Efeitos genotóxicos em profissionais expostos aos anestésicos inalatórios

JUSTIFICATIVA E OBJETIVOS: Neste estudo compararam-se médicos expostos aos gases anestésicos com indivíduos não expostos, para a investigação de alterações cromossômicas, verificação da possível interferência dos anestésicos inalatórios na cinética celular e avaliação do risco genotóxico associado à exposição ocupacional. MÉTODO: Foram realizadas culturas temporárias de linfócitos do sangue periférico para a obtenção de metáfases, necessárias para a análise de aberrações cromossômicas e trocas entre cromátides irmãs. RESULTADOS: A análise citogenética mostrou um aumento nas freqüências de aberrações cromossômicas por célula no grupo exposto, quando comparado ao grupo controle, denotando o efeito clastogênico desses compostos. Com relação ao parâmetro de trocas entre cromátides irmãs, os gases anestésicos não demonstraram efeito indutor. A comparação entre os índices mitótico e de proliferação celular também mostrou que não há diferenças significativas entre os grupos exposto e controle. CONCLUSÕES: Os resultados obtidos sugerem que os anestesiologistas podem representar um grupo de risco entre pessoas ocupacionalmente expostas e as condições de trabalho devem ser melhoradas.

REDUCAO DA CONCENTRACAO ALVEOLAR MINIMA DO ISOFLURANO E DO SEVOFLURANO PELO SUFENTANIL

Background and Objectives - Inhalational anesthetics have a mild analgesic effect. The reduction of alveolar concentration (MAC) of potent volatile anesthesics by increasing plasma concentrations of opioids is desired in inhalational anesthesia. The purpose of this study was to determine the role of sufentanil in reducing sevoflurane and isoflurane MAC. Methods - Thirty eight adult patients of both genders, physical status ASA I or II, submitted to major abdominal procedures were randomly allocated into two groups. Group I (n = 24) received inahalational anesthesia with sevoflurane and Group II (n = 14) received inhalational anesthesia with isoflurane, both diluted in a mixture of N2O (1 liter) and O2 (0.5 liter). A semi-closed system with CO2 absorber and partial reinhalation was used. Ventilation was mechanically controlled. Sufentanil infusion was administered aiming at obtaining 0.5 ng.ml-1 of plasma concentration. Sufentanil plasma concentration was previously calculated by a computer software. End-tidal concentrations were obtained through a gas analyzer and measured at 15 minutes (M1), 30 minutes (M2), 60 minutes (M3), 90 minutes (M4) and 120 minutes (M5). Systolic and diastolic blood pressure (SBP and DBP) and heart rate (RR) were measured during the same periods with the addition of M0 (pre-anesthetic period). Hourly consumption of the inhalational anesthetic agent (IAC), extubation time (ET = time between admission to the recovery room and extubation) and stay in the post anesthesia recovery room (PA-RR) were also measured. Results - Type and duration of surgeries were similar for both groups. There were no statistically significant differences in MAC, SBP, DBP, RR, IAC, TE and PA-RR between groups. Systolic blood pressure in group I (sevoflurane) showed differences among periods F = 3.82 p < O.05; (M2 = M3)(M4 = M5) and M1 had a intermediate value. MAC in group I showed differences among periods F = 9.0 p < 0.05; M1 < M3. MAC in group II also showed differences among periods F = 13.03 p < O.05; M1 < (M2,M3,M4,M5). Conclusions - Both groups had similar behavior when associated to sufentanil in major abdominal surgeries. Group II showed a higher cardiac and circulatory stability.

An inhalational anesthetic binding domain in the nicotinic acetylcholine receptor.

To determine inhalational anesthetic binding domains on a ligand-gated ion channel, I used halothane direct photoaffinity labeling of the nicotinic acetylcholine receptor (nAChR) in native Torpedo membranes. [14C]Halothane photoaffinity labeling of both the native Torpedo membranes and the isolated nAChR was saturable, with Kd values within the clinically relevant range. All phospholipids were labeled, with greater than 95% of the label in the acyl chain region. Electrophoresis of labeled nAChR demonstrated no significant subunit selectivity for halothane incorporation. Within the alpha-subunit, greater than 90% of label was found in the endoprotease Glu-C digestion fragments which contain the four transmembrane regions, and the pattern was different from that reported for photoactivatable phospholipid binding to the nAChR. Unlabeled halothane reduced labeling more than did isoflurane, suggesting differences in the binding domains for inhalational anesthetics in the nAChR. These data suggest multiple similar binding domains for halothane in the transmembrane region of the nAChR.

ENHANCED AMPEROMETRIC DETECTOR FOR LOCAL-ANESTHETICS IN LIQUID-CHROMATOGRAPHY WITH METAL-OXIDE DISPERSED GLASSY-CARBON ELECTRODES

Chemically modified electrodes (CMEs) prepared by the dispersion of metal oxide particles on a glassy carbon (GC) substrate greatly enhance the voltammetric response and amperometric detection of local anesthetics following liquid chromatography (LC). The enhancement is more pronounced with the GC electrodes dispersed by the metal oxides of higher oxidation states (+3, +4) and for the species exhibiting relatively slow electrode kinetics under given conditions. With an applied potential of 1.2 V (vs. SCE), LC amperometric detection of the analytes at the alpha-alumina modified GC surface gives detection limits 2-5 times lower than those obtained at the bare electrode. The metal oxide-dispersed electrodes display significant improvement in sensitivity, and selectivity and indicate excellent preparation reproducibility and performance stability.

Evaluación e intervención interdisciplinaria del dolor en Unidades de Cuidado Intensivo

El dolor es un problema importante para los pacientes hospitalizados en las UCI porque genera malestar y distrés. Además, la investigación ha demostrado que en algunos pacientes críticos el dolor agudo puede persistir después de alta y convertirse en crónico. La gestión eficaz del dolor en pacientes críticos requiere un enfoque interdisciplinario, que incorpore la visión y trabajo de expertos que representan una amplia variedad de especialidades clínicas. Así, la utilización de la intervención psicológica en el tratamiento del dolor es una parte integral de un enfoque global. Basado en una revisión de la evidencia científica, se identifican y señalan: (1) los tipos de dolor más comunes; (2) las características del dolor; (3) las patologías más frecuentes asociadas con la presencia de dolor; (4) los procedimientos que generan dolor en la UCI; (5) los métodos de evaluación del dolor; (6) la intervención del mismo y; (7) la contribución del psicólogo en la evaluación y manejo del dolor con el paciente, los familiares y los profesionales de la salud. La revisión realizada indica que los procesos psicológicos influyen tanto en la experiencia del dolor como en los resultados del tratamiento, por lo tanto la integración de los principios psicológicos en el tratamiento del dolor parecen tener potencial mejora de los resultados beneficiando la salud del paciente.

Pungent general anesthetics activate transient receptor potential-A1 to produce hyperalgesia and neurogenic bronchoconstriction

BACKGROUND: Volatile anesthetics such as isoflurane and halothane have been in clinical use for many years and represent the group of drugs most commonly used to maintain general anesthesia. However, despite their widespread use, the molecular mechanisms by which these drugs exert their effects are not completely understood. Recently, a seemingly paradoxical effect of general anesthetics has been identified: the activation of peripheral nociceptors by irritant anesthetics. This mechanism may explain the hyperalgesic actions of inhaled anesthetics and their adverse effects in the airways. METHODS: To test the hypothesis that irritant inhaled anesthetics activate the excitatory ion-channel transient receptor potential (TRP)-A1 and thereby contribute to hyperalgesia and irritant airway effects, we used the measurement of intracellular calcium concentration in isolated cells in culture. For our functional experiments, we used models of isolated guinea pig bronchi to measure bronchoconstriction and withdrawal threshold to mechanical stimulation with von Frey filaments in mice. RESULTS: Irritant inhaled anesthetics activate TRPA1 expressed in human embryonic kidney cells and in nociceptive neurons. Isoflurane induces mechanical hyperalgesia in mice by a TRPA1-dependent mechanism. Isoflurane also induces TRPA1-dependent constriction of isolated bronchi. Nonirritant anesthetics do not activate TRPA1 and fail to produce hyperalgesia and bronchial constriction. CONCLUSIONS: General anesthetics induce a reversible loss of consciousness and render the patient unresponsive to painful stimuli. However, they also produce excitatory effects such as airway irritation and they contribute to postoperative pain. Activation of TRPA1 may contribute to these adverse effects, a hypothesis that remains to be tested in the clinical setting.

Anesthetic Activation of Central Respiratory Chemoreceptor Neurons Involves Inhibition of a THIK-1-Like Background K(+) Current

At surgical depths of anesthesia, inhalational anesthetics cause a loss of motor response to painful stimuli (i.e., immobilization) that is characterized by profound inhibition of spinal motor circuits. Yet, although clearly depressed, the respiratory motor system continues to provide adequate ventilation under these same conditions. Here, we show that isoflurane causes robust activation of CO(2)/pH-sensitive, Phox2b-expressing neurons located in the retrotrapezoid nucleus (RTN) of the rodent brainstem, in vitro and in vivo. In brainstem slices from Phox2b-eGFP mice, the firing of pH-sensitive RTN neurons was strongly increased by isoflurane, independent of prevailing pH conditions. At least two ionic mechanisms contributed to anesthetic activation of RTN neurons: activation of an Na(+)-dependent cationic current and inhibition of a background K(+) current. Single-cell reverse transcription-PCR analysis of dissociated green fluorescent protein-labeled RTN neurons revealed expression of THIK-1 (TWIK-related halothane-inhibited K(+) channel, K(2P)13.1), a channel that shares key properties with the native RTN current (i.e., suppression by inhalational anesthetics, weak rectification, inhibition by extracellular Na(+), and pH-insensitivity). Isoflurane also increased firing rate of RTN chemosensitive neurons in urethane-anesthetized rats, again independent of CO(2) levels. In these animals, isoflurane transiently enhanced activity of the respiratory system, an effect that was most prominent at low levels of respiratory drive and mediated primarily by an increase in respiratory frequency. These data indicate that inhalational anesthetics cause activation of RTN neurons, which serve an important integrative role in respiratory control; the increased drive provided by enhanced RTN neuronal activity may contribute, in part, to maintaining respiratory motor activity under immobilizing anesthetic conditions.

Micro and nanosystems for delivering local anesthetics

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Benzocaine and eugenol as anesthetics for Brycon hilarii

A utilização de produtos anestésicos durante práticas de manejo é frequentemente empregada, porém doses corretas de diferentes fármacos e para espécies distintas ainda estão em fases de pesquisa. O objetivo do estudo foi determinar a melhor concentração de benzocaína e eugenol para juvenis de piraputanga (B. hilarii). Foram utilizados 104 juvenis de piraputanga com peso médio de 50,04 ± 20,80 g e comprimento total médio de 16,30 ± 12,32 cm adquiridos em uma piscicultura comercial localizada na região Oeste do Estado do Paraná. O trabalho foi conduzido no Laboratório de Aquicultura do Grupo de Estudos de Manejo na Aquicultura - GEMAq da Universidade Estadual do Oeste do Paraná (UNIOESTE). Os animais foram submetidos a cinco concentrações de benzocaína (50,0; 100,0; 150,0; 200,0 e 250,0 mg L-1) e sete concentrações de eugenol (50,0; 100,0; 150,0; 200,0; 250,0; 300,0 e 350 mg L-1), para a aferição dos tempos referentes à letargia. Para a recuperação, os animais foram mantidos em aquários livre do anestésico e observado o tempo em que retornaram às atividades normais. A melhor dose de benzocaína verificada foi de 100 mg L-1, enquanto a melhor dose de eugenol foi entre 100 e 150 mg L-1.

A study of the effect of hemorrhage on the cardiorespiratory actions of halothane, isoflurane and sevoflurane in the dog

Objective To compare the cardiorespiratory changes induced by equipotent concentrations of halothane (HAL), isoflurane (ISO) and sevollurane (SEVO) before and after hemorrhage.Study design. Prospective, randomized clinical trial.Animals. Twenty-four healthy adult dogs weighing 15.4 +/- 3.4 kg (mean +/- SD).Methods. Animals were randomly allocated to one of three groups (n = 8 per group). In each group, anesthesia was maintained with 1.5 minimum alveolar concentration of HAL (1.3%), ISO (1.9%,) and SEVO (3.5%) in oxygen. Controlled ventilation was performed to maintain eucapnia. Cardiorespiratory variables were evaluated at baseline (between 60 and 90 minutes after induction), immediately after and 30 minutes after the withdrawal of 32 mL kg(-1) of blood (400% of the estimated blood volume) over a 30-minute period.Results. During baseline conditions, ISO and SEVO resulted in higher cardiac index (CI) than HAL. Heart rates were higher with SEVO at baseline. while mean arterial pressure (MAP) and mean pulmonary arterial pressure did not differ between groups. Although heart rate values were higher for ISO and SEVO after hemorrhage, only ISO resulted in a higher CI when compared with HAL. In ISO-anesthetized dogs, MAP was higher immediately after hemorrhage, and this was related to better maintenance of CI and to an increase in systemic vascular resistance index from baseline.Conclusions. Although the hemodynamic responses of ISO and SEVO are similar in normovolaemic dogs, ISO results in better maintenance of circulatory function during the early period following a massive blood loss. Clinical relevance Inhaled anesthetics should be used judiciously in animals presented with blood loss. However, if an inhalational agent is to be used under these circumstances, ISO may provide better hemodynamic stability than SEVO or HAL.

Efeitos do halotano, isoflurano e sevoflurano nas respostas cardiovasculares ao pinçamento aórtico infra-renal: estudo experimental em cães

JUSTIFICATIVA E OBJETIVOS: O pinçamento infra-renal da aorta abdominal pode produzir alterações hemodinâmicas. O objetivo do estudo foi avaliar os efeitos do halotano, isoflurano e sevoflurano sobre a função cardiovascular, em cães submetidos à pinçamento aórtico infra-renal. MÉTODO: O estudo aleatório foi realizado em 30 cães, distribuídos em três grupos, de acordo com o anestésico halogenado utilizado durante a anestesia, em concentrações equipotentes de 0,75 CAM: GH (n=10) - halotano a 0,67%; GI (n=10) - isoflurano a 0,96%; e GS (n=10) - sevoflurano a 1,8%. em todos os animais foi realizada ligadura infra-renal da aorta, por período de 30 min. Os atributos hemodinâmicos foram estudados nos momentos: C (Controle), Ao15 e Ao30, respectivamente após 15 e 30 minutos do pinçamento aórtico, e DAo e DAo15, respectivamente, imediatamente e após 15 min do despinçamento aórtico. RESULTADOS: Durante o pinçamento aórtico houve, em todos os grupos, aumento das pressões arterial média e do átrio direito, e dos índices cardíaco, sistólico e de trabalho sistólico dos ventrículos direito e esquerdo. A pressão da artéria pulmonar aumentou em GI e GS e a pressão pulmonar ocluída em GH e GI. Após o despinçamento aórtico, houve normalização dos atributos que haviam se elevado, com exceção dos índices cardíaco e sistólico, que continuaram elevados, acompanhados de diminuição do índice de resistência vascular sistêmica. Não houve diferença significante entre os grupos em relação aos atributos estudados, com exceção da freqüência cardíaca que foi sempre menor em GH, em relação aos demais grupos, durante o pinçamento e despinçamento aórtico. CONCLUSÕES: No cão, nas condições experimentais empregadas, a inalação do halotano, isoflurano e sevoflurano em concentrações equipotentes (0,75 CAM) não atenua as respostas cardiovasculares ao pinçamento aórtico infra-renal.

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 CO2 (PgCO(2)) and for the calculation of gastric-arterial PCO2 gradient (PCO2 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 PCO2 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 PCO2 gap values than the other groups (p < .05). After 60 min of shed blood replacement, all groups restored hemodynamics, systemic oxygenation, and PCO2 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.

Anestesia subaracnóidea em crianças

JUSTIFICATIVA E OBJETIVOS: Tem aumentado muito o emprego da anestesia subaracnóidea em crianças, principalmente neonatos com risco de desenvolver apnéia neonatal. O objetivo deste trabalho foi rever as diferenças anatômicas, fisiológicas e farmacológicas desta técnica em crianças. CONTEÚDO: A anestesia subaracnóidea em crianças, apesar de ter sido técnica empregada desde o início do século XX, teve sua popularidade diminuída com o advento dos anestésicos inalatórios e bloqueadores neuromusculares, para ser novamente resgatada em 1979. As características favoráveis desta técnica em pediatria são relativas à estabilidade cardiovascular, em crianças de até 8 anos de idade, à analgesia satisfatória e ao relaxamento muscular. Os anestésicos mais utilizados em crianças são a tetracaína e a bupivacaína, cujas doses são ajustadas tomando-se por base o peso corporal. Esta técnica é limitada pela duração relativamente curta, devendo ser utilizada para procedimentos cirúrgicos que não ultrapassem 90 minutos e também pela analgesia não abranger o pós-operatório. As complicações são as mesmas encontradas no paciente adulto, incluindo cefaléia por punção dural e irritação radicular transitória. As indicações são várias: cirurgias de abdômen inferior, genitália, membros inferiores, região perineal e, em alguns casos, até em cirurgias torácicas. Seu emprego tem particular interesse nos recém-nascidos prematuros, pelo risco de apresentarem a apnéia da prematuridade. CONCLUSÕES: A anestesia subaracnóidea em crianças é técnica relativamente segura, com poucas complicações e pode ser considerada como opção para anestesia geral, principalmente nos recém-nascidos prematuros com risco de apresentarem complicações respiratórias no pós-operatório.