Efecto antagonista del flumazenil sobre el isoflurano en la emersión de la anestesia general / Antagonist effect of flumazenil on isofluran in reversion of general anesthesia

INTRODUCTION AND OBJECTIVES: Isoflurane, an inhalational general anesthetic widely used in medical practice, belonging to the group of volatile liquids together with desflurane and sevoflurane, with various properties including sedation, hypnosis and anesthesia of patients undergoing treatment. surgical acts. Volatile inhalational anesthetics (halogenated) as mechanism of action, has the property of increasing inhibitory synaptic transmission at postsynaptic level by potentiating ion channels regulated by ligand activated by alpha-aminobutyric acid (GABA). Flumazenil is a benzodiazepine antagonist belonging to the group of imidazobenzodiazepine. It is currently known that there is no specific drug capable of antagonizing the effects of halogenates that allow the rapid and complete recovery of general anesthesia, for this reason this work focuses its efforts on demonstrating whether flumazenil has the ability to reverse the actions of the patient. isoflurane and allow an early restoration of the level of consciousness. MATERIAL AND METHODS: The study to be performed is a clinical type of longitudinal, prospective, unicentric and double blind. The sample will be formed by patients who are going to be subjected to a balanced general anesthesia. The sample will be divided into 2 large groups: group C (control) and group F (Flumazenil). At the end of the surgery, the mixture will be administered according to the selected group in a random manner (Flumazenil 0.25 mg or 0.9% solution in a 20 cc syringe) and the time of extubation, recovery time of the level of consciousness, time of discharge UCPA and hemodynamic state (FC, TAM and SO2). RESULTS: The flumazenil group showed a significantly shorter time from injection to extubation than the placebo group (p = 0.007). Differences in terms of shorter times needed to achieve Aldrete of 9 points in the flumazenil group (P = 0.04) were observed as were shorter anesthetic arousal times represented by a Ramsey 2. Heart rate, mean arterial pressure and saturation they had similar values between the 2 groups. CONCLUSION: The study showed that a single dose of 0.25 mg of flumazenil administered at the end of the surgical act, just after completing all surgical stimulation was beneficial (P = 0.007) in the context of extubation times and shorter anesthetic arousal times.

INTRODUCCIÓN Y OBJETIVOS: El isoflurano un anestésico general inhalatorio usado ampliamente en la práctica médica, perteneciente al grupo de los líquidos volátiles junto con el desflurano y sevoflurano, con variadas propiedades entre las que se encuentran la sedación, hipnosis y anestesia de los pacientes sometidos a actos quirúrgicos. Los anestésicos inhalatorios volátiles (halogenados) como mecanismo de acción, tiene la propiedad de aumentar la transmisión sináptica inhibidora a nivel postsináptico potenciando los canales iónicos regulados por ligando activados por ácido alfa-aminobutírico (GABA). El flumazenil es un antagonista benzodiazepínico perteneciente al grupo de los imidazobenzodiazepina. Se conoce actualmente que no existe un fármaco específico capaz de antagonizar los efectos de los halogenados que permitan la recuperación rápida y completa de la anestesia general, por tal motivo este trabajo centra sus esfuerzos en demostrar si el flumazenil tiene la capacidad para revertir las acciones del isoflurane y permitir un restablecimiento temprano del nivel de conciencia. MATERIALES Y MÉTODOS: El estudio a realizar es de tipo clínico de corte longitudinal, prospectivo, unicéntrico y doble ciego. La muestra se conformará por pacientes que vayan a ser sometidos a anestesia general balanceada. Se procederá a dividir la muestra en 2 grandes grupos: grupo C (control) y grupo F (flumazenil). Al final de la cirugía se administrará la mezcla según grupo seleccionado de manera al azar (flumazenil 0,25 mg o solución 0,9% en una jeringa de 20 cc) y se valorará el tiempo de extubación, tiempo de recuperación del nivel de conciencia, tiempo de alta de la UCPA y estado hemodinámico (FC, TAM y SO2). RESULTADOS: El grupo de flumazenil presentó un tiempo desde la inyección hasta la extubación significativamente más bajo que el grupo placebo (p = 0,007). Se observaron diferencias en términos de tiempos más bajos necesario para alcanzar Aldrete de 9 puntos en el grupo flumazenil (P = 0,04) al igual que tiempos de despertar anestésico más cortos representados por un Ramsey 2. La frecuencia cardíaca, presión arterial media y la saturación tuvieron valores similares entre los 2 grupos. CONCLUSIÓN: El estudio demostró que una única dosis de 0,25 mg de flumazenil administrado al final del acto quirúrgico, justo después de culminar toda estimulación quirúrgica fue beneficiosa (P = 0,007) en el contexto de tiempos de extubación y tiempos de despertar anestésico más cortos.

The use of flumazenil for benzodiazepine associated respiratory depression in postanesthesia recovery: risks and outcomes / O uso de flumazenil para depressão respiratória associada ao benzodiazepínico na recuperação pós-anestésica: riscos e resultados

Abstract Background and objectives The primary aim was to determine risk factors for flumazenil administration during postanesthesia recovery. A secondary aim was to describe outcomes among patients who received flumazenil. Methods Patients admitted to the postanesthesia recovery room at a large, academic, tertiary care facility after surgery under general anesthesia from January 1, 2010, to April 30, 2015, were identified and matched to 2 controls each, by age, sex, and surgical procedure. Flumazenil was administered in the recovery phase immediately after general anesthesia, according to the clinical judgment of the anesthesiologist. Demographic, procedural, and outcome data were extracted from the electronic health record. Conditional logistic regression, accounting for the 1:2 matched-set case-control study designs, was used to assess characteristics associated with flumazenil use. Results The incidence of flumazenil administration in the postanesthesia care unit was 9.9 per 10,000 (95% CI, 8.4-11.6) general anesthetics. History of obstructive sleep apnea (Odds Ratio [OR] = 2.27; 95% CI 1.02-5.09), longer anesthesia (OR = 1.13; 95% CI 1.03-1.24 per 30 minutes), use of total intravenous anesthesia (OR = 6.09; 95% CI 2.60-14.25), and use of benzodiazepines (OR = 8.17; 95% CI 3.71-17.99) were associated with risk for flumazenil administration. Among patients who received midazolam, cases treated with flumazenil received a higher median (interquartile range) dose than controls: 3.5 mg (2.0-4.0 mg) vs. 2.0 mg (2.0-2.0 mg), respectively (p < 0.001). Flumazenil use was correlated with a higher rate of unanticipated noninvasive positive pressure ventilation, longer postanesthesia care unit stay, and increased rate of intensive care unit admissions. Conclusions Patients who required flumazenil postoperatively had received a higher dosage of benzodiazepines and utilized more postoperative health care resources. More conservative perioperative use of benzodiazepines may improve postoperative recovery and use of health care resources.

Resumo Justificativa e objetivos Determinar os fatores de risco da administração de flumazenil durante a recuperação pós-anestésica e descrever os desfechos entre os pacientes que receberam flumazenil. Métodos Os pacientes admitidos em sala de recuperação pós-anestésica de um grande centro universitário em setor terciário de cuidados pós-cirurgia sob anestesia geral entre 1° de janeiro de 2010 e 30 de abril de 2015 foram identificados e pareados com dois controles cada por idade, sexo e procedimento cirúrgico. Flumazenil foi administrado na fase de recuperação imediatamente após a anestesia geral, de acordo com a avaliação clínica do anestesiologista. Os dados demográficos, dos procedimentos e dos desfechos foram extraídos do registro eletrônico de saúde. A regressão logística condicional para os desenhos do estudo de caso-controle pareado em 1:2 foi usada para avaliar as características associadas ao uso de flumazenil. Resultados A incidência da administração de flumazenil em sala de recuperação pós-anestésica foi de 9,9 por 10.000 (95% IC: 8,4-1,6) anestesias gerais. História da apneia obstrutiva do sono (razão de chances [OR] = 2,27; IC 95%: 1,02-5,09), anestesia de longa duração (OR = 1,13; IC 95%: 1,03-1,24 por 30 minutos), uso de anestesia intravenosa total (OR = 6,09; IC de 95%: 2,60-14,25) e uso de benzodiazepínicos (OR = 8,17; IC 95%: 3,71-17,99) foram associados a risco para a administração de flumazenil. Entre os pacientes que receberam midazolam, os casos tratados com flumazenil receberam uma dose mediana mais alta (intervalo interquartil) do que os controles: 3,5 mg (2,0-4,0 mg) vs. 2,0 mg (2,0-2,0 mg), respectivamente (p < 0,001). O uso de flumazenil foi correlacionado com uma taxa maior não prevista de ventilação não invasiva com pressão positiva, permanência mais longa em sala de recuperação pós-anestésica e aumento da taxa de admissões em unidade de terapia intensiva. Conclusão Os pacientes que precisaram de flumazenil no pós-operatório receberam uma dose maior de benzodiazepínicos e usaram mais recursos de cuidados da saúde no pós-operatório. O uso mais conservador de benzodiazepínicos no período perioperatório pode melhorar a recuperação e o uso de recursos de cuidados da saúde no pós-operatório.

Delayed Flumazenil Injection after Endoscopic Sedation Increases Patient Satisfaction Compared with Immediate Flumazenil Injection

BACKGROUND/AIMS: Flumazenil was administered after the completion of endoscopy under sedation to reduce recovery time and increase patient safety. We evaluated patient satisfaction after endoscopy under sedation according to the timing of a postprocedural flumazenil injection. METHODS: In total, 200 subjects undergoing concurrent colonoscopy and upper endoscopy while sedated with midazolam and meperidine were enrolled in our investigation. We randomly administered 0.3 mg of flumazenil either immediately or 15 minutes after the endoscopic procedure. A postprocedural questionnaire and next day telephone interview were conducted to assess patient satisfaction. RESULTS: Flumazenil injection timing did not affect the time spent in the recovery room when comparing the two groups of patients. However, the subjects in the 15 minutes injection group were more satisfied with undergoing endoscopy under sedation than the patients in the immediate injection group according to the postprocedural survey (p=0.019). However, no difference in overall satisfaction, memory, or willingness to undergo a future endoscopy was observed between the two groups when the telephone survey was conducted on the following day. CONCLUSIONS: This study demonstrated that a delayed flumazenil injection after endoscopic sedation increased patient satisfaction without prolonging recovery time, even though the benefit of the delayed flumazenil injection did not persist into the following day.

Segurança da ecocardiografia transesofágica em adultos: Estudo em um hospital multidisciplinar / Safety of transesophageal echocardiography in adults: study in a multidisciplinary hospital / Seguridad de la ecocardiografía transesofágica en adultos: Estudio en un hospital multidisciplinario

FUNDAMENTO: A ecocardiografia transesofágica (ETE) é um exame semi-invasivo amplamente utilizado e seu uso associado a sedativos poderá influenciar a segurança do procedimento. OBJETIVO: analisar aspectos da segurança da ETE associada ao uso de midazolam (MZ) e flumazenil (FL) e a influência de variáveis clínicas na taxa de eventos. MÉTODO: estudo prospectivo com 137 pacientes que realizaram ETE com MZ associado à sedação moderada. Analisamos as seguintes ocorrências: complicações com anestesia tópica, ao uso do MZ e complicações relacionadas ao procedimento. Análises uni e multivariada foram usadas para testar a influência das variáveis clínicas: idade, sexo, acidente vascular cerebral (AVC), miocardiopatia (MP), duração do exame, insuficiência mitral (IM) e dose de MZ. RESULTADOS: todos pacientes (65±16 anos; 58 por cento masculino) completaram o exame. As doses médias de MZ e FL foram de 4,3±1,9 mg e 0,28±0,2 mg, respectivamente. A duração do exame e a fração de ejeção (FE) média foram de 16.4±6.1 minutos e 60±9 por cento, respectivamente. O evento mais comum foi a hipóxia leve (SO2<90 por cento), em 11 pacientes; 3 pacientes (2 por cento) apresentaram hipóxia transitória por obstrução da via aérea superior na passagem da sonda, enquanto 8 (5,8 por cento) apresentaram hipóxia devido ao uso do MZ. Hipotensão transitória (PAS<90 mmHg) ocorreu em 1 paciente (0,7 por cento). A análise multivariada mostrou que insuficiência mitral (IM) importante, MP (FE<45 por cento) e altas doses do MZ (>5mg) tiveram associação com tais eventos (p<0,001). A FE no grupo com MP foi de 40 por cento, ao passo que, no grupo com insuficiência mitral (IM), esse percentual foi de 44 por cento, podendo ser este um fator associado a eventos clínicos neste último grupo. CONCLUSÃO: ETE com sedação tem baixas taxas de eventos. Não se observou eventos graves e não houve a necessidade de interrupção dos exames.

BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65±16 yrs; 58 percent males) finished the examination. The mean doses of MZ and FL were 4.3±1.9 mg and 0.28±0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4±6.1 minutes and 60±9 percent, respectively. Mild hypoxia (SO2<90 percent) was the most common event (11 patients); 3 patients (2 percent) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8 percent) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7 percent). The multivariate analysis showed that severe MR, MP (EF<45 percent) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40 percent, in the group with MP and 44 percent in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.

FUNDAMENTO: La ecocardiografía transesofágica (ETE) es un examen semiinvasivo ampliamente utilizado y su uso asociado a sedantes puede influir sobre la seguridad del procedimiento. OBJETIVO: Analizar aspectos de la seguridad de la ETE asociada al uso de midazolam (MZ) y flumazenil (FL) y la influencia de variables clínicas en la tasa de complicaciones. MÉTODO: Estudio prospectivo con 137 pacientes, a quienes se realizó ETE con MZ asociado a la sedación moderada. Analizamos los siguientes eventos: complicaciones con anestesia local, relacionadas al uso de MZ y complicaciones relacionadas con el procedimiento. Se utilizaron análisis uni y multivariados para evaluar la influencia de las variables clínicas: edad, sexo, accidente cerebrovascular (ACV), miocardiopatía (MP), duración del estudio, insuficiencia mitral (IM) y dosis de MZ. RESULTADOS: Todos los pacientes (65±16 años; 58 por ciento masculino) completaron el estudio. Las dosis promedio de MZ y FL fueron de 4,3±1,9 mg y 0,28±0,2 mg, respectivamente. La duración del estudio y la fracción de eyección (FE) promedio fueron de 16.4±6.1 minutos y 60±9 por ciento, respectivamente. El evento más común fue la hipoxia leve (SO2<90 por ciento), en 11 pacientes; 3 pacientes (2 por ciento) presentaron hipoxia transitoria por obstrucción de la vía aérea superior con el pasaje de la sonda, mientras que 8 (5,8 por ciento) presentaron hipoxia debido a la utilización del MZ. Un paciente (0.7 por ciento) padeció hipotensión transitoria (PAS<90 mmHg). El análisis multivariado mostró que IM significativa, MP (FE<45 por ciento) y altas dosis de MZ (>5mg) se asociaron a tales complicaciones (p<0,001). La FE en el grupo con MP fue de 40 por ciento, mientras que, en el grupo con insuficiencia mitral, ese porcentaje fue de 44 por ciento, pudiendo ser éste un factor asociado a complicaciones clínicas en este último grupo. CONCLUSIÓN: ETE con sedación presenta bajas tasas de ...

Midazolam en anestesia intravenosa / Midazolam in intravenous anesthesia

El midazolam es una imidobenzodiacepina, de vida media corta, hidrosoluble y muy lipofílica, que fue investigada intensamente en anestesiología y terapia intensiva. El posterior desarrollo de un antagonista, el flumazenil, mejoró su indicación clínica en la anestesia ambulatoria. El midazolam se aplica en la actualidad en técnicas para sedación o hipnosis o en asociación a otros fármacos fijos (analgésicos, relajantes musculares) en la denominada anestesia intravenosa total o bien en combinación con agentes inhalatorios. Su característica de no poseer efecto analgésico, necesariamente le impone la asociación con uno de ellos cuando el estudio o la cirugía así lo requiere. En esta revisión se estudiarán las diversas aplicaciones del midazolam y las asociaciones farmacológicas del mismo. Se analizarán sus acciones en relación a las técnicas anestesiológicas que lo han propuesto para la sedación, la inducción anestésica, la co-inducción, el mantenimiento asociado a fármacos fijos o inhalatorios y hasta su aplicación en la anestesia intravenosa total. Por último, se hará una breve reseña sobre el flumazenil, antagonista específico de las benzodiacepinas, cuyo desarrollo ha dado mayor manejo y seguridad a la anestesia con midazolam.

Reversäo pelo flumazenil do efeito cardiodepressor induzido pelo diazepam / Reversal by flumazenil of the cardiodepressant effect induced by diazepam

Foram estudados em sete ratos de raça wistar os efeitos do antagonista dos receptores GR (centrais). Flumazenil (8-fluoro-1,6-dihidro-5-metil-5-fenil-2h-1,4-benzodiazepina-3-carboxilato de etila) nas concentrações de dez mcg/ml, na depressÒo miocßrdica induzida pelo Diazepam (7-cloro-1,3-dihidro-1-metil-5-fenil-2h-1,4-benzodiazepin-1-ona) em doses de 100 mcg/ml em coraçöes isolados de ratos. Nestes experimentos foi utilizado o mÚtodo de LANGENDORFF e tÚcnica de GOTTLIEB e MAGNUS, modificada por PITCHON, utilizando como perfusato a soluçÒo de Krebs-Henseleit. Podemos constatar que nesta experimentaçÒo, o Flumazenil foi capaz de antagonizar os efeitos cardioinibidores do Diazepam. Estas açöes nos levam a sugerir a presença de receptores Gabarelacionados nos coraçöes isolados estudados.

A Aminofilina Antagoniza a Açäo do Midazolan / Aminophylline Antagonizes Midazolan-Induced Sedation

The efficacy of aminophylline in antagonizing midazolam-induced sedation was evaluated in a double-blind study involving 60 patients scheduled for epidural anesthesia. Premedication consisted of sublingual flunitrazepam 2mg. Intraoperative sedation was achieved with intermitent intravenous bolus of midazolam 1mg. At the end of the surgery patients received either aminophyline 2mg/Kg (Group A), flumazenil 0.01mg/Kg (Group F) or placebo 0.1 ML/Kg (Group P) intravenously. Central nervous system functions were evaluated according to the degree of sedation, orientation, and cooperation presented. At the end of the surgery sedation was such that no patient was "completely awake". Fifteen minutes after the "antagonist" drug was administered, 35 percent of the patients in Group A, 100 percent in Group F, and 0 percent in Group P were "completely awake". Regarding orientation, 5 percent vs 55 percent in Group A, 0 percent vs 100 percent in Group F and 10 percent vs - 15 percent in Group P were "completely oriented" before vs after the drugs. Regarding cooperation, 5 percent vs 70 percent in Group A, 5 percent vs 100 percent in Group F, and 15 percent vs 15 percent in Group P were "completely cooperative" before vs after drugs. It is suggested that aminophylline can be used for reversal of midazolam action, although it is less effective than flumazenil

Antídotos de uso reciente

Los antídotos son sustancias cuya función es contrarrestar el efecto farmacológico y tóxico de otras sustancias, teniendo en cuenta la importancia de las medidas generales en el manejo del intoxicado (baño general, emesis, lavado gástrico, carbón activado, catárticos). Cada día aparecen sustancias nuevas con dichas características. En el presente artículo se pretende dar información breve y detallada sobre las propiedades farmacológicas, indicaciones, dosificación, efectos secundarios y contraindicaciones de algunos de uso general (carbón activado, soluciones electrolíticas con polietilenglycol) y principalmente de algunos específicos de uso reciente: flumazenil, fragmentos Fab-antidigoxina, glucagón, naloxona, clonidina, N-acetil-cisteína, azul de metileno, nitrito y tiosulfato de sodio, ácido-2-3-dimercaptosuccínico, penicilina benzatínica, glicopirrolato y S-adenosil-metionina.

Flumazenil en la reversión de la sedación e hipnosis por Midazolam en anestesia intravenosa total con Procaina-Fentanil / Reversal of hypnosis due to Midazolam in T.I.V.A. with Procaine-Fentanyl by Flumazenil

Se estudiaron 50 pacientes: ASA 1-3 a los que se administró anestesia endovenosa total con procaína/midazolam en infusión, más fentanil y alcuronio intermitentes, y luego se revirtió el efecto hipnótico residual con el antagonista de las benzodiazepinas flumazenil. Se estudiaron los parámetros cardiovasculares (tensión arterial y frecuencia cardíaca) y de presión intraocular basales, a los 5 minutos de intubar, antes de cerrar la infusión y al revertir con el antagonista. Después de la reversión se registraron los parámetros involucrados en la escala de Alderete y, sobre todo, en los de conciencia, actividad y respiración, respecto a igual técnica, sin el concurso de flumazenil. El agregado de este reversor constituye un paso fundamental para un despertar predecible.

O uso do antagonista benzodiazepínico (flumazenil) para reversäo da sedaçäo por midazolam em endoscopia digestiva / The use of benzodiazepine antagonist (flumazenil) to revert midazolan sedation in digestive endoscopy

Sessenta e dois pacientes submetidos a endoscopia digestiva diagnóstica foram sedados com miazolam por via endovenosa e divididos em dois grupos após o término da endoscopia: 32 pacientes receberam o antagonista benzodiazepínico, flumazenil (grupo F); 30 pacientes (grupo M) permaneceram em repouso para recuperaçäo da sedaçäo, servindo como grupo controle. O flumazenil reverteu o efeito sedativo do midazolam após cinco minutos de sua administraçäo em 89,3% dos pacientes. O tempo médio de recuperaçäo completa foi de 97 min no grupo M e de 44 min no grupo F, com significância estatística. Näo foram observadas alteraçöes das funçöes vitais com o uso de midazolan e flumazenil, tendo sido bem tolerados em ambos os grupos. A amnésia anterógrada desencadeada pelo midazolam näo foi revertida pelo flumazenil. O midazolam é um agente eficaz na sedaçäo de procedimentos endoscópicos digestivos. O antagonista benzodiazepínico, flumazenil, reverteu o efeito sedativo do midazolam, sendo droga indispensável para uso eventual e/ou emergencial

Effect of post-training injections of flumazenil into the amygdala, hippocampus and septum on retention of habituation and of inhibitory avoidance in rats

Adult rats were submitted to two different behavioral tasks using the same apparantus: the habituation of exploration of the apparatus considered as a novel environment as measured by the decrease in number of reaings and of ambulation between training and testing, and step-down inhibitory avoidance as measured by the increase in the latency to step down from a start platform into an electrified grid between the training and the test session.The training-test interval for both tasks was 20 h.The immediate post-training injection of the benzodiazepine receptor antagonist flumazenil (10 nmol) bilateral into the hippocampus enhanced retention of the two tasks.Application of the same drug, at the same dose to the septum or amygdala had no effect on habituation but enhanced retention of the avoidance task. The data are consistent with previous findings showing that both tasks are accompanied by the release of benzodiazepine like immunoreactivity in the three structures and that this release is greater after the avoidance task. The present findings suggest a differential regional involvement of endogenous benzodiazepine-mediated mechanisms in memory modulation, according to the task undertaken

Anxiolytic effect of midazolam microinjected into the dorsal periaqueductal grey area of rats

In order to investigate the role of the dorsal periaqueductal grey (DPAG) area in the anxiolytic effect of benzodiazepines male Wistar rats (N=10), weighing 200-250 g at the time of surgery, were microinjected into this structure with midazolam (80 nmol) and submitted to the elevated plus-maze, an ethologically based model of anxiety. Midazolam significantly increased the percentage of open arm entries from 32.4 ñ 4.6 (control) to 49.5 ñ 3.0 and of time spent in the open arms from 21.0 ñ 4.5 (control) to 35.6 ñ4.8 without affecting the total number of entries into either open or enclosed arms. This effect typifies an anxiolytic effect in the test and was antagonized by the benzodiazepine receptor antagonist flumazenil (80 nmol) microinjection. Microinjection of flumazenil alone had no effect. These results provide additional evidence for the participation of the DPAG in the physiopathology of anxiety and suggest that it that it may be a site for the anxiolytic effect of systemically injected benzodiazepines

Effect of chronic treatment of Ro 15-1788 and its withdrawal on cortical and hippocampal EEG activity in rats.

Effect of chronic treatment with Ro 15-1788, a benzodiazepine (BZ) receptor antagonist, and its withdrawal, on the cortical and hippocampal electroencephalogram (EEG) was investigated in rats. Chronic treatment with Ro 15-1788 and its withdrawal (24 and 48 hr) were found to reduce the EEG amplitude in both cortical and hippocampal regions. This reduction in cortical and hippocampal EEG amplitude produced by chronic treatment with Ro 15-1788 and its withdrawal was reversed by gamma aminobutyric acid (GABA), pentobarbitone and picrotoxin, agents known to modulate the GABA/BZ synaptic events by acting at different sites on the complex. Baclofen a GABAB agonist and FG7142, a BZ inverse agonist were found to further reduce the EEG amplitude in the cortical and hippocampal regions of these rats, chronically treated with Ro 15-1788. Diazepam, a BZ agonist was found to have no significant effect on the alteration produced in the cortical and hippocampal EEG amplitude by chronic treatment with Ro 15-1788 or its withdrawal. It is suggested that the conformational changes produced on the GABA/BZ receptor complex by BZ receptor occupation, has a facilitatory effect on the actions of those drugs which act on the GABA/BZ receptor complex and the direction of this enhancement depended on the nature of the drug.

Eficacia del flumocenil en la reservacion de la sedacion con midazolam en pacientes bajo anestesia regional / Efficacy of flumazepil in the reversion of sedation with midazolam in patients under regional anesthesia

Con el fin de evaluar la efectividad y seguridad del Flumacenil (RO 15 17-88 o Anexate) como antagonista de los efectos sedantes de las benzodiacepinas, se estudiaron 30 pacientes sometidos a cirugia bajo anestesia regional (peridural o raquidea), sedados con Midozolam hasta obtener un nivel profundo de sedacion (grupo 1:0.60, grupo 2:0.66) y un bajo puntaje en la escala SOCA (grupo 1: 2.53, grupo 2:2.93). En el postoperatorio inmediato los pacientes del grupo 2 recibieron Flumacenil (0.22+0.07) obteniendo una rapida y tranquila reversion (p=0.005) de los efectos sedantes del Midazolam en menos de 5 minutos. No se encontraron efectos adversos a ninguna de las drogas utilizadas en el estudio