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Background: Renal dysfunction following intraoperative arterial hypotension is mainly caused by an insufficient renal blood flow. It is associated with higher mortality and morbidity rates. We hypothesised that the intraoperative haemodynamics are more stable during xenon anaesthesia than during isoflurane anaesthesia in patients undergoing partial nephrectomy., Methods: We performed a secondary analysis of the haemodynamic variables collected during the randomised, single-blinded, single-centre PaNeX study, which analysed the postoperative renal function in 46 patients who underwent partial nephrectomy. The patients received either xenon or isoflurane anaesthesia with 1:1 allocation ratio. We analysed the duration of the intraoperative systolic blood pressure decrease by > 40% from baseline values and the cumulative duration of a mean arterial blood pressure (MAP) of < 65 mmHg as primary outcomes. The secondary outcomes were related to other blood pressure thresholds, the amount of administered norepinephrine, and the analysis of confounding factors on the haemodynamic stability., Results: The periods of an MAP of < 65 mmHg were significantly shorter in the xenon group than in the isoflurane group. The medians [interquartile range] were 0 [0-10.0] and 25.0 [10.0-47.5] minutes, for the xenon and isoflurane group, respectively (P = 0.002). However, the cumulative duration of a systolic blood pressure decrease by > 40% did not significantly differ between the groups (P = 0.51). The periods with a systolic blood pressure decrease by 20% from baseline, MAP decrease to values < 60 mmHg, and the need for norepinephrine, as well as the cumulative dose of norepinephrine were significantly shorter and lower, respectively, in the xenon group. The confounding factors, such as demographic data, surgical technique, or anaesthesia data, were similar in the two groups., Conclusion: The patients undergoing xenon anaesthesia showed a better haemodynamic stability, which might be attributed to the xenon properties. The indirect effect of xenon anaesthesia might be of importance for the preservation of renal function during renal surgery and needs further elaboration., Trial Registration: ClinicalTrials.gov : NCT01839084. Registered 24 April 2013.

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.)

Background: Ischemic myocardial damage accompanying coronary artery bypass graft surgery remains a clinical challenge. We investigated whether xenon anesthesia could limit myocardial damage in coronary artery bypass graft surgery patients, as has been reported for animal ischemia models., Methods: In 17 university hospitals in France, Germany, Italy, and The Netherlands, low-risk elective, on-pump coronary artery bypass graft surgery patients were randomized to receive xenon, sevoflurane, or propofol-based total intravenous anesthesia for anesthesia maintenance. The primary outcome was the cardiac troponin I concentration in the blood 24 h postsurgery. The noninferiority margin for the mean difference in cardiac troponin I release between the xenon and sevoflurane groups was less than 0.15 ng/ml. Secondary outcomes were the safety and feasibility of xenon anesthesia., Results: The first patient included at each center received xenon anesthesia for practical reasons. For all other patients, anesthesia maintenance was randomized (intention-to-treat: n = 492; per-protocol/without major protocol deviation: n = 446). Median 24-h postoperative cardiac troponin I concentrations (ng/ml [interquartile range]) were 1.14 [0.76 to 2.10] with xenon, 1.30 [0.78 to 2.67] with sevoflurane, and 1.48 [0.94 to 2.78] with total intravenous anesthesia [per-protocol]). The mean difference in cardiac troponin I release between xenon and sevoflurane was -0.09 ng/ml (95% CI, -0.30 to 0.11; per-protocol: P = 0.02). Postoperative cardiac troponin I release was significantly less with xenon than with total intravenous anesthesia (intention-to-treat: P = 0.05; per-protocol: P = 0.02). Perioperative variables and postoperative outcomes were comparable across all groups, with no safety concerns., Conclusions: In postoperative cardiac troponin I release, xenon was noninferior to sevoflurane in low-risk, on-pump coronary artery bypass graft surgery patients. Only with xenon was cardiac troponin I release less than with total intravenous anesthesia. Xenon anesthesia appeared safe and feasible.

Background: Perioperative preservation of renal function has a significant impact on morbidity and mortality in kidney surgery. Nephroprotective effects of the anesthetic xenon on ischemia-reperfusion injury were found in several experimental studies., Objective: We aimed to explore whether xenon anesthesia can reduce renal damage in humans undergoing partial nephrectomy and to gather pilot data of possible nephroprotection in these patients., Design: A prospective randomized, single-blinded, controlled study., Setting: Single-center, University Hospital of Aachen, Germany between July 2013-October 2015., Patients: Forty-six patients with regular renal function undergoing partial nephrectomy., Interventions: Patients were randomly assigned to receive xenon- (n = 23) or isoflurane (n = 23) anesthesia., Main Outcome Measures: Primary outcome was the maximum postoperative glomerular filtration rate (GFR) decline within seven days after surgery. Secondary outcomes included intraoperative and tumor-related data, assessment of further kidney injury markers, adverse events and optional determination of renal function after 3-6 months., Results: Unexpected radical nephrectomy was performed in 5 patients, thus they were excluded from the per-protocol analysis, but included in the intention-to-treat analysis. The maximum postoperative GFR decline was attenuated by 45% in the xenon-group (10.9 ml min-1 1.73 cm-2 versus 19.7 ml min-1 1.73 cm-2 in the isoflurane group), but without significance (P = 0.084). Occurrence of adverse events was reduced (P = 0.003) in the xenon group. Renal function was similar among the groups after 3-6 months., Conclusion: Xenon anesthesia was feasible and safe in patients undergoing partial nephrectomy with regard to postoperative renal function. We found no significant effect on early renal function but less adverse events in the xenon group. Larger randomized controlled studies in more heterogeneous collectives are required, to confirm or refute the possible clinical benefit on renal function by xenon., Trial Registration: ClinicalTrials.gov NCT01839084 and EudraCT 2012-005698-30.

Background: The licensed anesthetic xenon, which exerts organ protective properties, was recently added by the World Anti-Doping Agency to the list of prohibited substances. Xenon is supposed to trigger the production of hypoxia-inducible factor 1α (HIF-1α) and subsequently erythropoietin, but data are limited to in vivo experimental work. Therefore we evaluated the effect of xenon on erythropoietin levels in healthy persons., Methods: Twenty-four healthy volunteers were randomly assigned either to a group spontaneously breathing xenon 30 % (Xe/O 2 30 %/60 %) or a group breathing control gas (N 2 /O 2 40 %/60 %) for 45 min. Primary outcome parameters were erythropoietin levels at several time-points after exposure. Secondary outcome parameters were serum levels of testosterone, cytokines, and growth factors as well as concentrations of xenon in blood and exhalation samples measured at several time-points after exposure. In addition, hemodynamic safety parameters were monitored during exposure., Results: The administration of xenon significantly increased erythropoietin levels 8 h after exposure (1.34 [±0.368]; p = 0.008), peaking at 24 h compared to the baseline values (1.45 [±0.498]; p = 0.01) and remained traceable in blood and exhalation probes until 24 h after exposure. In contrast, no significant change was observed in the control group. Measurement of stromal cell-derived factor 1 (SDF-1) revealed a significant increase of SDF-1 levels (p = 0.005), whereas no differences were observed with respect to growth factors, cytokines, or androgens. In an in vitro chemotaxis assay, endothelial progenitor cells (EPCs) showed a trend towards increased migration in serum samples received from participants after xenon exposure (p = 0.080)., Conclusion: The present study presents first evidence about a xenon-induced effect on increased erythropoietin levels in healthy volunteers. The study was registered at the European Medicines Agency (EudraCT-number: 2014-000973-38) and at ClinicalTrials.gov (NCT number: 02129400).

Objective: Like other inhalational anesthetics xenon seems to be associated with post-operative nausea and vomiting (PONV). We assessed nausea incidence following balanced xenon anesthesia compared to sevoflurane, and dexamethasone for its prophylaxis in a randomized controlled trial with post-hoc explorative analysis., Methods: 220 subjects with elevated PONV risk (Apfel score ≥2) undergoing elective abdominal surgery were randomized to receive xenon or sevoflurane anesthesia and dexamethasone or placebo after written informed consent. 93 subjects in the xenon group and 94 subjects in the sevoflurane group completed the trial. General anesthesia was maintained with 60% xenon or 2.0% sevoflurane. Dexamethasone 4mg or placebo was administered in the first hour. Subjects were analyzed for nausea and vomiting in predefined intervals during a 24h post-anesthesia follow-up., Results: Logistic regression, controlled for dexamethasone and anesthesia/dexamethasone interaction, showed a significant risk to develop nausea following xenon anesthesia (OR 2.30, 95% CI 1.02-5.19, p = 0.044). Early-onset nausea incidence was 46% after xenon and 35% after sevoflurane anesthesia (p = 0.138). After xenon, nausea occurred significantly earlier (p = 0.014), was more frequent and rated worse in the beginning. Dexamethasone did not markedly reduce nausea occurrence in both groups. Late-onset nausea showed no considerable difference between the groups., Conclusion: In our study setting, xenon anesthesia was associated with an elevated risk to develop nausea in sensitive subjects. Dexamethasone 4mg was not effective preventing nausea in our study. Group size or dosage might have been too small, and change of statistical analysis parameters in the post-hoc evaluation might have further contributed to a limitation of our results. Further trials will be needed to address prophylaxis of xenon-induced nausea., Trial Registration: EU Clinical Trials EudraCT-2008-004132-20 ClinicalTrials.gov NCT00793663.

Introduction: Cardiac surgery encompasses various stimuli that trigger pro-inflammatory mediators, reactive oxygen species and mobilization of leucocytes. The aim of this study was to evaluate the effect of xenon on the inflammatory response during cardiac surgery., Methods: This randomized trial enrolled 30 patients who underwent elective on-pump coronary-artery bypass grafting in balanced anaesthesia of either xenon or sevoflurane. For this secondary analysis, blood samples were drawn prior to the operation, intra-operatively and on the first post-operative day to measure the pro- and anti-inflammatory cytokines interleukin-6 (IL-6), interleukin-8/C-X-C motif ligand 8 (IL-8/CXCL8), and interleukin-10 (IL-10). Chemokines such as C-X-C motif ligand 12/ stromal cell-derived factor-1α (CXCL12/SDF-1α) and macrophage migration inhibitory factor (MIF) were measured to characterize xenon's perioperative inflammatory profile and its impact on migration of peripheral blood mononuclear cells (PBMC)., Results: Xenon enhanced the postoperative increase of IL-6 compared to sevoflurane (Xenon: 90.7 versus sevoflurane: 33.7 pg/ml; p = 0.035) and attenuated the increase of IL-10 (Xenon: 127.9 versus sevoflurane: 548.3 pg/ml; p = 0.028). Both groups demonstrated a comparable intraoperative increase of oxidative stress (intra-OP: p = 0.29; post-OP: p = 0.65). While both groups showed an intraoperative increase of the cardioprotective mediators MIF and CXCL12/SDF-1α, only MIF levels decreased in the xenon group on the first postoperative day (50.0 ng/ml compared to 23.3 ng/ml; p = 0.012), whereas it remained elevated after sevoflurane anaesthesia (58.3 ng/ml to 53.6 ng/ml). Effects of patients' serum on chemotactic migration of peripheral mononuclear blood cells taken from healthy volunteers indicated a tendency towards enhanced migration after sevoflurane anaesthesia (p = 0.07)., Conclusions: Compared to sevoflurane, balanced xenon anaesthesia triggers pro-inflammatory effects and suppresses the anti-inflammatory response in cardiac surgery patients even though the clinical significance remains unknown., Trial Registration: This clinical trial was approved by the European Medicines Agency (EudraCT-number: 2010-023942-63) and at ClinicalTrials.gov ( NCT01285271 ; first received: January 24, 2011).

Background: While most anaesthetics are known to suppress immune reactions, data from experimental studies indicate the enhancement of reactivity to inflammatory stimulators under xenon treatment. We investigated the effect of xenon anaesthesia on leucocyte function in surgical patients., Methods: We performed a subgroup analysis of subjects undergoing xenon or sevoflurane anaesthesia in a randomized clinical trial. After oral premedication with midazolam, two separate blood samples were obtained from subjects undergoing elective abdominal surgery, directly before and 1 h after induction of anaesthesia. General anaesthesia was maintained with either 60% xenon or 2.0% sevoflurane in 30% O2. Leucocyte count, phagocytotic function, and pro-inflammatory cytokine release after ex vivo lipopolysaccharide (LPS) stimulation were determined., Results: Except for lymphocyte numbers, leucocyte subpopulations did not differ between the groups. Phagocytosis and oxidative burst of granulocytes were reduced in both groups after 1 h of anaesthesia, whereas monocytes were not affected. Pro-inflammatory cytokine release in response to LPS was not affected., Conclusions: In vivo, xenon and sevoflurane anaesthesia did not have a pro-inflammatory effect, at least in combination with the types of surgery performed in this study. Notably, the impact of xenon anaesthesia did not differ significantly from sevoflurane anaesthesia with regard to leucocyte function. However, an underestimation of treatment effects due to limited sample sizes cannot be fully excluded.

Background: To date, only limited data exist about the use of xenon as an anaesthetic agent in patients undergoing cardiac surgery. The favourable cardio- and neuroprotective properties of xenon might attenuate postoperative complications, improve outcome, and reduce the incidence of delirium. Thus, the aims of this study were to investigate the feasibility and safety of balanced xenon anaesthesia in patients undergoing cardiac surgery and to gather pilot data for a future randomized multicentre study., Methods: Thirty patients undergoing elective coronary artery bypass grafting were enrolled in this randomized, single-blind controlled trial. They were randomized to receive balanced general anaesthesia with either xenon (45-50 vol%) or sevoflurane (1-1.4 vol%). The primary outcome was the occurrence of adverse events (AEs). Secondary outcome parameters were feasibility criteria (bispectral index, perioperative haemodynamic, and respiratory profile) and safety parameters (dosage of study treatments, renal function, intraoperative blood loss, need for inotropic support, regional cerebral tissue oxygenation). Furthermore, at predefined time points, systemic and pulmonary haemodynamics were assessed by the use of a pulmonary artery catheter., Results: There were no patient characteristic differences between the groups. Patients undergoing xenon anaesthesia did not differ with respect to the incidence of AE (6 vs 8, P=0.464) compared with the sevoflurane group. No differences were detected regarding secondary feasibility and safety criteria. The haemodynamic and respiratory profile was comparable between the treatment groups., Conclusions: Balanced xenon anaesthesia is feasible and safe compared with sevoflurane anaesthesia in patients undergoing coronary artery bypass surgery. Acronym CARDIAX: A pre- and post-coronary artery bypass graft implantation disposed application of xenon. Clinical trial registration ClinicalTrials.gov: NCT01285271; EudraCT-number: 2010-023942-63. Approved by the ethics committee 'Ethik-Kommission an der Medizinischen Fakultät der Rheinisch-Westfälischen Technischen Hochschule Aachen (RWTH Aachen)': EK-218/10.

Background: Xenon and isoflurane are known to have cardioprotective properties. We tested the hypothesis that these anesthetics positively influence myocardial remodeling 28 days after experimental perioperative myocardial infarction and compared their effects., Methods: A total of 60 male Sprague-Dawley rats were subjected to 60 min of coronary artery occlusion and 120 min of reperfusion. Prior to ischemia, the animals were randomized for the different narcotic regimes (0.6 vol% isoflurane, 70 vol% xenon, or intraperitoneal injection of s-ketamine). Acute injury was quantified by echocardiography and troponin I. After 4 weeks, left ventricular function was assessed by conductance catheter to quantify hemodynamic compromise. Cardiac remodeling was characterized by quantification of dilatation, hypertrophy, fibrosis, capillary density, apoptosis, and expression of fetal genes (α/β myosin heavy chains, α-skeletal actin, periostin, and sarco/endoplasmic reticulum Ca2+-ATPase)., Results: Whereas xenon and isoflurane impeded the acute effects of ischemia-reperfusion on hemodynamics and myocardial injury at a comparable level, differences were found after 4 weeks. Xenon in contrast to isoflurane or ketamine anesthetized animals demonstrated a lower remodeling index (0.7 ± 0.1 vs. 0.9 ± 0.3 and 1.0 ± 0.3g/ml), better ejection fraction (62 ± 9 vs. 49 ± 7 and 35 ± 6%), and reduced expression of β-myosin heavy chain and periostin. The effects on hypertrophy, fibrosis, capillary density, and apoptosis were comparable., Conclusions: Compared to isoflurane and s-ketamine, xenon limited progressive adverse cardiac remodeling and contractile dysfunction 28 days after perioperative myocardial infarction.

Volatile anaesthetics can reduce the infarction size in myocardial tissue when administered before and during experimentally induced ischaemia. The aim of this study was to investigate whether xenon is beneficial compared to isoflurane in limiting myocardial tissue apoptosis and inflammation induced by experimental ischaemia-reperfusion injury in a porcine right ventricular infarction model. Twenty-one animals used for this study randomly received isoflurane, xenon or thiopental, (n=6-8 per group). Myocardial infarction was induced for 90min, followed by reperfusion for 120min. Tissues from the left and right ventricles were removed from the sites of infarction, reperfusion and remote areas, and processed for immunohistochemistry. Apoptosis (caspase-3 staining) and neutrophilic infiltration (naphthol AS-D chloroacetate-specific esterase) were assessed and evaluated. Statistical analysis was performed using an ANOVA of repeated measures. Density of apoptotic cells were higher in tissues from animals that were anesthetized with xenon. This effect was significant in comparison to isoflurane (p=0.0177). Neutrophilic infiltration was significantly higher in the right compared to the left ventricle (p<0.001), whereas no significant differences in the number of granulocytes based on the anaesthetic regime or the different tissue areas were found. We conclude that xenon, in the early phase of ischaemia and reperfusion, induces a significant increase in apoptosis compared to isoflurane. Therefore, clinical use of this anaesthetic in cardiocompromised patients should be taken with care until more long-term studies have been carried out. The increased neutrophilic infiltration in the right vs. the left ventricle indicates the right ventricle being more susceptible to ischaemia-reperfusion injury., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

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

Background: Acute right ventricular afterload increase is a known perioperative challenge for the anaesthetic regime especially for patients with a compromised right ventricle. The accused negative inotropic action of volatile anaesthetics, with the exception of xenon, might be crucial for the adaptation of the right ventricle., Methods: Reversible pulmonary hypertension (mean pressure 40 mmHg) was induced by an infusion of the stable thromboxane A(2) analog U46619 in a porcine model (n = 35). The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were studied by conductance catheter technique. Inflammation and myocardial injury was quantified using serum probes [tumour necrosis factor α (TNFα), interleukin 6 (IL-6), troponin] and myocardial tissue [B natriuretic peptide (BNP), TNFα, activated caspase 3] by enzyme-linked immunosorbance assays and reverse-transcription polymerase chain reaction., Results: After wash in of xenon global haemodynamic parameters remained stable whereas isoflurane caused a systemic vasodilation. This led to a significant decrease in mean arterial pressure in the isoflurane group whereas cardiac output remained stable. Both substances did not alter the biventricular contractility nor did they induce changes in preload for both ventricles. Xenon led to an additional increase in right ventricular afterload, whereas isoflurane reduced pulmonary vascular resistance. No effects on systemic inflammatory response and myocardial injury were found, whereas higher apoptosis rate and expression of BNP and IL-6 was determined in the right ventricle., Conclusions: These results do not support the idea that xenon is more beneficial than isoflurane in right ventricular failure during pulmonary hypertension. Isoflurane did not compromise systolic ventricular function during acute PHT it only led to vasodilation in contrast to xenon., (© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta Anaesthesiologica Scandinavica Foundation.)

Objective: Despite the introduction of mild therapeutic hypothermia into postcardiac arrest care, cerebral and myocardial injuries represent the limiting factors for survival after cardiac arrest. Administering xenon may confer an additional neuroprotective effect after successful cardiopulmonary resuscitation due to its ability to stabilize cellular calcium homeostasis via N-methyl-D-aspartate-receptor antagonism., Design: In a porcine model, we evaluated effects of xenon treatment in addition to therapeutic hypothermia on neuropathologic and functional outcomes after cardiopulmonary resuscitation., Setting: Prospective, randomized, laboratory animal study., Subjects: Fifteen male pigs., Interventions: Following 10 mins of cardiac arrest and 6 mins of cardiopulmonary resuscitation, ten pigs were randomized to receive either mild therapeutic hypothermia (33°C for 16 hrs) or mild therapeutic hypothermia 1 xenon (70% for 1 hr). Five animals served as normothermic controls., Measurements and Main Results: Gross hemodynamic variables were measured using right-heart catheterization. Neurocognitive performance was evaluated for 5 days after cardiopulmonary resuscitation using a neurologic deficit score before the brains were harvested for histopathological analysis. All animals survived the observation period in the mild therapeutic hypothermia 1 xenon group while one animal in each of the other two groups died. Mild therapeutic hypothermia 1 xenon preserved cardiac output during the induction of mild therapeutic hypothermia significantly better than did mild therapeutic hypothermia alone (4.6 6 0.6 L/min vs. 3.2 6 1.6 L/min, p # .05). Both treatment groups showed significantly fewer necrotic lesions in the cerebral cortex, caudate nucleus, putamen, and in hippocampal sectors CA1 and CA3/4. However, only the combination of mild therapeutic hypothermia and xenon resulted in reduced astrogliosis in the CA1 sector and diminished microgliosis and perivascular inflammation in the putamen. Clinically, only the mild therapeutic hypothermia 1 xenon-treated animals showed significantly improved neurologic deficit scores over time (day 1 = 59.0 6 27.0 vs. day 5 = 4.0 6 5.5, p ø .05) as well as in comparison to the untreated controls on days 3 through 5 after cardiopulmonary resuscitation., Conclusions: These results demonstrate that even a short exposure to xenon during induction of mild therapeutic hypothermia results in significant improvements in functional recovery and ameliorated myocardial dysfunction.

Background: Previously, we showed a significant difference in the measurements of hypnotic depth by the bispectral index (BIS) and auditory-evoked potentials (AEPs) using the A-line autoregressive index during xenon anaesthesia. In the present study, we evaluate the alternative AEP-based auditory-evoked potential index (aepEX) for the measurement of hypnotic depth in patients undergoing general anaesthesia with xenon., Methods: Forty-two patients undergoing elective abdominal surgery were enrolled in this controlled, double-blinded, randomized, clinical study. Patients were randomized to receive either xenon (n=21) or sevoflurane anaesthesia (n=21). During anaesthesia, BIS values were recorded simultaneously with the aepEX monitoring. The anaesthetist performing the anaesthesia was blinded to the hypnotic depth monitors. After surgery, the incidence of recalls and awareness was evaluated., Results: Patients' characteristics such as gender, age, and weight did not differ between the groups. The aepEX and BIS values behaved similarly during anaesthesia. The comparison of aepEX values during xenon and sevoflurane anaesthesia revealed significantly lower aepEX values in the xenon group after 25 min [xenon: 32.9 (4.8) vs sevoflurane: 39.3 (9.0); P=0.008] and after 35 min [xenon: 31.4 (6.6) vs sevoflurane: 37.0 (6.8); P=0.012]. During anaesthesia, aepEX values correlated with the clinical evaluation of depth of anaesthesia (e.g. >20% changes of the baseline arterial pressure or heart rate, spontaneous breathing and/or intolerance of mechanical ventilation, coughing, abdominal pressing, sweating, eye tearing)., Conclusions: We found the aepEX monitor to provide index in the range of adequate depth of xenon anaesthesia, when combined with remifentanil infusion in intubated patients undergoing elective abdominal surgery.

The extracellular signal-regulated kinase (ERK) is involved in the cytokine production of immune cells. In this study, we show the influence of xenon on phosphatase activity, ERK 1/2 signalling and cytokine expression in microglia. The murine microglia cell line BV-2 was treated with 50 ng/ml lipopolysaccharide (LPS) and 74% xenon in 21% O(2) and 5% CO(2). Cytokine levels were examined by gene expression analysis, Western blot and enzyme-linked immunosorbent assay. Phosphatase inhibition was assessed with p-nitrophenylphosphate and phosphorylation of ERK 1/2 via Western blot. Xenon significantly enhanced LPS-mediated IL-1β expression. ERK 1/2 phosphorylation was observed after xenon or LPS treatment which was inhibited by the use of the MEK inhibitor U0126. Xenon and LPS in combination superimposed individual effects on ERK 1/2 activation. Xenon decreased cellular phosphatase activity in microglia by 20% and inhibited dephosphorylation of ERK 1/2 up to 1 h. The blocking of ERK 1/2 reduced IL-1β expression in xenon and LPS-treated cells to a level obtained by LPS alone. In conclusion, xenon enhanced LPS-induced IL-1β expression in microglia by activation of ERK 1/2 signalling. Xenon's interference with phosphatases may be a key feature to affect multiple intracellular signalling pathways.

Background: Xenon has only minimal hemodynamic side effects and induces pharmacologic preconditioning. Thus, the use of xenon could be an interesting option in patients at risk for perioperative myocardial ischemia. However, little is known about the effects of xenon anesthesia on myocardial blood flow (MBF) and coronary vascular resistance in humans., Methods: Myocardial blood flow was noninvasively quantified by H₂¹⁵O positron emission tomography in six healthy volunteers (age: 38 ± 8 yr). MBF was measured at baseline and during general anesthesia induced with propofol and maintained with xenon, 59 ± 0%. Absolute quantification of MBF was started after the calculated plasma concentration of propofol had decreased to less than 1.5 μg · ml⁻¹., Results: Compared with baseline (MBFbaseline, 1.03 ± 0.09 ml · min⁻¹ · g⁻¹; mean ± SD), MBF was decreased insignificantly by xenon (MBFxenon, 0.80 ± 0.22 ml · min⁻¹ · g⁻¹; -21%, P = 0.11). Xenon decreased the rate-pressure product (RPP; heart rate × systolic arterial pressure), an indicator of cardiac work and myocardial oxygen consumption (-15%, P < 0.04). When correcting for the RPP, the decrease in MBF observed during xenon anesthesia was reduced to -9% (MBFcorr-xenon, 1.42 ± 0.28 ml · g⁻¹ · mmHg⁻¹ vs. MBFcorr-baseline, 1.60 ± 0.28 ml · g⁻¹ · mmHg⁻¹, P = 0.32). Xenon did not affect the dependency of MBF on the RPP. Coronary vascular resistance did not significantly change (+15 ± 23%, P = 0.18) during xenon anesthesia., Conclusions: In healthy subjects, xenon has only minimal effects on coronary flow dynamics. These effects are probably of indirect nature, reflecting the decrease in myocardial oxygen consumption induced by the effects of xenon anesthesia on cardiac work.

The noble gas xenon exerts favorable anesthetic properties along with remarkable hemodynamic stability in healthy patients undergoing elective surgery. It represents the nearly ideal anesthetic and provides safe and well controllable anesthesia although the exact mechanism by which xenon produces anesthesia remains to be elucidated. In addition xenon offers organ protective properties for vital organs including the brain, heart and kidneys which seem to be synergistic when used in combination with therapeutic hypothermia. As the high cost of xenon will probably preclude its wider use as a routine anesthetic, data from extensive tests in large numbers of high risk patients is needed to confirm its possible superiority in this setting.

Background and Objective: In the elderly, monitoring depth of anaesthesia seems to be of particular importance. We evaluated the bispectral index (BIS) for monitoring depth of anaesthesia during clinically guided balanced xenon or sevoflurane anaesthesia in aged patients., Methods: In this randomized controlled clinical trial, 40 patients (65-75 years) undergoing elective noncardiac surgery were randomly assigned to balanced anaesthesia with either 53.2 +/- 0.8% xenon (n = 19) or 1.6 +/- 0.1% sevoflurane (n = 20) in minimum 30% oxygen and remifentanil titrated to clinical needs. Depth of anaesthesia was guided by end-tidal gas concentrations and clinical signs. The attending anaesthesiologist was blinded to the BIS values, which were recorded at 1 min rates during induction, at 5 min rates during maintenance and at 20 s rates during emergence. Emergence from anaesthesia was assessed by the times to open eyes, react on demand, extubation and orientation., Results: During induction and maintenance of anaesthesia, BIS values in the xenon group were comparable to sevoflurane and at the lower limit of the recommended range for deep anaesthesia. Emergence to full orientation was significantly faster from xenon than from sevoflurane. BIS values were significantly lower during emergence from xenon anaesthesia., Conclusion: During xenon and sevoflurane anaesthesia in the elderly, BIS-values show sufficient concordance with clinical signs of anaesthetic depth. Since during clinically guided anaesthesia values were at the lower recommended limit, additional BIS monitoring may help reduce anaesthetic consumption and costs.

Background: None of the currently available hypnosis monitoring systems have evaluated balanced xenon anaesthesia. We investigated the performance of the bispectral index (BIS) and the composite A-line autoregressive index (cAAI) while comparing balanced xenon with sevoflurane anaesthesia., Methods: Sixty patients undergoing elective abdominal surgery participated in this registered double-blinded, controlled trial and-after written informed consent-were randomly assigned to one of the study groups (xenon, n=30; sevoflurane, n=30). After induction, general anaesthesia was maintained with xenon 60% or sevoflurane 2.0% in 30% O2. Remifentanil was titrated to clinical needs. BIS and cAAI values were recorded electronically and blinded to the performing physician. Emergence from anaesthesia was evaluated and during 12 h follow-up, patients were questioned twice for signs of recalls., Results: During induction and maintenance of anaesthesia, BIS values in the xenon group were comparable with sevoflurane anaesthesia and within the recommended range. Although the cAAI remained stable in the sevoflurane group, values increased during balanced xenon anaesthesia and exceeded the recommended upper limit after 65 min. Emergence from xenon anaesthesia was significantly faster than from sevoflurane (eye opening at 3.8 vs 10.3 min, P<0.001), and BIS values were concordant with the washout of both anaesthetics. No incident of recall was reported., Conclusions: During surgery, xenon/remifentanil anaesthesia can be monitored using BIS and cAAI. However, cAAI values changed after about 1 h of anaesthesia. Further studies will be needed to address the question whether auditory signal processing is altered during extended xenon exposure.

Background and Objective: Stable haemodynamics and its cardioprotective and neuroprotective properties favour xenon as an ideal but expensive anaesthetic agent. The aim of this study was to optimize a semi-closed anaesthesia circuit for xenon anaesthesia with respect to economics and patient safety., Methods: A semi-closed nonrebreathing circuit was compared with a closed anaesthesia circuit. In 12 landrace pigs, we compared eight different wash-in procedures affecting xenon consumption. Additionally, the maintenance of anaesthesia was analysed with regard to minimizing xenon consumption., Results: The current study showed that, by optimization of the electronic regulation of the wash-in procedure for xenon anaesthesia, the consumption of the valuable gas can be reduced by up to 75% in a semi-closed circuit. The additional maintenance of anaesthesia under low flow conditions by coupling the xenon flow to the oxygen consumption is the most effective way to technically reduce the amount of xenon needed for anaesthesia.

Background: Although anesthetics have some cardioprotective properties, these benefits are often counterbalanced by their negative inotropic effects. Xenon, on the other hand, does not influence myocardial contractility. Thus, xenon may be a superior treatment for the maintenance of global hemodynamics, especially during right ventricular ischemia, which is generally characterized by a high acute complication rate., Methods: The effects of 70 vol% xenon and 0.9 vol% isoflurane on biventricular function were assessed in a porcine model (n=36) using the conductance catheter technique, and the expression of the type B natriuretic peptide (BNP) gene was measured. The animals underwent 90 min of right ventricular ischemia followed by 120 min of reperfusion. A barbiturate-anesthetized group was included as a control., Results: Cardiac output was compromised in unprotected animals during ischemia by 33+/-18% and during reperfusion by 53+/-17%. This was mainly due to impaired contractility in the left ventricle (LV) and increased stiffness. Isoflurane attenuated the increase in stiffness and resulted in a higher preload. In contrast, xenon increased the right ventricular afterload, which was compensated by an increase in contractility. Its effects on diastolic function were less pronounced. Upregulation of BNP mRNA expression was impeded in the remote area of the LV by both isoflurane and xenon., Conclusions: Xenon and isoflurane demonstrated equipotent effects in preventing the hemodynamic compromise that is induced by right ventricular ischemia and reperfusion, although they acted through somewhat differential inotropic and vasodilatory effects.

Objectives: To investigate if the protective effects of xenon and isoflurane against myocardial ischemia-reperfusion damage would be additive., Design: A prospective, randomized laboratory investigation., Setting: An animal laboratory of a university hospital., Participants: Thirty-six pigs (female German landrace)., Interventions: In an open-chest preparation with thiopental anesthesia, the left anterior descending artery was occluded to produce ischemia for 60 minutes. One hour previously, ischemic preconditioning, isoflurane (0.55 minimum alveolar concentration [MAC]) alone, or isoflurane together with xenon (0.55 MAC each) were started in the respective groups. A fourth (control) group received no protective intervention. Myocardial ischemia was followed by 2 hours of reperfusion., Measurements and Main Results: Hearts were excised and stained (Evans Blue/TTC) to measure infarct size as related to the area at risk. Myocardial infarct size was reduced (means +/- standard deviation) from 64% +/- 9% of the area at risk in the control group to 19% +/- 12% with ischemic preconditioning to 46% +/- 12% with isoflurane and to 39% +/- 13% with isoflurane and xenon. All intervention groups were significantly different from the control (p < 0.05), and both anesthetic groups were significantly different from ischemic preconditioning (p < 0.05)., Conclusion: Combined isoflurane/xenon anesthesia reduced infarct size but not more than isoflurane alone. Ischemic preconditioning was more effective than the anesthetics.

Background: Xenon (Xe) is neuroprotective when given 1h after cardiopulmonary resuscitation (CPR). Here, we investigated if an earlier administration of Xe or isoflurane (Iso) would also reduce neurological dysfunction., Methods: 10 min after CPR from 8 min of cardiac arrest 21 pigs were randomized to three groups (n=7/group) and then ventilated for 1h with gas mixtures as follows: (1) control: 30% O(2)+70% N(2); (2) Iso: 30% O(2)+69% N(2)+1% Iso; (3) Xe: 30% O(2)+70% Xe. Physiological variables were obtained before cardiac arrest and 10, 60 and 240 min post-CPR including cardiac output (CO) and mean arterial pressure (MAP). Four days after CPR we assessed functional performance using an established neurocognitive test and overall neurological status using a neurologic deficit score (NDS). On day 5, brains of the re-anaesthetized pigs were harvested for neurohistopathological analyses., Results: Prior to CPR there were no differences in hemodynamics and neurological status between groups. CO and MAP were significantly reduced after starting Iso administration. Both variables were also significantly lower in comparison to Xe and control animals. Control animals presented severe neurological dysfunction as measured by the NDS and the neurocognitive tests. Although Xe and Iso animals showed slightly better functional outcome this trend was not significant. Histopathological evaluation revealed ischaemic damage of neurons predominantly in the CA1 sector of the hippocampus with no differences between groups., Conclusions: In this study early administration of Xe and Iso did not significantly reduce neurological dysfunction and histopathological alterations induced by cardiac arrest and CPR.

The noble gas xenon exerts favorable anesthetic properties along with remarkable hemodynamic stability in healthy patients undergoing elective surgery. Recent investigations documented that it does not prolong the duration of widely used neuromuscular blocking agents, including mivacurium and rocuronium. Some studies also suggest reduced neurocognitive compromise in the very early phase after general anesthesia. These properties differ from those observed for conventional inhalational anesthetics like isoflurane, desflurane and sevoflurane. However, a wider use of xenon in daily clinical routine has been limited owing to its higher price and technical restraints regarding economic delivery. Although there are controversial opinions, xenon seems to exert its main anesthetic features via the glutamate receptor. Recently, a novel binding cavity on the NMDA-subtype glutamate receptor has been elucidated that is occupied by xenon as well as isoflurane. Studies utilizing advanced imaging technologies have furthermore revealed that xenon markedly suppresses cerebral blood flow and glucose metabolism in distinct regions of the human brain. These investigations promise to further the understanding of the basic mechanisms underlying the induction and maintenance of anesthesia in general. Results from in vitro studies and various animal models have consistently demonstrated organoprotective properties of xenon, mainly in settings of ischemia and reperfusion injury. Interestingly, these effects have frequently been observed at subanesthetic concentrations and seem to be synergistic when used in combination with therapeutic hypothermia. Future studies will have to prove whether the high costs of xenon administration might be outweighed by its ability to substantially reduce the sequelae of myocardial and cerebral ischemia.

Objective: Neurologic outcome after cardiopulmonary resuscitation from cardiac arrest carries a poor prognosis and treatment options to ameliorate brain damage are limited., Design: Report of two protocols investigating the effects of xenon (Xe) and isoflurane (Iso) in a porcine model of prolonged cardiac arrest and subsequent cardiopulmonary resuscitation on functional neurologic outcomes., Setting: Prospective, randomized, laboratory animal study., Subjects: Male domestic pigs (Sus scrofa)., Interventions: After successful resuscitation from 8 mins of cardiac arrest and 5 mins of cardiopulmonary resuscitation, pigs were randomized to receive either Xe for 1 or 5 hrs in comparison with untreated controls 1 hr after cardiopulmonary resuscitation (protocol 1) or to receive Iso or Xe in comparison with untreated controls 10 mins after cardiopulmonary resuscitation (protocol 2)., Measurements and Main Results: Animals were exposed to an established cognitive function test and gross neurologic performance was assessed using a neurologic deficit score. In protocol 1, Xe administration resulted in improved early cognitive and overall neurologic function, whereas in protocol 2 there was no significant effect on functional performance., Conclusions: Although Xe conferred functional neurologic improvement even when treatment was delayed for 1 hr, the early treatment with either Xe or Iso translated to only marginal functional improvement.

Background: Right ventricular (RV) function is an important determinant of post-operative outcome. Consequences of RV infarction might be limited by pre-conditioning with volatile anesthetic drugs. Therefore, we used a porcine model of RV ischemia and reperfusion (IR) injury to study the influence of isoflurane and xenon on the extent and degree of myocardial injury., Methods: IR injury was induced by a 90-min ligation of the distal right coronary artery and 120-min reperfusion in thiopental anesthetized pigs. A control group (n=12) was compared with two groups, which received either 0.55 minimum alveolar concentration (MAC) isoflurane (n=10) or xenon (n=12) starting 60 min before ischemia. Myocardial injury was described by three criteria: the infarct size related to area at risk (IS/AAR), the infiltration of neutrophils as determined by myeloperoxidase (MPO) activity, and the plasma levels of tumor necrosis factor alpha (TNFalpha), interleukin 6 (IL-6), myoglobin and troponin-T (TnT)., Results: IS/AAR was reduced from 58.3+/-6.2% in the control group to 41.8+/-7.8% after isoflurane and 42.7+/-8.5% after xenon pre-treatment, which equals an absolute reduction of 16.5% [95% confidence interval (CI): 10.9-22.1] and 15.5% (95% CI: 10.1-20.9). The maximum increase of TnT could be observed within the xenon group. Both treatment groups were characterized by lower MPO activity, in the infarct and periinfarct region and lower plasma concentrations of TNFalpha and IL-6., Conclusions: It could be demonstrated for the first time in a model of RV infarction that the continuous application of isoflurane or xenon before, during and after ischemia reduced the extent (size) and severity (inflammation) of myocardial injury.

Background: Over the last 15 years, there has been growing interest in the noble gas xenon as a new inhalational anesthetic. This is due to its favorable pharmacological properties such as short onset and offset, as well as its hemodynamic stability. However, most volatile anesthetics appear to play an important role in the multi-factorial etiology of perioperative liver injury by decreasing liver blood flow with a subsequent reduction of hepatic oxygen supply. However, the effects of the anesthetic gas xenon on hepatic perfusion and oxygenation have not been completely investigated., Methods: Following ethical approval, 18 anesthetized and acutely monitored pigs were randomly assigned to the two following groups: 9 animals received xenon anesthesia in increasing inspiratory concentrations of 0%, 20%, 50%, and 65% in addition to their basic intravenous anesthesia; 9 animals served as a control group. Measurement points for systemic and regional hemodynamic and oxygenation parameters were performed 30 min after changing the xenon concentration., Results: Xenon elicited dose-dependent systemic hemodynamic changes such that the mean arterial pressure did not change, while the heart rate and cardiac output decreased by about 30%, thereby indicating an increase in the systemic vascular resistance. Portal venous blood flow decreased, while hepatic arterial blood flow was unchanged. The oxygen supply of the liver was reduced, but not the rate of indocyanine plasma disappearance from the liver. Furthermore, the increase of liver surface pO2 to systemic hyperoxia was absent, and hepatic lactate uptake was reduced., Conclusion: Xenon, in addition to basic intravenous anesthesia, elicited a decrease in heart rate and cardiac output and an increase in mean arterial pressure. Similar to volatile anesthetics, xenon does reduce portal venous flow and influences hepatic tissue oxygenation. In contrast, hepatic arterial blood flow remains stable in the presence of xenon, and no changes in the hepatic arterial buffer responses were evident. Xenon does affect hepatic perfusion and oxygenation.

Background and Objective: The aim of this study was to compare waste gas concentrations during xenon or nitrous oxide anaesthesia., Methods: A total of 64 patients were included in this study. Gas concentrations were measured with a mass spectrometer during anaesthesia. The probes were taken beside the patient's head and thorax and at a height of 180 cm above and at the floor level., Results: In both groups, waste gas concentrations peak after intubation and extubation. Waste gas levels during xenon anaesthesia are low compared with nitrous oxide., Conclusions: The low waste gas levels of xenon seem to be beneficial compared to nitrous oxide.

Background: In contrast to other volatile anesthetics, xenon produces less cardiovascular depression with fewer fluctuations of various hemodynamic parameters, but reduces cardiac output (CO) in vivo. Besides an increase in left ventricular afterload and reduction of heart rate, an impairment of the right ventricular function might be an additional pathophysiological mechanism for the reduction of CO. Therefore, we used an animal model to study the effects of xenon as a supplemental anesthetic on right ventricular function, especially right ventricular afterload., Methods: Right ventricular function was monitored with a volumetric pulmonary artery catheter in 11 pigs during general anesthesia with thiopental. Six animals received additional 70% (volume) xenon (equivalent to 0.55 MAC minimum alveolar concentration). Parameters for systolic function, afterload, and preload were calculated at baseline and during 50 min of xenon application, and in a corresponding control group. Significant differences were detected by multivariate analyses of variance for repeated measures., Results: Xenon reduced CO on average by 30% and increased pulmonary arterial elastance by 60%, which led to a reduction of the right ventricular ejection fraction by 25%. Whereas right ventricular preload remained stable, maximal slope of pulmonary artery pressure and the right ventricular elastance increased. No effect on the ratio of stroke work and end-diastolic volume was found., Conclusion: The reduction in CO during xenon anesthesia was partly due to an impairment of the right ventricular function, mainly caused by an increased afterload, without an impairment of systolic ventricular function.

Objective: Treatment options to ameliorate brain damage following cardiopulmonary resuscitation from cardiac arrest are limited., Design: In a porcine model, we evaluated the effects of xenon treatment on neuropathologic and functional outcomes after cardiopulmonary resuscitation., Setting: Prospective, randomized laboratory animal study., Subjects: Male pigs., Interventions: Following successful resuscitation from 8 mins of cardiac arrest and 5 mins of cardiopulmonary resuscitation, 24 pigs were randomized to one of three groups receiving either 70% xenon for 1 or 5 hrs or untreated controls receiving 70% nitrogen., Measurements and Main Results: Gas exchange, hemodynamics, and lactate and glucose levels were measured at baseline and in the postresuscitation period. On four postoperative days, neurocognitive and overall neurologic deficits were assessed before day 5, when the brains were harvested for histologic analysis of predefined regions using a semiquantitative score (0-10% = 1, 10-20% = 2, 20-50% = 3, 50-80% = 4, 80-100% = 5). No differences in gas exchange, hemodynamics, or lactate and glucose levels were observed among the groups. Animals exposed to 1 and 5 hrs of xenon showed significantly reduced scores for necrotic neurons in the putamen (1.25 +/- 0.5 and 1.25 +/- 0.5 vs. 2.5 +/- 1.2; p < 0.05), accompanied by significantly lesser scores for perivascular inflammation in putamen (0.8 +/- 0.5 and 1.1 +/- 0.8 vs. 2.1 +/- 1.1; p < 0.05) and caudate nucleus (1.0 +/- 0.8 and 0.6 +/- 0.7 vs. 2.0 +/- 1.1; p < 0.05). This resulted in improved neurocognitive and neurologic function on day 1 to 3 after cardiopulmonary resuscitation in xenon-treated animals., Conclusions: In this experimental study of cardiac arrest-induced neurologic damage, xenon conferred neurohistopathologic protection, translating in transiently improved functional outcome.

Background: Xenon has been proved to be safe and efficacious for general anaesthesia in numerous trials. In addition, experimental studies demonstrate that xenon inhibits the 5-hydroxytryptamine type 3 (5-HT(3)) receptor. As 5-HT(3) receptor antagonists are known to decrease postoperative nausea and vomiting (PONV) to an extent comparable with a propofol-based total i.v. technique, we tested the hypothesis that general anaesthesia with xenon would result in a reduced incidence of PONV similar to that observed with propofol-based anaesthesia., Methods: After obtaining approval from the local ethics committee and written informed consent, 142 patients were randomized to receive xenon anaesthesia or propofol-based total i.v. anaesthesia (TIVA), both supplemented with remifentanil. The incidence of postoperative nausea and emetic episodes was recorded in the post-anaesthesia care unit and on the ward more than 24 h after anaesthesia., Results: A total of 142 patients were equally distributed between the xenon and TIVA groups. Anaesthesia was maintained with mean (sd) concentrations of either xenon 61 (2)% or propofol 100 (20) microg kg(-1) min(-1). Incidences of nausea and emetic episodes over the whole 24-h period were 66.2% and 35.2% in the xenon group and 26.8% and 16.9% in the TIVA group (P<0.001 and P<0.021)., Conclusion: Despite knowing the 5-HT(3) antagonistic properties of xenon, its use is associated with a higher incidence of nausea and emetic episodes compared with TIVA with propofol.

Background: The effects of xenon on regional cerebral blood flow (rCBF) are controversial. Moreover, the precise sites of action at which xenon exerts its effects in the human brain remain to be established., Methods: rCBF was sequentially assessed by H(2)(15)O positron emission tomography in six volunteers. rCBF was determined at baseline and during general anaesthesia induced with propofol and maintained with one minimum alveolar concentration xenon. rCBF measurements were started after the calculated plasma concentration of propofol had decreased to subanaesthetic levels (<1.0 microg ml(-1)). Changes in rCBF were calculated for 13 cerebral volumes of interest by measurement of a semi-quantitative perfusion index (PI). In addition, voxel-wise changes in rCBF were analysed using statistical parametric mapping., Results: Xenon had only minor effects on PI in grey matter volumes of interest. In contrast, PI was increased in white matter [from 1.01 (0.11) to 1.24 (0.15) kcnt ml(-1) MBq(-1), P=0.05, mean (SD)]. Voxel-based analysis showed an increase of rCBF in white matter and a relative decrease of rCBF during xenon anaesthesia in distinct grey matter regions, particularly the orbito- and mesiofrontal cortex, cingulate gyrus, thalamus, hippocampus and bilateral cerebellum (P<0.05 corrected). When correlating PI with cerebral metabolic rate of glucose (previously obtained in another group of six volunteers using (18)F-fluorodeoxyglucose as tracer), the flow-metabolism coupling was preserved during xenon anaesthesia., Conclusions: Xenon exerted distinct regional effects on CBF: relative decreases in several cortical, subcortical, and cerebellar areas were accompanied by an increase in white matter. Flow-metabolism coupling was not impaired during xenon anaesthesia.

Background: The results of two European multi-centre trials on xenon anaesthesia led to the hypothesis that a xenon-based anaesthetic would keep left ventricular (LV) and circulatory function more stable than a propofol-based anaesthetic, in patients with coronary artery disease (CAD)., Methods: In a prospective, randomized design, 40 patients of ASA classes III and IV with known CAD were anaesthetized for elective non-cardiac surgery with either xenon (n=20) or propofol (n=20), each combined with remifentanil. Target criteria were intraoperative LV function as evaluated by transoesophageal echocardiography (TOE: Tei index, circumferential fibre shortening), arterial pressure, and heart rate (HR)., Results: Mean arterial pressure was decreased with propofol but was stable at pre-anaesthetic level with xenon (P<0.02) and HR was lower with xenon (P<0.01). The Tei index (also known as myocardial performance index) improved from 0.53 (0.14) to 0.45 (0.10) after 1 h with xenon and changed from 0.50 (0.14) to 0.55 (0.20) with propofol anaesthesia [means (SD); P=0.01 between the groups]. Deviation of circumferential fibre shortening from expected value after 1 h was -2 (14)% with xenon and -14 (18)% with propofol [means (SD); P=0.03]. There were no perioperative signs of acute myocardial ischaemia (TOE, ECG, and troponin T release)., Conclusions: Xenon anaesthesia provided a higher arterial pressure level than propofol, with no signs of cardiovascular compromise, in patients with CAD. Echocardiographic indices showed better LV function with xenon.

Background: Volatile anesthetics protect the myocardium from ischemia reperfusion damage. Our hypothesis for this study was that xenon reduces the size of myocardial infarction similar in extent to the reduction associated with ischemic preconditioning., Methods: Thirty-six pigs weighing 30-35 kg were anesthetized with thiopental and then randomized into four groups: control (myocardial ischemia only), ischemic preconditioning (five 5-min episodes of intermittent myocardial ischemia), xenon preconditioning (three 10-min exposures to xenon 70% followed by myocardial ischemia), and xenon anesthesia (xenon 70%, continued before and after myocardial ischemia). Myocardial ischemia was induced by placing a tourniquet around the left anterior descending coronary artery for 60 min followed by 2 h of reperfusion. Myocardial infarct size and the area at risk for myocardial infarction were measured by Evans Blue and triphenyl tetrazolium chloride staining, respectively., Results: Mean (sd) myocardial infarct size was reduced from 64% +/- 9% of the area at risk in the control group to 19% +/- 12% with ischemic preconditioning (P < 0.001), and to 50% +/- 9% with xenon anesthesia (P < 0.05 versus control, P < 0.001 versus ischemic preconditioning). Myocardial infarct size was not reduced with xenon preconditioning compared with the control group (59% +/- 11%, P = 0.41)., Conclusion: Myocardial infarct size was reduced by ischemic preconditioning but less so by xenon anesthesia. Brief, intermittent exposure to xenon before myocardial ischemia did not reduce myocardial infarct size.

Background: Postoperative cognitive impairment after general anaesthesia, especially in the elderly, is a well-recognized problem. Xenon, known to be an N-methyl-d-aspartate antagonist, may be advantageous. In this study, the early cognitive function in the elderly after general anaesthesia with xenon was compared with that after desflurane., Methods: After approval by the local ethical committee and after obtaining written informed consent, patients were enrolled in this randomized, double-blinded, controlled study. Thirty-eight patients (65-75 yr old, ASA status I-III) undergoing an elective surgery with a planned duration of 60-180 min were allocated to either the xenon (n = 18) or the desflurane (n = 20) anaesthesia group. The primary outcome was the cognitive Test for Attentional Performance (TAP) with its subtests Alertness, Divided Attention, and Working Memory. After baseline assessment 12-24 h before operation, patients were followed-up 6-12 and 66-72 h after operation. Secondary outcomes were emergence times from anaesthesia and the modified Aldrete score., Results: No difference was found between the groups in the TAP at 6-12 and 66-72 h after operation. In the xenon group, emergence time was significantly faster for the following parameters: time to open eyes (P = 0.001), to react on demand (P = 0.001), to extubation (P = 0.001), and for time and spatial orientation (P = 0.007). The modified Aldrete score was significantly higher after 30, 45 and 60 min in the xenon group., Conclusions: There was no difference in the postoperative cognitive testing at 6-12 and 66-72 h. Xenon was associated in the elderly with a faster emergence from general anaesthesia than desflurane.

Background: The cardiovascular stability found with xenon anaesthesia may be caused by absence of circulatory depression. Xenon may also act directly on autonomic cardiovascular control., Methods: In a prospective, randomized design, 26 patients (ASA class III and IV) with increased cardiac risk were anaesthetized for elective non-cardiac surgery with either xenon (n = 13) or propofol (n = 13), each combined with remifentanil. From intraoperative Holter ECG, 5-min intervals of stable sinus rhythm were analysed at baseline anaesthesia with etomidate/remifentanil, and after 30 and 60 min of propofol or xenon anaesthesia. Target criteria were total power and ratio of low to high frequency power of the heart rate (HR) power spectrum between 0.003 and 0.4 Hz, indicating global activity and sympatho-vagal balance of autonomic modulation of HR., Results: When compared with baseline, total power decreased with propofol from 8.6 (1.6) to 7.1 (0.5) and to 7.8 (1.1) ms(2) at 30 and 60 min, respectively, [mean (sd) of logarithmic transform] and was unchanged with xenon (P = 0.02; anova). The low/high frequency power ratio changed from 3.0 (3.5) to 4.3 (4.3) and 4.1 (6.2), respectively, with xenon and from 3.9 (3.6) to 1.8 (1.5) and 1.8 (0.8) with propofol (P = 0.04; generalized linear model test). Mean arterial pressure was significantly higher with xenon throughout (P < 0.001; anova)., Conclusions: Propofol caused a decrease in arterial pressure as well as autonomic HR modulation, but xenon did not. The higher arterial pressure with xenon anaesthesia may be explained by less suppression of sympatho-vagal balance.

Background: Volatile anesthetics are commonly used for general anesthesia. However, these can induce profound cardiovascular alterations. Xenon is a noble gas with potent anesthetic and analgesic properties. However, it is uncertain whether xenon alters myocardial function. The aim of this study was therefore to investigate left ventricular function during anesthesia with xenon compared with isoflurane., Methods: The authors performed a randomized multicenter trial to compare xenon with isoflurane with respect to cardiovascular stability and adverse effects in patients without cardiac diseases scheduled for elective surgery. Two hundred fifty-nine patients were enrolled in this trial, of which 252 completed the study according to the protocol. Patients were anesthetized with xenon or isoflurane, respectively. Before administration of the study drugs and at four time points, the effects of both anesthetics on left ventricular function were investigated using transesophageal echocardiography., Results: Global hemodynamic parameters were significantly altered using isoflurane (P < 0.05 vs. baseline), whereas xenon only decreased heart rate (P < 0.05 vs. baseline). In contrast to xenon, left ventricular end-systolic wall stress decreased significantly in the isoflurane group (P < 0.05 vs. baseline). Velocity of circumferential fiber shortening was decreased significantly in the xenon group but showed a more pronounced reduction during isoflurane administration (P < 0.05 vs. baseline). The contractile index (difference between expected and actually measured velocity of circumferential fiber shortening) as an independent parameter for left ventricular function was significantly decreased after isoflurane (P < 0.0001) but unchanged using xenon., Conclusions: Xenon did not reduce contractility, whereas isoflurane decreased the contractile index, indicating that xenon enables favorable cardiovascular stability in patients without cardiac diseases.

Background: The precise mechanism by which the gaseous anesthetic xenon exerts its effects in the human brain remains unknown. Xenon has only negligible effects on inhibitory gamma-aminobutyric acid receptors, one of the putative molecular targets for most general anesthetics. Instead, xenon has been suggested to induce anesthesia by inhibiting excitatory glutamatergic signaling. Therefore, the authors hypothesized that xenon, similar to ketamine and nitrous oxide, increases global and regional cerebral metabolism in humans., Methods: The regional cerebral metabolic rate of glucose (rcMRGlu) was sequentially assessed in two groups of six volunteers each, using F-fluorodeoxyglucose as tracer. In the xenon group, rcMRGlu was determined at baseline and during general anesthesia induced with propofol and maintained with 1 minimum alveolar concentration xenon. In the control group, rcMRGlu was measured using the identical study protocol but without administration of xenon. rcMRGlu was assessed after the plasma concentration of propofol had decreased to subanesthetic levels (< 1.0 microg/ml). rcMRGlu was quantified in 10 cerebral volumes of interest. In addition, voxel-wise changes in rcMRGlu were analyzed using statistical parametric mapping., Results: Xenon reduced whole-brain metabolic rate of glucose by 26 +/- 7% (from 43 +/- 5 micromol x 100 g x min to 31 +/- 3 micromol x 100 g x min; P < 0.005) and significantly decreased rcMRGlu in all volumes of interest compared with the control group receiving propofol only. Voxel-based analysis revealed metabolic depression within the orbitofrontal, frontomesial, temporomesial, occipital, dorsolateral frontal, and lateral temporal cortices and thalami. No increases in rcMRGlu were detected during xenon anesthesia., Conclusions: Xenon induces metabolic depression in the human brain, suggesting that the inhibition of the glutamatergic system is likely to be of minor significance for the anesthetic action of xenon in vivo.

Purpose: The interaction between mivacurium and inhaled anesthetics is known, with the exception of xenon. We compared the pharmacodynamics of mivacurium during xenon anesthesia vs total iv anesthesia with propofol., Methods: This randomized controlled trial was carried out in the Aachen University Hospital. Forty-two adult patients ASA I or II, aged 18 to 60 yr, were randomized to receive either xenon or propofol anesthesia. Anesthesia was induced with propofol and remifentanil in both groups (each n = 21). The xenon group received xenon via face mask until an end-expiratory concentration of 60% was reached for one minute. Meanwhile, the acceleromyograph was calibrated and a train-of-four stimulation of the adductor pollicis muscle was started. After stabilization of the signal for five minutes, a single bolus of 0.16 mg.kg-1 mivacurium was injected. Anesthesia was maintained with xenon and remifentanil or with propofol and remifentanil., Results: There were no significant differences between groups with respect to onset time (xenon 180 +/- 64 vs propofol 195 +/- 77 sec; P = 0.39), duration (xenon 16.18 +/- 4.97 vs propofol 15.68 +/- 6.17 min; P = 0.73), recovery index (xenon 5.63 +/- 2.48 vs propofol 5.73 +/- 2.12 min; P = 0.42) and clinical recovery (xenon 8.75 +/- 2.57 vs propofol 9.28 +/- 2.28 min; P = 0.22)., Conclusion: We conclude that the neuromuscular blocking effects of mivacurium are similar when given during propofol vs xenon anesthesia.

Background and Objective: The aim of this study was to assess postoperative patients' self-evaluation after xenon anaesthesia compared to total intravenous anaesthesia with propofol., Methods: 160 patients aged 18-60 yr, ASA I-II undergoing elective surgery took part in this randomised-controlled trial. After approval by the local Ethics Committee and as soon as the patients had given their written informed consent, they were randomly allocated to either the xenon (n = 80) or propofol (n = 80) group. In both groups remifentanil was used as opioid. The postoperative patients' self-evaluation was assessed with a double-blind telephone poll. Early spatial orientation, patients' self-evaluation of anaesthesia, choice of the same anaesthesia for future operations and recall of uncomfortable feelings after anaesthesia were determined., Results: 116 Patients were analysed, 63 in the xenon and 53 in the propofol group. The two study groups were comparable with respect to age, weight, height, gender and ASA classification. The two groups indicated similar values in the early spatial orientation at the onset of recovery and thereafter. Patients' self-evaluation of anaesthesia with main emphasis at high marks and repetition of the same anaesthesia if necessary were similar in both groups. Recalls of uncomfortable feelings were comparable but not for postoperative pain and appetite/thirst which appeared with a significantly higher incidence in the xenon group., Conclusions: Patients' self-evaluation and memory of early spatial orientation following xenon anaesthesia are comparable to propofol.

Background: Circulatory response to hypoventilation is aimed at eliminating carbon dioxide and maintaining oxygen delivery (DO(2)) by increasing cardiac output (CO). The hypothesis that this increase is more pronounced with xenon than with isoflurane anaesthesia was tested in pigs., Methods: Twenty pigs received anaesthesia with xenon 0.55 MAC/remifentanil 0.5 microg kg(-1) min(-1) (group X, n=10) or isoflurane 0.55 MAC/remifentanil 0.5 microg kg(-1)min(-1) (group I, n=10). CO, heart rate (HR), mean arterial pressure (MAP) and left ventricular fractional area change (FAC) were measured at baseline, after 5 and 15 min of hypoventilation and after 5, 15 and 30 min of restored ventilation., Results: CO increased by 10-20% with both anaesthetics, with an equivalent rise in HR, maintaining DO(2) in spite of a 20% reduction in arterial oxygen content. Decreased left ventricular (LV) afterload during hypoventilation increased FAC, and this was more marked with xenon (0.60-0.66, P<0.05 compared with baseline and isoflurane). This difference is attributed to negative inotropic effects of isoflurane. Increased pulmonary vascular resistance during hypoventilation was found with both anaesthetics., Conclusion: The cardiovascular effects observed in this model of moderate hypoventilation were sufficient to maintain DO(2). Although the haemodynamic response appeared more pronounced with xenon, differences were not clinically relevant. An increase in FAC with xenon is attributed to its lack of negative inotropic effects.

Background: The hypothesis that xenon anaesthesia provided haemodynamic stability was tested in patients with heart failure in a prospective, randomized, single-blind design., Methods: Twenty-six patients scheduled for implantation of a cardioverter-defibrillator (ICD) received xenon 60-65% in oxygen (xenon group, n = 12) or propofol 3 mg/kg/h (propofol group, n = 14), both combined with remifentanil 0.2 microg/kg/min. After induction of anaesthesia with etomidate and remifentanil, heart rate (HR), mean arterial pressure (MAP) and left ventricular ejection fraction (LVEF) were recorded. After 60 min of propofol or xenon anaesthesia, the same parameters were recorded., Results: While HR decreased in both groups, MAP was unchanged with xenon (73 vs. 76 mmHg) and decreased with propofol (from 78 to 64 mmHg, P < 0.02). LVEF was stable in both groups [32% vs. 37%, xenon (NS), and 30% vs. 34%, propofol (NS)]. Preload, as measured by end-diastolic volume (EDV), did not change (66 vs. 63 ml with xenon; 79 vs. 81 ml with propofol, both NS). Afterload, as determined by end-systolic pressure-volume product (ESPV), decreased with propofol (6760 vs. 4920 ml mmHg) but not with xenon (4060 vs. 3780 ml mmHg, P < 0.01 between groups)., Conclusion: With propofol, MAP is reduced and LVEF is not increased in spite of reduced afterload. In contrast, MAP and LVEF are maintained with xenon.