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Anesthésie au xénon : du mythe à la réalité
Abstract
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 rarety 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.
... Noble gases (Ng) are an important class of industrial chemicals which have applications such as anesthetics [1][2][3][4], carrier gases [5], lighting [6,7], insulation [8], cryogenic refrigerants [9], etc. These applications make them important in several research areas such as electronics, medicine and the environment. ...
Systematic analysis of the noble gas (Ng = He – Rn) trapping capacity of the B12N12 cluster were performed at the PBE0-D3/def2-TZVP level by means of thermochemical data, topological analysis of the electron density (QTAIM), non-covalent interactions index (NCI), and energy decomposition analysis (EDA). The results indicate that the Ngn@B12N12 (n = 1, 12) cluster can be obtained below room temperature. Additionally, it was found that this cluster can trap up to 12 noble gas atoms without losing stability, Finally, the effect of an applied electric field has been analysed, showing that the interaction energy can be improved through this strategy.
... Noble gases (Ng) are an important class of industrial chemicals which have applications such as anesthetics, [1][2][3][4] carrier gases, [5] lighting, [6,7] insulation, [8] cryogenic refrigerants, [9] etc. These applications make them important in several research areas such as electronics, medicine and the environment. ...
Systematic analysis of the noble gas (Ng = He – Rn) trapping capacity of the B12N12 cluster were performed at the PBE0-D3/def2TZVP level by means of thermochemical data, topological analysis of the electron density (QTAIM), non-covalent interactions index (NCI), and energy decomposition analysis (EDA). The results indicate that the Ngn@B12N12 (n = 1,12) cluster can be obtained below room temperature. Additionally, it was found that this cluster can trap up to 12 noble gas atoms without losing stability, Finally, the effect of an applied electric field has been analysed, showing that the interaction energy can be improved through this strategy.
... Os gases nobres possuem propriedades anestésicas reconhecidas desde há mais de cinquenta anos, contudo, a sua aplicação clínica é uma prática recente. 1 O xénon foi identificado em 1898 pelos químicos britânicos Sir William Ramsay (Prémio Nobel da Química, em 1904) e Morris Travers, 2 e em 1951 foi utilizado pela primeira vez como anestésico geral em seres humanos, por Cullen e Gross. 3 Mais de 6,5 milhões de litros de xénon são produzidos anualmente dos quais apenas cerca de 5% são usados na prática médica; sendo que o seu uso na anestesiologia destaca--se como o principal responsável pelo consumo médico de xénon. 4,5 Nas duas últimas décadas recrudesceu o interesse no xénon, tendo vindo a ser investigados os seus mecanismos de acção e propriedades como anestésico geral. A realização de dois ensaios clínicos aleatorizados multicêntricos foi determinante para a aprovação, em Março de 2007, do seu uso como anestésico, pela European Medicines Agency (EMEA) em doentes com classificações de estado funcional I e II da American Association of Anesthesiology (ASA). ...
strong>Introduction: The Xenon, a noble gas, has anesthetics properties, associated with remarkable hemodynamic stability as well as cardioprotective, neuroprotective proprieties. Its physicochemical characteristics give him a quick induction and emergence of anesthesia, being free of deleterious effects in all organs and showing no teratogenicity. Such properties have led to a growing interest in improving the knowledge about this noble gas, in order to assess the mechanisms of neuro and cardioprotection induced and to assess the clinical indications for its use.
Material and Methods: Qualitative review of clinical trials on anesthesia with xenon. Studies were identified from MEDLINE and by hand-searching, using the following keywords: xenon, xenon anestesia, xenon neuroprotection, xenon cradioprotection.
Results: After several studies, including two randomized multicenter controlled trials, the use of xenon as an anesthetic in patients ASA I-II was approved in March 2007. However his use in clinical practice has been strongly limited by it´s high price. It seems unlikely that the advantages it offers in relation to other anesthetics justify it´s use in patients ASA I-II. Although, xenon may be a valuable asset in the reduction of co-morbilities and mortality in anesthesia of patients ASA III-IV, unfortunately, there are no large randomized control studies to prove it.
Discussion: Unfortunately, there are still no randomized or multicentric studies showing a favourable cost-benefit profile of xenon in ASA III-IV patients vs. other anaesthetics.
Conclusion: The usefulness of xenon in Anesthesiology requires more studies to be defined.
This chapter discusses the different aspects of general anesthetics and therapeutic gases. Gastrointestinal endoscopy is one of the most commonly performed invasive procedures in clinical practice. Propofol is a short-acting intravenous anesthetic with a rapid onset of action, a short half-life, and very favorable recovery characteristics, making it particularly suitable for day procedures. Dexmedetomidine has been compared with midazolam in a prospective randomized trial with 30 infants and children undergoing mechanical ventilation. Sevoflurane often causes postoperative delirium and agitation in children, and this can be severe. Rapid emergence and postoperative pain have been proposed as possible mechanisms. A mixture of nitrous oxide and oxygen in equal proportions is an effective analgesic for short-term pain and is generally considered safe. Subanesthetic low-dose ketamine is being used increasingly often for acute pain therapy, day-case surgery, and chronic pain management. Propofol is often the agent of choice in sedation of critically ill patients, particularly in neurological illnesses, as it allows rapid assessment on withdrawal. The use of extracorporeal cardiac support in the successful management of the cardiac failure associated with propofol infusion syndrome has also been described.
Solubility measurements of methane and of xenon in the ionic liquid 1-n-butyl-3-methylimidazolium methyl sulfate ([bmim][CH3SO4]) were performed with a high-pressure view-cell technique based on the synthetic method. The temperature ranged from 293.1 K to 413.2 K, and the maximum pressure (the maximum gas molality) was 8.9 MPa (0.19 mol·kg-1) for methane and 11.3 MPa (0.65 mol·kg-1) for xenon. Both gases become less soluble in [bmim][CH3SO4] with rising temperature, but xenon shows a significantly higher solubility at all conditions investigated. An extension of Henry's law is employed to correlate the solubility pressures in both cases. The final results for the Henry's constant (at zero pressure) of methane and xenon in [bmim][CH3SO4] (on the molality scale) are correlated within the experimental uncertainty (about ± 1.3 %) by ln( /MPa) = 6.216 − 564.5/(T/K) − 0.002566(T/K) and ln( /MPa) = 5.5906 − 928/(T/K) − 0.00141(T/K), respectively.
To analyze the current knowledge related to xenon anaesthesia.
References were obtained from computerized bibliographic research (Medline), recent review articles, the library of the service and personal files.
All categories of articles on this topic have been selected.
Articles have been analyzed for biophysics, pharmacology, toxicity and environmental effects, clinical effects and using prospect.
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.
Reducing its cost will help xenon to find its place among anaesthetic agents and extend its use to severe patients with specific pathologies.
Xenon (Xe) is an anesthetic with minimal side effects, now also showing promise as a neuroprotectant both in vitro and in vivo. Although scarce and expensive, Xe is insoluble and patient uptake is low, making closed circuits the optimum delivery method. Although the future of Xe anesthesia is uncertain, effective neuroprotection is highly desirable even if moderately expensive. A factor limiting Xe research in all these fields may be the perceived need to purchase special Xe anesthesia workstations that are expensive and difficult to service. We investigated the practicality of 1) true closed-circuit Xe delivery using an unmodified anesthesia workstation with gas monitoring/delivery attachments restricted to breathing hoses only, 2) a Xe delivery protocol designed to eliminate wastage, and 3) recovering Xe from exhaled gas.
Sixteen ASA physical status I/II patients were recruited for surgery of > 2 h. Denitrogenation with 100% oxygen was started during induction and tracheal intubation under propofol/remifentanil anesthesia. This continued after operating room transfer for 30 min. All fresh gases were then temporarily stopped, metabolic oxygen consumption then being replaced with 250-mL Xe boluses until F(I)Xe = 50%. A basal oxygen fresh gas flow was thereafter restored with additional Xe given as required via the expiratory hose to maintain a F(I)Xe > or = 50%. At no time, apart from during circle flushes every 90 min, were the bellows allowed to completely fill and spill gas, ensuring the circle remained closed. On termination of anesthesia, the first 10 exhaled breaths were collected as was residual gas from the circle, allowing measurement of the Xe content of each.
Total Xe consumption, including initial wash-in and circle flushes, was 12.62 (5.31) L or 4.95 (0.82) L/h, mean (sd). However, consumption during maintenance periods was lower: 3 L/h at 1 h and 2 L/h thereafter. Of the total Xe used, 8.98% (5.94%) could be recovered at the end of the procedure.
We report that closed-circuit Xe delivery can be achieved with a modified standard anesthesia workstation with breathing hose alterations only and that the protocol was very gas efficient, especially during the normally wasteful Xe wash-in. A Xe mixture of > or = 50% was delivered for up to 341 min (5 h 41 min) and Xe consumption was 4.95 (0.82) L/h, maintenance being achieved with 2-3 L/h. With this degree of efficiency, Xe recovery/recycling at the end of anesthesia may be of little additional benefit.
This chapter presents various aspects of the preparation of xenon and krypton derivatives and their use as heavy atoms or anomalous scatterers in protein crystallography. The noble gas atoms are able to diffuse rapidly toward potential interaction sites in proteins via the solvent channels that are always present in crystals of macromolecules. Xenon and krypton derivatives of proteins can be obtained by subjecting a native protein crystal to a xenon or krypton gas atmosphere pressurized in the range of 1–100 bar. The number and occupancies of xenon/krypton-binding sites vary with the applied pressure. The interaction of noble gas atoms with proteins is the result of noncovalent weak-energy van der Waals forces, and therefore the process of xenon/krypton binding is completely reversible. With proteins, however, the interactions of xenon and krypton are of noncovalent origin and are therefore similar in nature to the forces that give rise to the formation of other well-known complexes of xenon and krypton with small molecules. The key physical parameter in xenon/krypton–protein interactions is the electronic polarizability of the noble gas atoms. The usual repulsive forces between atoms and molecules that are in close contact with each other also play an important role because they determine the minimum size that a cavity must have for xenon or krypton to bind into it. With the current emphasis on high-throughput macromolecular crystallography, the use of xenon and krypton derivatives should feature prominently in the list of available tools to solve protein structures.
Patients with diabetes are more likely to undergo surgery than nondiabetics, and maintaining glycemic control in subjects with diabetes can be challenging during the perioperative period. Surgery in diabetic patients is associated with longer hospital stay, higher health care resource utilization, and greater perioperative mortality. In addition, several observational and interventional studies have indicated that hyperglycemia is associated with adverse clinical outcomes in surgical and critically ill patients. This paper reviews the pathophysiology of hyperglycemia during trauma and surgical stress and will provide practical recommendations for the preoperative, intraoperative, and postoperative care of diabetic patients.
Le PhysioFle™ est un ventilateur d'anesthésie en circuit fermé autorégulé, dont la conception originale permet l'anesthésie par inhalation à objectif de concentration dans le circuit patient. L'appareil est composé d'un circuit filtre dans lequel les valves ont été remplacées par une turbine qui fait circuler le mélange gazeux à un débit de 70 L·min−1. Le ventilateur est constitué de quatre chambres que l'on peut associer en parallèle autorisant le réglage du volume courant entre 50 et 2 000 mL. Le circuit primaire du ventilateur permet d'exercer un déplacement des membranes des chambres de ventilation, soit par compression manuelle du ballon, soit automatiquement en réglant les paramètres ventilatoires sur l'ordinateur de l'appareil. Un réglage standard des paramètres de ventilation est possible après avoir entré dans l'ordinateur, le sexe, l'âge et le poids du patient, sur la base du diagramme de Radford. L'air médical, le protoxyde d'azote et l'oxygène sont introduits dans le circuit par des valves électromagnétiques et l'agent volatil halogèné est injecté par une seringue dont le piston est actionné par un moteur pas à pas. Les agents volatils halogènes sont prélevés directement dans leur flacon d'origine qui est adapté à l'appareil. Le ventilateur, qui fonctionne en circuit totalement fermé, ne rejette ni protoxyde d'azote, ni agent halogèné dans l'atmosphère de la salle d'opération. Un absorbeur contenant du charbon activé qui fixe l'agent volatil halogèné permet de ré duire rapidement la concentration de celui-ci dans le circuit. Les variations de concentration de l'anesthésique volatil halogèné, tant à l'induction grâce à l'injecteur, qu'au réveil grâce à l'absorbeur, sont quasiment instantanées et la consommation réduite de façon considérable.
The purpose of this study was to examine the effects of xenon and nitrous oxide in equipotent doses of 0.3 MAC on pain threshold
and auditory response time in six healthy male volunteers. Compared with 100% oxygen inhalation, xenon and nitrous oxide significantly
increased the pain threshold as measured by a radiant heat algometer. There was no significant difference in analgesic effects
between xenon and nitrous oxide. Xenon significantly prolonged the response time to auditory stimuli compared with 100% oxygen,
but nitrous oxide did not. The inhibitory effect of xenon on the auditory response time was significantly greater than that
of nitrous oxide. The same six volunteers were studied to test if naloxone antagonized analgesia induced by xenon or nitrous
oxide. The analgesic effects of xenon and nitrous oxide did not differ with or without naloxone.
Nitrous oxide and isoflurane have different effects on absolute cerebral blood flow (CBF) and regional distribution of CBF in humans. In this study we examined the effects of isoflurane in combination with nitrous oxide on CBF. We studied 10 patients (two groups of five patients, ASA I) anaesthetized with 50% nitrous oxide and either 0.5 or 1.0 MAC of isoflurane during normocapnia (PaCO2 5.7 kPa) using two-dimensional CBF measurement (CBFxenon) (i.v. 133xenon washout technique) and a three-dimensional method for measurement of regional CBF (rCBF) distribution with SPECT (single photon emission computer-aided tomography with 99mTc- HMPAO). The results were compared with 1.0 MAC of isoflurane from a previous study performed in exactly the same way as the present investigation. During normocapnia, anaesthesia with 50% nitrous oxide and 0.5 MAC of isoflurane resulted in a mean CBFxenon of 45 (SEM 5) ISI units. Increasing the isoflurane concentration to 1.0 MAC had no significant effect on mean CBFxenon (53 (5) ISI units). Both flow values were significantly (P = 0.01) higher than the CBFxenon value obtained when 1 MAC of isoflurane was administered alone (33 (3) ISI units). There were no significant differences in rCBF distribution regardless of whether or not isoflurane was given alone or together with nitrous oxide at 0.5 or 1 MAC. In all situations there were higher relative flows in subcortical regions (thalamus and basal ganglia, 10%) and in the pons (7-10% above average). rCBF in the cerebellum was approximately 10% greater than average. In summary, we have found that mean CBF was greater with combined nitrous oxide and isoflurane anaesthesia than previously found with isoflurane alone; however, relative flow distribution was similar.
In order to investigate haemodynamic response and catecholamine release during anaesthesia with xenon, we conducted a study
on 28 pigs which were allocated randomly to one of four groups: total i.v. anaesthesia with pentobarbitone and buprenorphine,
and xenon anaesthesia with inspiratory concentrations of 30%, 50% or 70%, respectively, supplemented with pentobarbitone.
Haemodynamic variables were measured using arterial and Swan Ganz catheters. Depth of anaesthesia was monitored using spectral
edge frequency analysis. Plasma concentrations of dopamine, noradrenaline and adrenaline were measured by high pressure liquid
chromatography. All haemodynamic variables and plasma concentrations of dopamine and noradrenaline remained within normal
limits. Adrenaline concentrations were reduced significantly in all groups. Xenon anaesthesia was associated with a high degree
of cardiovascular stability. Significant reduction in adrenaline concentrations at inspiratory xenon concentrations of 30%
and 50% can be explained by analgesic effects of xenon below its MAC value.
Twitch response using accelerometry and plasma concentrations, of vecuronium and its metabolite were studied in 27 surgical
patients during xenon or sevoflurance anaesthesia after administration of vecuronium 0.05 mg kg-1. Anaesthesia was maintained
using oxygen-xenon (MAC = 71%) or oxygen-sevoflurane (MAC = 2%) at an end-tidal concentration equal to 0.8 MAC (i.e. 57% xenon
and 1.6% sevoflurane). Mean time from administration of vecuronium to 25% recovery of the first twitch of the train-of-four
response was significantly shorter in the xenon group than in the sevoflurane group (12.9 (SD 2.5) min vs 19.4 (6.0) min,
respectively). Plasma concentrations of vecuronium at 25% recovery were significantly higher during xenon than during sevoflurane
anaesthesia (187 (49) ng ml-1 vs 136 (40) ng ml-1, respectively), while those of 3-desacetylvecuronium were similar in both
groups.
40 patients (24 male, 16 female, aged 21-59 years) of American Society of Anesthesiologists class I or II who were undergoing routine surgery took part in a randomised, double-blind comparison of the anaesthetic efficacy and potency of xenon and nitrous oxide and their effects on the circulatory and respiratory systems. During anaesthesia, for each rise in blood pressure of more than 20% of the preanaesthetic (baseline) value, the patient received 0·1 mg fentanyl. The total amount of fentanyl required per patient was used as an index of the anaesthetic potency of the study gases. Patients in the xenon group required on average only 0·05 mg fentanyl, whereas those in the nitrous oxide group required 0·24 mg fentanyl; the duration of anaesthesia was similar in the two groups. Changes in blood pressure were significantly greater throughout the study in the nitrous oxide than in the xenon group. Thorax-lung compliance fell during the study period in the nitrous oxide group but not in the xenon group. Thus, xenon is a potent and effective anaesthetic which can be safely used under routine conditions.
In their descriptions of the hydrate theory of anesthetic action Pauling and Miller suggested that the action of two anesthetic gases might be synergistic if one gas formed a structure I and the other a structure II hydrate. The correlation of anesthetic potency and lipid solubility, however, suggests that combinations of anesthetics should result in an additive effect rather than synergism. We compared the anesthetic requirements, as defined by MAC, for xenon (structure I hydrate) and for halothane (structure II hydrate) with MAC values for xenon-halothane mixtures in man. The results indicate that xenon and halothane in combination have an additive rather than a synergistic anesthetic effect.
Background
During nitrous oxide (N2O) elimination, arterial oxygen tension (PaO2) decreases because of the phenomenon commonly called diffusive hypoxia. The authors questioned whether similar effects occur during xenon elimination.
Methods
Nineteen anesthetized and paralyzed pigs were mechanically ventilated randomly for 30 min using inspiratory gas mixtures of 30% oxygen and either 70% N2O or xenon. The inspiratory gas was replaced by a mixture of 70% nitrogen and 30% oxygen. PaO2 and carbon dioxide tensions were recorded continuously using an indwelling arterial sensor.
Results
The PaO2 decreased from 119+/-10 mm Hg to 102+/-12 mm Hg (mean+/-SD) during N2O washout (P<0.01) and from 116+/-9 mm Hg to 110+/-8 mm Hg during xenon elimination (P<0.01), with a significant difference (P<0.01) between baseline and minimum PaO2 values (deltaPaO2, 17+/-6 mm Hg during N2O washout and 6+/-3 mm Hg during xenon washout). The PaCO2 value also decreased (from 39.3+/-6.3 mm Hg to 37.6+/-5.8 mm Hg) during N2O washout (P<0.01) and during xenon elimination (from 35.4+/-1.6 mm Hg to 34.9+/-1.6 mm Hg; P< 0.01). The deltaPaCO2 was 1.7+/-0.9 mm Hg in the N2O group and 0.5+/-0.3 mm Hg in the xenon group (P<0.01).
Conclusion
Diffusive hypoxia is unlikely to occur during recovery from xenon anesthesia, probably because of the low blood solubility of this gas.
Xenon is an inert gas with a practical anesthetic potency (1 MAC = 71%). Because it is very expensive, the use of closed circuit anesthesia technique is ideal for the conduction of xenon anesthesia. Here we describe our methods of starting closed circuit anesthesia without excessive waste of xenon gas. We induce anesthesia with intravenous agents, and after endotracheal intubation, denitrogenate the patient for approximately 30 min with a high flow of oxygen. This is done to minimize accumulation of nitrogen in the anesthesia circuit during the subsequent closed-circuit anesthesia with xenon. Anesthesia is maintained with an inhalational anesthetic during this period. Then, we discontinue the inhalational agent and start xenon. For this transition, we feel it is unacceptable to simply administer xenon at a high flow until the desired endtidal concentration is reached because it is too costly. Instead. we set up another machine with its circuit filled in advance (i.e., primed) with at least 60% xenon in oxygen and switch the patient to this machine. To prime the circuit, we push xenon using a large syringe into a circuit, which was prefilled with oxygen. Oxygen inside the circuit is pushed out before it is mixed with xenon, and xenon waste will thus be minimized. In this way, we can achieve close to 1 MAC from the beginning of xenon anesthesia, and thereby minimize the risk of light anesthesia and awareness during transition from deni-trogenation to closed-circuit xenon anesthesia.
We described a minimal-flow system for xenon anesthesia during controlled ventilation. A computer maintained oxygen concentration in the anesthesia circle within +/- 2% of the value set by the anesthesiologist. The ventilator and the circle were connected via a large dead space, through which oxygen from the ventilator entered the circle but which prevented xenon from escaping. This arrangement simplified the computer program. The system was tested on a lung model and in six pigs (37-39 kg). The xenon expenditure and the amount of xenon washed out from the pigs after the anesthetic were measured. Additional experiments with nitrous oxide were made in three pigs. The xenon expenditure during 2 h of xenon anesthesia was 7.6 +/- 0.8 l (mean +/- 1 standard deviation). The corresponding expenditure of nitrous oxide was 16.5 +/- 2.7 l. About 75% of the xenon expenditure was in the 1st h of anesthesia; thereafter 20-40 ml.min-1 was needed to maintain oxygen concentration at 30%. Nitrogen concentration in the circle increased to 12-16% during the xenon anesthetic, although it was preceded by a 20 min denitrogenation period. During the washout phase after the xenon anesthesia, mean expired xenon concentration decreased to below 2% within 4 min. Subsequently, washout was slower and the expired concentration remained above 0.1% for more than 90 min. The estimated total amount of xenon washed out from the lungs and body tissues during 4 h of oxygen breathing was about 4 l. We conclude that xenon anesthesia via a fully automated minimal-flow system is feasible.(ABSTRACT TRUNCATED AT 250 WORDS)
40 patients (24 male, 16 female, aged 21-59 years) of American Society of Anesthesiologists class I or II who were undergoing routine surgery took part in a randomised, double-blind comparison of the anaesthetic efficacy and potency of xenon and nitrous oxide and their effects on the circulatory and respiratory systems. During anaesthesia, for each rise in blood pressure of more than 20% of the preanaesthetic (baseline) value, the patient received 0.1 mg fentanyl. The total amount of fentanyl required per patient was used as an index of the anaesthetic potency of the study gases. Patients in the xenon group required on average only 0.05 mg fentanyl, whereas those in the nitrous oxide group required 0.24 mg fentanyl; the duration of anaesthesia was similar in the two groups. Changes in blood pressure were significantly greater throughout the study in the nitrous oxide than in the xenon group. Thorax-lung compliance fell during the study period in the nitrous oxide group but not in the xenon group. Thus, xenon is a potent and effective anaesthetic which can be safely used under routine conditions.
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.
Measurements of cerebral blood flow (CBF) were performed using the microsphere technique in non-human primates (baboons) to assess the effect of non-radioactive xenon gas inhalation on CBF. Blood flows in small tissue volumes (approximately 1 cm3) were directly measured before and during the inhalation of xenon/oxygen gas mixtures. The results of these studies demonstrated that when inhaled in relatively high concentrations, xenon gas does increase CBF, but the changes are more global than tissue-specific. The problems and limitations of such evaluations are discussed.
Exposure of pregnant rats to the anesthetic nitrous oxide on the ninth day of gestation causes fetal resorption, skeletal
anomalies, and macroscopic lesions including encephalocele, anophthalmia, microphthalmia, and gastroschisis. The inert gas
xenon, which has anesthetic properties similar to those of nitrous oxide, does not cause teratogenic effects under the same
experimental conditions.
Xenon (Xe) may cause an increase in airway resistance due to its high density and viscosity. The object of this study was to examine the effects of Xe on pulmonary resistance using dog models with normal and methacholine-treated airways. During anaesthesia 22 mongrel dogs' tracheas were intubated and the lungs were mechanically ventilated with 70% N2/30% O2 as a control gas. The gases 70% nitrous oxide (N2O), 50% N2O, 70% Xe and 50% Xe were administered in a random order for 25 min. Bronchoconstriction was produced by a continuous infusion of methacholine, 0.22 mg.kg-1.hr-1. Pulmonary resistance (RL) was calculated by the isovolume method using flow at the airway opening, volume and transpulmonary pressure. In normal dogs, RL breathing 70% Xe (mean +/- SEM, 0.84 +/- 0.12 cm H2O.L-1.sec-1) was greater (P < 0.05) than with 70% N2O, 50% N2O or control gas (0.61 +/- 0.08, 0.59 +/- 0.06 and 0.62 +/- 0.06 cmH2O.L-1.sec-1). Breathing 50% Xe the RL (0.77 +/- 0.10 cmH2O.L-1.sec-1) was not different from 50% N2O or control. Methacholine infusion increased RL 3.92 +/- 1.98 (mean +/- SD) times. The RL breathing 50% Xe (2.55 +/- 0.44 cmH2O.L-1.sec-1) was not greater than during 50% N2O or control (2.08 +/- 0.33 and 2.13 +/- 0.33 cmH2O.L-1.sec-1) in methacholine-treated dogs. The data suggest that inhalation of high concentrations of Xe increases airway resistance, but only to a modest extent in dogs with normal or methacholine-treated airways.
Under moderate pressure, xenon can bind to proteins and form weak but specific interactions. Such protein-xenon complexes can be used as isomorphous derivatives for phase determination in X-ray crystallography.
Investigation of the serine proteinase class of enzymes shows that the catalytic triad, the common hydrolytic motif of these enzymes, is a specific binding site for one xenon atom and shows high occupancy at pressures below 12 bar. Complexes of xenon with two different serine proteinases, elastase and collagenase, were analyzed and refined to 2.2 A and 2.5 A resolution, respectively. In both cases, a single xenon atom with a low temperature factor is located in the active site at identical positions. Weak interactions exist with several side chains of conserved amino acids at the active site. Xenon binding does not induce any major changes in the protein structure and, as a consequence, crystals of the xenon complexes are highly isomorphous with the native protein structures. Xenon is also found to bind to the active site of subtilisin Carlsberg, a bacterial serine proteinase, that also has a catalytic triad motif.
As the region around the active site shows conserved structural homology in all serine proteinases, it is anticipated that xenon binding will prove to be a general feature of this class of proteins.
Perturbation of neuronal calcium homeostasis may alter neurotransmission in the brain, a phenomenon postulated to characterize the anesthetic state. Because of the central role of plasma membrane Ca(2+)-ATPase (PMCA) in maintaining Ca2+ homeostasis, the authors examined the effect of several inhalational anesthetics on PMCA function in synaptic plasma membranes (SPM) prepared from rat brain.
Ca(2+)-ATPase pumping activity was assessed by measurement of ATP-dependent uptake of Ca2+ by SPM vesicles. ATPase hydrolytic activity was assessed by spectrophotometric measurement of inorganic phosphate (Pi) released from ATP. For studies of anesthetic effects on PMCA activity, Ca2+ uptake or Pi release was measured in SPM exposed to halothane, isoflurane, xenon, and nitrous oxide at partial pressures ranging from 0 to 1.6 MAC equivalents. Halothane and isoflurane exposures were carried out under a gassing hood. For xenon and nitrous oxide exposures, samples were incubated in a pressure chamber at total pressures sufficient to provide anesthetizing partial pressures for each agent.
Dose-related inhibition of Ca(2+)-ATPase pumping activity was observed in SPM exposed to increasing concentrations of halothane and isoflurane, confirmed by ANOVA and multiple comparison testing (P < 0.05). Concentrations of halothane and isoflurane equivalent to one minimum effective dose (MED) depressed PMCA pumping approximately 30%. Xenon and nitrous oxide also inhibited Ca2+ uptake by SPM vesicles. At partial pressures of these two gases equivalent to 1.3 MAC, PMCA was inhibited approximately 20%. Hydrolysis of ATP by SPM fractions was also inhibited in a dose-related fashion. An additive effect occurred when 1 vol% of halothane was added to xenon or nitrous oxide at partial pressures equivalent to 0-1.6 MAC for the latter two agents.
Plasma membranes Ca(2+)-ATPase is significantly inhibited, in a dose-related manner, by clinically relevant partial pressures of halothane, isoflurane, xenon, and nitrous oxide. Furthermore, these anesthetics inhibit PMCA activity in accordance with their known potencies, and an additive effect was observed. How inhalational anesthetics inhibit the PMCA pump is not known at this time. It is noteworthy that the only shared characteristic of this group of agents of widely different structure is anesthetic action. The relevance of this dual commonality, anesthetic action and PMCA inhibition, to actual production of the anesthetic state remains to be determined.
The effects of xenon anaesthesia on myocardial function and cerebral blood flow velocities were investigated with transoesophageal echocardiography and transcranial Doppler sonography. Seventeen ASA 1 patients undergoing open cholecystectomy (n = 16) or abdominal hysterectomy (n = 1) were studied. Anaesthesia with 65% xenon in oxygen was induced by ventilating the lungs through a circle system with minimal fresh gas flow. The echocardiographically obtained mean (SD) fractional area change in a short axis view of the left ventricle at the level of the papillary muscles was 65 (10)% (n = 14) before xenon. There was no significant change after 5, 10 and 15 min of xenon anaesthesia. Cerebral blood flow velocities were unchanged during the first 5 min of xenon anaesthesia, but were significantly increased in the left and right middle, and the right anterior, cerebral arteries after 15 and 30 min (n = 16) (p < 0.05). In conclusion, xenon anaesthesia had no adverse effect on myocardial function, but probably increased cerebral flood flow.
Xenon is a more potent anesthetic than nitrous oxide, and give 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 = 1) 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 l of xenon (ATPD) was used, of which 5.6-8.1 l 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 for the first 15 min and then about 25 US$ for each subsequent hour of anesthesia.
We have studied recovery of post-tetanic twitch (PTT) and train-of-four (TOF) responses after administration of vecuronium
in 100 patients under different inhalation anaesthetics and neuroleptan-aesthesia. Patients were allocated randomly to five
groups of 20 patients each to receive: neuroleptanaesthesia (droperidol and fentanyl). halothane, isoflurane, enflurane or
sevoflurane (1 MAC in nitrous oxide and oxygen). The times from initial administration of vecuronium 0.2 mg kg−1 to the first appearances of T1, T2, T3 and T4 differed significantly between groups. However, the intervals to the first
appearance of PTT1, PTT10 and PTT20 did not differ significantly between groups. (Br. J. Anaesth. 1993; 70: 402–404)
We compared the effects of xenon (Xe) on the spinal cord dorsal horn neurons with those of nitrous oxide (N2O) in cats anesthetized with chrolarose and urethane. We assessed the potency of both anesthetics by the inhibition of wide dynamic range neuron responses evoked by cutaneous noxious (pinch) stimulation to a hindpaw. During 70% Xe inhalation, the responses of 7 of 11 neurons to pinch stimulation were suppressed. N2O, 70%, suppressed it in 8 of 11 neurons. The potency of Xe and N2O was compared in six neurons that were suppressed by both anesthetics. After 20 min of Xe inhalation, the response to pinch was suppressed to 49.5% +/- 8.2% (mean +/- SE), while N2O, 70% in oxygen, suppressed it to 45.9% +/- 7.9%. The difference between N2O and Xe was not significant. We conclude that Xe and N2O suppress the spinal cord dorsal horn neurons to a similar degree.
Xenon, an inert gas with anesthetic properties (minimum alveolar concentration [MAC] = 71%), has an extremely low blood:gas partition coefficient (0.14). Therefore, we predicted that xenon would provide more rapid emergence from anesthesia than does N2O+isoflurane or N2O+sevoflurane of equivalent MAC.
Thirty American Society of Anesthsiologists class I or II patients undergoing total abdominal hysterectomy were randomly assigned to receive 60% xenon, 60% N2O + 0.5% isoflurane, or 60% N2O + 0.70% sevoflurane (all concentrations are end-tidal: n = 10 per group). After placement of an epidural catheter, anesthesia was induced with standardized doses of midazolam, thiopental, and fentanyl. Thirty minutes later, xenon, N2O+isoflurane, or N2O+sevoflurane was started as previously assigned. These regimens were supplemented with epidural anesthesia with mepivacaine so that the mean arterial pressure and heart rate were controlled within 20% of the preoperative values. At the end of operation lasting approximately 2 h, all inhalational anesthetics were discontinued, and the patients were allowed to awaken while breathing spontaneously on an 8 l/min inflow of oxygen. A blinded investigator recorded the time until the patient opened her eyes on command (T1), was judged ready for extubation (T2), could correctly state her name, her date of birth, and the name of the hospital (T3), and could count backward from 10 to 1 in less than 15 s (T4).
Emergence times from xenon anesthesia were: T1, 3.4 +/- 0.9 min; T2, 3.6 +/- 1 min; T3, 5.2 +/- 1.4 min; and T4, 6.0 +/- 1.6 min (mean +/- SD). These were one half to one third of those from N2O+sevoflurane (T1, 6.0 +/- 1.7 min; T4, 10.5 +/- 2.5 min) or N2O+isoflurane (T1, 7.0 +/- 1.9 min; T4, 14.3 +/- 2.8 min) anesthesia. The three groups did not differ in terms of patient demographics, the duration of anesthesia, the amount of epidural mepivacaine administered, or the postoperative pain rating. No patient could recalls intraoperative events.
Emergence from xenon anesthesia is two or three times faster than that from equal-MAC N2O+isoflurane or N2O+sevoflurane anesthesia.
Unlabelled:
We attempted to clarify the mechanism of antinociceptive action induced by xenon and nitrous oxide. Eighty percent of nitrous oxide or 80% xenon was applied to rats inside enclosed clear plastic glass cylinders with their tails protruding for assessment of the tail-flick response to radiant heat. With repeated testing, there was a rapid reduction to nitrous oxide antinociception within 90 min, which was interpreted as development of tolerance, but not to xenon antinociception. Nitrous oxide antinociception was blocked by the intraperitoneal administration of 0.1 or 1.0 mg/kg yohimbine, but not by 1.0 or 5.0 mg/kg L659-066 or by 5.0 or 10 mg/kg naloxone. Xenon antinociception was not affected by any of these drugs. Yohimbine and L659-066 are characterized as alpha 2-adrenoceptor antagonists. Although yohimbine penetrates the blood-brain barrier after systemic administration, L659-066 does not penetrate it and act peripherally. Therefore, the results indicate that alpha 2-adrenoceptors, but not opioid receptors, may play a key role in antinociception induced by nitrous oxide in the central nervous system. Furthermore, the mechanism of xenon antinociception differs from that of nitrous oxide because it does not involve either alpha 2 or opioid receptors.
Implications:
The precise mechanism of antinociceptive action of nitrous oxide and xenon remains unknown. It is still controversial whether an opioid system plays a role in antinociception induced by nitrous oxide. The results of the study showed that antagonism of central alpha 2-adrenoceptors, but not opioid receptors, reverses the antinociception induced by nitrous oxide but not by xenon, which indicates that alpha 2-adrenoceptors may play a key role in nitrous oxide antinociception.
Xenon is an odorless gas with low blood-gas solubility coefficient and without occupational and environmental hazards. This investigation was performed to evaluate the speed of induction, and respiratory and cardiovascular reactions to inhalation induction with xenon compared to an equianesthetic concentration of sevoflurane.
Twenty-four adult ASA 1-2 patients premedicated with 0.05 mg/kg of midazolam were instructed to take vital capacity breaths of 1 minimum alveolar concentration (MAC) of either xenon or sevoflurane until they lost consciousness. Induction time, total ventilatory volume, tidal volume, respiratory rate, minute ventilation, end-tidal MAC fraction, cardiovascular parameters and oxygen saturation were recorded. The patients were interviewed on the following day to evaluate their acceptability rating of the inhalation inductions.
Compared to equianesthetic sevoflurane, xenon produced a faster induction of anesthesia (147 +/- 59 versus 71 +/- 21 s, respectively) with smaller decreases in respiratory rate, tidal volume and minute ventilation. Both agents showed comparable cardiovascular stability and oxygen saturation during induction. One patient in the sevoflurane group had breath-holding and movements of extremities and another had only breath-holding. No patients in the xenon group experienced any complications.
Xenon produced a faster induction of anesthesia without any complications than sevoflurane. Xenon had smaller decreases in tidal volume and respiratory rate during induction than sevoflurane. Xenon might offer an alternative to sevoflurane for an inhalation induction.
The blood-gas partition coefficients of xenon, reported more than 25 yr ago in the literature, vary considerably from 0.13
to 0.20. Consequently, we have determined this variable by directly injecting xenon-saturated blood into a gas chromatograph-mass
spectrometer. This technique yielded a blood-gas partition coefficient for xenon of 0.115 (95% confidence interval 0.107-0.123).
The solubility in water measured identically was 0.096, consistent with the reported value of 0.085. These data and a detailed
review of the literature strongly suggest that the blood-gas partition coefficient of xenon may be lower than the generally
accepted value of 0.14.
Clinical interest in xenon has been rekindled recently by new recycling systems that have decreased its relative cost. The cardiovascular effects of xenon were examined in isoflurane-anesthetized dogs before and after the development of rapid left ventricular (LV) pacing-induced cardiomyopathy.
Dogs (n = 10) were chronically instrumented to measure aortic and LV pressure, LV subendocardial segment length, and aortic blood flow. Hemodynamics were recorded, and indices of LV systolic and diastolic function and afterload were determined in the conscious state and during 1.5 minimum alveolar concentration isoflurane anesthesia alone and combined with 0.25, 0.42, and 0.55 minimum alveolar concentration xenon in dogs with and without cardiomyopathy.
Administration of xenon to healthy dogs anesthetized with isoflurane decreased heart rate and increased the time constant (tau) of isovolumic relaxation but did not alter arterial and LV pressures, preload recruitable stroke work slope, and indices of LV afterload. Chronic rapid LV pacing increased the baseline heart rate and LV end-diastolic pressure, decreased arterial and LV systolic pressures, and produced LV systolic and diastolic dysfunction. Administration of xenon to isoflurane-anesthetized, cardiomyopathic dogs did not alter heart rate, arterial and LV pressures, myocardial contractility, and indices of early LV filling and regional chamber stiffness. More pronounced increases in tau were accompanied by increases in total arterial resistance during administration of xenon to isoflurane-anesthetized cardiomyopathic compared with healthy dogs.
The results indicate that xenon produces minimal cardiovascular actions in the presence of isoflurane in dogs with and without experimental dilated cardiomyopathy.
Since the discovery that the gas xenon can produce general anaesthesia
without causing undesirable side effects, we have remained surprisingly
ignorant of the molecular mechanisms underlying this clinical activity
of an `inert' gas. Although most general anaesthetics enhance the
activity of inhibitory GABAA (γ-aminobutyric acid
type-A) receptors,, we find that the effects of xenon on these receptors
are negligible. Instead, xenon potently inhibits the excitatory NMDA
(N-methyl-D-aspartate) receptor channels, which may account for many of
xenon's attractive pharmacological properties.
The anesthetic gas xenon has distinctly different physical properties compared with air, nitrous oxide, or oxygen. This led us to predict that xenon would affect the performance of commercially available flowmeters.
Flow was generated by an anesthesia ventilator connected to a lung simulator via a semiclosed breathing circuit. With the system filled with air or with various concentrations of xenon or nitrous oxide in a balance of oxygen, the tidal volume was measured with two rotating vanes, a Pitot tube, a variable-orifice flowmeter, and two constant-temperature hot-wire flowmeters.
Although xenon minimally affected both rotating vane flowmeters, it caused the Pitot tube and the variable-orifice flowmeters to overread in proportion to the square root of the density of the gas mixture used (xenon is 4.6 times more dense than air). In contrast, the hot-wire anemometers underread with xenon; for example, their readings in the presence of 45% and 70% xenon were less than 10% of those displayed when air was used. Nitrous oxide minimally affected all the flowmeters except the variable-orifice device. The Pitot flowmeter was also affected, but only when its gas analyzer port was open to the ambient air so that it no longer corrected its readings for changes in gas composition. In these cases, nitrous oxide produced overreadings in the same manner as did xenon.
Among the four types of flowmeters studied, only the rotating-vane type is sufficiently accurate for use during anesthesia with xenon.
The authors evaluated the hemodynamic suppressive effects of xenon in combination with sevoflurane at skin incision in patients undergoing surgery.
Forty patients were assigned randomly to receive one of the following four anesthetics: 1.3 minimum alveolar concentration (MAC) sevoflurane, 0.7 MAC xenon with 0.6 MAC sevoflurane, 1 MAC xenon with 0.3 MAC sevoflurane, or 0.7 MAC nitrous oxide with 0.6 MAC sevoflurane (n = 10 each group). Systolic blood pressure and heart rate were measured before anesthesia, before incision, and approximately 1 min after incision.
The changes in hemodynamic variables in response to incision were less with sevoflurane in combination with xenon and nitrous oxide than with sevoflurane alone. Changes in heart rate (in beats/min) were 19+/-11 (+/- SD) for sevoflurane alone, 11+/-6 for 0.7 MAC xenon-sevoflurane, 4+/-4 for 1 MAC xenon-sevoflurane, and 8+/-7 for nitrous oxide-sevoflurane. Changes in systolic blood pressure were 35+/-18 mmHg for sevoflurane alone, 18+/-8 mmHg for 0.7 MAC xenon-sevoflurane, 16+/-7 mmHg for 1 MAC xenon-sevoflurane, and 14+/-10 mmHg for nitrous oxide-sevoflurane.
Xenon and nitrous oxide in combination with sevoflurane can reduce hemodynamic responses to skin incision compared with sevoflurane alone. One probable explanation may be that xenon has analgesic properties similar to those of nitrous oxide, although the exact mechanism is yet to be determined.
During nitrous oxide (N2O) elimination, arterial oxygen tension (PaO2) decreases because of the phenomenon commonly called diffusive hypoxia. The authors questioned whether similar effects occur during xenon elimination.
Nineteen anesthetized and paralyzed pigs were mechanically ventilated randomly for 30 min using inspiratory gas mixtures of 30% oxygen and either 70% N2O or xenon. The inspiratory gas was replaced by a mixture of 70% nitrogen and 30% oxygen. PaO2 and carbon dioxide tensions were recorded continuously using an indwelling arterial sensor.
The PaO2 decreased from 119+/-10 mm Hg to 102+/-12 mm Hg (mean+/-SD) during N2O washout (P<0.01) and from 116+/-9 mm Hg to 110+/-8 mm Hg during xenon elimination (P<0.01), with a significant difference (P<0.01) between baseline and minimum PaO2 values (deltaPaO2, 17+/-6 mm Hg during N2O washout and 6+/-3 mm Hg during xenon washout). The PaCO2 value also decreased (from 39.3+/-6.3 mm Hg to 37.6+/-5.8 mm Hg) during N2O washout (P<0.01) and during xenon elimination (from 35.4+/-1.6 mm Hg to 34.9+/-1.6 mm Hg; P< 0.01). The deltaPaCO2 was 1.7+/-0.9 mm Hg in the N2O group and 0.5+/-0.3 mm Hg in the xenon group (P<0.01).
Diffusive hypoxia is unlikely to occur during recovery from xenon anesthesia, probably because of the low blood solubility of this gas.
Unlabelled:
Xenon (Xe) suppresses wide dynamic range neurons in cat spinal cord to a similar extent as nitrous oxide (N2O). The antinociceptive action of N2O involves the descending inhibitory system. To clarify whether the descending inhibitory system is also involved in the antinociceptive action of Xe, we compared the effects of Xe on the spinal cord dorsal horn neurons with those of N2O in spinal cord-transected cats anesthetized with alpha-chloralose and urethane. We investigated the change of wide dynamic range neuron responses to touch and pinch by both anesthetics. Seventy percent Xe significantly suppressed both touch- and pinch-evoked responses in all 12 neurons. In contrast, 70% N2O did not show significant suppression in touch- and pinch-evoked responses. These results suggest that the antinociceptive action of Xe might not be mediated by the descending inhibitory system, but instead may be produced by the direct effect on spinal dorsal horn neurons.
Implications:
Xenon (Xe) is an inert gas with anesthetic properties. We examined the antinociceptive effects of Xe and nitrous oxide (N2O) in spinal cord-transected cats. Our studies indicate that Xe has a direct antinociceptive action on the spinal cord that is greater than that of N2O.
The authors' previous study demonstrated that xenon (Xe) and nitrous oxide (N2O) in combination with sevoflurane can attenuate cardiovascular responses to skin incision. To quantitatively evaluate their suppressive effects on cardiovascular responses, the authors compared the MAC-BAR (minimum alveolar concentration that blocks adrenergic or cardiovascular response to incision) values of sevoflurane when administered with Xe or N2O.
Forty-three patients received sevoflurane with one of three anesthetics; 1 MAC Xe, 0.7 MAC Xe and 0.7 MAC N2O. The MAC-BAR of sevoflurane was determined in each anesthetic using the "up and down" method. The response was considered positive if the heart rate or mean arterial pressure increased 15% or more. The end-tidal sevoflurane concentration given to the next patient was increased or decreased by 0.3 MAC if the response was positive or negative in the previous patient, respectively. The MAC-BAR was calculated as the mean of four independent cross-over responses.
The MAC-BAR of sevoflurane, including the contribution of Xe or N2O, was 2.1+/-0.2 MAC and 2.7+/-0.2 MAC when administered with 1 MAC and 0.7 MAC Xe, respectively, and 2.6+/-0.4 MAC when administered with 0.7 MAC N2O (mean +/- SD).
Although 1 MAC Xe has a more potent suppressive effect on cardiovascular responses to incision than 0.7 MAC Xe or N2O, Xe and N2O have a similar suppressive effect at 0.7 MAC.
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.
To evaluate the suppressive effects of xenon (Xe) on hypnotic arousal at skin incision.
Prospective, randomized study.
Operating rooms at a university hospital.
35 ASA physical status I and II patients presenting for elective lower abdominal surgery.
Patients were randomly assigned to receive one of the following regimens: 1.3 minimum alveolar concentration (MAC) isoflurane, 1.3 MAC sevoflurane, 0.7 MAC Xe with 0.6 MAC sevoflurane, 1 MAC Xe with 0.3 MAC sevoflurane, or 0.7 MAC nitrous oxide (N2O) with 0.6 MAC sevoflurane (n = 7 each group).
The bispectral index (BIS) was measured at baseline, during anesthesia, and after skin incision. BIS increased significantly at skin incision from the values noted during anesthesia in the sevoflurane and N2O groups, whereas it remained stable at incision in the other three groups (mean change in BIS: 0 +/- 9 for isoflurane, 15 +/- 8 for sevoflurane, 5 +/- 6 for 0.7 MAC Xe, 4 +/- 11 for 1 MAC Xe, and 9 +/- 5 for N2O).
Unlike N2O, Xe was able to suppress hypnotic arousal in response to surgical stimulation when administered with sevoflurane.
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.
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.
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.
The authors conclude that xenon does not trigger malignant hyperthermia in susceptible swine.
In previous studies, cytochrome P450 monooxygenases were shown to be appropriately sensitive to structurally diverse compounds varying widely in anesthetic potencies and to increasing carbon-number series of straight chain primary and secondary alcohols and rigid cyclic alcohols. We now report that xenon and nitrous oxide, at one atmosphere, occupy the P450 heme cavity and competitively inhibit catalytic activity. The heme enzymes appear to be the most relevant model of the site of general anesthesia, thus far identified.
Because of its high density and viscosity, xenon (Xe) may influence respiratory mechanics when used as an inhaled anesthetic. Therefore the authors studied respiratory mechanics during xenon and nitrous oxide (N2O) anesthesia before and during methacholine-induced bronchoconstriction.
Sixteen pentobarbital-anesthetized pigs initially were ventilated with 70% nitrogen-oxygen. Then they were randomly assigned to a test period of ventilation with either 70% xenon-oxygen or 70% N2O-oxygen (n = 8 for each group). Nitrogen-oxygen ventilation was then resumed. Tidal volume and inspiratory flow rate were set equally throughout the study. During each condition the authors measured peak and mean airway pressure (Pmax and Pmean) and airway resistance (R(aw)) by the end-inspiratory occlusion technique. This sequence was then repeated during a methacholine infusion.
Both before and during methacholine airway resistance was significantly higher with xenon-oxygen (4.0 +/- 1.7 and 10.9 +/- 3.8 cm H2O x s(-1) x 1(-1), mean +/- SD) when compared to nitrogen-oxygen (2.6 +/- 1.1 and 5.8 +/- 1.4 cm H2O x s(-1) x l(-1), P < 0.01) and N2O-oxygen (2.9 +/- 0.8 and 7.0 +/- 1.9, P < 0.01). Pmax and Pmean did not differ before bronchoconstriction, regardless of the inspired gas mixture. During bronchoconstriction Pmax and Pmean both were significantly higher with xenon-oxygen (Pmax, 33.1 +/- 5.5 and Pmean, 11.9 +/- 1.6 cm H2O) when compared to N2O-oxygen (28.4 +/- 5.7 and 9.5 +/- 1.6 cm H2O, P < 0.01) and nitrogen-oxygen (28.0 +/- 4.4 and 10.6 +/- 1.3 cm H2O, P < 0.01).
Airway pressure and resistance are increased during xenon anesthesia. This response is moderate and not likely to assume major importance for the general use of xenon in anesthesia.
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.
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.
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.
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.
The noble gas xenon (Xe) has been used as an inhalational anesthetic agent in clinical trials with little or no physiologic side effects. Like nitrous oxide, Xe is believed to exert minimal unwanted cardiovascular effects, and like nitrous oxide, the vapor concentration to achieve 1 minimum alveolar concentration (MAC) for Xe in humans is high, i.e., 70-80%. In the current study, concentrations of up to 80% Xe were examined for possible myocardial effects in isolated, erythrocyte-perfused guinea pig hearts and for possible effects on altering major cation currents in isolated guinea pig cardiomyocytes.
Isolated guinea pigs hearts were perfused at 70 mm Hg via the Langendorff technique initially with a salt solution at 37 degrees C. Hearts were then perfused with fresh filtered (40-microm pore) and washed canine erythrocytes diluted in the salt solution equilibrated with 20% O2 in nitrogen (control), with 20% O2, 40% Xe, and 40% N2, (0.5 MAC), or with 20% O2 and 80% Xe (1 MAC), respectively. Hearts were perfused with 80% Xe for 15 min, and bradykinin was injected into the blood perfusate to test endothelium-dependent vasodilatory responses. Using the whole-cell patch-clamp technique, 80% Xe was tested for effects on the cardiac ion currents, the Na+, the L-type Ca2+, and the inward-rectifier K+ channel, in guinea pig myocytes suffused with a salt solution equilibrated with the same combinations of Xe, oxygen, and nitrogen as above.
In isolated hearts, heart rate, atrioventricular conduction time, left ventricular pressure, coronary flow, oxygen extraction, oxygen consumption, cardiac efficiency, and flow responses to bradykinin were not significantly (repeated measures analysis of variance, P>0.05) altered by 40% or 80% Xe compared with controls. In isolated cardiomyocytes, the amplitudes of the Na+, the L-type Ca2+, and the inward-rectifier K+ channel over a range of voltages also were not altered by 80% Xe compared with controls.
Unlike hydrocarbon-based gaseous anesthetics, Xe does not significantly alter any measured electrical, mechanical, or metabolic factors, or the nitric oxide-dependent flow response in isolated hearts, at least partly because Xe does not alter the major cation currents as shown here for cardiac myocytes. The authors' results indicate that Xe, at approximately 1 MAC for humans, has no physiologically important effects on the guinea pig heart.
We have investigated the effects of xenon on regional cerebral blood flow (rCBF) and autoregulation in pigs sedated with propofol
4 mg kg-1 h-1. Balloon-tipped catheters were placed into the descending aorta and inferior vena cava of 15 Göttingen Minipigs
for manipulation of arterial pressure and blood sampling. rCBF was measured using the sagittal sinus outflow technique. Xenon
was adjusted randomly to end-tidal fractions (FE'Xe) of 0, 0.30, 0.50 and 0.70. After baseline measurements of heart rate
(HR), mean arterial pressure (MAP), rCBF, sagittal sinus pressure (SSP) and calculation of regional cerebrovascular resistance
(rCVR) at each respective FE'Xe, autoregulation was tested in the MAP range 60-120 mm Hg. Increasing FE'Xe had no effect on
HR, MAP, rCBF or SSP. rCVR increased with increases in MAP, regardless of FE'Xe. Autoregulation was not impaired. We conclude
that xenon inhalation had no effect on rCBF and autoregulation in our model, which could suggest that xenon is an adequate
adjunct for neurosurgical anaesthesia.
How much does xenon anesthesia cost ?
- Y Nakata
- T Goto
- K Terui
- S Takada
- Morita
Nakata Y, Goto T, Terui K, Takada S, Morita S. How much does xenon anesthesia cost ? Anesthesiology 1999 ; 91 : A1231.