Retinal risk of endoillumination: A comparison of different ophthalmic illumination systems.

OBJECTIVES: In vitreoretinal surgery, there is always a conflict between bright illumination of the field of operation and retinal safety. This study aimed to investigate different light sources and light guides for their potential retinal risk due to bright illumination. METHODS: Irradiances in the fovea of ex-vivo porcine eyes resulting from different light sources (halogen lamp, xenon lamp and LED) and light guides are investigated for varying distances between the illumination tip and the fovea. The results are examined with regard to their photochemical and thermal retinal hazard and the maximal exposure time. The examination is carried out with the maximum intensity setting of each light source and with normalization to its brightness. MAIN RESULTS: With decreasing distance of the tip of the light source, the retinal hazard increases. The photochemical and thermal retinal hazard at maximum brightness are smallest for the halogen lamp, next for the xenon lamp and highest for the LED. Thus, the exposition time is the longest for the halogen lamp followed by the xenon lamp and the LED. Normalizing the results to the same brightness the maximum exposition time is nearly the same for xenon lamp and LED, but still higher in case of the halogen lamp. CONCLUSIONS: The choice of the most suitable lamp and illumination fiber depends on the intensity and spectral distribution of the illumination system. Concerning brightness, xenon and LED lamp are relatively harmless, but the surgeon should avoid the maximum device intensity.

Comparison of the Spectral Features of the Frontal Electroencephalogram in Patients Receiving Xenon and Sevoflurane General Anesthesia.

BACKGROUND: Depth-of-anesthesia monitoring is often utilized for patients receiving xenon anesthesia. Processed electroencephalogram (EEG) depth-of-anesthesia monitoring relies to a significant extent on frequency domain analysis of the frontal EEG, and there is evidence that the spectral features observed under anesthesia vary significantly between anesthetic agents. The spectral features of the EEG during xenon anesthesia for a surgical procedure have not previously been described. METHODS: Twenty-four participants scheduled for general anesthesia for lithotripsy were randomized to receive either xenon anesthesia or sevoflurane anesthesia. Frontal EEG recordings were obtained from each participant via the Brain Anesthesia Response Monitor (BARM). Twenty-two EEG recordings were suitable for analysis: 11 in participants who received sevoflurane and 11 in participants who received xenon. Spectrograms for the duration of the anesthetic episode were produced for each participant. Group-level spectral analysis was calculated for two 30-second EEG epochs: one recorded at awake baseline and the other during maintenance anesthesia. A linear mixed-effects model was utilized to compare the changes in 5 frequency bands from baseline to maintenance between the 2 groups. RESULTS: The spectrograms of sevoflurane participants illustrate an increase in frontal delta (0.5-4 Hz), theta (4-8 Hz), and alpha (8-13 Hz) band power during maintenance anesthesia. In contrast, spectrograms of the xenon participants did not illustrate an increase in alpha power. The results of the linear mixed-effects model indicate that both agents were associated with a significant increase in delta power from baseline to maintenance. There was no significant difference in the magnitude of this increase observed between the agents. In contrast, sevoflurane anesthesia was associated with significantly greater absolute power in the theta, alpha, and beta (13-30 Hz) bands when compared to xenon. In terms of relative power, xenon was associated with a significant increase in delta power compared to sevoflurane, while sevoflurane was associated with greater increases in relative theta, alpha, and beta power. CONCLUSIONS: Both xenon anesthesia and sevoflurane anesthesia were associated with significant increases in delta power. Sevoflurane anesthesia was also associated with increases in theta, alpha, and beta power, while xenon anesthesia was associated with greater consolidation of power in the delta band. Xenon anesthesia and sevoflurane anesthesia are associated with distinct spectral features. These findings suggest that appropriate depth-of-anesthesia monitoring may require the development of agent-specific spectral measures of unconsciousness.

In vitro thrombus formation and in vivo hemostasis mediated by platelets irradiated with bactericidal ultraviolet C from xenon flash under flow conditions.

BACKGROUND: We previously reported a flow path-ultraviolet C (UVC) irradiation system for platelet concentrates (PCs) with platelet additive solution (PAS) to minimize contamination by bacteria. Here, we investigated functionalities of irradiated platelets (PLTs) in in vitro thrombus formation and in vivo hemostasis. STUDY DESIGN AND METHODS: PAS-PCs were irradiated with flash UVC using the flow path system. Their variables (PLT count, mean platelet volume, pH, glucose, lactate, glycoprotein [GP] Ib, and activated integrin αIIbß3) were evaluated. Static adhesion to collagen or fibrinogen was analyzed using fluorescent microscopy. Thrombus formation under flow conditions was assessed using a collagen-coated bead column. Adenosine diphosphate (ADP)-induced Akt phosphorylation was determined by western blot. In vivo hemostasis and circulatory survival of PLTs were assessed with a rabbit bleeding model. RESULTS: All variables, except for GPIb expression, were slightly, but significantly, impaired after flash UVC irradiation throughout the 6-day storage period. No difference was observed in static adhesion to either collagen or fibrinogen between irradiated and nonirradiated PAS-PCs. In vitro thrombus formation of flash UVC-irradiated PAS-PCs was significantly greater than that of nonirradiated PAS-PCs. ADP-induced Akt phosphorylation was enhanced in irradiated PAS-PCs. In vivo hemostatic efficacy was comparable between the groups on Day 1. The efficacy declined in nonirradiated PAS-PCs on Day 5, while it was retained in flash UVC-irradiated PAS-PCs. Circulatory survival of PLTs was lower in irradiated PAS-PCs. CONCLUSIONS: PAS-PCs irradiated with UVC from xenon flash have favorable properties to achieve hemostasis compared with nonirradiated PAS-PCs.

Effect of xenon and dexmedetomidine as adjuncts for general anesthesia on postoperative emergence delirium after elective cardiac catheterization in children: study protocol for a randomized, controlled, pilot trial.

BACKGROUND: Emergence delirium, a manifestation of acute postoperative brain dysfunction, is frequently observed after pediatric anesthesia and has been associated with the use of sevoflurane. Both xenon and dexmedetomidine possess numerous desirable properties for the anesthesia of children with congenital heart disease, including hemodynamic stability, lack of neurotoxicity, and a reduced incidence of emergence delirium. Combining both drugs has never been studied as a balanced-anesthesia technique. This combination allows the provision of anesthesia without administering anesthetic drugs against which the Food and Drug Administration (FDA) issued a warning for the use in young children. METHODS/DESIGN: In this phase-II, mono-center, prospective, single-blinded, randomized, controlled pilot trial, we will include a total of 80 children aged 0-3 years suffering from congenital heart disease and undergoing general anesthesia for elective diagnostic and/or interventional cardiac catheterization. Patients are randomized into two study groups, receiving either a combination of xenon and dexmedetomidine or mono-anesthesia with sevoflurane for the maintenance of anesthesia. The purpose of this study is to estimate the effect size for xenon-dexmedetomidine versus sevoflurane anesthesia with respect to the incidence of emergence delirium in children. We will also describe group differences for a variety of secondary outcome parameters including peri-interventional hemodynamics, emergence characteristics, incidence of postoperative vomiting, and the feasibility of a combined xenon-dexmedetomidine anesthesia in children. DISCUSSION: Sevoflurane is the most frequently used anesthetic in young children, but has been indicated as an independent risk factor in the development of emergence delirium. Xenon and dexmedetomidine have both been associated with a reduction in the incidence of emergence delirium. Combining xenon and dexmedetomidine has never been described as a balanced-anesthesia technique in children. Our pilot study will therefore deliver important data required for future prospective clinical trials. TRIAL REGISTRATION: EudraCT, 2018-002258-56. Registered on 20 August 2018. https://www.clinicaltrialsregister.eu.

Prospective qualification of early cerebral biomarkers in a randomised trial of treatment with xenon combined with moderate hypothermia after birth asphyxia.

BACKGROUND: The TOBY-Xe proof of concept randomised trial found no effect of xenon combined with hypothermia after birth asphyxia on the lactate to N-acetyl aspartate ratio (Lac/NAA) in the thalamus and fractional anisotropy (FA) in white matter tracts measured within 15 days of birth. To confirm that these biomarkers are qualified to predict long-term outcome after neural rescue therapy we assessed surviving participants at 2-3 years of age. METHODS: Of the 92 infants in TOBY-Xe, one was omitted from the study, 69 survived and we assessed 62 participants, 32 in the hypothermia and xenon and 30 in the hypothermia only groups. We examined the relation between Lac/NAA and FA and the scores of the Bayley Scales of Infant and Toddler Development III and calculated their predictive accuracy for moderate or severe disability or death. RESULTS: Fifteen of 62 participants (24%) developed moderate/severe disability, and 22/92 (24%) died. The Lac/NAA ratio (difference in medians 0.628, 95% CI -0.392 to 4.684) and FA (difference in means -0.055, 95% CI -0.033 to -0.077) differed significantly between participants with or without moderate or severe disability or death and were significantly related with development scores in both groups. Adverse outcomes were correctly identified in 95.65% of cases by Lac/NAA and 78.79% by FA, with adequate mean calibration of the model. INTERPRETATION: The results confirm the qualification of the cerebral magnetic resonance biomarkers employed in the TOBY-Xe study as predictors of outcome after neuroprotective therapy. FUND: The Centre for the Developing Brain, King's College London, UK.

Xenon anesthesia and beyond: pros and cons.

Xenon is a colorless and odorless noble gas, licensed for human use as an anesthetic gas as well as a radiological marker. The MAC of this gas is about 63% but xenon anesthesia is associated with fast recovery of cognitive function and cardiovascular stability. Nevertheless, postoperative nausea and vomiting (PONV) incidence for xenon anesthesia is very high. It has been reported that Xenon has cytoprotective effects that may have therapeutic values in both CNS protection, and in organ graft preservation. Currently, there are few studies about the effect of xenon on ischemia reperfusion injury of transplantable organs and insufficient clinical data upon its effect on intracranial and cerebral perfusion pressure. We shortly review the pros and cons of xenon as an anesthetic agent.

Xenon anesthesia for awake craniotomy: safety and efficacy.

BACKGROUND: The asleep-awake-asleep (AAA) craniotomy is a technique that offers the opportunity of having a patient fully cooperative during the awake phase, and minimizes the possible discomfort, due to the asleep phase. The aim of this prospective observational study was to test the use of xenon in the first asleep phase of an AAA craniotomy, in patients undergoing craniotomy for brain tumor resection. METHODS: The data have been collected from 40 awake craniotomy procedures, performed in patients with cerebral tumor, treated with the AAA technique. Patients were treated with xenon during the asleep phase, and quality of mapping, complications and qualitative judgment of the experience given by the patients were recorded. RESULTS: The mapping was carried out as planned in 37 out of 40 cases. The doses of xenon administered during the first asleep phase of the anesthesia was 13±2 L. Time for awakening after xenon was switched off was 5±1 minute. A combination of xenon and regional anesthesia (with no need for additional systemic anesthetics) was adequate to accomplish craniotomy in 27/40 patients (67.5%). On the day after the operation, 37 patients recalled the testing procedure for mapping during the awake period, none had recollection of local anesthetic injections for regional anesthesia or sound associated with the neurosurgical drill. Five patients (12.5%) reported mild pain during tumor removal (VAS Score less than three). CONCLUSIONS: In this case series, xenon anesthesia was successfully used for the sedative phase of an awake craniotomy accomplished with an AAA approach.

Evaluation of xenon, light-emitting diode (LED) and halogen light toxicity on cultured retinal pigment epithelial cells.

OBJECTIVE: To compare the possible toxic effects of three light sources used in vitreoretinal endoillumination systems; halogen, xenon, and light-emitting diode (LED) on retinal pigment epithelium (RPE) cell cultures, after two different exposure times. MATERIAL AND METHODS: ARPE-19 human RPE cell cultures were exposed to halogen, xenon, and LED light sources at a distance of 1.5 cm for 30 and 60 min with equal lumen output levels. Cells in the control group were not exposed. RPE cell cultures were compared in terms of cell viability, DNA damage, apoptosis rate, and IL-1ß, IL-6, and TNF- α levels. RESULTS: The halogen light group showed significantly more DNA damage, higher TNF-α, IL-1ß, and IL-6 levels, and lower viable cell count at 30 min compared to the control group. The rates of early and late apoptosis were also significantly higher at 60 min. There were no statistically significant differences in any of the parameters between the xenon and LED light sources and the control group at 30 or 60 min. CONCLUSION: New generation lights, xenon, and LED, seem to be safe in terms of RPE cells. Halogen light may cause toxic effects on RPE cells when used for a long time with maximal power output.

A Feasibility Study of Single-inhalation, Single-energy Xenon-enhanced CT for High-resolution Imaging of Regional Lung Ventilation in Humans.

RATIONALE AND OBJECTIVES: The objective of this study was to assess the feasibility of single-inhalation xenon-enhanced computed tomography (XeCT) to provide clinically practical, high-resolution pulmonary ventilation imaging to clinics with access to only a single-energy computed tomography scanner, and to reduce the subject's overall exposure to xenon by utilizing a higher (70%) concentration for a much shorter time than has been employed in prior studies. MATERIALS AND METHODS: We conducted an institutional review board-approved prospective feasibility study of XeCT for 15 patients undergoing thoracic radiotherapy. For XeCT, we acquired two breath-hold single-energy computed tomography images of the entire lung with a single inhalation each of 100% oxygen and a mixture of 70% xenon and 30% oxygen, respectively. A video biofeedback system for coached patient breathing was used to achieve reproducible breath holds. We assessed the technical success of XeCT acquisition and side effects. We then used deformable image registration to align the breath-hold images with each other to accurately subtract them, producing a map of lung xenon distribution. Additionally, we acquired ventilation single-photon emission computed tomography-computed tomography (V-SPECT-CT) images for 11 of the 15 patients. For a comparative analysis, we partitioned each lung into 12 sectors, calculated the xenon concentration from the Hounsfield unit enhancement in each sector, and then correlated this with the corresponding V-SPECT-CT counts. RESULTS: XeCT scans were tolerated well overall, with a mild (grade 1) dizziness as the only side effect in 5 of the 15 patients. Technical failures in five patients occurred because of inaccurate breathing synchronization with xenon gas delivery, leaving seven patients analyzable for XeCT and single-photon emission computed tomography correlation. Sector-wise correlations were strong (Spearman coefficient >0.75, Pearson coefficient >0.65, P value <.002) for two patients for whom ventilation deficits were visibly pronounced in both scans. Correlations were nonsignificant for the remaining five who had more homogeneous XeCT ventilation maps, as well as strong V-SPECT-CT imaging artifacts attributable to airway deposition of the aerosolized imaging agent. Qualitatively, XeCT demonstrated higher resolution and no central airway deposition artifacts compared to V-SPECT-CT. CONCLUSIONS: In this pilot study, single-breath XeCT ventilation imaging was generally feasible for patients undergoing thoracic radiotherapy, using an imaging protocol that is clinically practical and potentially widely available. In the future, the xenon delivery failures can be addressed by straightforward technical improvements to the patient biofeedback coaching system.

The effect of xenon-augmented sevoflurane anesthesia on intraoperative hemodynamics and early postoperative neurocognitive function in children undergoing cardiac catheterization: A randomized controlled pilot trial.

BACKGROUND: In adults, xenon has only minimal hemodynamic side effects when compared with other anesthetics. Moreover, in preclinical experiments, xenon has been demonstrated to possess cardio- and neuroprotective properties. Altogether, the favorable hemodynamic profile combined with its potential for organ-protection could render xenon an attractive option for anesthesia in children with cardiovascular compromise. AIMS: The aim of this study was to explore safety and feasibility of sevoflurane-augmented xenon anesthesia in school-aged children and to assess early postoperative neurocognitive effects of xenon-sevoflurane and sevoflurane anesthesia when compared to a control group that did not have anesthesia. METHODS: Forty children aged 4-12 years, suffering from congenital heart disease, undergoing diagnostic or interventional cardiac catheterization were randomized to either xenon-augmented sevoflurane anesthesia or sevoflurane alone. Safety was assessed by the incidence of intraprocedural hemodynamic instability and feasibility by anesthetic depth and respiratory profile. In addition, neurocognitive performance was assessed preoperatively, 2 hours after discharge from PACU and at 24 hours after anesthesia using the Amsterdam Neuropsychological Tasks system. A healthy control group of 22 age- and gender-matched children not exposed to anesthesia underwent an identical neurocognitive test battery, at comparable time intervals. RESULTS: Overall hemodynamics did not differ between groups. Xenon-sevoflurane anesthesia resulted in decreased intraoperative ephedrine requirements (median [IQR]) (0.00 mg/kg [0.00-0.00] vs 0.00 mg/kg [0.00-0.01], P = 0.047). Only neurocognitive tests in the domain of alertness were significantly impaired 2 hours postoperatively in both anesthesia groups in comparison with the control group (alertness variability: P = 0.02, odds ratio 5.8), but recovered at 24 hours. For working memory, inhibition, cognitive flexibility, and motor coordination tasks, no significant interaction effects of anesthesia were found in the early postoperative period. CONCLUSION: In this pilot trial, xenon-augmented sevoflurane anesthesia in school-aged children was feasible, and associated with decreased ephedrine requirements. All children exposed to anesthesia showed impaired neurocognitive performance in the immediate postoperative period when compared to control children; however, without significant differences between both treatment groups.

Renal function following xenon anesthesia for partial nephrectomy-An explorative analysis of a randomized controlled study.

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.

Photoprotection and photoreception of intraocular lenses under xenon and white LED illumination.

OBJECTIVE: To analyze the photoprotection and phototransmission that various intraocular lenses (IOLs) provide under the illumination of a xenon (Xe) lamp and white LEDs (light emitting diode). METHODS: The spectral transmission curves of six representative IOLs were measured using a Perkin-Elmer Lambda 35 UV/VIS spectrometer. Various filtering simulations were performed using a Xe lamp and white LEDs. The spectral emissions of these lamps were measured with an ILT-950 spectroradiometer. RESULTS: The IOLs analyzed primarily show transmission of nearly 100% in the visible spectrum. In the ultraviolet (UV) region, the filters incorporated in the various IOLs did not filter equally, and some of them let an appreciable amount of UV through. The Xe lamp presented a strong emission of ultraviolet A (UVA), and its emission under 300nm was not negligible. The white LED did not present an appreciable emission under 380nm. CONCLUSIONS: The cut-off wavelength of most filters is between 380 and 400nm (Physiol Hydriol60C(®), IOLTECH E4T(®), Alcon SA60AT(®), Alcon IQ SN60WF(®)), so that their UV protection is very effective. Nonetheless, the IOL OPHTEC Oculaid(®) contains a filter that, when a Xe lamp is used, lets through up to 20% for 350nm and up to 15% for 300nm, which at this point is ultraviolet B (UVB). The OPHTEC(®) Artisan IOL has a transmission peak below 300nm, which must be taken into account under Xe illumination. White LEDs do not emit energy below 380nm, so no special protection is required in the UV region.

Nausea and Vomiting following Balanced Xenon Anesthesia Compared to Sevoflurane: A Post-Hoc Explorative Analysis of a Randomized Controlled Trial.

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.

Preclinical neuroprotective actions of xenon and possible implications for human therapeutics: a narrative review.

PURPOSE: The purpose of this report is to facilitate an understanding of the possible application of xenon for neuroprotection in critical care settings. This narrative review appraises the literature assessing the efficacy and safety of xenon in preclinical models of acute ongoing neurologic injury. SOURCE: Databases of the published literature (MEDLINE® and EMBASE™) were appraised for peer-reviewed manuscripts addressing the use of xenon in both preclinical models and disease states of acute ongoing neurologic injury. For randomized clinical trials not yet reported, the investigators' declarations in the National Institutes of Health clinical trials website were considered. PRINCIPAL FINDINGS: While not a primary focus of this review, to date, xenon cannot be distinguished as superior for surgical anesthesia over existing alternatives in adults. Nevertheless, studies in a variety of preclinical disease models from multiple laboratories have consistently shown xenon's neuroprotective properties. These properties are enhanced in settings where xenon is combined with hypothermia. Small randomized clinical trials are underway to explore xenon's efficacy and safety in clinical settings of acute neurologic injury where hypothermia is the current standard of care. CONCLUSION: According to the evidence to date, the neuroprotective efficacy of xenon in preclinical models and its safety in clinical anesthesia set the stage for the launch of randomized clinical trials to determine whether these encouraging neuroprotective findings can be translated into clinical utility.

Xenon Anesthesia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Xenon anesthesia has been studied for decades. However, no meta-analysis of randomized controlled trials (RCTs) on xenon anesthesia has been conducted. The aim of this study was to systematically review all available evidence from RCTs comparing xenon and other inhaled and IV anesthetics on anesthetic outcomes. Our meta-analysis attempted to quantify the effects of xenon anesthesia on clinical outcomes in relation to other anesthetics. METHODS: We found 43 RCTs from PubMed, MEDLINE, CENTRAL, EMBASE, and CINAHL (until January 2015). A total of 31 studies comparing xenon (841 patients) with other inhaled agents (836 patients) and 12 studies comparing xenon (373 patients) with propofol (360 patients) were found. We evaluated clinical outcomes, such as intraoperative hemodynamics, emergence, and postoperative nausea and vomiting (PONV). RESULTS: Patients undergoing xenon anesthesia had a lower heart rate and higher mean arterial pressure (MAP) intraoperatively than those receiving volatile anesthesia (mean difference = -6 min⁻¹ [99% confidence interval {99% CI} -10.0 to -2.3]; mean difference = 9 mm Hg [99% CI 3.1-14.4]) and propofol anesthesia (mean difference = -10 min⁻¹ [99% CI -12.4 to -6.6]; mean difference = 7 mm Hg [99% CI 0.85-13.2]). Compared with baseline, intraoperative MAP remained relatively stable (change < 5.5%, 99% CI within ±20% of the baseline) under xenon anesthesia, but MAP decreased by ≥15% under volatile (mean difference = -17 mm Hg [99% CI -29.5 to - 4.9], percentage change = -17.5%) and propofol (mean difference = -14 mm Hg [99% CI -26.1 to -2.5], percentage change = -15.0%) anesthesia. Patients had faster emergence from xenon than from volatile anesthesia: eyes opening (versus all volatile agents: mean 4 vs 7 minutes, percentage change = -49.8% [99% CI -55.1% to -44.0%]), tracheal extubation (versus all volatile agents: mean 4 vs 8 minutes percentage change = -44.6% [99% CI -57.3% to -28.1%]), orientation (versus sevoflurane: mean 5 vs 10 minutes, percentage change = -45.1% [99% CI -58.5% to -28.1%]), countdown (versus sevoflurane: mean 6 vs 10 minutes, percentage change = -41.7% [99% CI -50.3% to -31.6%]; versus isoflurane: mean 6 vs 14 minutes, percentage change = -57.7% [99% CI -65.7% to -48.3%]), and reaction on demand (versus sevoflurane: mean 4 vs 8 minutes, percentage change = -53.2% [99% CI -65.7% to -35.6%]). However, xenon anesthesia increased the risks of PONV (incidence 34.4% vs 19.9%; risk ratio = 1.72 [99% CI 1.10-2.69], risk difference = 0.19 [99% CI 0.04-0.33]). CONCLUSIONS: Xenon anesthesia provides relatively more stable intraoperative blood pressure, lower heart rate, and faster emergence from anesthesia than volatile and propofol anesthesia. However, xenon is associated with a higher incidence of PONV.

Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial.

BACKGROUND: Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. METHODS: Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36-43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. FINDINGS: The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments and were included in the analysis of the primary outcomes. We noted no significant differences in lactate to N-acetyl aspartate ratio in the thalamus (geometric mean ratio 1·09, 95% CI 0·90 to 1·32) or fractional anisotropy (mean difference -0·01, 95% CI -0·03 to 0·02) in the posterior limb of the internal capsule between the two groups. Nine infants died in the cooling group and 11 in the xenon group. Two adverse events were reported in the xenon group: subcutaneous fat necrosis and transient desaturation during the MRI. No serious adverse events were recorded. INTERPRETATION: Administration of xenon within the delayed timeframe used in this trial is feasible and apparently safe, but is unlikely to enhance the neuroprotective effect of cooling after birth asphyxia. FUNDING: UK Medical Research Council.

Xenon for the prevention of postoperative delirium in cardiac surgery: study protocol for a randomized controlled clinical trial.

BACKGROUND: Postoperative delirium (POD) is a manifestation of acute postoperative brain dysfunction that is frequently observed after cardiac surgery. POD is associated with short-term complications such as an increase in mortality, morbidity, costs and length of stay, but can also have long-term sequelae, including persistent cognitive deficits, loss of independence, and increased mortality for up to 2 years. The noble gas xenon has been demonstrated in various models of neuronal injury to exhibit remarkable neuroprotective properties. We therefore hypothesize that xenon anesthesia reduces the incidence of POD in elderly patients undergoing cardiac surgery with the use of cardiopulmonary bypass. METHODS/DESIGN: One hundred and ninety patients, older than 65 years, and scheduled for elective cardiac surgery, will be enrolled in this prospective, randomized, controlled trial. Patients will be randomized to receive general anesthesia with either xenon or sevoflurane. Primary outcome parameter will be the incidence of POD in the first 5 postoperative days. The occurrence of POD will be assessed by trained research personnel, blinded to study group, with the validated 3-minute Diagnostic Confusion Assessment Method (3D-CAM) (on the intensive care unit in its version specifically adapted for the ICU), in addition to chart review and the results of delirium screening tools that will be performed by the bedside nurses). Secondary outcome parameters include duration and severity of POD, and postoperative cognitive function as assessed with the Mini-Mental State Examination. DISCUSSION: Older patients undergoing cardiac surgery are at particular risk to develop POD. Xenon provides remarkable hemodynamic stability and has been suggested in preclinical studies to exhibit neuroprotective properties. The present trial will assess whether the promising profile of xenon can be translated into a better outcome in the geriatric population. TRIAL REGISTRATION: EudraCT Identifier: 2014-005370-11 (13 May 2015).

Xenon triggers pro-inflammatory effects and suppresses the anti-inflammatory response compared to sevoflurane in patients undergoing cardiac surgery.

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).