Comparison between inhalational anesthetics in terms of DNA damage and immunological markers.

This study compared genetic damage and immunological markers between surgical patients who underwent inhalational anesthesia with isoflurane or sevoflurane. Blood samples were collected from surgical patients (n = 18 in the isoflurane group and n = 17 in the sevoflurane group) at baseline (before the anesthesia procedure) and the day after anesthesia. DNA damage was detected using an alkaline comet assay; proinflammatory interleukin (IL)-6 was detected by flow cytometry, and white blood cells were detected via an automatic hematology analyzer. The characteristics of both groups were similar, and neither of the two anesthetics induced DNA damage. Similarly, mild neutrophilia was observed after anesthesia in both groups. Increased IL-6 levels were observed 1 day after anesthesia regardless of the type of anesthetic, but this increase was greater in the isoflurane group. Our study suggested that isoflurane and sevoflurane administration may contribute to changes in the immune parameters measured, though no genotoxic hazard was identified, in healthy adult patients who undergo low-stress surgery.

Global neonatal perioperative mortality: A systematic review and meta-analysis.

STUDY OBJECTIVE: There are large differences in health care among countries. A higher perioperative mortality rate (POMR) in neonates than in older children and adults has been recognized worldwide. The aim of this study was to provide a systematic review of published 24-h and 30-day POMRs in neonates from 2011 to 2022 in countries with different Human Development Index (HDI) levels. DESIGN AND SETTING: A systematic review with a meta-analysis of studies that reported 24-h and 30-day POMRs in neonates was performed. We searched the databases from January 2011 to July 30, 2022. MEASUREMENTS: The POMRs (per 10,000 procedures under anesthesia) were analyzed according to country HDI. The HDI levels ranged from 0 to 1, representing the lowest and highest levels, respectively (very-high-HDI: ≥ 0.800, high-HDI: 0.700-0.799, medium-HDI: 0.550-0.699, and low-HDI: < 0.550). The magnitude of the POMRs by country HDI was studied using meta-analysis. MAIN RESULTS: Eighteen studies from 45 countries were included. The 24-h (n = 96 deaths) and 30-day (n = 459 deaths) POMRs were analyzed from 33,729 anesthetic procedures. The odds ratios (ORs) of the 24-h POMR in low-HDI countries were higher than those in very-high- (OR 8.4, 95% CI 1.7-40.4; p = 0.008), high- (OR 7.3, 95% CI 2.2-24.4; p = 0.001) and medium-HDI countries (OR 7.7, 95% CI 3.1-18.7; p < 0.0001) but with no odds differences between very-high- and high-HDI countries (p = 0.879), very-high- and medium-HDI countries (p = 0.915) and high- and medium-HDI countries (p = 0.689). The odds of a 30-day POMR in low-HDI countries were higher than those in very-high-HDI countries (OR 6.9, 95% CI 1.9-24.6; p = 0.002) but not in high-HDI countries (OR 1.4, 95% CI 0.6-3.0; p = 0.396). CONCLUSIONS: The review demonstrated very high global POMRs in a surgical population of neonates independent of the country HDI level. We identified differences in 24-h and 30-day POMRs between low-HDI countries and other countries with higher HDI levels.

Modulation of gene expression and inflammation but not DNA damage after sevoflurane anesthesia.

This study assessed, for the first time, the expression of the genes hOGG1, TP53, and IL-6 in leukocytes by real-time quantitative polymerase chain reaction in surgical patients before (baseline), during (2 h of anesthesia) and 1 day after sevoflurane anesthesia. Additionally, DNA damage was detected by the comet assay, serum interleukin (IL)-6 was detected by flow cytometry, and differential leukocyte counting was also performed. TP53 and hOGG1 expression was downregulated on the day after anesthesia compared to before anesthesia. However, IL-6 expression did not change, and no DNA damage induction was observed during or after anesthesia. At the systemic level, mild neutrophilia and an increase in IL-6 levels occurred after anesthesia. Our findings suggest that sevoflurane anesthesia downregulates gene expression (hOGG1 and TP53) and contributes to an inflammatory status (increased systemic IL-6 and mild neutrophilia) but is not associated with DNA damage in patients without comorbidities who undergo minor elective surgery.

A correlation between anaesthesia-related cardiac arrest outcomes and country human development index: A narrative review.

Studies have demonstrated gaps between developed and developing countries in the quality of surgical and anaesthesia care. The aim of this review was to provide a critical overview of documented outcomes from the 2010s of anaesthesia-related cardiac arrest events in countries with largely differing Human Development Indexes (HDIs). The HDI ranges from 0 to 1, representing the lowest and highest levels of development, respectively. Most related studies conducted between 2011 and 2020 showed low rates (from 0 to 215 per million anaesthetics) of anaesthesia-related mortality up to the 30th postoperative day in very high-HDI countries (HDI ≥ 0.800) and higher rates (from 0 to 915.4 per million anaesthetics) in high-HDI countries (HDI: 0.700-0.799). Low-HDI countries (HDI < 0.550) showed higher anaesthesia-related mortality rates, which were greater than 1500 per million anaesthetics. The anaesthesia-related mortality rates per quartile demonstrated a gap in the anaesthesia-related safety between very high- and high-HDI countries, and especially between very high- and low-HDI countries. Anaesthesia-related cardiac arrest showed similarly high survival proportions in very high-HDI countries (45.9% to 100%) and high-HDI countries (62.9% to 100%), while in a low-HDI country, the anaesthesia-related cardiac arrest survival was lower (22.2%). Our review demonstrates large gaps among countries with largely differing HDIs regarding anaesthesia-related cardiac arrest outcomes in the last decade. This finding highlights the need to improve patient safety care in low-HDI countries. Anaesthesia patient safety has improved in high-HDI countries, but there is still a persistent gap in the health care systems of these countries and those of very high-HDI countries. Our review also found a consistent improvement in anaesthesia patient safety in very high-HDI countries.

Oxidative stress, DNA damage, inflammation and gene expression in occupationally exposed university hospital anesthesia providers.

Considering the importance and lack of data of toxicogenomic approaches on occupational exposure to anesthetics, we evaluated possible associations between waste anesthetic gases (WAGs) exposure and biological effects including oxidative stress, DNA damage, inflammation, and transcriptional modulation. The exposed group was constituted by anesthesia providers who were mainly exposed to the anesthetics sevoflurane and isoflurane (10 ppm) and to a lesser degree to nitrous oxide (150 ppm), and the control group was constituted by physicians who had no exposure to WAGs. The oxidative stress markers included oxidized DNA bases (comet assay), malondialdehyde (high-performance liquid chromatography [HPLC]), nitric oxide metabolites (ozone-chemiluminescence), and antioxidative markers, including individual antioxidants (HPLC) and antioxidant defense marker (ferric reducing antioxidant power by spectrophotometry). The inflammatory markers included high-sensitivity C-reactive protein (chemiluminescent immunoassay) and the proinflammatory interleukins IL-6, IL-8 and IL-17A (flow cytometry). Telomere length and gene expression related to DNA repair (hOGG1 and XRCC1), antioxidant defense (NRF2) and inflammation (IL6, IL8 and IL17A) were evaluated by real-time quantitative polymerase chain reaction. No significant differences (p > .0025) between the groups were observed for any parameter evaluated. Thus, under the conditions of the study, the findings suggest that occupational exposure to WAGs is not associated with oxidative stress or inflammation when evaluated in serum/plasma, with DNA damage evaluated in lymphocytes and leucocytes or with molecular modulation assessed in peripheral blood cells in university anesthesia providers. However, it is prudent to reduce WAGs exposure and to increase biomonitoring of all occupationally exposed professionals.

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.

Perioperative cardiac arrest and mortality in trauma patients: A systematic review of observational studies.

STUDY OBJECTIVE: Factors that influence the occurrence of perioperative cardiac arrest (CA) and its outcomes in trauma patients are not well known. The novelty of our study lies in the performance of a systematic review conducted worldwide on the occurrence of perioperative CA and/or mortality in trauma patients. DESIGN: A systematic review was performed to identify observational studies that reported the occurrence of CA and/or mortality due to trauma and CA and/or mortality rates in trauma patients up to 24 h postoperatively. We searched the MEDLINE, EMBASE, LILACS and SciELO databases through January 29, 2020. SETTING: Perioperative period. MEASUREMENTS: The primary outcomes evaluated were data on the epidemiology of perioperative CA and/or mortality in trauma patients. MAIN RESULTS: Nine studies were selected, with the first study being published in 1994 and the most recent being published in 2019. Trauma was an important factor in perioperative CA and mortality, with rates of 168 and 74 per 10,000 anesthetic procedures, respectively. The studies reported a higher proportion of perioperative CA and mortality in trauma patients who were males, young adults and adults, patients with American Society of Anesthesiologists (ASA) physical status ≥ III, patients undergoing general anesthesia, and in abdominal or neurological surgeries. Uncontrolled hemorrhage was the main cause of perioperative CA and mortality after trauma. Survival rates after perioperative CA were low. CONCLUSIONS: Trauma is an important factor in perioperative CA and mortality, especially in young adult and adult males and in patients classified as having an ASA physical status ≥ III mainly due to uncontrollable bleeding after blunt and perforating injuries. Trauma is a global public health problem and has a strong impact on perioperative morbidity and mortality.

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.

Detrimental effects detected in exfoliated buccal cells from anesthesiology medical residents occupationally exposed to inhalation anesthetics: An observational study.

Operating room professionals are scarcely aware of their individual occupational exposure to waste anesthetic gases (WAGs). Medical residents spend several hours per day in operating rooms and consequently experience occupational exposure to WAGs. Considering that no studies have yet evaluated the potential toxicity in medical residents exposed to WAGs using the buccal micronucleus cytome (BMCyt) assay, this pioneering study aimed to compare the BMCyt assay markers, including DNA damage, cell proliferation, and cell death in the exfoliated buccal cells of surgery and anesthesiology residents occupationally exposed to WAGs. The study enrolled a total of 60 physicians, including internal medicine residents (unexposed group), and residents from surgery and anesthesiology programs who were occupationally exposed to sevoflurane, isoflurane and nitrous oxide. WAGs were measured, and the mean values were higher than the international recommendation. The anesthesiology residents (high exposure) showed statistically significant lower frequencies of basal cells, and statistically significant higher frequencies of micronuclei, karyorrhexis, pyknosis, and differentiated cells than did the unexposed group; karyolysis frequencies were significantly higher in anesthesiology residents than were those in the unexposed group or in surgical residents (low exposure). The findings suggest a genetic risk for young professionals exposed to WAGs at the beginning of their careers. Thus, exposure to high WAGs concentrations leads to impairment of the buccal cell proliferative potential, genomic instability and cell death, especially in anesthesiology residents, demonstrating an early impact on their health.

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.

Occupational hazards, DNA damage, and oxidative stress on exposure to waste anesthetic gases / Riscos ocupacionais, danos no material genético e estresse oxidativo frente à exposição aos resíduos de gases anestésicos

Abstract Background and objectives The waste anesthetic gases (WAGs) present in the ambient air of operating rooms (OR), are associated with various occupational hazards. This paper intends to discuss occupational exposure to WAGs and its impact on exposed professionals, with emphasis on genetic damage and oxidative stress. Content Despite the emergence of safer inhaled anesthetics, occupational exposure to WAGs remains a current concern. Factors related to anesthetic techniques and anesthesia workstations, in addition to the absence of a scavenging system in the OR, contribute to anesthetic pollution. In order to minimize the health risks of exposed professionals, several countries have recommended legislation with maximum exposure limits. However, developing countries still require measurement of WAGs and regulation for occupational exposure to WAGs. WAGs are capable of inducing damage to the genetic material, such as DNA damage assessed using the comet assay and increased frequency of micronucleus in professionals with long-term exposure. Oxidative stress is also associated with WAGs exposure, as it induces lipid peroxidation, oxidative damage in DNA, and impairment of the antioxidant defense system in exposed professionals. Conclusions The occupational hazards related to WAGs including genotoxicity, mutagenicity and oxidative stress, stand as a public health issue and must be acknowledged by exposed personnel and responsible authorities, especially in developing countries. Thus, it is urgent to stablish maximum safe limits of concentration of WAGs in ORs and educational practices and protocols for exposed professionals.

Resumo Justificativa e objetivos Os Resíduos de Gases Anestésicos (RGA) presentes no ar ambiente das Salas de Operação (SO) são associados a riscos ocupacionais diversos. O presente artigo propõe-se a discorrer sobre exposição ocupacional aos RGA e seu impacto em profissionais expostos, com ênfase em danos genéticos e estresse oxidativo. Conteúdo Apesar do surgimento de anestésicos inalatórios mais seguros, a exposição ocupacional aos RGA ainda é preocupação atual. Fatores relacionados às técnicas anestésicas e estação de anestesia, além da ausência de sistema de exaustão de gases em SO, contribuem para poluição anestésica. Para minimizar os riscos à saúde em profissionais expostos, recomendam-se limites máximos de exposição. Entretanto, em países em desenvolvimento, ainda carece a mensuração de RGA e de regulamentação frente à exposição ocupacional aos RGA. Os RGA são capazes de induzir danos no material genético, como danos no DNA avaliados pelo teste do cometa e aumento na frequência de micronúcleos em profissionais com exposição prolongada. O estresse oxidativo também é associado à exposição aos RGA por induzir lipoperoxidação, danos oxidativos no DNA e comprometimento do sistema antioxidante em profissionais expostos. Conclusões Por tratar-se de questão de saúde pública, é imprescindível reconhecer os riscos ocupacionais relacionados aos RGA, inclusive genotoxicidade, mutagenicidade e estresse oxidativo. Urge a necessidade de mensuração dos RGA para conhecimento desses valores nas SO, especialmente em países em desenvolvimento, de normatização das concentrações máximas seguras de RGA nas SO, além de se adotarem práticas de educação com conscientização dos profissionais expostos.

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.

[Occupational hazards, DNA damage, and oxidative stress on exposure to waste anesthetic gases]. / Riscos ocupacionais, danos no material genético e estresse oxidativo frente à exposição aos resíduos de gases anestésicos.

BACKGROUND AND OBJECTIVES: The waste anesthetic gases (WAGs) present in the ambient air of operating rooms (OR), are associated with various occupational hazards. This paper intends to discuss occupational exposure to WAGs and its impact on exposed professionals, with emphasis on genetic damage and oxidative stress. CONTENT: Despite the emergence of safer inhaled anesthetics, occupational exposure to WAGs remains a current concern. Factors related to anesthetic techniques and anesthesia workstations, in addition to the absence of a scavenging system in the OR, contribute to anesthetic pollution. In order to minimize the health risks of exposed professionals, several countries have recommended legislation with maximum exposure limits. However, developing countries still require measurement of WAGs and regulation for occupational exposure to WAGs. WAGs are capable of inducing damage to the genetic material, such as DNA damage assessed using the comet assay and increased frequency of micronucleus in professionals with long-term exposure. Oxidative stress is also associated with WAGs exposure, as it induces lipid peroxidation, oxidative damage in DNA, and impairment of the antioxidant defense system in exposed professionals. CONCLUSIONS: The occupational hazards related to WAGs including genotoxicity, mutagenicity and oxidative stress, stand as a public health issue and must be acknowledged by exposed personnel and responsible authorities, especially in developing countries. Thus, it is urgent to stablish maximum safe limits of concentration of WAGs in ORs and educational practices and protocols for exposed professionals.

The Humidity in a Low-Flow Dräger Fabius Anesthesia Workstation with or without Thermal Insulation or a Heat and Moisture Exchanger: A Prospective Randomized Clinical Trial.

BACKGROUND: During anesthesia, as compared with intensive care, the time of the tracheal intubation is much shorter. An inhaled gas minimum humidity of 20 mgH2O.L-1 is recommended to reduce the deleterious effects of dry gas on the airways during anesthesia with tracheal intubation. The Fabius GS Premium® anesthesia workstation (Dräger Medical, Lübeck, Germany) has a built-in hotplate to heat gases in the breathing circuit. A heat and moisture exchanger (HME) is used to further heat and humidify the inhaled gas. The humidity of the gases in the breathing circuit is influenced by the ambient temperature. We compared the humidity of the inhaled gases from a low-flow Fabius anesthesia workstation with or without thermal insulation (TI) of the breathing circuit and with or without an HME. METHODS: We conducted a prospective randomized trial in 41 adult female patients who underwent elective abdominal surgery. The patients were allocated into four groups according to the devices used to ventilate their lungs using a Dräger Fabius anesthesia workstation with a low gas flow (1 L.min-1): control, with TI, with an HME or with TI and an HME (TIHME). The mean temperature and humidity of the inhaled gases were measured during 2-h after connecting the patients to the breathing circuit. RESULTS: The mean inhaled gas temperature and absolute humidity were higher in the HME (29.2±1.3°C; 28.1±2.3 mgH2O·L-1) and TIHME (30.1±1.2°C; 29.4±2.0 mgH2O·L-1) groups compared with the control (27.5±1.0°C; 25.0±1.8 mgH2O·L-1) and TI (27.2±1.1°C; 24.9±1.8 mgH2O·L-1) groups (P = 0.003 and P<0.001, respectively). CONCLUSIONS: The low-flow Fabius GS Premium breathing circuit provides the minimum humidity level of inhaled gases to avoid damage to the tracheobronchial epithelia during anesthesia. TI of the breathing circuit does not increase the humidity of the inhaled gases, whereas inserting an HME increases the moisture of the inhaled gases closer to physiological values.

Occupational exposure to anesthetics leads to genomic instability, cytotoxicity and proliferative changes.

Data on the genotoxic and mutagenic effects of occupational exposure to the most frequently used volatile anesthetics are limited and controversial. The current study is the first to evaluate genomic instability, cell death and proliferative index in exfoliated buccal cells (EBC) from anesthesiologists. We also evaluated DNA damage and determined the concentrations of the anesthetic gases most commonly used in operating rooms. This study was conducted on physicians who were allocated into two groups: the exposed group, which consisted of anesthesiologists who had been exposed to waste anesthetic gases (isoflurane, sevoflurane, desflurane and nitrous oxide - N2O) for at least two years; and the control group, which consisted of non-exposed physicians matched for age, sex and lifestyle with the exposed group. Venous blood and EBC samples were collected from all participants. Basal DNA damage was evaluated in lymphocytes by the comet assay, whereas the buccal micronucleus (MN) cytome (BMCyt) assay was applied to evaluate genotoxic and cytotoxic effects. The concentrations of N2O and anesthetics were measured via a portable infrared spectrophotometer. The average concentration of waste gases was greater than 5 parts per million (ppm) for all of the halogenated anesthetics and was more than 170ppm for N2O, expressed as a time-weighted average. There was no significant difference between the groups in relation to lymphocyte DNA damage. The exposed group had higher frequencies of MN, karyorrhexis and pyknosis, and a lower frequency of basal cells compared with the control group. In conclusion, exposure to modern waste anesthetic gases did not induce systemic DNA damage, but it did result in genomic instability, cytotoxicity and proliferative changes, which were detected in the EBC of anesthesiologists. Thus, these professionals can be considered at risk for developing genetic alterations resulting from occupational exposure to these gases, suggesting the need to minimize this exposure.

Evaluation of genotoxicity of general anesthesia maintained with desflurane in patients under minor surgery.

There is controversy over the genotoxic effects of volatile anesthetics. The available literature on the genotoxicity of desflurane, one of the newest volatile halogenated agents used for general anesthesia maintenance, is scarce. This study aimed to evaluate the genotoxic potential of desflurane in 15 patients without comorbidities, of both sexes, who underwent minor surgeries lasting at least 90 min. Patients enrolled in the study received desflurane anesthesia (6%); blood samples were collected before anesthesia induction (T0), 90 min after the beginning of anesthesia (T1), and on the day following surgery (T2). DNA damage was evaluated in lymphocytes using the alkaline comet assay. We found statistically significant increases in DNA damage in T2 samples compared to T0. The findings suggest that desflurane anesthesia induces DNA strand breaks/alkali-labile sites on the day after minimally invasive surgery in healthy patients.

Perioperative and Anesthesia-Related Mortality: An 8-Year Observational Survey From a Tertiary Teaching Hospital.

In 2006, a previous study at our institution reported high perioperative and anesthesia-related mortality rates of 21.97 and 1.12 per 10,000 anesthetics, respectively. Since then, changes in surgical practices may have decreased these rates. However, the actual perioperative and anesthesia-related mortality rates in Brazil remains unknown. The study aimed to reexamine perioperative and anesthesia-related mortality rates in one Brazilian tertiary teaching hospital.In this observational study, deaths occurring in the operation room and postanesthesia care unit between April 2005 and December 2012 were identified from an anesthesia database. The data included patient characteristics, surgical procedures, American Society of Anesthesiologists (ASA) physical status, and medical specialty teams, as well as the types of surgery and anesthesia. All deaths were reviewed and grouped by into 1 of 4 triggering factors groups: totally anesthesia-related, partially anesthesia-related, surgery-related, or disease/condition-related. The mortality rates are expressed per 10,000 anesthetics with 95% confidence intervals (CIs).A total of 55,002 anesthetics and 88 deaths were reviewed, representing an overall mortality rate of 16.0 per 10,000 anesthetics (95% CI: 13.0-19.7). There were no anesthesia-related deaths. The major causes of mortality were patient disease/condition-related (13.8, 95% CI: 10.7-16.9) followed by surgery-related (2.2, 95% CI: 1.0-3.4). The major risks of perioperative mortality were children younger than 1-year-old, older patients, patients with poor ASA physical status (III-V), emergency, cardiac or vascular surgeries, and multiple surgeries performed under the same anesthetic technique (P < 0.0001).There were no anesthesia-related deaths. However, the high mortality rate caused by the poor physical conditions of some patients suggests that primary prevention might be the key to reducing perioperative mortality. These findings demonstrate the need to improve medical perioperative practices for high-risk patients in under-resourced settings.

Does occupational exposure to anesthetic gases lead to increase of pro-inflammatory cytokines?

INTRODUCTION: There is great concern about the possible harmful effects of exposure to volatile anesthetics. The current study aimed at evaluating, for the first time, the effects of occupational exposure to anesthetic gases on physicians who work in operating rooms, by determining several inflammatory cytokines. MATERIALS AND METHODS: Plasma inflammatory cytokines (IL-1ß, -6, -8, -10, -12, TNF-α) were investigated in 30 individuals who were allocated into two groups of 15: the exposed group, consisting of operating room medical personnel exposed to a mixture of anesthetic gases for 3 years, and a control group composed of medical personnel not exposed to anesthetic gases. The concentrations of volatile anesthetics were measured in the operating room by means of an infrared portable analyzer RESULTS AND CONCLUSIONS: Our findings suggest an increase of the pro-inflammatory IL-8 (p<0.05) in medical personnel exposed to high concentrations of anesthetic gases, even for a relatively short period.