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Noble gases are chemically inert elements, some of which exert biological activity. Experimental neuroprotection in particular has been widely shown for xenon, argon and helium. The underlying mechanisms of action are not yet fully understood. Besides an interference with neuronal ion-gated channels and cellular signaling pathways as well as anti-apoptotic effects, the modulation of neuroinflammation seems to play a crucial role. This review presents the current knowledge on neuroprotection by noble gases with a focus on interactions with the neuronal-glial network and neuroinflammation and the perspectives on clinical applications.

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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.

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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.

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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.

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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.

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