Vanessa Henriques Carvalho

Influence of Local Anesthetics on the Neuromuscular Blockade Produced by Rocuronium. Effects of Lidocaine and 50% Enantiomeric Excess Bupivacaine on the Neuromuscular Junction

BACKGROUND AND OBJECTIVES The effects of local anesthetics (LA) on neuromuscular transmission and their influence on the neuromuscular blockade produced by competitive neuromuscular blockers have not been fully investigated. The objective of this study was to evaluate, in vitro, the effects of lidocaine and 50% enantiomeric excess bupivacaine (S75-R25) on the neuromuscular blockade produced by rocuronium. METHODS The rats were divided in five groups (n = 5) according to the drug used: isolated lidocaine, bupivacaine (S75-R25), or rocuronium (groups I, II, and II); and rocuronium in preparations previously exposed to LAs (groups IV and V). The concentrations used were as follows: 20 microg x mL(-1), 5 microg x mL(-1), and 4 microg x mL(-1) of lidocaine, bupivacaine (S75-R25), and rocuronium, respectively. The following parameters were evaluated: 1) the strength of muscular contraction of the diaphragm to indirect electrical stimulations, before and 60 minutes after the isolated addition of the LAs and rocuronium, and the association AL-rocuronium; and 2) the effects of LAs on membrane potential (MP) and miniature end-plate potentials (MEPP). The effect of LAs on muscle contraction in response to acetylcholine was evaluated in chick biventer cervicis preparations. RESULTS Isolated lidocaine and bupivacaine (S75-R25) did not change the muscular response and the levels of MPs. In preparations exposed to LAs, rocuroniuminduced blockade was significantly greater than that produced by rocuronium alone. In chick biventer cervicis preparations, lidocaine and bupivacaine (S75R25) decreased contraction in response to acetylcholine. Lidocaine increased the frequency of MEPPs, which was followed by the blockade; bupivacaine (S75R25) caused a reduction in MEPPs followed by blockade. CONCLUSIONS Local anesthetics caused a potentiation of the neuromuscular blockade produced by rocuronium. The results showed pre- and post-synaptic effects.

Influência de anestésicos locais sobre o bloqueio neuromuscular produzido pelo rocurônio: ação da lidocaína e da mistura enantiomérica em excesso de 50% de bupivacaína na junção neuromuscular

JUSTIFICATIVA Y OBJETIVOS: Los efectos de los anestesicos locales (AL), en la transmision neuromuscular y su influencia en el bloqueo neuromuscular producido por bloqueadores neuromusculares competitivos, todavia no se ha investigado lo suficiente. El objetivo del estudio, fue evaluar in vitro los efectos de la lidocaina y de la mezcla enantiomerica en exceso de 50% de bupivacaina (S75-R25) en el bloqueo neuromuscular producido por el rocuronio. METODOS: Algunos ratones se distribuyeron en cinco grupos (n = 5) de acuerdo con el farmaco estudiado: lidocaina, bupivacaina (S75-R25), rocuronio, aisladamente (Grupos I, II, III); rocuronio en preparaciones previamente expuestas a los AL (Grupos IV, V). Las concentraciones utilizadas fueron: 20 µg.mL-1, 5 µg.mL-1 y 4 µg.mL-1, para lidocaina, bupivacaina (S75-R25), y rocuronio, respectivamente. Se evaluo: 1) la fuerza de contraccion muscular del diafragma a la estimulacion electrica indirecta, antes y 60 minutos despues de la adicion de los AL y rocuronio aisladamente, y la asociacion AL - rocuronio; 2) efectos de los AL sobre el potencial de la membrana (PM) y potenciales de placa terminal en miniatura (PPTM). En una preparacion biventer cervicis de pollito, se evaluo el efecto de los AL en la respuesta de contraccion a la acetilcolina. RESULTADOS: La lidocaina y la bupivacaina (S75-R25) aisladamente, no alteraron las respuestas musculares y los valores del PM. En las preparaciones expuestas a los AL, el bloqueo por el rocuronio fue significativamente mayor con relacion al producido por el rocuronio aisladamente. En una preparacion biventer cervicis de pollito, la lidocaina y la bupivacaina (S75-R25), redujeron la respuesta de contraccion a la acetilcolina. La lidocaina aumento la frecuencia de los PPTM, seguido de bloqueo; la bupivacaina (S75-R25) genero una disminucion seguida de bloqueo. CONCLUSIONES: Los anestesicos locales potenciaron el bloqueo neuromuscular causado por el rocuronio. Los resultados mostraron una accion presinaptica y postsinaptica.

Evidence of presynaptic and postsynaptic action of local anesthetics in rats

PURPOSE To assess the probable actions of ropivacaine, 50% enantiomeric excess bupivacaine mixture (S75-R25) and levobupivacaine on neuromuscular transmission in vitro. METHODS Thirty rats were distributed into groups (n=5) according to the drug used: ropivacaine, bupivacaine (S75-R25) and levobupivacaine. The concentration used for the three local anesthetics (LA) was 5 µg.mL. (-1)The following parameters were evaluated: 1) LA effects on membrane potential (MP) and miniature end plate potential (MEPP). A chick biventer cervicis preparation was also used to evaluate LA effects on the contracture response to acetylcholine. RESULTS LA did not alter MP values and decreased the frequency and amplitude of MEPP. In a chick biventer cervicis preparation, bupivacaine (S75-R25) and levobupivacaine decreased the contracture response to acetylcholine with statistical significance, in comparison to ropivacaine. CONCLUSIONS In the concentrations used, levobupivacaine and bupivacaine (S75-R25) exhibited presynaptic and postsynaptic actions evidenced by alterations in miniature end plate potentials and contracture response to acetylcholine. Ropivacaine only had a presynaptic action.

Dose preparatória versus injeção única: estudo comparativo entre diferentes doses de cisatracúrio

JUSTIFICATIVA E OBJETIVOS: A tecnica da dose preparatoria e uma alternativa para encurtar o tempo de latencia dos bloqueadores neuromusculares adespolarizantes. O objetivo deste estudo foi avaliar o tempo para instalacao do bloqueio neuromuscular maximo, as condicoes de intubacao traqueal e as alteracoes cardiocirculatorias ocasionadas por diferentes doses de cisatracurio em injecao unica e em doses fracionadas. METODO: Foram estudados 80 pacientes, estado fisico ASA I e II, distribuidos em dois grupos de acordo com a dose de cisatracurio: Grupo I (0,1 mg.kg-1) e Grupo II (0,2 mg.kg-1). Formaram-se subgrupos de acordo com a tecnica de curarizacao usada: Subgrupos P1 e P2 (dose preparatoria) - 0,02 mg.kg-1ou 0,04 mg.kg-1 de cisatracurio, respectivamente, seguido apos um minuto de 0,08 mg.kg-1 ou 0,16 mg.kg-1 do mesmo bloqueador neuromuscular, respectivamente; Subgrupos U1 e U2 - injecao unica de dose total de 0,1 mg.kg-1 ou 0,2 mg.kg-1 de cisatracurio, respectivamente. A Inducao anestesica foi feita com etomidato precedido de alfentanil. A funcao neuromuscular foi monitorizada empregando-se a SQE a cada 12 segundos. Foram avaliados: o tempo para instalacao do bloqueio neuromuscular maximo; as alteracoes de pressao arterial media e de frequencia cardiaca, e as condicoes de intubacao traqueal. RESULTADOS: Os tempos para instalacao do bloqueio neuromuscular maximo foram: Grupo I (3,90 ± 0,60 min e 3,88 ± 0,74 min, nos subgrupos P1 e U1, respectivamente) e Grupo II (1,40 ± 0,40 min e 2 ± 0,30 min, nos subgrupos P2 e U2, respectivamente) sem diferenca significativa. A comparacao entre os subgrupos P1 e P2 e os subgrupos U1 e U2, mostrou diferenca significativa. As condicoes de intubacao traqueal foram aceitaveis em todos os pacientes sem alteracoes cardiocirculatorias. CONCLUSOES: As doses empregadas de cisatracurio nao encurtou o tempo para a instalacao do bloqueio neuromuscular maximo, em relacao ao seu emprego em injecao unica, porem proporcionaram condicoes aceitaveis de intubacao traqueal, sem alteracoes cardiocirculatorias.BACKGROUND AND OBJECTIVES The priming technique is an alternative to shorten nondepolarizing neuromuscular blockers onset time. This study aimed at evaluating maximum neuromuscular block onset, tracheal intubation conditions and cardiocirculatory changes determined by different cisatracurium single or fractional doses. METHODS Participated in this study 80 patients physical status ASA I and II, who were distributed into two groups according to cisatracurium doses: Group I (0.1 mg.kg-1) and Group II (0.2 mg.kg-1). Subgroups were constituted according to the curarization technique employed: subgroups P1 and P2 (priming-dose) - 0.02 mg.kg-1 or 0.04 mg.kg-1cisatracurium, respectively, followed one minute later, by 0.08 mg.kg-1 or 0.16 mg.kg-1 of the same neuromuscular blocker, respectively; subgroups U1 and U2 - total bolus injection of 0.1 mg.kg-1 or 0.2 mg.kg-1 cisatracurium, respectively. Anesthesia was induced with etomidate, preceded by alfentanil. Train of Four (TOF) stimulation was applied at 12-second intervals to monitor neuromuscular function. Maximum neuromuscular blockade onset time, tracheal intubation conditions and changes in hemodynamic parameters (arterial mean blood pressure and heart rate) were evaluated. RESULTS Mean times for maximum neuromuscular block onset were: Group I (3.90 +/- 0.60 min and 3.88 +/- 0.74 min, for subgroups P1 and U1, respectively) and Group II (1.40 +/- 0.40 min and 2 +/- 0.30 min, for subgroups P2 and U2, respectively) with no significant differences. Comparison between subgroups P1 and P2 and between subgroups U1 and U2, has shown statistically significant differences. Tracheal intubation conditions were acceptable in all patients and there were no cardiovascular changes. CONCLUSIONS Fractional cisatracurium doses have not shortened maximum neuromuscular block onset as compared to bolus injections. They have however produced acceptable tracheal intubation conditions without cardiovascular changes.

Association between levobupivacaine and pancuronium. Interference in neuromuscular transmission and blockade in rats

PURPOSE To evaluate the effects of levobupivacaine on neuromuscular transmission and neuromuscular blockade produced by pancuronium in vitro. METHODS Thirty rats were distributed into groups (n = 5) according to the drug used alone or in combination: Group I - levobupivacaine (5 µg.mL-1); Group II - pancuronium (2 µg.mL-1); Group III - pancuronium (2 µg.mL-1) + levobupivacaine (5µg.mL-1). The following parameters were evaluated: 1) amplitude of diaphragmatic response to indirect stimulation, before and 60 minutes after the addition of levobupivacaine and pancuronium alone, and after the addition of levobupivacaine combined with pancuronium; 2) membrane potentials (MP) and miniature endplate potentials (MEPP). RESULTS Levobupivacaine alone did not alter the amplitude of muscle response and MP. In preparations previoulsy exposed to levobupivacaine, the block with pancuronium was significantly denser (90.2 ± 15.2%), showing a significant difference (p=0.031) in comparison to the block produced by pancuronium alone (48.9% ± 9.8%). There was a decrease in the frequency and amplitude of MEPPs. CONCLUSION Levobupivacaine potentiated the neuromuscular blockade produced by pancuronium, confirming a presynaptic action by a decrease in miniature endplate potentials.

Efeito da associação ropivacaina‐pancurônio na transmissão neuromuscular e eficácia da neostigmine e 4‐aminopiridina na reversão do bloqueio: estudo experimental ☆

BACKGROUND AND OBJECTIVES The local anesthetic effects on neuromuscular junction and its influence on blockade produced by nondepolarizing neuromuscular blockers are still under-investigated; however, this interaction has been described in experimental studies and in humans. The aim of this study was to evaluate in vitro the interaction between ropivacaine and pancuronium, the influence on transmission and neuromuscular blockade, and the effectiveness of neostigmine and 4-aminopyridine to reverse the blockade. METHODS Rats were divided into groups (n=5) according to the study drug: ropivacaine (5μgmL(-1)); pancuronium (2μg.mL(-1)); ropivacaine+pancuronium. Neostigmine and 4-aminopyridine were used at concentrations of 2μgmL(-1) and 20μgmL(-1), respectively. The effects of ropivacaine on membrane potential and miniature end-plate potential, the amplitude of diaphragm responses before and 60minutes after the addition of ropivacaine (degree of neuromuscular blockade with pancuronium and with the association of pancuronium-ropivacaine), and the effectiveness of neostigmine and 4-aminopyridine on neuromuscular block reversal were evaluated. RESULTS Ropivacaine did not alter the amplitude of muscle response (the membrane potential), but decreased the frequency and amplitude of the miniature end-plate potential. Pancuronium blockade was potentiated by ropivacaine, and partially and fully reversed by neostigmine and 4-aminopyridine, respectively. CONCLUSIONS Ropivacaine increased the neuromuscular block produced by pancuronium. The complete antagonism with 4-aminopyridine suggests presynaptic action of ropivacaine.

Effect of 50% enantiomeric excess bupivacaine mixture combined with pancuronium on neuromuscular transmission in rat phrenic nerve-diaphragm preparation; a pilot study

Background and Aims: Local anaesthetics are drugs that are widely used in clinical practice. However, the effects of these drugs on the neuromuscular junction and their influence on the blockade produced by non-depolarising neuromuscular blocking drugs are still under investigation. The aim of this study was to evaluate, in vitro, the influence of a 50% enantiomeric excess bupivacaine mixture on neuromuscular transmission and neuromuscular block produced by pancuronium. Methods: Rats were distributed into three groups (n = 5) according to the drug studied namely, 50% enantiomeric excess bupivacaine mixture (5 μg/mL); pancuronium (2 μg/mL); 50% enantiomeric excess bupivacaine mixture + pancuronium. The following parameters were evaluated: (1) Effects of a 50% enantiomeric excess bupivacaine mixture on membrane potential (MP) and miniature endplate potentials (MEPPs); (2) amplitude of diaphragmatic response before and 60 min after the addition of a 50% enantiomeric excess bupivacaine mixture; the degree of neuromuscular block with pancuronium and pancuronium combined with a 50% enantiomeric excess bupivacaine mixture. Results: A 50% enantiomeric excess bupivacaine mixture did not alter the amplitude of muscle response (MP) but decreased the frequency and amplitude of MEPP. The block produced by pancuronium was potentiated by a 50% enantiomeric excess bupivacaine mixture. Conclusion: A 50% enantiomeric excess bupivacaine mixture used alone did not affect neuromuscular transmission, but potentiated the neuromuscular block produced by pancuronium. No action was shown on the muscle fibre, and alterations on MEPPs demonstrated a presynaptic action.

Priming versus bolus: a comparative study with different cisatracurium doses

JUSTIFICATIVA E OBJETIVOS: A tecnica da dose preparatoria e uma alternativa para encurtar o tempo de latencia dos bloqueadores neuromusculares adespolarizantes. O objetivo deste estudo foi avaliar o tempo para instalacao do bloqueio neuromuscular maximo, as condicoes de intubacao traqueal e as alteracoes cardiocirculatorias ocasionadas por diferentes doses de cisatracurio em injecao unica e em doses fracionadas. METODO: Foram estudados 80 pacientes, estado fisico ASA I e II, distribuidos em dois grupos de acordo com a dose de cisatracurio: Grupo I (0,1 mg.kg-1) e Grupo II (0,2 mg.kg-1). Formaram-se subgrupos de acordo com a tecnica de curarizacao usada: Subgrupos P1 e P2 (dose preparatoria) - 0,02 mg.kg-1ou 0,04 mg.kg-1 de cisatracurio, respectivamente, seguido apos um minuto de 0,08 mg.kg-1 ou 0,16 mg.kg-1 do mesmo bloqueador neuromuscular, respectivamente; Subgrupos U1 e U2 - injecao unica de dose total de 0,1 mg.kg-1 ou 0,2 mg.kg-1 de cisatracurio, respectivamente. A Inducao anestesica foi feita com etomidato precedido de alfentanil. A funcao neuromuscular foi monitorizada empregando-se a SQE a cada 12 segundos. Foram avaliados: o tempo para instalacao do bloqueio neuromuscular maximo; as alteracoes de pressao arterial media e de frequencia cardiaca, e as condicoes de intubacao traqueal. RESULTADOS: Os tempos para instalacao do bloqueio neuromuscular maximo foram: Grupo I (3,90 ± 0,60 min e 3,88 ± 0,74 min, nos subgrupos P1 e U1, respectivamente) e Grupo II (1,40 ± 0,40 min e 2 ± 0,30 min, nos subgrupos P2 e U2, respectivamente) sem diferenca significativa. A comparacao entre os subgrupos P1 e P2 e os subgrupos U1 e U2, mostrou diferenca significativa. As condicoes de intubacao traqueal foram aceitaveis em todos os pacientes sem alteracoes cardiocirculatorias. CONCLUSOES: As doses empregadas de cisatracurio nao encurtou o tempo para a instalacao do bloqueio neuromuscular maximo, em relacao ao seu emprego em injecao unica, porem proporcionaram condicoes aceitaveis de intubacao traqueal, sem alteracoes cardiocirculatorias.BACKGROUND AND OBJECTIVES The priming technique is an alternative to shorten nondepolarizing neuromuscular blockers onset time. This study aimed at evaluating maximum neuromuscular block onset, tracheal intubation conditions and cardiocirculatory changes determined by different cisatracurium single or fractional doses. METHODS Participated in this study 80 patients physical status ASA I and II, who were distributed into two groups according to cisatracurium doses: Group I (0.1 mg.kg-1) and Group II (0.2 mg.kg-1). Subgroups were constituted according to the curarization technique employed: subgroups P1 and P2 (priming-dose) - 0.02 mg.kg-1 or 0.04 mg.kg-1cisatracurium, respectively, followed one minute later, by 0.08 mg.kg-1 or 0.16 mg.kg-1 of the same neuromuscular blocker, respectively; subgroups U1 and U2 - total bolus injection of 0.1 mg.kg-1 or 0.2 mg.kg-1 cisatracurium, respectively. Anesthesia was induced with etomidate, preceded by alfentanil. Train of Four (TOF) stimulation was applied at 12-second intervals to monitor neuromuscular function. Maximum neuromuscular blockade onset time, tracheal intubation conditions and changes in hemodynamic parameters (arterial mean blood pressure and heart rate) were evaluated. RESULTS Mean times for maximum neuromuscular block onset were: Group I (3.90 +/- 0.60 min and 3.88 +/- 0.74 min, for subgroups P1 and U1, respectively) and Group II (1.40 +/- 0.40 min and 2 +/- 0.30 min, for subgroups P2 and U2, respectively) with no significant differences. Comparison between subgroups P1 and P2 and between subgroups U1 and U2, has shown statistically significant differences. Tracheal intubation conditions were acceptable in all patients and there were no cardiovascular changes. CONCLUSIONS Fractional cisatracurium doses have not shortened maximum neuromuscular block onset as compared to bolus injections. They have however produced acceptable tracheal intubation conditions without cardiovascular changes.

Anestesia para parto cesáreo em paciente portadora de síndrome de Klippel‐Trenaunay

INTRODUCTION Klippel-Trenaunay syndrome is a rare congenital vascular disease characterized by cutaneous hemangiomas, varicosities, and limb asymmetry, which may evolve with coagulation disorders and hemorrhage as those more frequent complications in pregnant patients. Pregnancy is not advised in women with this syndrome due to increased obstetrical risk. CASE REPORT Female patient, 29 years old, 99kg, 167cm, BMI 35.4kg.m-2, physical status ASA III, with 27 weeks of gestational age and diagnosis of Klippel-Trenaunay syndrome. She was admitted to attempt inhibition of preterm labor. As manifestations of Klippel-Trenaunay syndrome, the patient presented with cerebral and cutaneous hemangioma mainly in the trunk and lumbar region, paresis in the left upper and lower limbs, and limb asymmetry requiring the use of a walking stick. Physical examination revealed absence of airway vascular malformations and Mallampati class 3. Laboratory tests were normal and abdominal angiotomography showed irregular uterus, with multiple varices and vessels of arterial origin and bilateral periadnexal varices. She evolved with failure in preterm labor inhibition, and cesarean section under total intravenous anesthesia was indicated. Monitoring, central and peripheral venous access, radial artery catheterization, and diuresis were secured. Cesarean section was performed with median incision and longitudinal uterine body section for fetal extraction. Two episodes of arterial hypotension were seen intraoperatively. The postoperative evolution was uneventful. The choice of anesthesia was dependent on the clinical manifestations and the lack of imaging tests proving the absence of neuraxial hemangiomas.

Aplicação de protocolo e avaliação da incidência de curarização residual pós‐operatória na ausência de aceleromiografia intraoperatória – Ensaio clínico randomizado

OBJECTIVE Evaluate the incidence of postoperative residual curarization (PORC) in the post-anesthesia care unit (PACU) after the use of protocol and absence of intraoperative acceleromyography (AMG). METHODS Randomized clinical trial with 122 patients allocated into two groups (protocol and control). Protocol group received initial and additional doses of rocuronium (0.6mg.kg-1 and 10mg, respectively); the use of rocuronium was avoided in the final 45minutes; blockade reversal with neostigmine (50μg.kg-1); time ≥ 15minutes between reversion and extubation. CONTROL initial and additional doses of rocuronium, blockade reversal, neostigmine dose, and extubation time, all at the discretion of the anesthesiologist. AMG was used in the PACU and PORC considered at T4/T1 ratio<1.0. RESULTS The incidence of PORC was lower in protocol group than in control group (25% vs. 45.2%, p=0.02). In control group, total dose of rocuronium was higher in patients with PORC than without PORC (0.43 vs. 0.35mg.kg-1.h-1, p=0.03) and the time interval between the last administration of rocuronium and neostigmine was lower (75.0 vs. 101.0min, p<0.01). In protocol group, there was no difference regarding the analyzed parameters (with PORC vs. without PORC). Considering the entire study population and the presence or absence of PORC, total dose of rocuronium was higher in patients with PORC (0.42 vs. 0.31mg.kg-1.h-1, p=0.01), while the time interval between the last administration of rocuronium and neostigmine was lower (72.5 vs. 99.0min, p ≤ 0.01). CONCLUSION The proposed systematization reduced PORC incidence in PACU in the absence of intraoperative AMG.