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.