Use of Xenon anesthesia in patients at high risk for postoperative organ dysfunction

Despite being originally described to be chemically inert, noble gases including xenon, argon and helium have been repeatedly demonstrated to exhibit remarkable biological properties. The first use of xenon anaesthesia in humans was performed by Cullen and Gross in 1951. However, only the development of closed-circuit anaesthesia machines in the 1990'ies has made xenon available to a broader spectrum of patients. Unfortunately, the scarcity (air contains only 87 ppb xenon) and herewith-associated high costs of xenon have limited a wider use of this gas in clinical routine. Hence, strategies by which xenon consumption can be reduced without compromising its protective properties should significantly improve the cost-effectiveness of this noble gas. Xenon has been repeatedly demonstrated to produce only minimal haemodynamic side effects when compared to volatile or intravenous anaesthetics. Moreover, recent evidence indicates that xenon - in contrast to the majority of conventionally used general anaesthetics - is virtually devoid of negative inotropic effects and improves recovery from post-ischemic contractile dysfunction. Furthermore, xenon was also found to induce both early and late pharmacological preconditioning in experimental models of myocardial ischemia. The favourable haemodynamic profile of xenon anaesthesia as well as its cardioprotective properties could render this noble gas an attractive anaesthetic for patients undergoing cardiac surgery. These patients are known to carry a high risk for perioperative myocardial ischemia and perioperative haemodynamic instability. Up to now, there is a paucity of data regarding the safety and efficacy of xenon for cardiac anaesthesia. Xenon is thought to induce its biological effects mainly through non-competitive inhibition of the N-methyl-D-aspartate (NMDA) receptor, a subtype of the excitatory glutamate receptors, with no or only minimal effects on the γ-aminobutyric acid A (GABAA) receptor and non-NMDA glutamatergic receptors. Xenon has also been demonstrated to offer neuroprotection in different animal models of neuronal injury, such as in traumatic brain injury, cardiopulmonary bypass-associated neuronal injury, hypoxia, neuronal ischemia, anaesthetic-induced neurotoxicity, and neonatal asphyxia. All the above mentioned neuroprotective properties of xenon could make this gas attractive for the management of patients with a high risk for the development of postoperative neurological complications, specifically postoperative delirium (POD). Though, there is a lack of adequately powered studies on xenon related neuroprotection in humans. In conclusion, an extensive body of evidence suggests that xenon might have the potential to prevent perioperative organ injury. However, this promise is mainly derived from preclinical findings, and clinical trials investigating the efficacy of xenon for perioperative organ protection are sparse. The overall aim of the current PhD project is to investigate the haemodynamic profile, safety, feasibility and organ protective effects (heart and brain) of xenon anaesthesia in patients with a particularly high risk for perioperative organ dysfunction.status: publishe

Neuroprotective properties of xenon in different types of CNS injury

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A retrospective study of suspected anaphylactic reactions during anesthesia in Belgium

© Acta Anaesthesiologica Belgica, 2018. Background: Since 2008, Belgian anesthe siologists can report suspected anaphylactic reactions during anesthesia on the website of the Society for Anesthesia and Resuscitation of Belgium (SARB). Material & Methods: We analyzed the database retrospectively, covering a period from January 2008 to May 2013. Results: Out of 97 cases, two were excluded because of insufficient data. Fifty-six % of cases were reported by the 2 hospitals that conducted the survey. The incidence of severe reactions was higher in regional hospitals than in university hospitals. Respiratory symptoms were more frequent in patients with a history of respiratory disease. Mast cell tryptase (MCT) after the reaction was measured correctly in only 54% of cases, and was positive in 66% of cases (MCT > 13.5 figfL). Basal MCT was measured in 64% of patients. Skin testing was done in 72% and was positive in 51 (75%) of them. Most frequently incriminated agents were neuromuscular blocking drugs (NMBDs) (63%) and antibiotics (18%). Cross-sensitivity between NMBDs occurred in 78% of cases. A complete investigation (MCT at 30-90 min, basal MCT at distance from the reaction, and skin testing) was conducted in 38% of cases. Conclusion: There was probably severe underreporting of suspected anaphylactic reactions in Belgium. Moreover, in a majority of cases, necessary investigations were carried out incompletely. Underreporting and incomplete investigation increases the risk for new episodes of anaphylaxis during subsequent anesthesia.status: publishe

The hip fracture surgery in elderly patients (HIPELD) study to evaluate xenon anaesthesia for the prevention of postoperative delirium: a multicentre, randomized clinical trial

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 (P¼0.33). Overall SOFA scores were significantly lower with xenon (least-squares mean difference: 0.33 [95% CI: 0.60 to 0.06]; P¼0.017). For xenon and sevoflurane, the incidence of serious AEs and fatal AEs was 8.0% vs 15.9% (P¼0.05) and 0% vs 3.8% (P¼0.06), 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.status: publishe

The hip fracture surgery in elderly patients (HIPELD) study to evaluate xenon anaesthesia for the prevention of postoperative delirium: a multicentre, randomized clinical trial

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