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地氟烷复合或不复合氧化亚氮麻醉对患者 DNA 损伤和氧化应激的比较:一项前瞻性随机临床试验。

Comparison of DNA Damage and Oxidative Stress in Patients Anesthetized With Desflurane Associated or Not With Nitrous Oxide: A Prospective Randomized Clinical Trial.

机构信息

From the Universidade Estadual Paulista (Unesp), Faculdade de Medicina, Departamento de Anestesiologia, Botucatu, São Paulo, Brazil.

Antioxidants Research Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Massachusetts.

出版信息

Anesth Analg. 2018 Apr;126(4):1198-1205. doi: 10.1213/ANE.0000000000002729.

DOI:10.1213/ANE.0000000000002729
PMID:29293177
Abstract

BACKGROUND

Little is known about the effects of desflurane associated or not with nitrous oxide (N2O) on oxidative stress and patient genetic material. The aim of this study was to compare the effects of anesthesia maintained with desflurane associated or not with N2O on DNA damage (as a primary outcome) and oxidative stress (as a secondary outcome) in patients who underwent an elective minimally invasive surgery.

METHODS

This prospective randomized clinical trial analyzed 40 patients of both sexes with an American Society of Anesthesiologists physical status I who were 18-50 years of age and scheduled for septoplasty. The patients were randomly allocated into 2 groups according to anesthesia maintenance as follows: desflurane (n = 20) or desflurane/N2O (n = 20). Blood samples were collected before anesthesia (T1 = baseline), 1.5 hours after anesthesia induction (T2), and on the morning of the postoperative first day (T3). Basal and oxidative DNA damage (determined using formamidopyrimidine DNA glycosylase to detect oxidized purines and endonuclease III to detect oxidized pyrimidines) were evaluated using the comet assay. Oxidative stress markers were evaluated based on lipid peroxidation (by assessing 4-hydroxynonenal and 8-iso-prostaglandin F2α [8-isoprostane] using enzyme linked immunosorbent immunoassay), protein carbonyls (assessed by enzyme linked immunosorbent immunoassay), and antioxidant defense (ferric-reducing antioxidant power by spectrophotometry). The effect size was expressed as the mean differences between groups and the corresponding 95% confidence interval (CI).

RESULTS

There was no significant mean difference between groups in relation to DNA damage (-1.7 [95% CI, -7.0 to 3.5]), oxidized DNA pyrimidines (-1.8 [95% CI, -12.5 to 8.9]) and purines (-1.9 [95% CI, -13.9 to 10.1]), 4-hydroxynonenal (-0.2 [95% CI, -2.8 to 2.4]), 8-isoprostane (549 [95% CI, -2378 to 3476]), protein carbonyls (0.2 [95% CI, -2.1 to 2.3]), or ferric-reducing antioxidant power (24 [95% CI, -52.0 to 117.2]).

CONCLUSIONS

The coadministration of 60% N2O with desflurane did not seem to impair the effects on DNA or the redox status compared with desflurane anesthesia, suggesting that both studied anesthetic techniques can be suitable options for healthy individuals who undergo minimally invasive surgery lasting at least 1.5 hours. However, due to the low power of the study, more research is necessary to confirm our findings.

摘要

背景

关于地氟烷联合或不联合一氧化二氮(N2O)对氧化应激和患者遗传物质的影响知之甚少。本研究旨在比较维持麻醉时使用地氟烷联合或不联合 N2O 对接受择期微创手术的患者的 DNA 损伤(主要结果)和氧化应激(次要结果)的影响。

方法

这是一项前瞻性随机临床试验,分析了 40 名美国麻醉医师协会(ASA)身体状况 I 级的 18-50 岁的男女患者,他们计划行鼻中隔成形术。根据麻醉维持情况,将患者随机分为两组:地氟烷组(n = 20)或地氟烷/N2O 组(n = 20)。在麻醉诱导前(T1 = 基线)、麻醉诱导后 1.5 小时(T2)和术后第一天早上(T3)采集血样。使用碱基切除修复酶(UNG)测定法通过检测氧化嘌呤(通过测定 FPG 来评估)和氧化嘧啶(通过测定 8-异前列腺素 F2α [8-iso-PGF2α] 来评估)来评估基础和氧化 DNA 损伤(通过彗星试验评估)。通过酶联免疫吸附免疫测定法评估脂质过氧化(通过测定 4-羟基壬烯醛和 8-异前列腺素 F2α [8-iso-PGF2α] 来评估)、蛋白质羰基(通过酶联免疫吸附免疫测定法评估)和抗氧化防御(通过分光光度法评估铁还原抗氧化能力)来评估氧化应激标志物。效应大小表示为组间均值差异及其相应的 95%置信区间(CI)。

结果

在 DNA 损伤(-1.7 [95%CI,-7.0 至 3.5])、氧化嘧啶(-1.8 [95%CI,-12.5 至 8.9])和嘌呤(-1.9 [95%CI,-13.9 至 10.1])、4-羟基壬烯醛(-0.2 [95%CI,-2.8 至 2.4])、8-异前列腺素(549 [95%CI,-2378 至 3476])、蛋白质羰基(0.2 [95%CI,-2.1 至 2.3])或铁还原抗氧化能力(24 [95%CI,-52.0 至 117.2])方面,两组间无显著的平均差异。

结论

与地氟烷麻醉相比,地氟烷联合 60%N2O 似乎并没有损害 DNA 或氧化还原状态的影响,这表明两种研究的麻醉技术都可以作为至少持续 1.5 小时的微创手术的健康个体的合适选择。然而,由于研究的效力较低,需要进一步的研究来证实我们的发现。

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