Gene and systemic inflammatory effects and neuroendocrine response in surgical patients anesthetized with desflurane-nitrous oxide or desflurane-nitrous oxide-free: A randomized trial.

There is growing interest in assessing possible immunotoxicological effects in anesthetized patients. There are controversial findings concerning the effect of nitrous oxide (N2O) anesthetic gas effect on inflammatory response. We tested the hypothesis that N2O associated with desflurane (inhalational anesthetic) was likely to worsen neuro-immune-endocrine effects when compared with desflurane alone in this randomized trial. The primary endpoint of this study was to evaluate the systemic proinflammatory interleukin (IL)-6, and the secondary endpoints included other systemic (IL-1ß, TNF-α, IL-8, IL-10, IL-17A and high-sensitivity C-reactive protein - hs-CRP) and genetic inflammatory markers (NF-kB, IL-6 and COX-2) as well as hormones (adrenocorticotropic hormone, cortisol and prolactin) comparing patients undergoing minor surgery with or without N2O-desflurane. As a second aim, we assessed whether there were changes in the neuro-immune-endocrine profiles within each group. Blood samples were collected before anesthesia, 90 min after anesthesia induction, and the day after surgery. We assessed serum cytokines using a cytometric bead array and hs-CRP by chemiluminescent immunoassay. Expression of three proinflammatory transcripts was assessed by real-time quantitative polymerase chain reaction, and neuroendocrine hormones were detected by chemiluminescent microparticle immunoenzymatic assay. There were no significant between-group differences for any analyzed biomarkers. However, there was a significant increase in: (a) systemic IL-6 and hs-CRP values one day after surgery in both groups and (b) prolactin levels in the intraoperative period compared to baseline and postoperative period levels for both groups. In conclusion, N2O does not impair the inflammatory profile and neuroendocrine response compared to patients who receive only desflurane anesthesia.

High concentrations of waste anesthetic gases induce genetic damage and inflammation in physicians exposed for three years: A cross-sectional study.

This cross-sectional study analyzed the impact of occupational waste anesthetic gases on genetic material, oxidative stress, and inflammation status in young physicians exposed to inhalational anesthetics at the end of their medical residency. Concentrations of waste anesthetic gases were measured in the operating rooms to assess anesthetic pollution. The exposed group comprised individuals occupationally exposed to inhalational anesthetics, while the control group comprised individuals without anesthetic exposure. We quantified DNA damage; genetic instability (micronucleus-MN); protein, lipid, and DNA oxidation; antioxidant activities; and proinflammatory cytokine levels. Trace concentrations of anesthetics (isoflurane: 5.3 ± 2.5 ppm, sevoflurane: 9.7 ± 5.9 ppm, and nitrous oxide: 180 ± 150 ppm) were above international recommended thresholds. Basal DNA damage and IL-17A were significantly higher in the exposed group [27 ± 20 a.u. and 20.7(19.1;31.8) pg/mL, respectively] compared to the control group [17 ± 11 a.u. and 19.0(18.9;19.5) pg/mL, respectively], and MN frequency was slightly increased in the exposed physicians (2.3-fold). No significant difference was observed regarding oxidative stress biomarkers. The findings highlight the genetic and inflammatory risks in young physicians exposed to inhalational agents in operating rooms lacking adequate scavenging systems. This potential health hazard can accompany these subjects throughout their professional lives and reinforces the need to reduce ambient air pollution and consequently, occupational exposure.

Inflammation and DNA damage induction in surgical patients maintained with desflurane anesthesia.

The use of anesthetics during surgical interventions may contribute to disorders in the perioperative period. Desflurane is the newest volatile halogenated anesthetic to be introduced in clinical practice. Considering that inflammation and genotoxicity are linked events, and that little is known regarding possible genetic and inflammatory effects of desflurane in surgical patients, this study evaluated DNA damage, systemic inflammatory cytokines and related gene expression in adult patients without comorbidities who underwent minor otorhinological surgeries under general anesthesia maintained with the inhalational anesthetic desflurane. This study involved a self-controlled design in which venous blood samples were collected from subjects before anesthesia administration and after the surgical procedure. The comet assay was applied to assess DNA lesions, while the cytokines IL-1ß, IL-6, IL-8, IL-10, IL-17A and TNF-α were evaluated by flow cytometry. A genotoxic effect was observed (p = 0.027), and pro-inflammatory IL-6 and IL-8 levels were significantly increased after surgery (p = 0.001 and p = 0.02, respectively), whereas the levels of the other cytokines did not significantly change. Considering that serum IL-6 and IL-8 were increased, we further evaluated IL-6 and IL-8 gene expression by quantitative real-time polymerase chain reaction (qPCR). However, IL-6 and IL-8 gene expression was unaltered (p >  0.05). In conclusion, anesthetic maintenance with the modern agent desflurane during minor surgeries led to genotoxic and inflammatory effects without altering the expression of inflammation related-genes the day after surgery in patients without comorbidities.

Monitoring early cell damage in physicians who are occupationally exposed to inhalational anesthetics.

Worldwide, millions of professionals who work in operating rooms are occupationally exposed to inhalational anesthetics. Thus, the potential health effects of the continuous exposure to inhalational anesthetics on individuals in the operating room remain a subject of debate. Human biomonitoring is a potentially useful tool for assessing the health of exposed professionals. No report has yet evaluated the possible cytotoxic and genotoxic effects of the most commonly used inhalational anesthetics on young professionals who are occupationally exposed. Considering the importance of this issue, we monitored physicians who were exposed to inhalational anesthetics during their first year of a medical residency program to evaluate the possible early damage events. Twenty-six young physicians who had been occupationally exposed to the anesthetics isoflurane, sevoflurane, desflurane, and nitrous oxide and who worked in operating rooms using modern anesthesia workstations during their medical residency program, participated in this study. Blood samples were evaluated before the start of the program (before the exposure), and after 1/2 year and 1 year of exposure. We monitored the subjects by assessing the cytotoxicity (early apoptosis and loss of the mitochondrial membrane potential) using flow cytometry and genotoxicity using the comet assay. No significant changes were observed in the biomarkers of cytotoxicity or genotoxicity (p > 0.05). Thus, biomonitoring showed that short-term exposure to inhalational anesthetics did not induce early cell damage during the first year of medical residency. Based on the results, brief occupational exposure to anesthetics does not induce either cytotoxicity or genotoxicity in mononuclear cells under the conditions of this study. Thus, young physicians should undergo additional biomonitoring at the beginning of their careers to determine possible toxic effects on their cells and genetic material, and further investigations are warranted to determine whether a longer exposure to inhalational anesthetics results in mitochondrial depolarization, apoptosis and DNA breaks.

Expression and promoter methylation status of two DNA repair genes in leukocytes from patients undergoing propofol or isoflurane anaesthesia.

Despite the widespread use of the anaesthetics propofol (PROP) and isoflurane (ISO), data about their toxicogenomic potential and interference in epigenetic events are unknown. This study evaluated the expression and methylation profile of two important DNA-repair genes (XRCC1 and hOGG1) in 40 patients undergoing elective and minimally invasive surgery (tympanoplasty and septoplasty) under ISO or PROP anaesthesia. The endpoints were examined at three sampling times: before anaesthesia (T0), 2 h after the beginning of anaesthesia (T2) and 24 h after the beginning of surgery (T24). Both gene expressions were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), whereas methylation specific-PCR (MS-PCR) evaluated the DNA methylation patterns. Increased expression of XRCC1 was observed at T2 only in the PROP group. On the other hand, hOGG1 and XRCC1 expressions were decreased at T24 in both groups. There were no statistical significant differences between the two anaesthetics at the respective sampling times. The methylation status of XRCC1 (methylated at T0) and hOGG1 (unmethylated at T0) remained unchanged in the three sampling times. In conclusion, this study showed modulations of hOGG1 and XRCC1 expression especially 1 day after elective surgery in patients undergoing PROP and ISO anaesthesia. However, the data indicated that methylation was not the mechanism by which the genes were regulated. More studies are warranted to further investigate the possible epigenetic mechanisms involved after exposure to anaesthetics.

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

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.