with both normal and constricted airways. They concluded that xenon may be a safe anaesthetic gas as far as lung mechanics are concerned [41]. Similar work has been carried out in ventilated pigs in which inspiratory resistance, peak and mean airway pressures were measured with various gas mixtures, with and without methacholine-induced bronchoconstriction [42]. A significant increase (p < 0.05) in inspiratory airway resistance, with and without bronchoconstriction, was seen with a 70% xenon/30% oxygen mixture when compared with a 70% nitrogen/30% oxygen mixture used as a control. This effect was not observed when the study was repeated with a 70% N2O/30% oxygen mixture. Nonsignificant increases in peak and mean airway pressures were seen with both xenon and N2O. Lachmann et al. compared the effects of 70% xenon/30% O2 and 70% N2O/30% O2 on lung mechanics. These workers demonstrated that expiratory lung resistance was higher in both the xenon and N2O groups compared with baseline, but there was no significant difference between the two groups [43]. Oxygen saturation decreased below 92% in eight patients in the N2O group but not in any patient in the xenon group. They concluded that there was only slight deterioration in lung mechanics during xenon anaesthesia, and suggested that it can be used safely in older patients and those with chronic lung diseases. If a patient who has been breathing a gas mixture rich in N2O then abruptly switches to room air, a reduction in arterial oxygen partial pressure is seen, known as diffusion hypoxia or the Fink effect. As the alveolar N2O tension diminishes, rapid equilibration with mixed pulmonary capillary blood releases N2O into the alveoli, whilst nitrogen diffuses only slowly in the opposite direction. The expired volume can exceed the inspired volume as the alveoli are flooded with N2O and the alveolar concentration of oxygen is reduced, causing a decline in arterial oxygen saturation. A similar phenomenon with xenon may also occur. This has been anecdotally suggested in Russian work where 100% oxygen had not been administered at the end of the period of xenon anaesthesia; some volunteers experienced periods of reduced levels of consciousness during recovery [6]. The arterial partial pressure of oxygen has, however, recently been studied in pigs during the elimination phases of both xenon and N2O [44]. It was found to decrease less with xenon than with N2O and the authors concluded that diffusion hypoxia with xenon was unlikely to occur. An explanation may be that where diffusion of gas across a blood or water film occurs, the main factor determining the diffusion rate is the solubility of the gas in the liquid. Since the blood/gas partition coefficient of xenon is much lower than that of nitrous oxide, then xenon may diffuse into alveoli more slowly than N2O in a potential diffusion hypoxia situation. In studies on human volunteers during clinical anaesthesia xenon appears to produce cardiovascular stability with no significant changes in myocardial contractility as assessed by echocardiography, cardiac index, blood pressure or systemic vascular resistance [567]. Examples of such studies include one in which 70% xenon in oxygen was compared with 70% N2O in oxygen. The xenon mixture resulted in cardiostable anaesthesia with much reduced requirements for fentanyl during gynaecological, plastic and orthopaedic surgery [5]. In another study, there were no observed haemodynamic changes during different inhaled concentrations of xenon of 30, 50 and 70% in acutely instrumented laboratory animals [10]. In many studies the heart rate has been reported to have a tendency to decrease with increased variability of the cardiac rhythm as this slowing occurs [789]. This phenomenon has also been noted by Marx et al., although their findings were not statistically significant [10]. These minimal cardiovascular effects of xenon in oxygen are in contrast to current volatile agents which can all produce a decrease in arterial blood pressure; halothane and enflurane also decrease cardiac output [45, 46]. The mechanism of heart rate reduction in humans is not yet known and in a recent report it has been suggested that xenon actually attenuates the myocardiodepressant effect of isoflurane [11]. In animal models, all current routinely used anaesthetic agents depress ion currents in isolated ventricular myocytes. In contrast, when tested at a concentration of 80%, xenon was found to have no inhibitory effect on cardiac ion channels for calcium, sodium and inward potassium flow [47]. Cerebral blood flow (CBF) during xenon anaesthesia has been well investigated in connection with its applications in neuroradiology. However, there seems to have been very little research on the effects of xenon on blood flow to other regions of the body. Though somewhat limited, a study by Lachmann et al. is the only work in this area known to us [48]. They examined the effects of three different anaesthetics on the cardiac output and the blood flow through the brain, liver, kidneys and small intestine in pigs. Each animal received three types of anaesthetic in random order: (a) 66% N2O in oxygen supplemented with 1% halothane; (b) 70% xenon in oxygen with no opioid or volatile agent supplementation; and (c) a combination of thiopentone and fentanyl, the doses of which were not given. The xenon was noted to produce the highest regional blood flow in all these organ groups when compared with the other anaesthetic regimens. Interestingly, the largest percentage increase was seen in cerebral blood flow. Inhaled stable xenon can be used to enhance computerised tomography (CT) images and the radioactive isotope 133Xe can be used to measure cerebral blood flow. Despite its clinical utility, the safety and accuracy of xenon-enhanced scanning has been questioned because there have been inconsistent reports of its effect on cerebral blood flow. In awake monkeys, stable xenon (33% inhaled concentration) reduced CBF by 12% and cerebral oxygen consumption by 16% but had no effect on either parameter when the animals were anaesthetised with fentanyl [49]. In another study, however, xenon (80% inhaled concentration) produced anaesthesia and a 50% increase in CBF [50]. In experimental freeze-induced intracranial hypertension, xenon 33% did not increase intracranial pressure [51]. Investigations carried out on human volunteers using xenon (33% inhaled) have demonstrated an increase in CBF [52]. In acute head injury patients, an increase in ICP and reduction of cerebral perfusion pressure has been reported during inhalation of 33% xenon although no cerebral oligaemia or ischaemia resulted from this. The authors concluded that xenon-enhanced CT scanning was safe as long as hyperventilation was employed to protect against any rise in intracranial pressure [53]. Inhalation protocols are being developed to shorten the period of xenon inhalation for enhanced CT scanning because of the possibility of increased CBF [54]. A transcranial Doppler study in humans has also registered regional increases in blood velocities of some cerebral arteries during 65% xenon in oxygen anaesthesia for abdominal surgery [8]. Xenon cannot be recommended as a suitable anaesthetic for neurosurgical procedures on the basis of current knowledge. The discrepancy between the results in primates and humans may be explained by interspecies variation in the sensitivity to xenon. Indeed, the MAC of xenon in Rhesus monkeys is reported to be 98% whilst in humans it is 71% [55, 56]. Since MAC values for other anaesthetic agents seem to be similar between species, this discrepancy is unusual. It may reflect the fact that previous MAC studies have used relatively small sample sizes due to the extreme cost of using xenon in nonrebreathing circuits. The MAC value for monkeys for example is derived from the study of just seven animals. We are aware that larger MAC studies are in progress in the United Kingdom to clarify the value in humans with a greater degree of confidence. Russian experience suggests that a 60% xenon concentration produces clinical anaesthesia in humans under conditions of minor surgical stimulus [6]. We are not aware of any studies concerning specific renal effects apart from that of Lachmann et al. suggesting increased renal blood flow [48]. In a Russian study, 38 surgical patients received anaesthesia with either N2O or xenon in oxygen with supplementary doses of fentanyl as required according to a protocol. Patients' lungs were ventilated using a muscle relaxant to facilitate tracheal intubation and mechanical ventilation. Plasma concentrations of ACTH, cortisol and prolactin were measured using radio-immunological methods. There was a higher fentanyl requirement in the N2O group and the concentrations of all these hormones were increased in both groups. The authors concluded that xenon does not impair the stress response to surgery [57]. Boomsma et al. in a similar experiment compared the cardiovascular stability of xenon anaesthesia with N2O in humans [5]. Incremental doses of fentanyl were given during anaesthesia if the arterial blood pressure rose by more than 20% above the pre-anaesthetic value, with more being required in the N2O group. Several different surgical procedures were performed and plasma concentrations of dopamine, adrenaline, noradrenaline, cortisol, prolactin and growth hormone were measured on up to 11 occasions before, during and after anaesthesia. Peri-operatively, plasma noradrenaline and prolactin increased in both groups. In contrast, adrenaline and cortisol increased in the N2O group but remained unchanged in the xenon group. Growth hormone reduced to less than control values in the xenon group but not in the N2O group; dopamine was unchanged in both. Postoperatively, concentrations of noradrenaline, adrenaline, cortisol and prolactin were increased in both groups and dopamine was raised in the N2O group. All values returned to normal over a 220-min postoperative measurement period. To control for the differences in surgical stimuli in such experiments, Marx et al. recently investigated plasma dopamine, adrenaline and noradrenaline concentrations in pigs mechanically ventilated with varying concentrations of xenon and subjected to a standard surgical stress [10]. These were compared to a control group receiving total intravenous anaesthesia with pentobarbitone and an identical surgical stimulus. Both groups received a single dose of buprenorphine analgesia. Depth of anaesthesia was held as constant as possible by assessment of spectral edge frequency. Whilst dopamine and noradrenaline concentrations remained within normal limits, it was noted that adrenaline concentrations were significantly reduced in all the xenon groups. This included those receiving concentrations of less than 1 MAC (50% and 30%) [10]. In volunteers, nitrous oxide and halothane have been reported to increase sympathetic nerve activity and increase plasma noradrenaline concentrations [58]. Similar effects are seen with isoflurane and desflurane [59]. Dramatic sympathetic activation can be observed when there is a rapid increase in the inspired desflurane concentration [60]. It has been suggested that this might be an effect due to the pungency of the agent or to the rapid wash-in characteristics of desflurane. Xenon has a three-fold lower blood/gas solubility than desflurane with extremely rapid wash-in characteristics. A rapid change from 0 to 70% xenon concentration in the work by Marx et al. failed to produce any such sympathetic reaction however, suggesting that the rapidity of wash-in alone does not account for this phenomenon [10]. It is now well known that nitrous oxide has haematological, fetotoxic and neurological effects with prolonged exposure due to its interaction with vitamin B12 [1617181920]. There are few such studies on xenon, although due to its low reactivity such effects are unlikely. In a Russian experiment, dogs inhaled a mixture of 80% xenon and 20% oxygen for 2 h every 3 days for a period of 2 weeks. The authors stated that there were no toxic effects on the basis of their functional, biochemical, haematological and morphological findings [61]. One study investigating mechanisms of anaesthesia has shown that aggregation of platelets is inhibited by nitrous oxide but potentiated by xenon. These effects, however, only become statistically significant at greater than two atmospheres of pressure so these effects may only be of importance to deep-sea divers breathing specialist gas mixtures [62]. In one study, four groups of pregnant rats were subjected to mixtures of oxygen, oxygen and nitrogen, oxygen and xenon and oxygen and N2O for 24 h. Twenty days later, the fetuses were examined and in the first three groups the incidence of microscopic organ abnormalities such as hydrocephalus and gastroschisis was 1–3%. In the nitrous oxide group, however, the incidence was very significantly higher at 15%, with an incidence of skeletal abnormalities of 37% [63]. Nitrous oxide may be teratogenic because of metabolite formation, an effect on blood flow through the uterus or its well known effects on vitamin B12 biosynthesis. Since xenon is at least as potent as nitrous oxide, the mechanism for teratogenicity of nitrous oxide is not related to the intrinsic mechanism of anaesthesia. Rabbits exposed to 50–70% xenon for 48 h show no microscopic changes in any organs [64]. Biochemical investigation of patients before and after xenon anaesthesia has shown no pathological changes [65]. There is evidence emerging to suggest that xenon does not trigger malignant hyperthermia. Muscle specimens from 16 patients susceptible to malignant hyperthermia have been exposed to xenon. Such samples typically show lower contracture thresholds to agents such as caffeine and halothane. When exposed to xenon, none of these samples demonstrated any similar effects and no evidence was obtained to suggest that xenon triggers malignant hyperthermia in humans [66]. N2O, by comparison, may be a weak triggering agent although it is considered by some to be safe for use in susceptible patients. There has been at least one reported case of nitrous oxide triggering the condition [67]. It is well known that N2O can diffuse into and enlarge closed spaces such as the bowel, pneumothoraces, the middle ear and tracheal tube cuffs. An enclosed space containing air can enlarge in the presence of an inhaled N2O/oxygen (i.e. nitrogen-free) mixture because it will diffuse into the space about 25 times faster than the nitrogen present can diffuse out. The theoretical maximum increase in volume of the gas within the gut when breathing a 66% N2O/33% oxygen mixture is 200%. Xenon accumulation in the bowel has been demonstrated in pigs during anaesthesia [68]. Differences in gas density have only small effects on the rate of diffusion but where gas transfer across blood or water films is concerned, the major factor determining diffusion rate is the solubility of the gas in the liquid. The blood/gas partition coefficient of N2O is 0.47 but the value for xenon is only 0.14, so it is likely that this phenomenon will be observed with xenon but to a lesser degree than is currently seen with N2O. Xenon is a noble gas and under special conditions it is capable of forming compounds with very reactive elements. Known compounds include clathrates, fluorides, chloride fluorides, chlorides, oxides, oxyfluorides, xenates, fluoroxenates, perxenates and complex salts. Enzymic reactions have also been observed. It is extremely unlikely that xenon is involved in any biochemical reactions when used as an anaesthetic, although the possibility cannot be ruled out completely [69]. Elimination of xenon is mainly through the lungs and this aspect has been studied by Luttropp et al. in animals ventilated with 100% oxygen after a period of 2 h of 70% xenon anaesthesia. In pigs of 37–39 kg, it was estimated that it took 5–10 min to recover 1 litre of xenon in expired air, 15–20 min to recover another litre and 30 min to recover a third litre. In the pig in whom xenon washout was studied the longest, about 4.4 l had been recovered after 4 h of oxygen breathing [21]. For more than 30 years xenon has been used for investigation of cerebral blood flow as a whole or for mapping the different vascular regions of the brain [70, 71]. Xenon has been applied in two forms − as a stable radiodense molecule for xenon-enhanced computed tomography (Xe/CT) or as the radioactive isotope 133Xe for extracranial detection of its clearance. It can be given by intracarotid injection, intravenous injection or by inhalation [717273]. The estimation of the cerebral blood flow by xenon clearance is based on the principle that the uptake and clearance of an inert diffusable gas is proportional to the blood flow in the tissue. Xenon also has potential as a contrast agent in magnetic resonance imaging (MRI) since it can be 'hyperpolarised' by laser light to give off strong MRI signals [74]. When dissolved in suitable fluids and injected, the image quality is similar to that currently obtained with radioisotopes. The use of xenon in neuroradiology has been an important tool in studying regional variations in cerebral blood flow in occlusive cerebrovascular disease, dementia and psychiatric disorders. Xenon has also been used to monitor changes in CBF in patients with severe head injuries [75] and to study cerebral perfusion during anaesthesia [76]. In 1951, Cullen used xenon on an 81-year-old having an orchidectomy [77]. After 10 min pre-oxygenation, the xenon was then administered at 80% concentration and the patient lost consciousness in 3 min. Surgery began 10 min after the anaesthetic started. At the end of the anaesthetic the patient was conscious after 2 min and fully orientated within 5 min. During radiological investigations it has been noticed that xenon in concentrations of more than 50% can lead to euphoria which can progress to respiratory depression and loss of consciousness. A common observation in such investigations with ≈ 33% xenon is that the respiratory rate slows and the tidal volume tends to rise, partially compensating for this [36]. Owing to its very low blood/gas solubility coefficient, one would expect the onset of anaesthesia to be very rapid. In one study, 24 patients were premedicated with 0.05 mg.kg−1 of midazolam and asked to take vital capacity breaths of 1 MAC xenon or sevoflurane in oxygen until they lost consciousness [13]. The patients breathing xenon lost consciousness more rapidly than those receiving sevoflurane, mean (SD) induction times being 71 (21) s and 147 (59) s, respectively. In this study, the respiratory rate and tidal volume were reduced in both groups but this was less apparent in the xenon group [13]. Four stages of xenon anaesthesia have been described from observations on 12 patients in a Russian study in which 70% xenon/30% oxygen was administered [6]. The first is a stage of paraesthesia and hypoalgesia with a 'pins and needles' sensation all over the body. The second stage is euphoria, with increased psychomotor activity as if the subjects were trying to share their feelings with observers. At this stage subjects tried to remove the mask and did not follow commands although they had full recollection of the commands that were given. The third stage is described as analgesia and partial amnesia and this occurs by the third or fourth minute. The fourth stage is the stage of surgical anaesthesia; a degree of muscle relaxation is seen with pronounced diaphragmatic breathing. In this study all the patients woke up within 2 min and were fully conscious within 4 min. As they first started to regain consciousness the patients were initially disorientated and reported feeling that they were in an unknown environment where all the observers appeared as manikins. The pain threshold took longer to return than did full consciousness, being back to normal by 10–12 min after cessation of xenon administration [6]. In a recent Japanese study, recovery times were recorded in humans after approximately 2 h of anaesthesia with three different anaesthetic regimens: 60% xenon, 60% N2O + 0.5% isoflurane, 60% N2O + 0.7% sevoflurane. The mean (SD) times taken until the patients could count backwards from 10 to 1 in less than 15 s were; 6 (1.6), 14.3 (2.8) and 10.5 (2.5) min, respectively [14]. It has also been suggested that fast emergence from xenon anaesthesia is seen regardless of the duration of the anaesthetic and this is consistent with its low blood/gas partition coefficient [78]. Xenon has been used in anaesthesia for many different types of surgery, including general, gynaecological and orthopaedic operations. It has also been used for at least one Caesarean section without any reported problems [65, 79]. A comparison of the anaesthetic efficacy and potency of a 70% xenon/30% oxygen mixture in comparison to a 70% N2O/30% oxygen mixture was performed by Lachmann et al. [43]. In this study, the xenon group required only one-fifth of the amount of fentanyl required by the N2O group in order to attain predetermined haemodynamic stability targets. It must be noted in this study, however, that equi-MAC concentrations of the agents were not compared. Luttropp et al. found that the mean dose of fentanyl needed to supplement xenon anaesthesia was rather low, and supports the previous findings of Boomsma et al. who also concluded that xenon is a potent analgesic [5, 9]. Experiments have also been carried out to investigate the analgesic properties of xenon at subanaesthetic concentrations. A Japanese study examined the effect of 0.3 MAC of either xenon or nitrous oxide on pain threshold and auditory response time. There was no difference in analgesic effect between the two groups. When compared to 100% oxygen, the response time to auditory stimuli was prolonged with xenon but not with nitrous oxide. The analgesic effects of neither gas were reversible with naloxone [80]. A Russian report describes the use of xenon for the treatment of angina pain and for analgesia during painful changing of dressings [6]. The low concentration of xenon in air means that xenon recovery is only practicable where there are large air separation plants producing over 1000 tonnes of oxygen per day. Russia extracts 25–30% of the world's xenon. It is noteworthy that although all their oxygen plants have the facility to extract xenon this process only takes place in about half of them. A 1000 tonne per day oxygen plant will only produce around 4 cubic metres of xenon per day, obtained as a concentrate in combination with krypton. Owing to the small volumes involved at this point in the process, the final separation from krypton is currently done on a laboratory scale. The current cost of manufacture is US$10 per litre and £10 per litre in the UK. World production is around 6 million litres a year. By 2001 this value is predicted to rise to 9.5 million litres, and all manufacturers have announced an increase in manufacturing capacity. Three million litres of this, however, will be for aerospace use in the near future. Ionised xenon will be used to produce thrust to manoeuvre satellites, and also to counteract static electricity build up on the international space station. Most of the gas used in these ways will be lost from the atmosphere forever. In the medium term the cost may therefore not fall despite increased production, and in the extreme long-term xenon could become even scarcer. Increasing production rate of a commodity can often lead to a decrease in unit cost; however, the prospects for making xenon affordable for anaesthesia in this way are by no means certain. Approaches based on very efficient breathing systems and/or recovery devices will also be required. Studies have been conducted in Russia with 70% xenon/30% oxygen anaesthesia in spontaneously breathing patients via face mask and laryngeal mask airway, using a xenon fresh gas flow of 2 l.mi
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