A xenon recirculating ventilator for the newborn piglet: developing clinical applications of xenon for neonates.

CONTEXT: The clinical applications of xenon for the neonate include both anaesthesia and neuroprotection. However, due to the limited natural availability of xenon, special equipment is required to administer and recapture the gas to develop xenon as a therapeutic agent. OBJECTIVE: In order to test the xenon recirculating ventilator for the application of neuroprotection in a preclinical trial, our primary objective was to test the efficiency, reliability and safety of administering 50% xenon for 24 h in hypoxic ischaemic piglets. DESIGN: A prospective observational study. SETTING: Institute for Women's Health, University College London, January 2008 to March 2008. ANIMALS: Four anaesthetised male piglets, less than 24 h old, underwent a global hypoxic ischaemic insult for approximately 25 min prior to switching to the xenon recirculating ventilator. INTERVENTION: Between 2 and 26 h after hypoxic ischaemia, anaesthetised piglets were administered a mixture of 50% xenon, air, oxygen and isoflurane. MAIN OUTCOME MEASURES: The primary outcome measure was blood gas PaCO2 (kPa) and secondary outcome measure was xenon gas use (l h), over the 24-h duration of xenon administration. RESULTS: The xenon recirculating ventilator provided effective ventilation, automated control of xenon/air gas mixtures, and stable blood gas PaCO2 (4.5 to 6.3 kPa) for 24 h of ventilation with the xenon recirculating ventilator. Total xenon use was minimal at approximately 0.6 l h at a cost of approximately &OV0556;8 h. Additional features included an isoflurane scavenger and bellows height alarm. CONCLUSION: Stable gas delivery to a piglet with minimal xenon loss and analogue circuitry made the xenon recirculating ventilator easy to use and it could be modified for other large animals and noble gas mixtures. The technologies, safety and efficiency of xenon delivery in this preclinical system have been taken forward in the development of neonatal ventilators for clinical use in phase II clinical trials for xenon-augmented hypothermia and for xenon anaesthesia.

Feasibility and safety of delivering xenon to patients undergoing coronary artery bypass graft surgery while on cardiopulmonary bypass: phase I study.

BACKGROUND: Postoperative neurocognitive deficit is prevalent after cardiac surgery. Xenon may prevent or ameliorate acute neuronal injury, but it also may aggravate injury during cardiac surgery by increasing bubble embolism. Before embarking on a randomized clinical trial to test the safety and efficacy of xenon for postoperative neurocognitive deficit, we undertook a phase I study to investigate the safety of administering xenon to patients undergoing coronary artery bypass grafting while on cardiopulmonary bypass and to assess the practicability of our xenon delivery system. METHODS: Sixteen patients scheduled for coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass gave their informed consent to participate in an open-label dose-escalation study (0, 20, 35, 50% xenon in oxygen and air). Xenon was delivered throughout surgery using both a standard anesthetic breathing circuit and the oxygenator. Gaseous and blood xenon partial pressures were measured five times before, during, and after cardiopulmonary bypass. Middle cerebral artery Doppler was used to assess embolic load, and major organ system function was assessed before and after surgery. RESULTS: Middle cerebral artery Doppler showed no evidence of increased emboli with xenon. Patients receiving xenon had no major organ dysfunction: Troponin I and S100beta levels tended to be lower in patients receiving xenon. Up to 25 l xenon was used per patient. Xenon partial pressure in the blood tracked the delivered concentration throughout. CONCLUSIONS: Xenon was safely and efficiently delivered to coronary artery bypass grafting patients while on cardiopulmonary bypass. Prevention of nervous system injury by xenon should be tested in a large placebo-controlled, randomized clinical trial.