William Adalberto Silva

Early colloid replacement therapy in a near-fatal model of hemorrhagic shock

Several controlled, experimental, hypotensive models of hemorrhagic shock have evaluated the effects of timing, rate, and types of fluid replacement. In a near-fatal experimental model we evaluated the hemodynamic and metabolic effects of two types of solutions for fluid resuscitation. In this study, 30 young Large-White pigs were randomly assigned to three groups: Group I (control, n= 10), not bled; Group II (hydroxyethyl starch, HES, n = 10), submitted to controlled hemorrhage to a mean arterial blood pressure (MAP) of 30 mm Hg and blood lactate >10 mM/L, at which time resuscitation was initiated with 7 mL/kg of HES 130/0.4 6% followed by 33 mL/kg of lactated Ringers solution (LR) and retransfusion; Group III (LR, n = 10), submitted to controlled hemorrhage to a MAP of 30 mm Hg and blood lactate >10 mM/L, at which time resuscitation was initiated with 40 mL/kg of LR followed by retransfusion. The resuscitation with HES 130/0.4 proved to be superior to LR, expressed by hemodynamic and perfusion variables. Despite improvement in tissue perfusion, MAP did not totally return to baseline values. In conclusion, early colloid infusion resulted in prompt recovery of tissue perfusion when compared with infusion with an equal volume of crystalloid.

Hemodynamic effects of local anesthetics intoxication: experimental study in swine with levobupivacaine and bupivacaine

PURPOSE To compare the hemodynamic repercussions following a toxic dose of levobupivacaine and bupivacaine intravascularly injected in swines. METHODS Large White pigs were anesthetized with thiopental, tracheal intubation was performed and mechanical ventilation was instituted. Hemodynamic variables were recorded with invasive pressure monitoring and pulmonary artery catheterization (Swan-Ganz catheter). After a 30-minute resting period, the animals were randomly divided into two groups in a double-blinded fashion and received a bolus injection of 4 mg/kg of either agent for intoxication. Hemodynamic results were then evaluated at 1, 5, 10, 15, 20 and 30 minutes. RESULTS Levobupivacaine had greater hemodynamic repercussions than racemic bupivacaine. These results disagree with those found when the levorotatory isomer of bupivacaine was used in humans, but are in agreement with recently reported findings in animals. CONCLUSION Levobupivacaine was shown to be more toxic in pigs than racemic bupivacaine when large doses are injected intravenously.

Mechanisms underlying gas exchange alterations in an experimental model of pulmonary embolism

The aim of the present study was to determine the ventilation/perfusion ratio that contributes to hypoxemia in pulmonary embolism by analyzing blood gases and volumetric capnography in a model of experimental acute pulmonary embolism. Pulmonary embolization with autologous blood clots was induced in seven pigs weighing 24.00 +/- 0.6 kg, anesthetized and mechanically ventilated. Significant changes occurred from baseline to 20 min after embolization, such as reduction in oxygen partial pressures in arterial blood (from 87.71 +/- 8.64 to 39.14 +/- 6.77 mmHg) and alveolar air (from 92.97 +/- 2.14 to 63.91 +/- 8.27 mmHg). The effective alveolar ventilation exhibited a significant reduction (from 199.62 +/- 42.01 to 84.34 +/- 44.13) consistent with the fall in alveolar gas volume that effectively participated in gas exchange. The relation between the alveolar ventilation that effectively participated in gas exchange and cardiac output (V Aeff/Q ratio) also presented a significant reduction after embolization (from 0.96 +/- 0.34 to 0.33 +/- 0.17 fraction). The carbon dioxide partial pressure increased significantly in arterial blood (from 37.51 +/- 1.71 to 60.76 +/- 6.62 mmHg), but decreased significantly in exhaled air at the end of the respiratory cycle (from 35.57 +/- 1.22 to 23.15 +/- 8.24 mmHg). Exhaled air at the end of the respiratory cycle returned to baseline values 40 min after embolism. The arterial to alveolar carbon dioxide gradient increased significantly (from 1.94 +/- 1.36 to 37.61 +/- 12.79 mmHg), as also did the calculated alveolar (from 56.38 +/- 22.47 to 178.09 +/- 37.46 mL) and physiological (from 0.37 +/- 0.05 to 0.75 +/- 0.10 fraction) dead spaces. Based on our data, we conclude that the severe arterial hypoxemia observed in this experimental model may be attributed to the reduction of the V Aeff/Q ratio. We were also able to demonstrate that V Aeff/Q progressively improves after embolization, a fact attributed to the alveolar ventilation redistribution induced by hypocapnic bronchoconstriction.

Comparação entre os efeitos hemodinâmicos da intoxicação aguda com bupivacaína racêmica e a mistura com excesso enatiomérico de 50% (S75-R25): estudo experimental em cães

JUSTIFICATIVA Y OBJETIVOS: La bupivacaina racemica ha sido ampliamente utilizada en bloqueos locorregionales por la calidad y duracion de la anestesia proporcionada. Su toxicidad cardiovascular, sin embargo ya hace mucho tiempo preocupa a los anestesiologos y nuevas opciones han sido buscadas. Una de ellas es la utilizacion de su isomero levogiro que por una menor afinidad con los receptores de los canales de sodio de la celula cardiaca que seria menos cardiotoxico. En nuestro medio existe la presentacion que contiene un 75% del isomero levogiro y 25% del isomero dextrogiro, denominada mezcla con exceso enantiomerico de 50% (S75-R25). El objetivo de este estudio fue comparar en animales los efectos hemodinamicos de la intoxicacion aguda con bupivacaina racemica y con la mezcla S75-R25. METODO: Cuarenta y cuatro perros fueron anestesiados con pentobarbital, entubados y ventilados mecanicamente, siendo en seguida instalada la monitorizacion hemodinamica con cateter de Swan-Ganz y presion invasiva. Despues del periodo de reposo fueron divididos aleatoriamente en dos grupos de estudio encubierto, segun la intoxicacion con uno u otro agente en la dosis de 5 mg.kg-1. Los resultados hemodinamicos se recolectaron durante 30 minutos, tratados estadisticamente permitiendo la comparacion de la accion de los dos agentes. RESULTADOS: La mezcla S75-R25 causo mayores repercusiones hemodinamicas, particularmente, con importante disminucion de la presion arterial promedio, del indice cardiaco y del indice de trabajo del ventriculo izquierdo. CONCLUSIONES: Esos resultados se contraponen con los encontrados en humanos, cuando se utiliza el isomero levogiro puro, pero estan de acuerdo con estudios recientes en animales. Rebasar datos obtenidos en animales para seres humanos exige mucha cautela. Nuevos estudios se hacen necesarios en muestras mas abarcadoras y en grupos mas homogeneos.BACKGROUND AND OBJECTIVES Racemic bupivacaine has been widely used in locoregional anesthesia due to the quality and duration of its anesthetic action. However, its cardiovascular toxicity has worried anesthesiologists for a long time, and new options have been sought. One of them is the use of its levorotatory isomer that, due to a lesser affinity for the sodium channel receptors in the cardiac cell, would be less toxic. The presentation containing 75% of the levorotatory isomer and 25% of the dextrorotatory isomer, named 50% enantiomeric excess mixture (S75-R25), is available in our country. The objective of this study was to compare the hemodynamic effects of the acute intoxication with racemic bupivacaine and with the S75-R25 mixture in animals. METHODS Forty-four dogs were anesthetized with pentobarbital, intubated and placed on mechanical ventilation. Hemodynamic monitorization was accomplished with a Swan-Ganz catheter and intra-arterial blood pressure measurements. After a period of rest, they were randomly and blindly divided in two groups, according to the intoxication with either agent at a dose of 5 mg.Kg-1. Hemodynamic data were collected during 30 minutes and analyzed statically to allow for the comparison of both agents. RESULTS The mixture S75-R25 had more hemodynamic repercussions causing, especially, a significant reduction of the mean arterial pressure, cardiac index, and the left ventricle work index. CONCLUSIONS These results contradict those found in human beings regarding the pure levorotatory isomer, but confirm recent animal studies. One must be very careful when extrapolating animal data to human beings. Further studies involving larger samples and more homogeneous groups are necessary.

Hemodynamic effects of volume replacement with saline solution and hypertonic hydroxyethyl starch in dogs

PURPOSE To investigate hemodynamic response to volume replacement with saline solution and hypertonic hydroxyethyl starch in hypovolemic dogs. METHODS Forty dogs under general anesthesia and hemodynamic monitoring, following measurements at baseline, were bled 20 ml x Kg(-1) and parameters were measured again after 10 minutes. The animals were randomly divided in two groups and volume replacement was performed with saline solution twice the volume removed or 4 ml x Kg(-1) of hypertonic hydroxyethyl starch. Hemodynamic data were again measured after 5, 15, 30, 45 and 60 minutes. RESULTS With both solutions values returned to satisfactory hemodynamic levels. With saline solution, there was a greater amplitude in variations that tended to decrease progressively. With hypertonic hydroxyethyl starch, the parameters studied returned more rapidly to levels similar to those at baseline and varied less. CONCLUSION Both solutions proved to be efficient at replacing volume in the short period studied, although hypertonic hydroxyethyl starch produced more stable results.

Hemodynamic effects of ropivacaine and levobupivacaine intravenous injection in swines

PURPOSE To compare the hemodynamic effects following a toxic dose of either agent after intravenous injection in swines, as might accidentally occur during regional anesthesia in humans. METHODS Large White pigs were anesthetized with thiopental, tracheal intubation was performed and mechanical ventilation was instituted. Hemodynamic variables were recorded with invasive pressure monitoring and pulmonary artery catheterization. After a 30-minute resting period, the animals were randomly divided into two groups in a double-blinded fashion and received a bolus intravenous injection of 4 mg.kg-1 of either agent. Hemodynamic results were evaluated at rest and 1, 5, 10, 15, 20 and 30 minutes after intoxication. RESULTS Hemodynamic repressions of acute intoxication with levobupivacaine were more important and more prolonged than those of ropivacaína. CONCLUSION In pigs, levobupivacaine was shown to be more toxic than ropivacaine when the same large doses are injected intravenously.

Efeitos hemodinâmicos da intoxicação aguda com bupivacaína e a mistura enantiomérica: estudo experimental em suínos

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.

Comparação das alterações hemodinâmicas na intoxicação aguda com bupivacaína e ropivacaína por via venosa em suínos

JUSTIFICATIVA E OBJETIVOS: A ropivacaina apresentada na forma levogira pura foi introduzida para proporcionar alternativa mais segura que a bupivacaina nas anestesias locorregionais. O objetivo deste estudo foi comparar as repercussoes hemodinâmicas apos injecao por via venosa dos dois agentes em suinos, simulando intoxicacao que pode ocorrer durante anestesia locorregional em humanos. METODO: Suinos da raca Large-White foram anestesiados com tiopental, realizada intubacao traqueal e instituida ventilacao controlada mecânica. As variaveis hemodinâmicas foram medidas atraves de monitorizacao invasiva da pressao arterial e cateterizacao de arteria pulmonar. Apos periodo de repouso de 30 minutos os animais foram aleatoriamente divididos em dois grupos e receberam por via venosa 4 mg.kg-1 de um ou outro agente sem conhecimento do pesquisador. Os resultados hemodinâmicos foram avaliados em repouso e 1, 5, 10, 15, 20 e 30 minutos apos a intoxicacao. RESULTADOS: As repercussoes hemodinâmicas da intoxicacao aguda com bupivacaina foram mais importantes e mais prolongadas do que as com ropivacaina. Com bupivacaina o indice cardiaco teve diminuicao maior e mais prolongado, a pressao arterial media e a frequencia cardiaca diminuicoes mais prolongadas, a pressao venosa central aumento mais prolongado e a pressao capilar pulmonar aumentou mais e por mais tempo. O impacto no indice de resistencia vascular sistemica mostrou que a vasomotricidade foi parcialmente mantida, houve aumento nos dois grupos e, paradoxalmente, maior e por mais tempo com bupivacaina. CONCLUSOES: Em suinos a ropivacaina causou menos repercussoes hemodinâmicas do que a bupivacaina quando as mesmas doses foram injetadas por via venosa.

Comparison of Hemodynamic Changes in Acute Intoxication with Intravenous Bupivacaine and Ropivacaine in Swine

BACKGROUND AND OBJECTIVES Pure levorotatory ropivacaine was introduced to provide a safer alternative to bupivacaine in regional blocks. The objective of this study was to compare the hemodynamic repercussions after the intravenous administration of both agents in swine, simulating the intoxication that can be seen during regional blocks in humans. METHODS Large-White swine were anesthetized with thiopental, followed by endotracheal intubation and controlled mechanical ventilation. Hemodynamic parameters included non-invasive blood pressure and catheterization of the pulmonary artery. After 30 minutes, animals were randomly divided into two groups, and 4 mg.kg-1 of one of the agents was administered intravenously without the knowledge of the investigator. Hemodynamic parameters were evaluated at rest and 1, 5, 10, 15, 20, and 30 minutes after intoxication. RESULTS The hemodynamic repercussions of acute bupivacaine intoxication were more important and prolonged than in ropivacaine intoxication. With bupivacaine, the cardiac index showed greater and more prolonged reduction, mean arterial pressure and heart rate had more prolonged reduction, central venous pressure showed a more prolonged increase, and pulmonary wedge pressure increased more for more prolonged time. The impact on the systemic vascular resistance index showed that vasomotricity was partially maintained, increased in both groups, and, paradoxically, was greater and longer-lasting with bupivacaine. CONCLUSIONS In swine, ropivacaine caused less hemodynamic repercussions than bupivacaine when the same doses were administered intravenously.

Hemodynamic effects of the acute intoxication with bupivacaine, levobupivacaine and 50% enantiomeric excess mixture: an experimental study in pigs.

BACKGROUND AND METHODS Until recently, bupivacaine had been the anesthetic of choice for loco-regional blocks due to the quality and duration of the anesthesia. But its cardiovascular toxicity is a source of concern for anesthesiologists who seek new pharmacological options with a smaller degree of this problem. Its levorotatory isomer, levobupivacaine, that would be less cardiotoxic due a smaller affinity for the receptors of the sodium channels of the cardiac cell, is one of these options. In Brazil, a presentation containing 75% of the levorotatory isomer and 25% of the dextrorotatory isomer, called 50% enantiomeric excess mixture is available. The aim of this study was to evaluate the hemodynamic repercussions of the intravascular injection of a toxic dose of those three agents to determine which one has the least impact in the case of an accident. METHODS Large White pigs were anesthetized with thiopental, intubated, and placed on mechanical ventilation. Hemodynamic monitoring was achieved with a Swan-Ganz catheter and invasive blood pressure. After a period of rest, the animals were randomly divided in three groups. The intoxication was performed, on a double-blind fashion, with 4 mg kg(-1) of one of the drugs. Hemodynamic parameters were evaluated during 30 minutes. Analytical tests were used to compare the results among the groups. RESULTS The 50% enantiomeric excess mixture and levobupivacaine had greater hemodynamic repercussions than the racemic mixture, which were more pronounced with the first drug. These results go against those found in humans, especially regarding the pure levorotatory isomer, but are similar to recent results reported in animals. One should be careful when extrapolating the data obtained in pigs to humans and further studies are necessary. CONCLUSIONS In pigs, the 50% enantiomeric excess mixture, in particular, and levobupivacaine were more toxic when administered intravenously than racemic bupivacaine.JUSTIFICATIVA Y OBJETIVOS: La bupivacaina ha sido hasta hace poco tiempo el anestesico por eleccion en los bloqueos loco-regionales en razon de la calidad de la anestesia proporcionada y por su duracion. A pesar de eso, su toxicidad cardiovascular preocupa a los anestesiologos que buscan nuevas opciones farmacologicas con un menor grado de ese inconveniente. Una de ellas es su isomero levogiro, la levobupivacaina, que por una menor afinidad con los receptores de los canales de sodio de la celula cardiaca, seria menos cardiotoxica. En nuestro medio esta disponible la presentacion que contiene un 75% del isomero levogiro y un 25% del isomero dextrogiro, denominada mezcla con exceso enantiomerico de 50%. El objetivo de este estudio fue el de evaluar las repercusiones hemodinamicas de la inyeccion intravascular de dosis toxica de esos tres agentes, buscando encontrar cual de ellos registra un menor impacto en caso de accidente. METODO: Cerdos de la raza Large White fueron anestesiados con tiopental, intubados y ventilados mecanicamente, siendo a continuacion instalada la monitorizacion hemodinamica con cateter de Swan-Ganz y presion invasiva para estudio de las variables hemodinamicas. Despues del reposo, fueron divididos aleatoriamente en tres grupos y realizada intoxicacion doble encubierta con uno de los agentes en dosis de 4 mg.kg-1. Los resultados hemodinamicos fueron evaluados durante 30 minutos. A los resultados se les aplico pruebas estadisticas para la comparacion entre los grupos. RESULTADOS: La mezcla con exceso enantiomerico de 50% y la levobupivacaina causaron mayores repercusiones hemodinamicas que la mezcla racemica, siendo esas mas fuertes con el primer agente. Esos resultados se oponen a los ya encontrados en humanos, particularmente cuando se utiliza el isomero levogiro puro, pero estan a tono con los resultados recientes tambien obtenidos en animales. Rebasar los datos obtenidos en cerdos con los obtenidos en seres humanos, exige mucha cautela y nuevos estudios se hacen necesarios. CONCLUSIONES: En cerdos, la mezcla con exceso enantiomerico de 50% particularmente, y la levobupivacaina fueron mas toxicas cuando se administraron por via venosa que la bupivacaina racemica.