Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

PURPOSE: To study racemic bupivacaine, non-racemic bupivacaine and ropivacaine on myocardial contractility. METHODS: Isolated Wistar papillary muscles were submitted to 50 and 100 mM racemic bupivacaine (B50 and B100), non-racemic bupivacaine (NR50 and NR100) and ropivacaine (R50 and R100) intoxication. Isometric contraction data were obtained in basal condition (0.2 Hz), after increasing the frequency of stimulation to 1.0 Hz and after 5, 10 and 15 min of local anesthetic intoxication. Data were analyzed as relative changes of variation. RESULTS: Developed tension was higher with R100 than B100 at D1 (4.3 ± 41.1 vs -57.9 ± 48.1). Resting tension was altered with B50 (-10.6 ± 23.8 vs -4.7 ± 5.0) and R50 (-14.0 ± 20.5 vs -0.5 ± 7.1) between D1 and D3. Maximum rate of tension development was lower with B100 (-56.6 ± 38.0) than R50 (-6.3 ± 37.9) and R100 (-1.9 ± 37.2) in D1. B50, B100 and NR100 modified the maximum rate of tension decline from D1 through D2. Time to peak tension was changed with NR50 between D1 and D2. CONCLUSIONS: Racemic bupivacaine depressed myocardial contractile force more than non-racemic bupivacaine and ropivacaine. Non-racemic and racemic bupivacaine caused myocardial relaxation impairment more than ropivacaine. .

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

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 por cento do isômero levógiro e 25 por cento 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.

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 percent of levogyre isomer and 25 percent 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.

Efectos de fentanyl adicionado a bupivacaína en anestesia peridural para operación cesárea / Effects of peridural fentanyl as coadjutant of the local anesthetist for cesarean section

Con el objetivo de identificar los efectos del fentanyl peridural como coadyuvante de los anestésicos locales para operación cesárea, se realizó un experimento clinico, aleatorizado, doble ciego y controlado en 60 maternas llevadas a cesárea en el Hospital Universitario Ramón González Valencia de Bucaramanga, Colombia. Treinta y una pacientes recibieron 2 cc. (100 mcgr.) de fentanyl junto a la dosis total de bupivacaína peridural, mientras que a veintinueve pacientes se les agregó 2 cc. de solución salina normal. Se aplicó dosis única de la mezcla anestésica y se registró la latencia del bloqueo sensitivo y motor. Se tuvo en cuenta, además, la calidad de la analgesia intraoperatoria y postoperatoria, medidas por medio de escala verbal simple y por la necesidad de analgesia suplementaria. Se registraron la cantidad y clase de efectos secundarios. Utilizando el promedio de las variables y determinando la significancia por medio de la t de Student, se obtuvo una latencia del efecto anestésico de 11.43 +/- 2.40 minutos para el grupo fentanyl y de 12.07 +/- 2.26 minutos para el grupo control; sin diferencias significativas. Un 43 por ciento de las pacientes que recibieron placebo necesitaron analgesia suplementaria, contra un 16.7 por ciento de quienes recibieron fentanyl ( p < 0.03). No se afectó el Apgar de los recién nacidos. No hubo diferencias en el comportamiento postoperatorio entre los grupos. Igualmente los efectos secundarios fueron similares, con leve ventaja para el fentanyl, en referencia a escalofríos. Concluimos que la real ventaja de adicionar fentanyl a la bupivacaína peridural es la mejoría de la calidad de la analgesia intraoperatoria. No son claros sus beneficios sobre el aspecto preoperatorio y postoperatorio

Comparative study between hyperbaric spinal levobupivacine and racemic bupivacaine in orthopaedic surgery

Levobupivacaine is the isolated Senantiomer of bupivacaine and may be a favorable alternative to spinal bupivacaine. However, its clinical efficacy relative to bupivacaine and its dose-response characteristics, in spinal anesthesia, must first be known. This, double-blinded randomized, study was designed to compare the clinical efficacy of hyperbaric levobupivacaine and bupivacaine for spinal anesthesia. Forty patients undergoing elective lower limb orthopaedic surgeries received either 3.5 mL levobupivacaine 0.5% hyerbaric or 3.5 mL bupivacaine 0.5% hyerbaric. Sensory blockade was assessed with the pinprick test; motor blockade was documented by using a modified Bromage score. Haemodynamic variables [e.g., blood pressure, heart rate, pulse oximetry] were also recorded as well as time for discharge criteria. In both groups sensory and motor block were similar between the same doses of levobupivacaine and bupivacaine [P > 0.06]. The duration of motor block at the quadriceps was 281 +/- 48 versus 284 +/- 4.2 min levobupivacaine and racemic bupivacaine respectively. Intergroup differences between levobupivacaine and bupivacaine were insignificant both in respect to the onset time and the duration of sensory and motor blockade [11.8 +/- 1.4 versus 12 .4 +/- 1.1 min; 10 +/- 3 versus 9 +/- 3 min; 225 +/- 50 versus 235 +/- 47min; 281 +/- 48 versus 284 +/- 42 min]. There were no statistically significant differences between the two groups except for the fact that the transition from Bromage scale 0 to 2 was significantly faster in the Levobupivacaine [4 +/- 1 min] than in the Bupivacaine group [7 +/- 2 min]. By comparison, there was no significant difference in first VAS scores at the PACU [3.1 +/- 0.5] in the Levobupivacaine versus [3.4 +/- 0.8] in the bupivacaine group. In both groups slight reductions in heart rate and mean arterial pressure were recorded, but there was no intergroup statistical difference haemodynamic parameters. There was no significant difference with regards time until achievement of discharge criteria. We conclude that intrathecal levobupivacaine is equal in efficacy to racemic bupivacaine

Effect of pH adjustment of bupivacaine on onset and duration of epidural anaesthesia.

The effect of pH adjustment of bupivacaine on onset and duration of sensory and motor block was studied in 45 patients undergoing lower abdominal and lower limb surgery. The study was done in 3 groups with the mean pH adjustment of 5.85, 7.14 and 7.21. Each patient was given 30 ml of 0.4% pH adjusted bupivacaine solution in epidural space. Onset of sensory block and duration were noticed by pin-prick method while motor block was observed by asking the patient to raise the thigh. It was observed that increase in pH of bupivacaine solution quickens the onset of sensory and motor block and increases the overall duration of neural blockade.