RESUMO
The extensive use of inhalational anesthetics contributes to both indoor and outdoor (environmental) pollution. The influence of genetic susceptibility on DNA damage and oxidative stress and the possible modulation of gene expression have not yet been investigated upon occupational exposure to waste anesthetic gases (WAGs). This study assessed 8-oxoguanine DNA glycosylase 1 (OGG1) and superoxide dismutase 2 (SOD2) gene expression, which are related to oxidized DNA repair and antioxidant capacity, respectively, and the influence of their polymorphisms (OGG1 rs1052133 and SOD2 rs4880) in 100 professionals highly exposed to WAGs and 93 unexposed volunteers (control group). Additionally, X-ray repair cross complementing 1 (XRCC1 rs25487 and rs1799782) and ataxia telangiectasia mutated (ATM rs600931) gene polymorphisms as well as genetic instability (micronucleus-MN and nuclear bud-NBUD) and oxidative stress (malondialdehyde-MDA and ferric reducing antioxidant power-FRAP) biomarkers were assessed in the groups (control and exposed) and in the subgroups of the exposed group according to job occupation (anesthesiologists versus surgeons/technicians). Except for the ATM TT controls (associated with increased FRAP), there were no influences of OGG1, XRCC1, ATM, and SOD2 polymorphisms on MN, NBUD, MDA, and FRAP values in exposed or control subjects. No significant difference in the expression of either gene evaluated (OGG1 and SOD2) was found between the exposed and control groups. Increased OGG1 expression was observed among OGG1 -/Cys individuals only in the control group. Among the exposed group, anesthesiologists had a greater duration of WAG exposure (both h/week and years) than surgeons/technicians, which was associated with increased MDA and decreased antioxidant capacity (FRAP) and SOD2 expression (redox status). Higher expression of OGG1 was found in -/Cys surgeons/technicians than in anesthesiologists with the same genotype. Increased antioxidant capacity was noted in the surgeons/technicians carrying the ATM T allele and in those carrying XRCC1 -/Gln. Increased MN was influenced by OGG1 -/Cys in surgeons/technicians. Anesthesiologists with ATM CC exhibited increased MN, and those carrying the C allele (CC/CT genotype) exhibited increased NBUD. SOD2 polymorphism did not seem to be relevant for WAG exposure. These findings contribute to advancing the knowledge on genetic susceptibility/gene expression/genetic instability/oxidative stress, including differences in job occupation considering the workload, in response to occupational exposure to WAGs.
Assuntos
Antioxidantes , Exposição Ocupacional , Humanos , Polimorfismo Genético , Dano ao DNA , Reparo do DNA , Genótipo , Predisposição Genética para Doença , Oxirredução , Expressão Gênica , Estudos de Casos e Controles , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genéticaRESUMO
Evaluation of the possible toxic effects of occupational exposure to anesthetics is of great importance, and the literature is limited in assessing the possible association between occupational exposure to anesthetics and oxidative stress and genetic damage. To contribute to the gap of knowledge in relation to cause-effect, this cohort study was the first to monitor exposure assessment and to evaluate oxidative stress, DNA damage, and gene expression (OGG1, NRF2, HO-1, and TP53) in young adult physicians occupationally exposed to the most modern halogenated anesthetics (currently the commonly used inhalational anesthetics worldwide) in addition to nitrous oxide gas during the medical residency period. Therefore, the physicians were evaluated before the beginning of the medical residency (before the exposure to anesthetics-baseline), during (1 1/2 year) and at the end (2 1/2 years) of the medical residency. Anesthetic air monitoring was performed in operating rooms without adequate ventilation/scavenging systems, and biological samples were analyzed for lipid peroxidation, protein carbonyl content, primary and oxidative DNA damage, antioxidant enzymes and plasma antioxidant capacity, and expression of some key genes. The results showed induction of lipid peroxidation, DNA damage, glutathione peroxidase activity, and NRF2 and OGG1 expression up to the end of medical residency. Plasma antioxidant capacity progressively increased throughout medical residency; oxidative DNA damage levels started to increase during medical residency and were higher at the end of residency than at baseline. Protein carbonyls increased during but not at the end of medical residency compared to baseline. The antioxidant enzyme superoxide dismutase activity remained lower than baseline during and at the end of medical residency, and HO-1 (related to antioxidant defense) expression was downregulated at the end of medical residency. Additionally, anesthetic concentrations were above international recommendations. In conclusion, high concentrations of anesthetic in the workplace induce oxidative stress, gene expression modulation, and genotoxicity in physicians during their specialization period.
Assuntos
Anestésicos Inalatórios , Internato e Residência , Exposição Ocupacional , Médicos , Adulto Jovem , Humanos , Antioxidantes/farmacologia , Carbonilação Proteica , Estudos de Coortes , Fator 2 Relacionado a NF-E2 , Anestésicos Inalatórios/toxicidade , Exposição Ocupacional/análise , Estresse Oxidativo , Dano ao DNA , Expressão GênicaRESUMO
This is the first study to monitor anesthetic pollution in veterinary operating rooms (VOR) and assess the toxicological impact of the inhalational anesthetic isoflurane (exposed group) compared to matched volunteers (control group). DNA damage was evaluated in mononuclear cells by the comet assay while genetic instability (including micronucleus-MN), cell proliferation, and cell death markers were assessed by the buccal MN cytome assay. Residual isoflurane concentrations in VOR (air monitoring) lacking the scavenging system were assessed by infrared spectrophotometry; the mean concentration was 11 ppm (≥ 5 times above the international recommended threshold). Comet assay results did not differ between groups; however, both younger exposed professionals (with higher week workload) compared to older individuals exposed for the same period and older professionals with greater time of exposure (years) compared to those in the same age group with fewer years of exposure presented higher DNA damage. The exposed group had a higher frequency of MN, nuclear buds, binucleated cells, karyorrhexis, and karyolysis and a lower frequency of basal cells than the control group. Exposed women were more vulnerable to genetic instability and proliferative index; exposed men presented more cytotoxicity. High WAG exposure has deleterious effects on exposed professionals.
Assuntos
Poluição do Ar em Ambientes Fechados , Anestésicos Inalatórios , Isoflurano , Exposição Ocupacional , Animais , Ensaio Cometa , Dano ao DNA , Feminino , Hospitais Veterinários , Humanos , Masculino , Testes para Micronúcleos/métodos , Exposição Ocupacional/análiseRESUMO
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.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Citocinas/metabolismo , Desflurano/administração & dosagem , Óxido Nitroso/administração & dosagem , Adulto , Citocinas/sangue , Feminino , Cirurgia Geral , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nitroso/efeitos adversos , Estudos ProspectivosRESUMO
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.
Assuntos
Poluentes Ocupacionais do Ar/análise , Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Anestésicos Inalatórios/análise , Exposição Ocupacional/estatística & dados numéricos , Feminino , Humanos , Masculino , Salas Cirúrgicas , Médicos , Sevoflurano/análiseRESUMO
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 (pâ¯=â¯0.027), and pro-inflammatory IL-6 and IL-8 levels were significantly increased after surgery (pâ¯=â¯0.001 and pâ¯=â¯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 (pâ¯>⯠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.
Assuntos
Anestésicos Inalatórios/toxicidade , Dano ao DNA , Desflurano/toxicidade , Inflamação/induzido quimicamente , Interleucinas/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Adulto , Ensaio Cometa , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/sangue , Interleucinas/sangue , Interleucinas/genética , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Procedimentos Cirúrgicos Operatórios , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genética , Adulto JovemRESUMO
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.
Assuntos
Anestesia por Inalação/instrumentação , Anestesiologia/instrumentação , Gases/administração & dosagem , Intubação Intratraqueal/instrumentação , Adolescente , Adulto , Anestésicos/administração & dosagem , Feminino , Alemanha , Humanos , Umidade , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Masculino , Pessoa de Meia-Idade , Respiração Artificial/instrumentação , TemperaturaRESUMO
Objectives Compare the efficacy and safety of fibrin gel to 8% papain gel for wound dressing of venous ulcers. Method Patients with chronic venous ulcers were randomly assigned to one in three groups: Group 1-fibrin gel; Group 2-8% papain gel; Group 3-carbopol gel (control). Patients were seen every 15 days during 2 months, verifying reduction of the ulcer area, local infection, exudation, and epithelization. All serious or nonserious adverse events were recorded. Results Fifty-five patients (total of 63 ulcers) were randomly distributed in three groups (G1 = 21; G2 = 19; G3 = 23). No patient was excluded or discontinued treatment throughout the study. The areas of the ulcers were similarly reduced in all groups (14.3%, 21.1%, and 30.4% in groups 1, 2, and 3, respectively), and all had significant reduction in exudation and contamination. Conclusion The data demonstrate that neither fibrin gel nor papain gel were able to improve the process of ulcer-healing, as compared to control.
Assuntos
Fibrina/uso terapêutico , Géis , Papaína/uso terapêutico , Úlcera Varicosa/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bandagens , Doença Crônica , Método Duplo-Cego , Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , CicatrizaçãoRESUMO
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 (Pâ<â0.0001).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.
Assuntos
Anestesia/mortalidade , Hospitais de Ensino/estatística & dados numéricos , Período Perioperatório/mortalidade , Centros de Atenção Terciária/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVES: A previous survey performed in our institution demonstrated perioperative pediatric cardiac arrest and mortality rates of 22.9 and 9.8 per 10,000 anesthetics, respectively, and an anesthesia-related cardiac arrest rate of 4.58 per 10,000 anesthetics. Changes in pediatric practices (i.e., safer anesthesia techniques and change in population) may have altered cardiac arrest rates. The aim of this investigation was to reexamine the perioperative and anesthesia-related cardiac arrest rates, causes, and outcomes in a Brazilian institution. DESIGN: Observational study. SETTING: Tertiary teaching hospital. PATIENTS: Children less than 18 years old, who were administered an anesthetic between January 1, 2005, and December 31, 2010, were included in this study. The cardiac arrest cases were identified from an anesthesia database. The data included children's characteristics, surgical procedures, American Society of Anesthesiologists physical status classification, surgical areas, and surgery type. The outcomes were perioperative cardiac arrest and mortality and anesthesia-related (totally or partially) cardiac arrest and mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 10,649 anesthetics during the study period, with 22 perioperative cardiac arrests and 11 deaths (20.65 and 10.32 per 10,000 anesthetics, respectively). A high incidence of perioperative cardiac arrest occurred in American Society of Anesthesiologists IV-V neonates and infants who underwent emergency surgery. There were no perioperative cardiac arrests in children aged 13 through 17, no anesthesia-related cardiac arrest in American Society of Anesthesiologists I-III children, and no totally anesthesia-related cardiac arrest. The anesthesia-related cardiac arrest rate was 2.81 per 10,000 anesthetics, with no anesthesia-related mortality. Respiratory events accounted for all of the anesthesia-related cardiac arrests. CONCLUSIONS: Despite the improvements achieved in the pediatric anesthesia safety in our institution, the perioperative cardiac arrest rates are still high and similar to the developing countries rates, with the child's disease or condition being the most important trigger for cardiac arrest. Airway management continues to be the greatest cause of anesthesia-related cardiac arrest.