Emergence delirium in children is not related to intraoperative burst suppression - prospective, observational electrography study.

BACKGROUND: Emergence-delirium is the most frequent brain dysfunction in children recovering from general anaesthesia, though the pathophysiological background remains unclear. The presented study analysed an association between emergence delirium and intraoperative Burst Suppression activity in the electroencephalogram, a period of very deep hypnosis during general anaesthesia. METHODS: In this prospective, observational cohort study at the Charité - university hospital in Berlin / Germany children aged 0.5 to 8 years, undergoing planned surgery, were included between September 2015 and February 2017. Intraoperative bi-frontal electroencephalograms were recorded. Occurrence and duration of Burst Suppression periods were visually analysed. Emergence delirium was assessed using the Pediatric Assessment of Emergence Delirium Score. RESULTS: From 97 children being analysed within this study, 40 children developed emergence delirium, and 57 children did not. Overall 52% of the children displayed intraoperative Burst Suppression periods; however, occurrence and duration of Burst Suppression (Emergence delirium group 55% / 261 + 462 s vs. Non-emergence delirium group 49% / 318 + 531 s) did not differ significantly between both groups. CONCLUSIONS: Our data reveal no correlation between the occurrence and duration of intraoperative Burst Suppression activity and the incidence of emergence delirium. Burst Suppression occurrence is frequent; however, it does not seem to have an unfavourable impact on cerebral function at emergence from general anaesthesia in children. TRAIL REGISTRATION: NCT02481999, June 25, 2015.

Better haemodynamic stability under xenon anaesthesia than under isoflurane anaesthesia during partial nephrectomy - a secondary analysis of a randomised controlled trial.

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.

Emergence delirium in children is related to epileptiform discharges during anaesthesia induction: An observational study.

BACKGROUND: Epileptiform discharges frequently occur in children during induction of anaesthesia. However, studies analysing the impact of epileptiform discharges on postoperative emergence delirium in children are still scarce. The aim of this study is to correlate the incidence of epileptiform activity during anaesthesia induction with the occurrence of emergence delirium during stay in the recovery room. OBJECTIVES: Prospective, observational cohort study in children 0.5 to 8 years old undergoing planned surgery. Bifrontal electroencephalogram electrodes were placed before induction of anaesthesia. Visual electroencephalogram analysis was performed from start of anaesthetic agent administration until intubation with regard to epileptiform patterns: rhythmic polyspikes; periodic epileptiform discharges; delta with spikes; and suppression with spikes. Emergence delirium was assessed during stay in the recovery room using the Pediatric Assessment of Emergence Delirium Score. DESIGN: Prospective, observational cohort study. SETTING: University hospital - Germany/Berlin. Children were included between September 2015 and February 2017. PATIENTS: A total of 62 Children, aged 0.5 to 8 years old undergoing planned surgery were included. MAIN OUTCOME MEASURES: Primary outcome was emergence delirium. Secondary outcomes, peri-operative Electroencephalography (EEG) data analysis. The presented study analysed an association between emergence delirium and the occurrence of epileptiform discharges during anaesthesia induction. RESULTS: A total of 43.5% of the children developed emergence delirium and 56.5% did not. Epileptiform discharges were observed more often in children developing emergence delirium (63%) compared with children not developing emergence delirium (43%). But only the occurrence of interictal spike events - such as rhythmic polyspikes; periodic epileptiform discharges and delta with spikes - were significantly related to emergence delirium (emergence delirium-group 48% vs. nonemergence delirium-group 14%, OR = 5.6 [95% CI: 1.7 to 18.7]; P = 0.004). CONCLUSION: Emergence delirium in children is significantly related to interictal spike events occurring during induction of anaesthesia. CLINICAL TRIAL: NCT02481999.

Incidence of epileptiform discharges in children during induction of anaesthesia using Propofol versus Sevoflurane.

OBJECTIVE: In pediatric patients, anaesthesia induction is often performed with intravenous Propofol or Sevoflurane inhalation. Although epileptiform discharges have been observed during inductions with Sevoflurane, their occurrence has not been investigated for i.v. Propofol inductions. The aim of this study is to compare the incidence of epileptiform discharges in children during anaesthesia induction using Propofol versus Sevoflurane. METHODS: Prospective, observational cohort study in children aged 0.5-8 years undergoing elective surgery. Children were anaesthetized with either Propofol or Sevoflurane. Bi-frontal electroencephalograms electrodes were placed before start of anaesthesia. Visual electroencephalogram analysis was performed from start of anesthetic agent administration until Intubation with regard to identify epileptiform patterns, i.e. delta with spikes; rhythmic polyspikes; periodic, epileptiform discharges; or suppression with spikes. RESULTS: 39 children were anaesthetized with Propofol, and 18 children with Sevoflurane. Epileptiform discharges were seen in 36% of the children in the Propofol group, versus 67% in the Sevoflurane group (p = 0.03). Incidence of the distinct types of epileptiform discharge differed for periodic, epileptiform discharges (Sevoflurane group 39% vs. Propofol group 3%; p < 0.001). Higher concentration of Remifentanil (≥0.15 µg/kg/min) was associated with less frequent epileptiform discharges (Exp 5.8; CI 95% 1.6/21.2; p = 0.008). CONCLUSIONS: Propofol i.v. induction of anaesthesia in children triggers epileptiform discharges, whereas to a lesser extent than Sevoflurane does. SIGNIFICANCE: Presuming that epileptiform discharges have an impact on postoperative brain function, it is advisable to use Propofol rather than Sevoflurane and higher level of Remifentanil for anaesthesia induction in children.

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.

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.

Immunotoxicity Monitoring in a Population Exposed to Polychlorinated Biphenyls.

The relationship between polychlorinated biphenyl (PCB) burden and several indicators of immune function was investigated as part of the HELPcB (Health Effects in High-Level Exposure to PCB) program, offering bio-monitoring to workers, relatives, and neighbors exposed to PCBs by a German transformers and capacitors recycling company. The present retrospective observational study evaluates the correlation of plasma levels of total PCBs, five indicator congeners (28, 101, 138, 153, 180), and seven dioxin-like congeners (105, 114, 118, 156, 157, 167, 189) with several parameters of immune function. The cross-sectional study was performed immediately after the end of exposure (258 subjects), and one (218 subjects), and two (177 subjects) years later. At the first time point, measurements showed significant positive correlation between congeners with low to medium chlorination and the relative proportion of CD19 positive B-cells among lymphocytes, as well as a negative correlation of PCB114 with serum IgM, and of PCB 28 with suppressor T-cell and NK-cell numbers. Congeners with a high degree of chlorination, in particular PCB157 and 189, were positively associated with expression of the activation marker CD25 on T-cells in the cohort of the second time point. No associations between PCB levels and IFN-y production by T-cells and killing by NK-cells were found. In conclusion, there were several effects on the cellular composition of adaptive immunity, affecting both T- and B-cells. However, the values were not generally outside the reference ranges for healthy adult individuals and did not indicate overt functional immunodeficiency, even in subjects with the uppermost PCB burden.

Argon: systematic review on neuro- and organoprotective properties of an "inert" gas.

Argon belongs to the group of noble gases, which are regarded as chemically inert. Astonishingly some of these gases exert biological properties and during the last decades more and more reports demonstrated neuroprotective and organoprotective effects. Recent studies predominately use in vivo or in vitro models for ischemic pathologies to investigate the effect of argon treatment. Promising data has been published concerning pathologies like cerebral ischemia, traumatic brain injury and hypoxic ischemic encephalopathy. However, models applied and administration of the therapeutic gas vary. Here we provide a systematic review to summarize the available data on argon's neuro- and organoprotective effects and discuss its possible mechanism of action. We aim to provide a summary to allow further studies with a more homogeneous setting to investigate possible clinical applications of argon.

Expression analysis following argon treatment in an in vivo model of transient middle cerebral artery occlusion in rats.

BACKGROUND: Argon treatment following experimental neurotrauma has been found neuroprotective in an array of in vivo and in vitro models. The inherent cellular and molecular mechanisms are still unknown. We seeked to shed light on these processes by examinig the cellular distribution and the expression of inflammatory markers and growth factors in argon treated brain tissue. METHODS: Male adult Sprague-Dawley rats were randomly assigned to one of the study groups: sham surgery + placebo, sham surgery + argon, tMCAO + placebo, and tMCAO + argon. Animals underwent 2 h-transient middle cerebral artery occlusion (tMCAO) using the endoluminal thread model or sham surgery without tMCAO. After the first hour of tMCAO or sham surgery a 1 h inhalative argon (50% argon/50% O2) or placebo (50% N2/50% O2) treatment was performed. Brains were removed and evaluated after 24 h. RealTime-PCR was performed from biopsies of the penumbra and contralateral corresponding regions. Paraffin sections were immunostained with antibodies against GFAP, NeuN, and Iba1. Cell counts of astrocytes, neurons and microglia in different cortical regions were performed in a double-blinded manner. RESULTS: Fifteen animals per tMCAO group and twelve sham + placebo respectively eleven sham + argon animals completed the interventional procedure. We identified several genes (IL-1ß, IL-6, iNOS, TGF-ß, and NGF) whose transcription was elevated 24 h after the study intervention, and whose expression levels significantly differed between argon treatment and placebo following tMCAO. Except for the core region of ischemia, cell numbers were comparable between different treatment groups. CONCLUSION: In our study, we found an elevated expression of several inflammatory markers and growth factors following tMCAO + argon compared to tMCAO + placebo. Although conflicting the previously described neuroprotective effects of argon following experimental ischemia, these findings might still be associated with each other. Further studies will have to evaluate their relevance and potential relationship.

Xenon consumption during general surgery: a retrospective observational study.

BACKGROUND: High costs still limits the widespread use of xenon in the clinical practice. Therefore, we evaluated xenon consumption of different delivery modes during general surgery. METHODS: A total of 48 patients that underwent general surgery with balanced xenon anaesthesia were retrospectively analysed according to the mode of xenon delivery during maintenance phase (ECO mode, AUTO mode or MANUAL mode). RESULTS: Xenon consumption was highest during the wash-in phase (9.4 ± 2.1l) and further decreased throughout maintenance of anaesthesia. Comparison of different xenon delivery modes revealed significant reduced xenon consumption during ECO mode (18.5 ± 3.7L (ECO) vs. 24.7 ± 11.5L (AUTO) vs. 29.6 ± 14.3L (MANUAL); p = 0.033). No differences could be detected with regard to anaesthetic depth, oxygenation or performance of anaesthesia. CONCLUSION: The closed-circuit respirator Felix Dual offers effective reduction of xenon consumption during general surgery when ECO mode is used.

Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury.

BACKGROUND: The α2-adrenoreceptor agonist dexmedetomidine is known to provide neuroprotection under ischemic conditions. In this study we investigated whether dexmedetomidine has a protective effect in an in vitro model for traumatic brain injury. METHODS: Organotypic hippocampal slice cultures were subjected to a focal mechanical trauma and then exposed to varying concentrations of dexmedetomidine. After 72 h cell injury was assessed using propidium iodide. In addition, the effects of delayed dexmedetomidine application, of hypothermia and canonical signalling pathway inhibitors were examined. RESULTS: Dexmedetomidine showed a protective effect on traumatically injured hippocampal cells with a maximum effect at a dosage of 1 µM. This effect was partially reversed by the simultaneous administration of the ERK inhibitor PD98059. CONCLUSION: In this TBI model dexmedetomidine had a significant neuroprotective effect. Our results indicate that activation of ERK might be involved in mediating this effect.

The noble gas argon modifies extracellular signal-regulated kinase 1/2 signaling in neurons and glial cells.

Recently, the noble gas argon has been identified as a potent neuroprotective agent, but little is known about its cellular effects. In this in vitro study, we investigated argon's influence on the extracellular signal-regulated kinase (ERK) 1/2, a ubiquitous enzyme with numerous functions in cell proliferation and survival. Primary neuronal and astroglial cell cultures and the microglial cell line BV-2 were exposed to 50 vol.% argon. Further possible effects were studied following stimulation of microglia with 50 ng/ml LPS. ERK 1/2 activation was assessed by phosphorylation state-specific western blotting, cytokine levels by real-time PCR and western blotting. Total phosphotyrosine phosphatase activity was examined with p-nitrophenylphosphate. After 30 min exposure, argon significantly activated ERK 1/2 signaling in microglia. Enhanced phosphorylation of ERK 1/2 was also found in astrocytes and neurons following argon exposure, but it lacked statistical significance. In microglia, argon did not substantially interfere with LPS-induced ERK1/2 activation and inflammatory cytokine induction. Addition of the MEK-Inhibitor U0126 abolished the induced ERK 1/2 phosphorylation. Cellular phosphatase activity and the inactivation of phosphorylated ERK 1/2 were not altered by argon. In conclusion, argon enhanced ERK 1/2 activity in microglia via the upstream kinase MEK, probably through a direct mode of activation. ERK 1/2 signaling in astrocytes and neurons in vitro was also influenced, although not with statistical significance. Whether ERK 1/2 activation by argon affects cellular functions like differentiation and survival in the brain in vivo will have to be determined in future experiments.

Early cognitive function, recovery and well-being after sevoflurane and xenon anaesthesia in the elderly: a double-blinded randomized controlled trial.

BACKGROUND: The postoperative cognitive function is impaired in elderly patients after general anaesthesia. The fast recovery after xenon anaesthesia was hypothesized to be advantageous in this scenario. We compared early postoperative cognitive function after xenon and sevoflurane anaesthesia in this study. METHODS: The study was approved by the local ethics committee and written informed consent was obtained from each patient. Patients aged 65-75 years (ASA I-III) scheduled for elective surgery (duration 60-180 min) were enrolled. Investigators performing cognitive testing and patients were blinded towards allocation to either xenon or sevoflurane anaesthesia. Baseline assessment of cognitive function was carried out 12-24 h before the operation. The results were compared to follow-up tests 6-12 and 66-72 h after surgery. Primary outcome parameter was the subtest "Alertness" of the computerized Test of Attentional Performance (TAP). Secondary outcome parameters included further subtests of the TAP, several Paper-Pencil-Tests, emergence times from anaesthesia, modified Aldrete scores and patients' well-being. RESULTS: 40 patients were randomized and equally allocated to both groups. No significant differences were found in the TAP or the Paper-Pencil-Tests at 6-12 and 66-72 h after the operation. All emergence times were faster after xenon anaesthesia. The modified Aldrete scores were significantly higher during the first hour in the xenon group. No difference in well-being could be detected between both groups. CONCLUSIONS: The results show no difference in the incidence of postoperative cognitive dysfunction (POCD) after xenon or sevoflurane anaesthesia. Emergence from general anaesthesia was faster in the xenon group.

Solulin reduces infarct volume and regulates gene-expression in transient middle cerebral artery occlusion in rats.

BACKGROUND: Thrombolysis after acute ischemic stroke has only proven to be beneficial in a subset of patients. The soluble recombinant analogue of human thrombomodulin, Solulin, was studied in an in vivo rat model of acute ischemic stroke. METHODS: Male SD rats were subjected to 2 hrs of transient middle cerebral artery occlusion (tMCAO). Rats treated with Solulin intravenously shortly before reperfusion were compared to rats receiving normal saline i.v. with respect to infarct volumes, neurological deficits and mortality. Gene expression of IL-6, IL-1ß, TNF-α, MMP-9, CD11B and GFAP were semiquantitatively analyzed by rtPCR of the penumbra. RESULTS: 24 hrs after reperfusion, rats were neurologically tested, euthanized and infarct volumes determined. Solulin significantly reduced mean total (p=0.001), cortical (p=0.002), and basal ganglia (p=0.036) infarct volumes. Hippocampal infarct volumes (p=0.191) were not significantly affected. Solulin significantly downregulated the expression of IL-1ß (79%; p<0.001), TNF-α (59%; p=0.001), IL-6 (47%; p=0.04), and CD11B (49%; p=0.001) in the infarcted cortex compared to controls. CONCLUSIONS: Solulin reduced mean total, cortical and basal ganglia infarct volumes and regulated a subset of cytokines and proteases after tMCAO suggesting the potency of this compound for therapeutic interventions.

Neuroprotective effects of argon in an in vivo model of transient middle cerebral artery occlusion in rats.

OBJECTIVE: The neuroprotective effects of the noble gas xenon are well known. Argon, in contrast to xenon, is abundant, inexpensive, and therefore widely applicable. In this study, we analyzed the possible neuroprotective role of argon in an in vivo rat model of acute focal cerebral ischemia. DESIGN: Controlled laboratory study. SETTING: Academic research laboratory. SUBJECTS: Male adult Sprague-Dawley rats. INTERVENTIONS: Twenty-two rats underwent 2 hrs of transient middle cerebral artery occlusion using the endoluminal thread model. One hr after transient middle cerebral artery occlusion induction, spontaneously breathing rats received either 50 vol % argon/50 vol % O2 (argon group, n = 11) or 50 vol % N2/50 vol % O2 (control group, n = 11) for 1 hr through a face mask. Twenty-four hrs after reperfusion, rats were neurologically and behaviorally tested and euthanized. Rat brains were stained with 2,3,5-triphenyltetrazolium chloride and infarct volumes determined by planimetry. MEASUREMENTS AND MAIN RESULTS: After 2 hrs of transient middle cerebral artery occlusion in the rat, we found in the argon group a significant reduction in the overall (p = .004) and after subdivision in the cortical (p = .007) and the basal ganglia (p = .02) infarct volumes. Argon treatment resulted in a significant improvement of the composite adverse outcome (p = .034). However, there was no advantage in acute survival 24 hrs after transient middle cerebral artery occlusion (p = .361). CONCLUSION: We were able to demonstrate argon's neuroprotective effects in an in vivo experimental rat model of acute focal cerebral ischemia. Animals breathing spontaneously 50 vol % argon 1 hr after induction of transient middle cerebral artery occlusion for 1 hr by face mask showed significantly reduced infarct volumes and composite adverse outcomes.

Expression analysis of the early chemokine response 4 h after in vitro traumatic brain injury.

OBJECTIVE AND DESIGN: The importance of cytokine- and chemokine-mediated neuroinflammation in the progress of brain injury is becoming increasingly evident. We investigated the early local cytokine and chemokine expression and the development of tissue injury after moderate mechanical hippocampus trauma. MATERIAL OR SUBJECTS: Mouse organotypic hippocampal slice cultures. TREATMENT: Drop-weight trauma in the CA1 region of the hippocampus. METHODS: Staining of necrotic tissue, PCR array and evaluation, real-time PCR, statistical analysis with a two-tailed, independent t test. RESULTS: At 12 and 24 h after trauma, the tissue injury spread from the primary mechanical lesion to the entire hippocampal formation. A pronounced up-regulation of distinct chemokine transcripts was found 4 h after in vitro traumatic brain injury which preceded the development of the secondary injury. CONCLUSIONS: The enhanced expression of inflammatory genes might contribute to the development of the secondary trauma and could pinpoint future neuroinflammatory and neuroprotective targets for research and treatment.

Xenon enhances LPS-induced IL-1ß expression in microglia via the extracellular signal-regulated kinase 1/2 pathway.

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-1ß 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-1ß expression in xenon and LPS-treated cells to a level obtained by LPS alone. In conclusion, xenon enhanced LPS-induced IL-1ß 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.

Bispectral index monitoring during balanced xenon or sevoflurane anaesthesia in elderly patients.

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.

Argon: neuroprotection in in vitro models of cerebral ischemia and traumatic brain injury.

INTRODUCTION: Recently, it has been shown in several experimental settings that the noble gases xenon and helium have neuroprotective properties. In this study we tested the hypothesis that the noble gas argon has a neuroprotective potential as well. Since traumatic brain injury and stroke are widespread and generate an enormous economic and social burden, we investigated the possible neuroprotective effect in in vitro models of traumatic brain injury and cerebral ischemia. METHODS: Organotypic hippocampal slice cultures from mice pups were subjected to either oxygen-glucose deprivation or to a focal mechanical trauma and subsequently treated with three different concentrations (25, 50 and 74%) of argon immediately after trauma or with a two-or-three-hour delay. After 72 hours of incubation tissue injury assessment was performed using propidium iodide, a staining agent that becomes fluorescent when it diffuses into damaged cells via disintegrated cell membranes. RESULTS: We could show argon's neuroprotective effects at different concentrations when applied directly after oxygen-glucose deprivation or trauma. Even three hours after application, argon was still neuroprotective. CONCLUSIONS: Argon showed a neuroprotective effect in both in vitro models of oxygen-glucose deprivation and traumatic brain injury. Our promising results justify further in vivo animal research.