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.

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

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

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

BACKGROUND: Little is known about the effects of desflurane associated or not with nitrous oxide (N2O) on oxidative stress and patient genetic material. The aim of this study was to compare the effects of anesthesia maintained with desflurane associated or not with N2O on DNA damage (as a primary outcome) and oxidative stress (as a secondary outcome) in patients who underwent an elective minimally invasive surgery. METHODS: This prospective randomized clinical trial analyzed 40 patients of both sexes with an American Society of Anesthesiologists physical status I who were 18-50 years of age and scheduled for septoplasty. The patients were randomly allocated into 2 groups according to anesthesia maintenance as follows: desflurane (n = 20) or desflurane/N2O (n = 20). Blood samples were collected before anesthesia (T1 = baseline), 1.5 hours after anesthesia induction (T2), and on the morning of the postoperative first day (T3). Basal and oxidative DNA damage (determined using formamidopyrimidine DNA glycosylase to detect oxidized purines and endonuclease III to detect oxidized pyrimidines) were evaluated using the comet assay. Oxidative stress markers were evaluated based on lipid peroxidation (by assessing 4-hydroxynonenal and 8-iso-prostaglandin F2α [8-isoprostane] using enzyme linked immunosorbent immunoassay), protein carbonyls (assessed by enzyme linked immunosorbent immunoassay), and antioxidant defense (ferric-reducing antioxidant power by spectrophotometry). The effect size was expressed as the mean differences between groups and the corresponding 95% confidence interval (CI). RESULTS: There was no significant mean difference between groups in relation to DNA damage (-1.7 [95% CI, -7.0 to 3.5]), oxidized DNA pyrimidines (-1.8 [95% CI, -12.5 to 8.9]) and purines (-1.9 [95% CI, -13.9 to 10.1]), 4-hydroxynonenal (-0.2 [95% CI, -2.8 to 2.4]), 8-isoprostane (549 [95% CI, -2378 to 3476]), protein carbonyls (0.2 [95% CI, -2.1 to 2.3]), or ferric-reducing antioxidant power (24 [95% CI, -52.0 to 117.2]). CONCLUSIONS: The coadministration of 60% N2O with desflurane did not seem to impair the effects on DNA or the redox status compared with desflurane anesthesia, suggesting that both studied anesthetic techniques can be suitable options for healthy individuals who undergo minimally invasive surgery lasting at least 1.5 hours. However, due to the low power of the study, more research is necessary to confirm our findings.

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.

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.

An update on the mechanisms and risk factors for anesthesia-related cardiac arrest in children: a narrative review.

The relation between surgery and anesthesia safety in children and a country's Human Development Index (HDI) value has been described previously. The aim of this narrative review was to provide an update on the mechanisms and risk factors of Anesthesia-Related Cardiac Arrest (ARCA) in pediatric surgical patients in countries with different HDI values and over time (pre-2001 vs. 2001‒2024). Electronic databases were searched up to March 2024 for studies reporting ARCA events in children. HDI values range from 0 to 1 (very-high-HDI countries: ≥ 0.800, high-HDI countries: 0.700‒0.799, medium-HDI countries: 0.550‒0.699, and low-HDI countries: < 0.550). Independent of time, the proportion of children who suffered perioperative Cardiac Arrest (CA) attributed to anesthesia-related causes was higher in very-high-HDI countries (50%) than in countries with HDI values less than 0.8 (15‒36%), but ARCA rates were higher in countries with HDI values less than 0.8 than in very-high-HDI countries. Regardless of the HDI value, medication-related factors were the most common mechanism causing ARCA before 2001, while cardiovascular-related factors, mainly hypovolemia, and respiratory-related factors, including difficulty maintaining patent airways and adequate ventilation, were the major mechanisms in the present century. Independent of HDI value and time, a higher number of ARCA events occurred in children with heart disease and/or a history of cardiac surgery, those aged younger than one year, those with ASA physical status III‒V, and those who underwent emergency surgery. Many ARCA events were determined to be preventable. The implementation of specialized pediatric anesthesiology and training programs is crucial for anesthesia safety in children.

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.

Comparison of inflammatory cytokine profiles in plasma of patients undergoing otorhinological surgery with propofol or isoflurane anesthesia.

OBJECTIVE AND DESIGN: The effects of anesthetics on cytokine release in patients without comorbidities who undergo minor surgery are not well defined. We compared inflammatory cytokine profiles in adult patients undergoing minimally invasive surgery who received isoflurane or propofol anesthesia. METHODS: Thirty-four patients without comorbidities undergoing minor surgery were randomly assigned to receive an inhaled anesthetic (isoflurane; n = 16) or an intravenous anesthetic (propofol; n = 18). Blood samples were drawn before premedication and anesthesia (T1), 120 min after anesthesia induction (T2), and on the first post-operative day (T3). Plasma concentrations of interleukins (IL-) 1ß, 6, 8, 10 and 12 and tumor necrosis factor (TNF)-α were measured using flow cytometry. RESULTS: The pro-inflammatory cytokine IL-6 was increased in the isoflurane group at T2 and T3 compared to T1 (P < 0.01). In the propofol group, IL-6 and IL-8 were significantly increased at T3 compared to T1. However, there were no significant differences in cytokine concentrations between the isoflurane and propofol groups. CONCLUSION: An inflammatory response occurred earlier in patients who received an inhaled agent compared with an intravenous anesthetic, but no differences in plasma cytokine profiles were evident between isoflurane and propofol anesthesia in patients without comorbidities undergoing minimally invasive surgeries.

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.

Genotoxicity, cytotoxicity and gene expression in patients undergoing elective surgery under isoflurane anaesthesia.

There are numerous studies reporting on the effects of inhalation anaesthesia in cells of exposed individuals but not much is known about the ability of isoflurane (ISF) to induce oxidative DNA damage. However, surgery is often associated with a temporary perioperative immunological alteration, and some volatile anaesthetics seem to contribute to a transient lymphocytopenia after surgery. We conducted a study to evaluate a possible genotoxic effect, including oxidative DNA damage, and apoptosis in peripheral lymphocytes of 20 patients American Society of Anaesthesiologists physical status I undergoing minor elective surgery lasting at least 120 min, under anaesthesia with ISF. We also investigated the expression of several genes in blood cells. Blood samples were collected at three time points: before anaesthesia (T(1)), 2 h after the beginning of anaesthesia (T(2)) and on the first post-operative day (T(3)). General DNA damage and oxidised bases (Fpg and endo III-sites) in blood lymphocytes were evaluated using the comet assay. Lymphocytes were phenotyped and apoptosis was evaluated by flow cytometry. In addition, expressions of hOGG1 and XRCC1, genes involved in DNA repair, and BCL2, a gene related to apoptosis, were assessed by quantitative real-time polymerase chain reaction. Results showed no statistically significant difference in the level of DNA damage and oxidised bases among the three sampling times. Anaesthesia with ISF did not increase the percentage of cells in early or late apoptosis in cytotoxic or helper T lymphocytes. Lower hOGG1 and BCL2 expressions were detected at T(3) in comparison to the other two previous time points, and there was significantly lower expression of XRCC1 at T(3) in relation to T(2). In conclusion, the exposure to ISF did not result in genotoxicity and cytotoxicity in lymphocytes and in toxicogenomic effect in leukocytes, although DNA repair and apoptosis-related genes were down-regulated on the first post-operative day.

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.

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.

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.

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.

[Epidemiology of perioperative cardiac arrest and mortality in Brazil: a systematic review]. / Epidemiologia de parada cardíaca e de mortalidade perioperatória no Brasil: revisão sistemática.

BACKGROUND AND OBJECTIVES: The perioperative cardiac arrest (CA) and mortality rates in Brazil, a developing country, are higher than in developed countries. The hypothesis of this review was that knowledge of the epidemiology of perioperative CA and mortality in Brazil enables the comparison with developed countries. The systematic review aimed to verify, in studies conducted in Brazil, the epidemiology of perioperative CA and mortality. METHOD AND RESULTS: A search strategy was carried out on different databases (PubMed, EMBASE, SciELO and LILACS) to identify observational studies that reported perioperative CA and/or mortality up to 48 hours postoperatively in Brazil. The primary outcomes were data on epidemiology of perioperative CA and mortality. In 8 Brazilian studies, there was a higher occurrence of perioperative CA and mortality in males; in extremes of age; in patients in worse physical status according to the American Society of Anesthesiologists (ASA); in emergency surgeries; in general anesthesia; and in cardiac, thoracic, vascular, abdominal and neurological surgeries. The patient's disease/condition was the main triggering factor, with sepsis and trauma as the main causes. CONCLUSIONS: The epidemiology of both perioperative CA and mortality events reported in Brazilian studies does not show important differences and, in general, is similar to studies in developed countries. However, sepsis represents one of the major causes of perioperative CA and mortality in Brazilian studies, contrasting with studies in developed countries in which sepsis is a secondary cause.

Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing elective surgery.

BACKGROUND AND OBJECTIVES: Inhaled anaesthetics have been studied regarding their genotoxic and mutagenic potential in vivo. Propofol differs from volatile anaesthetics because it does not show mutagenic effects and it has been reported to be an antioxidant. However, there are no studies with propofol and genotoxicity in vivo. The study aimed to evaluate the hypothesis that propofol is not genotoxic and it inhibits lipid peroxidation [malondialdehyde (MDA)] in patients undergoing propofol anaesthesia. METHODS: ASA physical status I patients scheduled for elective surgery, lasting at least 90 min, were enrolled in this study. Initially, the estimated plasma concentration of propofol was targeted at 4 microg ml(-1) and then maintained at 2-4 microg ml(-1) until the end of surgery. Haemodynamic data were determined at baseline (before premedication) and in conjunction with target-controlled infusion of propofol: after tracheal intubation, 30, 60 and 90 min after anaesthesia induction and at the end of the surgery. Venous blood samples were collected at baseline, after tracheal intubation, at the end of the surgery and on the postoperative first day for evaluating DNA damage in white blood cells (WBCs), by comet assay, and MDA levels. RESULTS: Haemodynamic data did not differ among times. No statistically significant differences were observed for the levels of DNA damage in WBCs, nor in plasma MDA, among the four times. CONCLUSION: Propofol does not induce DNA damage in WBCs and does not alter MDA in plasma of patients.

Does the choice of the halogenated anesthetic influence renal function during hemorrhagic shock and resuscitation?

INTRODUCTION: Halogenated anesthetics can cause changes in the variables that modify the cardiac output necessary to maintain renal hemodynamic during hemorrhagic shock and resuscitation. However, halogenated anesthetics seem to protect against renal ischemia-reperfusion injury. In a model of pressure-guided hemorrhagic shock in dogs, we studied the comparative effects of three halogenated anesthetics-halothane, sevoflurane, and isoflurane-at equipotent concentrations on renal responses after resuscitation. METHODS: Thirty dogs were anesthetized with 1.0 minimum alveolar anesthetic concentration (MAC) of halothane, sevoflurane, or isoflurane. The dogs were splenectomized and hemorrhaged to hold mean arterial pressure at 40-50 mm Hg over 45 min and then resuscitated with the shed blood volume. Hemodynamic variables were measured at baseline, after 45 min of hemorrhage, and 15 and 60 min after resuscitation. Renal variables were measured at baseline and 15 and 60 min after resuscitation. RESULTS: Hemorrhage induced reductions of mean arterial pressure, filling pressures, and cardiac index (p < 0.05), without significant differences among groups (p > 0.05). After 60 min of shed blood replacement, all groups restored hemodynamic and renal variables to the prehemorrhage levels (p > 0.05), without significant differences among groups (p > 0.05), with the exception of sodium fractional excretion, the values for which were significantly higher in isoflurane group, in relation to the other groups after 15 min of re-transfusion (p < 0.05), and renal vascular resistance, the values for which remain lower than baseline in halothane group (p < 0.05). CONCLUSIONS: We conclude that no difference could be detected between choosing equipotent doses of halothane, sevoflurane, or isoflurane in relation to renal variables in dogs submitted to pressure-adjusted hemorrhagic shock and resuscitation.

Clinical, histological and electron microscopic aspects of vocal fold granulomas.

UNLABELLED: Granulomas are bilateral and pediculated lesions of the vocal apophysis. Etiologies: intubation, reflux, trauma, vocal abuse, idiopathic origin. AIM: To analyze the clinical and morphological aspects of post intubation granulomas. METHODS: retrospective study of patients submitted to microsurgery for post intubation laryngeal granulomas seen at our Medical School starting in 2002. We analyzed: age, gender, indication and time of intubation, symptoms, videolaryngoscopic diagnosis and biopsy findings. Light microscopy was performed on all specimens, and electron microscopy on three of them. RESULTS: ten patients (7 females and 3 males), between the ages of 2 and 72 years, intubation time between 4h and 21 days. Hoarseness was a frequent symptom, starting in the first week following extubation. Histology shows mild epithelial hyperplasia, severe inflammation and vessel proliferation in the corion. Under SEM, the epithelium presented mild superficial desquamation. Under TEM, intracellular junctions showed widening with structural changes in the desmosomes. In the corion there were vessel proliferations, inflammation and fibroblasts with structural alterations. CONCLUSIONS: post intubation granulomas appear in any age and hoarseness is a frequent symptom. Morphological alterations occur in the corion as vessel proliferations, inflammation, and intracytoplasmatic alterations in fibroblasts suggesting cellular dysfunction and damage.

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.

Gastric mucosal perfusion in dogs: effects of halogenated anesthetics and of hemorrhage.

The gastrointestinal tract is one of the first organs affected by hypoperfusion during hemorrhagic shock. The hemodynamics and oxygen transport variables during hemorrhagic shock and resuscitation can be affected by the anesthetics used. In a model of pressure-guided hemorrhagic shock in dogs, we studied the effects of three halogenated anesthetics--halothane, sevoflurane, and isoflurane--at equipotent concentrations on gastric oxygenation. Thirty dogs were anesthetized with 1.0 minimum alveolar anesthetic concentration (MAC) of either halothane, sevoflurane, or isoflurane. A gastric tonometer was placed in the stomach to determine mucosal gastric CO(2) (PgCO(2)) and for the calculation of gastric-arterial PCO(2) gradient (PCO(2) gap). The dogs were splenectomized and hemorrhaged to hold mean arterial pressure at 40-50 mm Hg over 45 min and then resuscitated with the shed blood volume. Hemodynamics, systemic oxygenation, and PCO(2) gap were measured at baseline, after 45 min of hemorrhage, and at 15 and 60 min after blood resuscitation. Hemorrhage induced reductions of mean arterial pressure and cardiac index, while systemic oxygen extraction increased (p < .05), without significant differences among groups (p > .05). Halothane group showed significant lower PCO(2) gap values than the other groups (p < .05). After 60 min of shed blood replacement, all groups restored hemodynamics, systemic oxygenation, and PCO(2) gap to the prehemorrhage levels (p > .05), without significant differences among groups (p > .05). We conclude that halothane is superior to preserve the gastric mucosal perfusion in comparison to isoflurane and sevoflurane, in dogs submitted to pressure-guided hemorrhagic shock at equipotent doses of halogenated anesthetics.