Modulation of gene expression and influence of gene polymorphisms related to genotoxicity and redox status on occupational exposure to inhaled anesthetics.

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.

High anesthetic exposure leads to oxidative damage and gene expression changes in physicians during medical residency: a cohort study.

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.

Prevalence of chronic pulmonary aspergillosis regarding time of tuberculosis diagnosis in Brazil.

BACKGROUND: Data on the prevalence of chronic pulmonary aspergillosis (CPA) in patients with active or cured tuberculosis (TB) are scarce, mainly due to diagnostic difficulties. The diagnosis of CPA is based on pulmonary symptoms and chest computed tomography (CT) scans and is considered confirmed when there is microbiological or serological evidence of Aspergillus spp. OBJECTIVES: To estimate the prevalence of CPA in patients treated or undergoing treatment for PTB, seen in two referral hospitals in Mato Grosso do Sul, Brazil. PATIENTS AND METHODS: A total of 193 consecutive patients who were treated or previously treated for pulmonary tuberculosis underwent prospective evaluation: (a) clinical evaluation; (b) chest CT scan; (c) sputum examination-culture for fungi and smears for direct mycology; (d) detection of anti-Aspergillus fumigatus antibodies using an enzyme-linked immunosorbent assay Platelia® test; and (e) anti-Aspergillus spp. antibodies were assessed via a DID test. RESULTS: The global prevalence of CPA was 10.9% (95% confidence interval, 7.2%-16.1%), but it increased with the time of TB diagnosis. The variables independently associated with CPA were previous pulmonary tuberculosis over 4 years ago and haemoptysis. Cavities, pleural thickening and the presence of a fungal ball were the most frequent tomographic findings in patients with CPA. CONCLUSIONS: The high prevalence observed and its increase over time suggest the need for continuous surveillance of CPA in patients with active or previous pulmonary tuberculosis and throughout life, with clinical, tomographic and serological evaluations (ELISA) for a timely diagnosis and a better prognosis.

High anesthetic (isoflurane) indoor pollution is associated with genetic instability, cytotoxicity, and proliferative alterations in professionals working in a veterinary hospital.

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.

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.

Comparison of clinico-epidemiological and radiological features in paracoccidioidomycosis patients regarding serological classification using antigens from Paracoccidioides brasiliensis complex and Paracoccidioides lutzii.

Genotyping of the genus Paracoccidioides showed its diversity and geographical distribution. Four species constituting the Paracoccidioides brasiliensis complex and Paracoccidioides lutzii are etiological agents of paracoccidioidomycosis (PCM). However, there are no studies comparing the clinical and epidemiological aspects between PCM caused by the P. brasiliensis complex and by P. lutzii. Demographic and clinical data from 81 patients with PCM-confirmed by mycological and/or histopathological examination-from Mato Grosso do Sul state (Brazil) were studied. All patients underwent serology by immunodiffusion with antigens obtained from the P. brasiliensis complex (ExoPb and gp43) and Cell Free Antigens obtained from P.lutzii (CFAPl).The cases were classified regarding their serological profile into three groups: G1: PCM patients seropositive to ExoPb and/or gp43 and seronegative to CFAPl (n = 51), assumed to have PCM caused by P. brasiliensis complex; G2: PCM patients seronegative to gp43 and seropositive to CFAPl (n = 16), with PCM caused by P. lutzii; and G3: PCM patients seropositive to ExoPb or gp43 and seropositive to CFAPl (n = 14), with undetermined serological profile, was excluded from the analyses. The Fisher's exact test or the Mann-Whitney U test, and cluster analysis according to Ward's method and Euclidean distance were used to analyze the results. Patients with serological profile suggestive of P. lutzii lived predominantly in municipalities in the Central and Southern regions of the state, while those with serological profile indicative of the P. brasiliensis complex were distributed throughout the state. No differences were found between the two groups regarding gender, age, schooling, rural work, clinical form, severity, organs involved, intensity of pulmonary involvement, degree of anemia, erythrocyte sedimentation rate values, and therapeutic response. PCM patients with serological profile suggestive of P. lutzii and PCM patients with serological profile indicative of P. brasiliensis complex showed the same clinical and radiological presentations.

Meta-Analysis of the Association Between the rs228570 Vitamin D Receptor Gene Polymorphism and Arterial Hypertension Risk.

The association between FokI polymorphism in the vitamin D receptor (VDR) gene and susceptibility to arterial hypertension (HT) is controversial. Thus, we evaluated the relation between FokI and HT according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using MEDLINE® (Medical Literature Analysis and Retrieval System Online)/PubMed, Scopus, and Cochrane Library CENTRAL databases. Data from case-control studies, including the number of participants, age, 25-hydroxyvitamin D concentrations, systolic and diastolic blood pressure values, FokI allele, and genotype frequency were extracted by 2 independent authors and OR was calculated with the 95% CI to assess the strength of the association between the FokI variant and odds of HT. In general and subgroup analyses, we used allelic (f compared with F), common (ff compared with FF + Ff), risk (ff + Ff compared with FF), and additive (ff compared with FF) models. Six case-control studies including 3140 cases and 3882 controls were reviewed in the meta-analysis. Global assessment revealed a correlation between FokI and reduced odds of HT in the additive/homozygote model (ff compared with FF; OR: 0.65; 95% CI: 0.45-0.94) and common/recessive model (ff compared with FF + Ff; OR: 0.75; 95% CI: 0.57-0.99). In Asian subjects, there was a significant reduction in the odds of HT in additive (ff compared with FF; OR: 0.84; 95% CI: 0.73-0.98) and risk models (ff + Ff compared with FF; OR: 0.87, 95% CI: 0.78-0.97), in particular, for Indians (South). In Africans, the statistically significant association occurred in the additive and common models. Allele f in the FokI polymorphism of the VDR gene was associated with reduced odds of HT in the general population based on the risk model. Thus, nutritional genomics can help understand the influence of nutrition on metabolic homeostasis pathways and the clinical consequences of hypertension. This study shows the need for healthy, anti-inflammatory, and antioxidant compounds to prevent or treat chronic complications.

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.

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.

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.

Fibrin gel versus papain gel in the healing of chronic venous ulcers: A double-blind randomized controlled trial.

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.

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.

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.

Pediatric perioperative cardiac arrest and mortality: a study from a tertiary teaching hospital.

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.

Intraoperative and anesthesia-related cardiac arrest and its mortality in older patients: a 15-year survey in a tertiary teaching hospital.

BACKGROUND: Little information is known about factors that influence perioperative and anesthesia-related cardiac arrest (CA) in older patients. This study evaluated the incidence, causes and outcome of intraoperative and anesthesia-related CA in older patients in a Brazilian teaching hospital between 1996 and 2010. METHODS: During the study, older patients received 18,367 anesthetics. Data collected included patient characteristics, surgical procedures, American Society of Anesthesiologists (ASA) physical status, anesthesia type, medical specialty team and outcome. All CAs were categorized by cause into one of four groups: patient's disease/condition-related, surgery-related, totally anesthesia-related or partially anesthesia-related. RESULTS: All intraoperative CAs and deaths rates are shown per 10,000 anesthetics. There were 100 CAs (54.44; 95% confidence intervals [CI]: 44.68-64.20) and 68 deaths (37.02; 95% CI: 27.56-46.48). The majority of CAs were patient's disease-/condition-related (43.5; 95% CI: 13.44-73.68). There were six anesthesia-related CAs (3.26; 95% CI: 0.65-5.87) - 1 totally and 5 partially anesthesia-related, and three deaths, all partially anesthesia-related (1.63; 95% CI: 0.0-3.47). ASA I-II physical status patients presented no anesthesia-related CA. Anesthesia-related CA, absent in the last five years of the study, was due to medication-/airway-related causes. ASA physical status was the most important predictor of CA (odds ratio: 14.52; 95% CI: 4.48-47.08; P<0.001) followed by emergency surgery (odds ratio: 8.07; 95% CI: 5.14-12.68; P<0.001). CONCLUSIONS: The study identified high incidence of intraoperative CAs with high mortality in older patients. The large majority of CAs were caused by factors not anesthesia-related. Anesthesia-related CA and mortality rates were 3.26 and 1.63 per 10,000 anesthetics, with no anesthesia-related CA in the last five years of the study. Major predictors of intraoperative CAs were poorer ASA physical status and emergency surgery. All anesthesia-related CAs were medication-related or airway-related, which is important for prevention strategies.

The humidity in a Dräger Primus anesthesia workstation using low or high fresh gas flow and with or without a heat and moisture exchanger in pediatric patients.

BACKGROUND: An inhaled gas absolute humidity of 20 mg H2O·L is the value most considered as the threshold necessary for preventing the deleterious effects of dry gas on the epithelium of the airways during anesthesia. Because children have small minute ventilation, we hypothesized that the humidification of a circle breathing system is lower in children compared with adults. The Primus anesthesia workstation (Dräger Medical, Lübeck, Germany) has a built-in hotplate to heat the patient's exhaled gases. A heat and moisture exchanger (HME) is a device that can be used to further humidify and heat the inhaled gases during anesthesia. To evaluate the humidifying properties of this circle breathing system during pediatric anesthesia, we compared the temperature and humidity of inhaled gases under low or high fresh gas flow (FGF) conditions and with or without an HME. METHODS: Forty children were randomly allocated into 4 groups according to the ventilation of their lungs by a circle breathing system in a Dräger Primus anesthesia workstation with low (1 L·min) or high (3 L·min) FGF without an HME (1L and 3L groups) or with an HME (Pall BB25FS, Pall Biomedical, East Hills, NY; HME1L and HME3L groups). The temperature and absolute humidity of inhaled gases were measured at 10, 20, 40, 60, and 80 minutes after connecting the patient to the breathing circuit. RESULTS: The mean inhaled gas temperature was higher in HME groups (HME1L: 30.3°C ± 1.1°C; HME3L: 29.3°C ± 1.2°C) compared with no-HME groups (1L: 27.0°C ± 1.2°C; 3L: 27.1°C ± 1.5°C; P < 0.0001). The mean inhaled gas absolute humidity was higher in HME than no-HME groups and higher in low-flow than high-flow groups ([HME1L: 25 ± 1 mg H2O·L] > [HME3L: 23 ± 2 mg H2O·L] > [1L: 17 ± 1 mg H2O·L] > [3L: 14 ± 1 mg H2O·L]; P < 0.0001). CONCLUSIONS: In a pediatric circle breathing system, the use of neither high nor low FGF provides the minimum humidity level of the inhaled gases thought to reduce the risk of dehydration of airways. Insertion of an HME increases the humidity and temperature of the inhaled gases, bringing them closer to physiological values. The use of a low FGF enhances the HME efficiency and consequently increases the inhaled gas humidity values. Therefore, the association of an HME with low FGF in the breathing circuit is the most efficient way to conserve the heat and the moisture of the inhaled gas during pediatric anesthesia.

Intraoperative cardiac arrest and mortality in trauma patients. A 14-yr survey from a Brazilian tertiary teaching hospital.

BACKGROUND: Little information on the factors influencing intraoperative cardiac arrest and its outcomes in trauma patients is available. This survey evaluated the associated factors and outcomes of intraoperative cardiac arrest in trauma patients in a Brazilian teaching hospital between 1996 and 2009. METHODS: Cardiac arrest during anesthesia in trauma patients was identified from an anesthesia database. The data collected included patient demographics, ASA physical status classification, anesthesia provider information, type of surgery, surgical areas and outcome. All intraoperative cardiac arrests and deaths in trauma patients were reviewed and grouped by associated factors and also analyzed as totally anesthesia-related, partially anesthesia-related, totally surgery-related or totally trauma patient condition-related. FINDINGS: Fifty-one cardiac arrests and 42 deaths occurred during anesthesia in trauma patients. They were associated with male patients (P<0.001) and young adults (18-35 years) (P=0.04) with ASA physical status IV or V (P<0.001) undergoing gastroenterological or multiclinical surgeries (P<0.001). Motor vehicle crashes and violence were the main causes of trauma (P<0.001). Uncontrolled hemorrhage or head injury were the most significant associated factors of intraoperative cardiac arrest and mortality (P<0.001). All cardiac arrests and deaths reported were totally related to trauma patient condition. CONCLUSIONS: Intraoperative cardiac arrest and mortality incidence was highest in male trauma patients at a younger age with poor clinical condition, mainly related to uncontrolled hemorrhage and head injury, resulted from motor vehicle accidents and violence.

Undergraduate research in medical education: a descriptive study of students' views.

BACKGROUND: Medical students engage in curricular and extracurricular activities, including undergraduate research (UR). The advantages, difficulties and motivations for medical students pursuing research activities during their studies have rarely been addressed. In Brazil, some medical schools have included undergraduate research into their curriculum. The present study aimed to understand the reality of scientific practice among medical students at a well-established Brazilian medical school, analyzing this context from the students' viewpoint. METHODS: A cross-sectional survey based on a questionnaire applied to students from years one to six enrolled in an established Brazilian medical school that currently has no curricular UR program. RESULTS: The questionnaire was answered by 415 students, 47.2% of whom were involved in research activities, with greater participation in UR in the second half of the course. Independent of student involvement in research activities, time constraints were cited as the main obstacle to participation. Among students not involved in UR, 91.1% said they favored its inclusion in the curriculum, since this would facilitate the development of such activity. This approach could signify an approximation between the axes of teaching and research. Among students who had completed at least one UR project, 87.7% said they would recommend the activity to students entering the course. CONCLUSION: Even without an undergraduate research program, students of this medical school report strong involvement in research activities, but discussion of the difficulties inherent in its practice is important to future developments.

Taste and temperature in swallowing transit time after stroke.

BACKGROUND: Oropharyngeal dysphagia is common in individuals after stroke. Taste and temperature are used in dysphagia rehabilitation. The influence of stimuli, such as taste and temperature, on swallowing biomechanics has been investigated in both healthy individuals and in individuals with neurological disease. However, some questions still remain unanswered, such as how the sequence of offered stimuli influences the pharyngeal response. The goal of the present study was to determine the influence of the sequence of stimuli, sour taste and cold temperature, on pharyngeal transit time during deglutition in individuals after stroke. METHODS: The study included 60 individuals with unilateral ischemic stroke, 29 males and 31 females, aged 41-88 years (mean age: 66.2 years) examined 0-50 days after ictus (median: 6 days), with mild to moderate oropharyngeal dysphagia. Exclusion criteria were hemorrhagic stroke patients, patients with decreased level of consciousness, and clinically unstable patients, as confirmed by medical evaluation. The individuals were divided into two groups of 30 individuals each. Group 1 received a nonrandomized sequence of stimuli (i.e. natural, cold, sour, and sour-cold) and group 2 received a randomized sequence of stimuli. A videofluoroscopic swallowing study was performed to analyze the pharyngeal transit time. Four different stimuli (natural, cold, sour, and sour-cold) were offered. The images were digitalized and specific software was used to measure the pharyngeal transit time. Since the values did not present regular distribution and uniform variances, nonparametric tests were performed. RESULTS: Individuals in group 1 presented a significantly shorter pharyngeal transit time with the sour-cold stimulus than with the other stimuli. Individuals in group 2 did not show a significant difference in pharyngeal transit time between stimuli. CONCLUSIONS: The results showed that the sequence of offered stimuli influences the pharyngeal transit time in a different way in individuals after stroke and suggest that, when the sour-cold stimulus is offered in a randomized sequence, it can influence the response to the other stimuli in stroke patients. Hence, the sour-cold stimulus could be used as a therapeutic aid in dysphagic stroke patients.