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      Efeitos hemodinâmicos da intoxicação aguda com bupivacaína e a mistura enantiomérica: estudo experimental em suínos Translated title: Haemodynamic effects of intoxication with bupivacaine and enantiomeric excess mixture: experimental study in swine

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          Abstract

          OBJETIVOS: A bupivacaína racêmica tem sido o anestésico local de escolha nos bloqueios regionais pela qualidade e duração de sua anestesia. Sua cardiotoxicidade é motivo de preocupações, e pesquisas têm sido realizadas para encontrar drogas com menor impacto. Seu isômero levógiro, a levobupivacaína, seria menos cardiotóxico pela menor afinidade aos receptores dos canais de sódio do coração, e é uma opção. Em nosso país, uma apresentação contendo 75% do isômero levógiro e 25% do isômero dextrógiro, denominada mistura enantiomérica, está disponível. O objetivo deste estudo foi comparar as repercussões hemodinâmicas da injeção intravascular de uma dose tóxica destes dois agentes em suínos. MÉTODOS: Suínos da raça Large White foram anestesiados com tiopental, entubados e ventilados mecanicamente, sendo, em seguida, instalada monitorização hemodinâmica com pressão invasiva e cateter de Swan-Ganz numa artéria pulmonar. Após repouso de 30 minutos, os animais foram divididos aleatoriamente em dois grupos, e foi realizada em duplo-cego intoxicação com um dos agentes na dose de 4 mg/kg. Os resultados hemodinâmicos foram avaliados então a um minuto, aos cinco, 10, 15, 20 e 30 minutos. RESULTADOS: A mistura enantiomérica causou maiores repercussões hemodinâmicas do que a bupivacaína racêmica. Estes resultados se opõem aos encontrados em humanos com o isômero levógiro, mas estão de acordo com achados recentes em animais. Extrapolar resultados de animais para seres humanos requer cautela, e novas pesquisas são necessárias. CONCLUSÃO: Em suínos, a mistura enantiomérica mostrou-se mais tóxica do que a bupivacaína racêmica, quando grandes doses são injetadas por via endovenosa.

          Translated abstract

          BACKGROUND: Racemic bupivacaine has been the local anaesthetic of choice in regional blocks due to quality and duration of anesthesia. However its cardiovascular toxicity has been a source of concern and research has been made for lesser impact drugs. One choice is its levogyre isomer, levobupivacaine, apparently less cardiotoxic due a lower affinity to the heart sodium channels. In Brazil, a drug containing 75% of levogyre isomer and 25% of dextrogyre isomer, called enantiomeric excess mixture, is available. This study intends to evaluate haemodynamic effects of the intravascular injection of a toxic dose of both agents in swine. METHODS: Large White pigs were anaesthetized with thiopental, intubated and placed on mechanical ventilation. Haemodynamic monitoring was performed with an invasive blood pressure and Swan-Ganz catheter on a pulmonary artery. After a 30 minute rest period, animals were randomly divided in two groups and the intoxication was performed on a double-blind method with 4 mg.kg-1 of one of the drugs. Haemodynamic parameters were then evaluated at 1, 5, 10, 15, 20 and 30 minutes. RESULTS: The enantiomeric excess mixture caused greater haemodynamic effects than the racemic bupivacaine. These results diverge from those found in humans with levogyre isomer but are similar to recent results reported in animals. Care should be taken when extrapolating data obtained in swine to humans and further research is necessary. CONCLUSION: When high doses are injected in swine, the enantiomeric excess mixture was more toxic than the racemic bupivacaine.

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          Most cited references 23

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          Cardiac arrest following regional anesthesia with etidocaine or bupivacaine.

           Lisa Albright (1979)
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            Toxicological and Local Anaesthetic Effects of Optically Active Isomers of Two Local Anaesthetic Compounds

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              The myocardial and vascular effects of bupivacaine, levobupivacaine, and ropivacaine using pressure volume loops.

               Colin Royse,  A Royse (2005)
              Ropivacaine and levobupivacaine were developed to reduce the risk of fatal accidental overdose reported with bupivacaine. The myocardial depressant potential of these drugs in sublethal dosage is unknown. Pressure volume loops can be used to separate myocardial from vascular effects. We acquired dose-response curves to incremental infusions in seven anesthetized, open-chest New Zealand white rabbits in each of bupivacaine, levobupivacaine, ropivacaine, and saline control groups. Simultaneous high-fidelity left ventricular pressure and volume data were acquired during caval occlusion with a combined conductance-pressure catheter inserted via an apical stab. Measurements of contractility (V(100)), diastolic function (tau and end-diastolic pressure volume relation), and vascular resistance were performed after each dose increase. Drugs were infused at a ratio of 0.125:0.2 for levobupivacaine and bupivacaine/ropivacaine to simulate clinical usage, with a log(2) (8 step) dose escalation protocol. Over 40 min, the accumulated doses were 2.66/4.25 mg/kg. Levobupivacaine (P = 0.013) and bupivacaine (P = 0.019) significantly impaired contractility at doses exceeding 1.32 mg/kg, whereas ropivacaine was not different from control at 4.25 mg/kg. Bupivacaine reduced ejection fraction (EF) and cardiac index, and increased vascular resistance. Levobupivacaine reduced EF and cardiac index and demonstrated a biphasic vascular response, increasing vascular resistance at larger dosage. Ropivacaine increased vascular resistance and reduced EF without effect on contractility. Mean arterial blood pressure and diastolic function were unchanged for all drugs. Significant decline in contractility from control occurs with bupivacaine and levobupivacaine, but not with ropivacaine, at doses achievable in routine clinical practice.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                ramb
                Revista da Associação Médica Brasileira
                Rev. Assoc. Med. Bras.
                Associação Médica Brasileira (São Paulo )
                1806-9282
                2007
                : 53
                : 6
                : 502-505
                Affiliations
                [1 ] Universidade Estadual de Campinas Brazil
                Article
                S0104-42302007000600016
                10.1590/S0104-42302007000600016
                Product
                Product Information: website
                Categories
                MEDICINE, GENERAL & INTERNAL

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