From the Departments of Anesthesiology.
Medical Genetics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin.
Anesth Analg. 2018 Jun;126(6):1979-1986. doi: 10.1213/ANE.0000000000002906.
Exposure to anesthetics is common in the majority of early survivors of life-threatening injuries. Whether and to what degree general anesthetics influence outcomes from major trauma is unknown. Potential confounding effects of general anesthetics on outcome measures are usually disregarded. We hypothesized that exposure to isoflurane or sevoflurane modulates the outcome from blunt trauma with traumatic brain injury (bTBI).
We tested the hypothesis in a novel model of bTBI implemented in Drosophila melanogaster. Fruit flies of the standard laboratory strain w were cultured under standard conditions. We titrated the severity of bTBI to a mortality index at 24 hours (MI24) of approximately 20% under control conditions. We administered standard doses of isoflurane and sevoflurane before, before and during, or after bTBI and measured the resulting MI24. We report the MI24 as mean ± standard deviation.
Isoflurane or sevoflurane administered for 2 hours before bTBI reduced the MI24 from 22.3 ± 2.6 to 10.4 ± 1.8 (P < 10, n = 12) and from 19.3 ± 0.9 to 8.9 ± 1.1 (P < .0001, n = 8), respectively. In contrast, administration of isoflurane after bTBI increased the MI24 from 18.5% ± 4.3% to 25.3% ± 9.1% (P = .0026, n = 22), while sevoflurane had no effect (22.4 ± 7.1 and 21.5 ± 5.8, n = 22).
In a whole animal model of bTBI, general anesthetics were not indifferent with respect to early mortality. Therefore, collateral effects of general anesthetics should be considered in the interpretation of results obtained in vertebrate trauma models. Invertebrate model organisms can serve as a productive platform to interrogate anesthetic targets that mediate collateral effects and to inform trauma research in higher organisms about the potential impact of anesthetics on outcomes.
在大多数危及生命的创伤的早期幸存者中，接触麻醉剂是很常见的。全身麻醉是否以及在何种程度上影响大创伤的结果尚不清楚。全身麻醉对结果测量的潜在混杂影响通常被忽视。我们假设异氟烷或七氟醚会调节伴有创伤性脑损伤（bTBI）的钝性创伤的结果。
我们在果蝇（Drosophila melanogaster）的新型 bTBI 模型中检验了这一假设。标准实验室品系 w 的果蝇在标准条件下培养。我们将 bTBI 的严重程度滴定到 24 小时死亡率指数（MI24）约为 20%的对照条件下。我们在 bTBI 之前、之前和期间或之后给予标准剂量的异氟烷和七氟烷，并测量由此产生的 MI24。我们将 MI24 报告为平均值±标准差。
在 bTBI 之前给予 2 小时的异氟烷或七氟烷可将 MI24 从 22.3±2.6 降至 10.4±1.8（P<10，n=12）和从 19.3±0.9 降至 8.9±1.1（P<.0001，n=8）。相比之下，bTBI 后给予异氟烷会将 MI24 从 18.5%±4.3%增加到 25.3%±9.1%（P=0.0026，n=22），而七氟烷没有影响（22.4±7.1 和 21.5±5.8，n=22）。
在 bTBI 的整体动物模型中，全身麻醉对早期死亡率并不是无差别的。因此，在解释脊椎动物创伤模型中获得的结果时，应考虑全身麻醉的附带影响。无脊椎动物模型生物可以作为一个富有成效的平台，用于探究介导附带影响的麻醉靶点，并为高等生物的创伤研究提供有关麻醉对结果潜在影响的信息。
