Closed circuit xenon delivery for 72h in neonatal piglets following hypoxic insult using an ambient pressure automated control system: Development, technical evaluation and pulmonary effects

Abstract

Background Therapeutic hypothermia (TH) for 72h is the standard treatment following neonatal encephalopathy (NE). However, one-third do not benefit and adjunctive therapies are urgently needed. Xenon enhances neuroprotection with TH when administered at 50% concentration within 5hours of hypoxia in experimental studies. Delayed initiation (~10 hours of age) of 30% xenon for 24 hours during TH did not improve early adverse biomarkers in a clinical trial of Xenon+TH vs TH. After hypoxia-ischemia, excitotoxic injury via N-methyl-D-aspartate receptor overactivation lasts days. Since xenon partially inhibits this receptor, we hypothesised that giving 50% xenon throughout the entire 72h TH and rewarming periods would enhance neuroprotection. Xenon costs $30/litre, so a closed-circuit breathing system is desirable with automated fresh gas delivery. Methods Seven mechanically ventilated newborn pigs were randomized to receive 50% inhaled xenon for 72h during hypothermia (rectal-temperature 35˚C) and subsequent rewarming following a global hypoxic-ischemic insult (XeHT, N = 4) or under normothermia for 72h (rectal-temperature 38.5˚C) following sham insult (XeNT, N = 3). An automated fresh gas delivery system injected oxygen/air/xenon boluses into a closed-circuit based on measured gas concentrations.

Noble gas and neuroprotection: From bench to bedside

“…John et al developed an automated gas controller to monitor changes of breathing gas composition recirculated in a closed-circuit system and inject oxygen, air, or xenon as required to make the gas mixture achieve preset values ( Dingley et al, 2020 ). The automated controller successfully maintained the concentration of inhaled xenon close to 50% for 72–78 h at a xenon cost of $11.1/h in a model of hypoxic neonatal piglets ( Dingley et al, 2020 ). A previous study by John et al described a single-use closed-circuit Xe delivery system that proved both feasible and cost-efficient ( Chakkarapani et al, 2009 ).…”