Department of Anaesthetics ABM University Health Board, Swansea and College of Medicine, Swansea University, Swansea, Wales, United Kingdom.
Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, England, United Kingdom.
PLoS One. 2020 Jan 21;15(1):e0224447. doi: 10.1371/journal.pone.0224447. eCollection 2020.
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.
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.
Median (IQR) xenon consumption was 0.31 L/h (0.18, 0.50) and 0.34L/h (0.32, 0.49) for hypothermic and normothermic groups respectively, 0.34L/h (0.25, 0.53) overall. 92% of 9626 xenon and 69% of 9635 oxygen measurements were within 20% variation from targets. For xenon concentration, the median absolute performance errors for the XeHT and XeNT groups were 6.14% and 3.84% respectively and 4.31% overall. For oxygen these values were 13.42%, 15.05% and 12.4% respectively. There were no adverse pulmonary pathophysiology findings. Clinical problems over the total period included three related to sensors, seven breathing system leaks, ten partial and one complete tracheal tube occlusion episodes.
The automated controller functioned as intended maintaining an inhaled xenon concentration close to the 50% target for 72-78h at a xenon cost of $11.1/h.
治疗性低体温（TH）72 小时是新生儿脑病（NE）后的标准治疗方法。然而，三分之一的患者没有从中受益，因此急需辅助治疗。在实验研究中，氙气在缺氧后 5 小时内以 50%的浓度与 TH 联合使用可增强神经保护作用。在一项氙气+TH 与 TH 对照临床试验中，在 TH 期间延迟（约 10 小时龄）开始 30%氙气 24 小时，并未改善早期不良生物标志物。在缺氧缺血后，通过 N-甲基-D-天冬氨酸受体过度激活引起的兴奋性毒性损伤持续数天。由于氙气部分抑制该受体，我们假设在整个 72 小时 TH 和复温期间给予 50%的氙气会增强神经保护作用。氙气每升 30 美元，因此需要带有自动新鲜气体输送的闭路呼吸系统。
七只机械通气的新生仔猪随机接受 72 小时的 50%吸入氙气，在体温 35°C 下进行低温治疗，并在经历全球缺氧缺血性损伤后进行复温（XeHT，N=4）或在体温 38.5°C 下接受假损伤后进行 72 小时的常温和 72 小时的复温（XeNT，N=3）。基于测量的气体浓度，自动新鲜气体输送系统将氧气/空气/氙气脉冲注入闭路系统。
低温组和常温组的中位（IQR）氙气消耗量分别为 0.31 L/h（0.18，0.50）和 0.34 L/h（0.32，0.49），总消耗量为 0.34 L/h（0.25，0.53）。9626 次氙气和 9635 次氧气测量中有 92%和 69%分别在 20%的目标变化范围内。对于氙气浓度，XeHT 和 XeNT 组的中位数绝对性能误差分别为 6.14%和 3.84%，总误差为 4.31%。对于氧气，这些值分别为 13.42%、15.05%和 12.4%。没有发现不良的肺病理生理学发现。整个治疗期间的临床问题包括三个与传感器相关的问题、七个呼吸系统泄漏、十个部分和一个完全气管插管阻塞事件。
自动控制器按预期运行，在 72-78 小时内将吸入的氙气浓度维持在 50%的目标附近，氙气成本为 11.1 美元/小时。
