Search

Background: The anaesthetic xenon shows potent organ-protective properties. Due to high density and dynamic viscosity, peak inspiratory pressure (P max ) increases during xenon application. Thus, barotrauma may counteract organ protection. Accordingly, we investigated the influence of xenon on lung mechanics and lung aeration in patients with normal and reduced thoracic wall compliance., Methods: After registration and ethical approval, 20 patients free of pulmonary disease undergoing routine xenon-based anaesthesia were mechanically ventilated. The primary outcome variable transpulmonary pressure (P tp ) was determined from plateau pressure and intraoesophageal pressure before and after xenon wash-in. We recorded P max , and calculated airway resistance (R AW ), and static (C stat ) and dynamic (C dyn ) respiratory compliances. Finally, lung aeration was quantified by electrical impedance tomography-derived centre of ventilation index (CVI) and global inhomogeneity index (GI) in the awake state, before and during xenon., Results: Xenon increased P max [20.8 (SD 3) vs 22.6 (3) cm H 2 O, P<0.001] and R AW [0.9 (0.2) vs 1.4 (0.3) cm H 2 O litre -1  s, P<0.001], without affecting P tp [1.5 (4) vs 2.0 (4) cm H 2 O, P=0.15]. While C stat remained unchanged, C dyn was reduced [33.9 (7) vs 31.2 (6) ml (cm H 2 O) -1 , P<0.001). A ventral tidal volume shift after anaesthesia induction [CVI 0.53 (0.03) vs 0.59 (0.04), P<0.001] was unaltered during xenon [CVI 0.59 (0.04), P=0.29]. Homogeneity of lung aeration was also unchanged during xenon [GI 0.37 (0.03) vs 0.37 (0.03), P=0.99]. There were no clinically meaningful differential BMI-related effects., Conclusions: Xenon increases calculated airway resistance and peak inspiratory pressure without affecting transpulmonary pressure, independent of BMI., Clinical Trial Registration: NCT02682758., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Postoperative delirium occurs frequently in elderly hip fracture surgery patients and is associated with poorer overall outcomes. Because xenon anaesthesia has neuroprotective properties, we evaluated its effect on the incidence of delirium and other outcomes after hip fracture surgery., Methods: This was a phase II, multicentre, randomized, double-blind, parallel-group, controlled clinical trial conducted in hospitals in six European countries (September 2010 to October 2014). Elderly (≥75yr-old) and mentally functional hip fracture patients were randomly assigned 1:1 to receive either xenon- or sevoflurane-based general anaesthesia during surgery. The primary outcome was postoperative delirium diagnosed through postoperative day 4. Secondary outcomes were delirium diagnosed anytime after surgery, postoperative sequential organ failure assessment (SOFA) scores, and adverse events (AEs)., Results: Of 256 enrolled patients, 124 were treated with xenon and 132 with sevoflurane. The incidence of delirium with xenon (9.7% [95% CI: 4.5 -14.9]) or with sevoflurane (13.6% [95% CI: 7.8 -19.5]) were not significantly different (P=0.33). Overall SOFA scores were significantly lower with xenon (least-squares mean difference: -0.33 [95% CI: -0.60 to -0.06]; P=0.017). For xenon and sevoflurane, the incidence of serious AEs and fatal AEs was 8.0% vs 15.9% (P=0.05) and 0% vs 3.8% (P=0.06), respectively., Conclusions: Xenon anaesthesia did not significantly reduce the incidence of postoperative delirium after hip fracture surgery. Nevertheless, exploratory observations concerning postoperative SOFA-scores, serious AEs, and deaths warrant further study of the potential benefits of xenon anaesthesia in elderly hip fracture surgery patients., Clinical Trial Registration: EudraCT 2009-017153-35; ClinicalTrials.gov NCT01199276., (Copyright © 2017. Published by Elsevier Ltd.)

Xenon is a modern inhalative anaesthetic with a very low solubility in tissues providing rapid elimination and weaning from anaesthesia. Besides its anaesthetic properties, Xenon promotes the endogenous erythropoietin biosynthesis and thus has been enlisted as prohibited substance by the World Anti-Doping Agency (WADA). For effective doping controls, knowledge about the elimination kinetics of Xenon and the duration of traceability are of particular importance. Seventy-seven full blood samples were obtained from 7 normal weight patients undergoing routine Xenon-based general anaesthesia with a targeted inspiratory concentration of 60% Xenon in oxygen. Samples were taken before and during Xenon inhalation as well as one, two, 4, 8, 16, 24, 32, 40, and 48 h after exposure. Xenon concentrations were assessed in full blood by gas chromatography and triple quadrupole tandem mass spectrometry with a detection limit of 0.25 µmol/L. The elimination of Xenon was characterized by linear regression of log-transformed Xenon blood concentrations, as well as non-linear regression. Xenon exposure yielded maximum concentrations in arterial blood of 1.3 [1.1; 1.6] mmol/L. Xenon was traceable for 24 to 48 h. The elimination profile was characterized by a biphasic pattern with a rapid alpha phase, followed by a slower beta phase showing a first order kinetics (c[Xe] = 69.1e -0.26x , R 2  = 0.83, t 1/2  = 2.7 h). Time in hours after exposure could be estimated by 50*ln(1.39/c[Xe] 0.077 ). Xenon's elimination kinetics is biphasic with a delayed beta phase following a first order kinetics. Xenon can reliably be detected for at least 24 h after brief exposure. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Impaired cardiac repolarization, indicated by prolonged QT interval, may cause critical ventricular arrhythmias. Many anesthetics increase the QT interval by blockade of rapidly acting potassium rectifier channels. Although xenon does not affect these channels in isolated cardiomyocytes, the authors hypothesized that xenon increases the QT interval by direct and/or indirect sympathomimetic effects. Thus, the authors tested the hypothesis that xenon alters the heart rate-corrected cardiac QT (QTc) interval in anesthetic concentrations., Methods: The effect of xenon on the QTc interval was evaluated in eight healthy volunteers and in 35 patients undergoing abdominal or trauma surgery. The QTc interval was recorded on subjects in awake state, after their denitrogenation, and during xenon monoanesthesia (FetXe > 0.65). In patients, the QTc interval was recorded while awake, after anesthesia induction with propofol and remifentanil, and during steady state of xenon/remifentanil anesthesia (FetXe > 0.65). The QTc interval was determined from three consecutive cardiac intervals on electrocardiogram printouts in a blinded manner and corrected with Bazett formula., Results: In healthy volunteers, xenon did not alter the QTc interval (mean difference: +0.11 ms [95% CI, -22.4 to 22.7]). In patients, after anesthesia induction with propofol/remifentanil, no alteration of QTc interval was noted. After propofol was replaced with xenon, the QTc interval remained unaffected (417 ± 32 ms vs. awake: 414 ± 25 ms) with a mean difference of 4.4 ms (95% CI, -4.6 to 13.5)., Conclusion: Xenon monoanesthesia in healthy volunteers and xenon/remifentanil anesthesia in patients without clinically relevant cardiovascular disease do not increase QTc interval.

Background: In contrast to volatile anaesthetics, xenon acts by antagonism at N-methyl-d-aspartate receptors and antagonizes 5-hydroxytryptamine type 3 receptors that mediate nausea and vomiting. Therefore, it is unknown whether the same risk factors for postoperative nausea and vomiting (PONV) after volatile anaesthetics apply to xenon-based anaesthesia., Methods: With ethics committee approval and written informed consent, 502 consecutive patients undergoing xenon-based anaesthesia were included in a multicentre prospective observational study. Antiemetic prophylaxis was administered at the discretion of the attending anaesthetists. Postoperative nausea and vomiting and need for antiemetic rescue medication were assessed for 24 h after anaesthesia. Multivariate logistic regression analysis was performed to quantify risk factors for PONV and need for rescue medication., Results: Four hundred and eighty-eight subjects were available for the final analysis. The incidence of PONV in subjects without prophylaxis was lower than expected according to the Apfel Score (28% observed; 42% expected, P<0.001). Independent predictors for PONV were (adjusted odds ratio; 95% confidence interval) female sex (1.76; 1.08-2.89), younger patient age (0.82 per 10 yr; 0.69-0.97), and longer duration of anaesthesia (1.36 per hour; 1.17-1.59)., Conclusions: The incidence of PONV was significantly lower than predicted by the Apfel Score. Female sex, younger age, and longer duration of anaesthesia are risk factors for PONV after xenon-based anaesthesia., Clinical Trial Registration: German Federal Institute for Drugs and Medical Devices number AL-PMS-01/07GER., (© The Author 2015. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Intraoperative hypotension is associated with increased risk of perioperative complications. The N-methyl-d-aspartate (NMDA) receptor (NMDA-R) antagonist xenon (Xe) induces general anaesthesia without impairment of cardiac output and vascular resistance. Mechanisms involved in cardiovascular stability have not been identified., Methods: Muscle sympathetic activity (MSA) (microneurography), sympathetic baroreflex gain, norepinephrine (NE) plasma concentration (high-performance liquid chromatography), anaesthetic depth (Narcotrend(®) EEG monitoring), and vital parameters were analysed in vivo during Xe mono-anaesthesia in human volunteers (n=8). In vitro, NE transporter (NET) expressing HEK293 cells and SH-SY5Y neuroblastoma cells were pre-treated with ketamine, MK-801, NMDA/glycine, or vehicle. Subsequently, cells were incubated with or without Xe (65%). NE uptake was measured by using a fluorescent NET substrate (n=4) or [(3)H]NE (n=6)., Results: In vivo, Xe anaesthesia increased mean (standard deviation) arterial pressure from 93 (4) to 107 (6) mm Hg and NE plasma concentration from 156 (55) to 292 (106) pg ml(-1), P<0.01. MSA and baroreflex gain were unaltered. In vitro, ketamine decreased NET activity (P<0.01) in NET-expressing HEK293 cells, while Xe, MK-801, and NMDA/glycine did not. Xe reduced uptake in SH-SY5Y cells expressing NET and NMDA-Rs (P<0.01). MK-801 (P<0.01) and ketamine (P<0.01) also reduced NET activity, but NMDA/glycine blocked the effect of Xe on [(3)H]NE uptake., Conclusions: In vivo, Xe anaesthesia does not alter sympathetic activity and baroreflex gain, despite increased mean arterial pressure. In vitro, Xe decreases the uptake of NE in neuronal cells by the inhibition of NET. This inhibition might be related to NMDA-R antagonism and explain increased NE concentrations at the synaptic cleft and in plasma, contributing to cardiovascular stability during Xe anaesthesia.