Ageing delays emergence from general anaesthesia in rats by increasing anaesthetic sensitivity in the brain
Ageing delays emergence from general anaesthesia in rats by increasing anaesthetic sensitivity in the brain
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DOI：
10.1093/bja/aev112
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发表时间：
2015-07-01
影响因子：
9.8
通讯作者：
Solt, K.
中科院分区：
文献类型：
--
作者：
Chemali, J. J.;Kenny, J. D.;Solt, K.
背景：对于大脑中与年龄相关的变化影响全身麻醉后的苏醒，我们所知甚少。我们使用年轻的成年大鼠和年老的Fischer 344大鼠来验证衰老通过增加大脑的麻醉敏感性来延迟全身麻醉的出现这一假设。方法：测定异氟醚（1.5 vol%, 45 min）和异丙酚（8 mg kg（-1）静脉注射）的出现时间。在年轻成年大鼠和老年大鼠中建立了维持失直（LOR）所需的异氟醚剂量。研究了哌醋甲酯对全身麻醉后LOR逆转的疗效。分别使用植入脑电图（EEG）电极的年轻成年大鼠和老年大鼠来测试衰老是否增加对麻醉诱导的爆发抑制的敏感性。结果：异氟醚麻醉苏醒的平均时间为47 s [95% CI 33,60；年轻人)，而243例（95% CI 185, 308；老年人）。异丙酚的平均出现时间为13.1分钟（95% CI 11.9, 14.0；年轻人），而23.1分钟（95% CI 18.8, 27.9；老年人）。这些差异具有统计学意义。异丙酚后给予哌醋甲酯，平均出现时间降至6.6 min （95% CI 5.9, 7.1；年轻人）和10.2 min （95% CI 7.9, 12.3；老年人）。这些减少在统计学上是显著的。哌醋甲酯在持续异氟醚麻醉期间恢复了所有大鼠的翻身。老年大鼠脑电图功率较低，对麻醉诱发的发作抑制更为敏感。结论：衰老延迟全身麻醉的出现。这至少在一定程度上是由于大脑对麻醉的敏感性增加。有必要进一步研究以确定潜在的原因。
Background: Little is known about ageing-related changes in the brain that affect emergence from general anaesthesia. We used young adult and aged Fischer 344 rats to test the hypothesis that ageing delays emergence from general anaesthesia by increasing anaesthetic sensitivity in the brain.Methods: Time to emergence was determined for isoflurane (1.5 vol% for 45 min) and propofol (8 mg kg(-1) i.v.). The dose of isoflurane required to maintain loss of righting (LOR) was established in young adult and aged rats. The efficacy of methylphenidate to reverse LOR from general anaesthesia was tested. Separate young adult and aged rats with implanted electroencephalogram (EEG) electrodes were used to test whether ageing increases sensitivity to anaesthetic-induced burst suppression.Results: Mean time to emergence from isoflurane anaesthesia was 47 s [95% CI 33, 60; young adult) compared with 243 s (95% CI 185, 308; aged). For propofol, mean time to emergence was 13.1 min (95% CI 11.9, 14.0; young adult) compared with 23.1 min (95% CI 18.8, 27.9; aged). These differences were statistically significant. When methylphenidate was administered after propofol, the mean time to emergence decreased to 6.6 min (95% CI 5.9, 7.1; young adult) and 10.2 min (95% CI 7.9, 12.3; aged). These reductions were statistically significant. Methylphenidate restored righting in all rats during continuous isoflurane anaesthesia. Aged rats had lower EEG power and were more sensitive to anaesthetic-induced burst suppression.Conclusions: Ageing delays emergence from general anaesthesia. This is due, at least in part, to increased anaesthetic sensitivity in the brain. Further studies are warranted to establish the underlying causes.