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

Nogueira, Flávia, R., BSc*,†; Braz, Leandro, G., MD, PhD*; Souza, Kátina, M., MSc*; Aun, Aline, G., MSc*; Arruda, Nayara, M., BSc*; Carvalho, Lídia, R., PhD; Chen, Chung-Yen, O., PhD; Braz, José Reinaldo, C., MD, PhD*; Braz, Mariana, G., PhD*,†

doi: 10.1213/ANE.0000000000002729
Patient Safety: Original Clinical Research Report

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.

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

Departamento de Bioestatística, Instituto de Biociências, Universidade Estadual Paulista (Unesp), Botucatu, São Paulo, Brazil.

Published ahead of print December 29, 2017.

Accepted for publication November 2, 2017.

Funding: Supported by grant 2013/16842-0 from the São Paulo Research Foundation (FAPESP). F. R. Nogueira was granted a scholarship from the National Council for Scientific and Technological Development-CNPq (2014–2015) and from the Coordination of Improvement for Higher Education Personnel-CAPES (2016), and J. R. C. Braz received a fellowship from CNPq (303673/2015-0).

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

This report was previously presented in part at Euroanaesthesia 2016, London, United Kingdom, May 28-30, 2016.

Clinical trial number: the Brazilian Clinical Trials Registry (RBR-6jg23g; Trial Identification UTN Number: U1111-1150-0903).

Registry URL:

Reprints will not be available from the authors.

Address correspondence to Mariana G. Braz, PhD, Department of Anesthesiology, Botucatu Medical School, São Paulo State University (UNESP), Professor Mário Rubens G. Montenegro Av, 18618–687, Botucatu, SP, Brazil. Address e-mail to

© 2018 International Anesthesia Research Society
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