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.

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.(AU)

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

ABSTRACT 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.

Effect of ropivacaine combined with pancuronium on neuromuscular transmission and effectiveness of neostigmine and 4-aminopyridine for blockade reversal: experimental study / Efeito da associação ropivacaina-pancurônio na transmissão neuromuscular e eficácia da neostigmine e 4-aminopiridina na reversão do bloqueio: estudo experimental / Efecto de la asociación ropivacaína-pancuronio en la transmisión neuromuscular. Eficacia de la neostigmina y 4-aminopiridina en la reversión del bloqueo. Estudio 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 (5 µg mL-1); pancuronium (2 µg mL-1); ropivacaine + pancuronium. Neostigmine and 4-aminopyridine were used at concentrations of 2 µg mL-1 and 20 µg mL-1, respectively. The effects of ropivacaine on membrane potential and miniature endplate potential, the amplitude of diaphragm responses before and 60 min 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 endplate 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. .

JUSTIFICATIVA E OBJETIVOS: Os efeitos dos anestésicos locais na junção neuromuscular e sua influência no bloqueio produzido por bloqueadores neuromusculares não-despolarizantes é ainda alvo de pouca investigação, no entanto esta interação tem sido descrita em trabalhos experimentais e em humanos. O objetivo deste estudo foi avaliar in vitro, a interação da ropivacaína com o pancurônio, a influência na transmissão e bloqueio neuromuscular e a efetividade da neostigmina e 4-aminopiridina na reversão do bloqueio. MÉTODO: Ratos foram distribuídos em grupos (n = 5) de acordo com o fármaco estudado: ropivacaína (5 µg mL-1); pancurônio (2 µg mL-1); ropivacaína + pancurônio. A neostigmina e a 4-aminopiridina foram usadas nas concentrações de 2 µg mL-1 e 20 µg.mL-1, respectivamente. Avaliou-se: 1) efeitos da ropivacaína sobre o potencial de membrana e potenciais de placa terminal em miniatura; 2) a amplitude das respostas do diafragma antes e 60 minutos após a adição da ropivacaína; o grau de bloqueio neuromuscular com o pancurônio e com a associação pancurônio - ropivacaína; 3) a efetividade da neostigmina e 4-aminopiridina na reversão do bloqueio neuromuscular. RESULTADOS: A ropivacaína não alterou a amplitude das respostas musculares, os potenciais de membrana, mas diminuiu a frequência e a amplitude dos potenciais de placa terminal em miniatura. O bloqueio produzido pelo pancurônio foi potencializado pela ropivacaína, e parcial e totalmente revertido pela neostigmina e 4-aminopiridina, respectivamente. CONCLUSÕES: A ropivacaína potencializou o bloqueio neuromuscular produzido pelo pancurônio. O antagonismo completo com a 4-aminopiridina sugere ação pré-sináptica da ropivacaína. .

JUSTIFICACIÓN Y OBJETIVOS: Los efectos de los anestésicos locales en la unión neuromuscular y su influencia en el bloqueo producido por bloqueantes neuromusculares no-despolarizantes todavía son poco investigados, sin embargo, esta interacción ha sido descrita en trabajos experimentales y en seres humanos. El objetivo de este estudio fue evaluar in vitro la interacción de la ropivacaína con el pancuronio, la influencia en la transmisión y bloqueo neuromuscular y la efectividad de la neostigmina y 4-aminopiridina en la reversión del bloqueo. MÉTODO: Unos ratones fueron distribuidos en grupos (n = 5) de acuerdo con el fármaco estudiado: ropivacaína (5 µg/ml-1); pancuronio (2 µg/ml-1); ropivacaína + pancuronio. La neostigmina y la 4-aminopiridina fueron usadas en concentraciones de 2 µg/ml-1 y 20 µg/ml-1, respectivamente. Evaluamos: 1) efectos de la ropivacaína sobre el potencial de membrana y potenciales de placa terminal en miniatura; 2) la amplitud de las respuestas del diafragma antes y 60 min después de la adición de la ropivacaína; el grado de bloqueo neuromuscular con el pancuronio y con la asociación pancuronio-ropivacaína; 3) la efectividad de la neostigmina y 4-aminopiridina en la reversión del bloqueo neuromuscular. RESULTADOS: La ropivacaína no alteró la amplitud de las respuestas musculares, los potenciales de membrana, pero disminuyó la frecuencia y la amplitud de los potenciales de placa terminal en miniatura. El bloqueo producido por el pancuronio fue potenciado por la ropivacaína, y parcial y totalmente revertido por la neostigmina y 4-aminopiridina, respectivamente. CONCLUSIONES: La ropivacaína potenció el bloqueo neuromuscular producido por el pancuronio. El antagonismo completo con la 4-aminopiridina muestra una acción presináptica de la ropivacaína. .

The comparison of spontaneous breathing and muscle paralysis in two different severities of experimental lung injury.

OBJECTIVES: The benefits of spontaneous breathing over muscle paralysis have been proven mainly in mild lung injury; no one has yet evaluated the effects of spontaneous breathing in severe lung injury. We investigated the effects of spontaneous breathing in two different severities of lung injury compared with muscle paralysis. DESIGN: Prospective, randomized, animal study. SETTING: University animal research laboratory. SUBJECTS: Twenty-eight New Zealand white rabbits. INTERVENTIONS: Rabbits were randomly divided into the mild lung injury (surfactant depletion) group or severe lung injury (surfactant depletion followed by injurious mechanical ventilation) group and ventilated with 4-hr low tidal volume ventilation with spontaneous breathing or without spontaneous breathing (prevented by a neuromuscular blocking agent). Inspiratory pressure was adjusted to control tidal volume to 5-7 mL/kg, maintaining a plateau pressure less than 30 cm H2O. Dynamic CT was used to evaluate changes in lung aeration and the regional distribution of tidal volume. MEASUREMENTS AND RESULTS: In mild lung injury, spontaneous breathing improved oxygenation and lung aeration by redistribution of tidal volume to dependent lung regions. However, in severe lung injury, spontaneous breathing caused a significant increase in atelectasis with cyclic collapse. Because of the severity of lung injury, this group had higher plateau pressure and more excessive spontaneous breathing effort, resulting in the highest transpulmonary pressure and the highest driving pressure. Although no improvements in lung aeration were observed, muscle paralysis with severe lung injury resulted in better oxygenation, more even tidal ventilation, and less histological lung injury. CONCLUSIONS: In animals with mild lung injury, spontaneous breathing was beneficial to lung recruitment; however, in animals with severe lung injury, spontaneous breathing could worsen lung injury, and muscle paralysis might be more protective for injured lungs by preventing injuriously high transpulmonary pressure and high driving pressure.

Adenosine A(2A) receptor antagonists are broad facilitators of antinicotinic neuromuscular blockade monitored either with 2 Hz train-of-four or 50 Hz tetanic stimuli.

1. The 2 Hz train-of-four ratio (TOF(ratio)) is used to monitor the degree of patient curarization. Using a rat phrenic nerve-hemidiaphragm preparation, we showed that antinicotinic agents, such as hexamethonium, d-tubocurarine and pancuronium, but not cisatracurium, decreased contractions produced by physiological nerve activity patterns (50 Hz) more efficiently than those caused by 2 Hz trains. Uncertainty about the usefulness of the TOF(ratio) to control safe recovery from curarization prompted us to investigate the muscarinic and adenosine neuromodulation of tetanic (50 Hz) fade induced by antinicotinic agents at concentrations that cause a 25% reduction in the TOF(ratio) (TOF(fade)). 2. Tetanic fade caused by d-tubocurarine (1.1 µmol/L), pancuronium (3 µmol/L) and hexamethonium (5.47 mmol/L) was attenuated by blocking presynaptic inhibitory muscarinic M(2) and adenosine A(1) receptors with methoctramine (1 µmol/L) and 1,3-dipropyl-8-cyclopentylxanthine (2.5 nmol/L), respectively. These compounds enhanced rather than decreased tetanic fade induced by cisatracurium (2.2 µmol/L), but they consistently attenuated cisatracurium-induced TOF(fade). The effect of the M(1) receptor antagonist pirenzepine (10 nmol/L) on fade produced by antinicotinic agents at 50 Hz was opposite to that observed with TOF stimulation. Blockade of adenosine A(2A) receptors with ZM 241385 (10 nmol/L) attenuated TOF(fade) caused by all antinicotinic drugs tested, with the exception of the 'pure' presynaptic nicotinic antagonist hexamethonium. ZM 241385 was the only compound tested in this series that facilitated recovery from tetanic fade produced by cisatracurium. 3. The data suggest that distinct antinicotinic relaxants interfere with fine-tuning neuromuscular adaptations to motor nerve stimulation patterns via activation of presynaptic muscarinic and adenosine receptors. These results support the use of A(2A) receptor antagonists together with atropine to facilitate recovery from antinicotinic neuromuscular blockade.

SUGAMADEX: novos horizontes para a reversão do bloqueio neuromuscular / SUGAMMADEX: new horizons for the reversal of neuromuscular blockade

O sugamadex é uma droga nova e revolucionária desenvolvida como antagonista seletivo dos agentes bloqueadores neuromusculares (ABNM) esteroides (rocurônio > vecurônio ¼ pancurônio). O medicamento é uma y-ciclodextrina modificada e hidrossolúvel que forma um composto estável com o ABNM na razão de 1:1. Ele se liga ao ABNM livre no plasma, criando um gradiente de concentração que desloca o ABNM dos receptores nicotínicos na junção neuromuscular, levando à reversão completa e duradoura do BNM. O sugamadex não se liga às proteínas ou a qualquer outro receptor no organismo, o que lhe confere ótimo perfil de tolerância. O sugamadex pode ser usado na reversão do BNM profundo, promovendo recuperação mais rápida em relação à succinilcolina. Seu emprego pode diminuir a necessidade de monitorização do BNM, a incidência de bloqueio residual e ainda evitar os efeitos adversos causados pelos anticolinesterásicos e anticolinérgicos. Entretanto, também há limitações em relação à utilização 00 sugamadex. Ele impede o uso dos AB- NMs esteroides durante 24 horas, caso seja necessário novo BNM, e pode aumentar o risco do emprego desnecessário e indiscriminado dos ABNMs. Além disso, faltam dados da sua utilização em alguns grupos populacionais e de seu uso em larga escala. Por fim, deve-se considerar também o fator econômico, visto que se trata de uma droga nova e de valor ainda elevado no mercado...

Sugammadex is a novel and unique compaund designed as a selective antaganist ot steroidal neuromuscular blaeking agents (NMBA) (rocuronium>vecuronium¼pancuronium). The drug is a modified water-saluble y-cyclodextrin that forms a stable complex at a 1:1 ratio with the NMBA. It combines with the NMBA creating a concentration gradient favoring the movement ot the NMBA from the nicotine receptors ot the neuromuscular junction leading to the complete and lasting reversal af the neuromuscular blockade (NMB). Sugamadex does not bind to plasma proteins or any other receptors system in the body what provides him a great tolerance profile. Sugamadex can be used in the reversal af deep neuromuscular blockade with a faster recovery time in relation to succinylcholine. Its use can diminish the necessity af monitoring af the NMB, the incidence ot residual blockade and still prevent the adverse effects caused by the antiecholinesterase and anticholinergic drugs. However, there are limitatians regarding the use af Sugammadex. It hinders the use ot the steroidal NMBA during 24 hours if a new NMB must be restablished and it can increase the risk ot unnecessary and indiscriminate use af the NMBA. Mareaver, there is a laek ot data regarding the its use in some population groups and in large scale. Final/y, the economic factor must be also considered, since it is a new drug with a still raised value in market...

Presynaptic M1, M2, and A1 receptors play roles in tetanic fade induced by pancuronium or cisatracurium.

PURPOSE: We investigated whether presynaptic facilitatory M1 and/or inhibitory M2 muscarinic receptors contributed to pancuronium- and cisatracurium-induced tetanic fade. METHODS: Phrenic nerve-diaphragm muscle preparations of rats were indirectly stimulated with tetanic frequency (75 +/- 3.3 Hz; mean +/- SD). Doses of pancuronium, cisatracurium, hexamethonium, and d-tubocurarine for producing approximately 25% fade were determined. The effects of pirenzepine and methoctramine, blockers of presynaptic M1 and M2 receptors, respectively, on the tetanic fade were investigated. RESULTS: The concentrations required for approximately 25% fade were 413 microM for hexamethonium (26.8 +/- 2.4% 4% fade), 55 nM for d-tubocurarine (28.7 +/- 2.55% fade), 0.32 microM for pancuronium (25.4 +/- 2.2% fade), and 0.32 microM for cisatracurium (24.7 +/- 0.8% fade). Pirenzepine or methoctramine alone did not produce the fade. Methoctramine, 1 microM, attenuated the fade induced by hexamethonium (to 16.0 +/- 2.5% fade), d-tubocurarine (to 6.0 +/- 1.6 fade), pancuronium (to 8.0 +/- 4.0% fade), and cisatracurium (to 11.0 +/- 3.3% fade). 10 nM pirenzepine attenuated only the fades produced by pancuronium (to 5.0 +/- 0.11% fade) and cisatracurium (to 13.3 +/- 5.3% fade). Cisatracurium (0.32 microM) showed antiacetylcholinesterase activity (in plasma, 14.2 +/- 1.6%; 6%; in erythrocyt 17.2 +/- 2.66%) similar to that of pancuronium (0.32 microM). The selective A1 receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 2.5 nM), also attenuated the fades induced by pancuronium and cisatracurium. CONCLUSION: The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine.

Anestesia inalatória ou anestesia balanceada em suínos / Inhalation anesthesia or balanced anesthesia in swine

Introdução: O suíno é utilizado como modelo animal em cirurgias experimentais. Objetivos: Visando determinar possíveis alterações nos parâmetros fisiológicos, determinados pela anestesia inalatória e pela anestesia balanceada em pacientes submetidos a toracoscopia, foram utilizados 14 animais entre 15 e 20 Kg, divididos em grupo I (anestesia inalatória) e grupo II (anestesia balanceada). Métodos: Todos os suínos receberam como medicação pré-anestésica, atropina e midazolam. No grupo I (anestesia inalatória), a anestesia geral foi induzida com tiopental sódico e a manutenção realizada com oxigênio em fluxo constante e isoflurano. No grupo II (anestesia balanceada), a anestesia foi induzida por uma associação de fentanil e midazolan, seguidos de tiopental sódico e pancurônio, e submetidos à ventilação mecânica. Além do anestésico inalatório esse grupo recebeu a administração contínua de fentanil e pancurônio a cada 20 minutos. Para comparar os grupos, as variáveis cardiocirculatórias, respiratórias e temperatura foram mensuradas. Resultados: A PaO2 do grupo II, em T0 apresentou uma redução significativa quando comparada ao grupo I, de 415,43 ± 47,35 para 332,06 ± 55,81 mmHg, que pode ser causada pela apnéia após o uso do pancurônio. A PaCO2 do grupo II apresentou uma redução significativa em todos os tempos. Os valores médios dos 04 tempos em mmHg foram no grupo I de 35,33 ± 8,67 e do grupo II de 24,20 ± 10,98, justificada pelo menor metabolismo e menor produção de CO2 com o uso do pancurônio associado aos efeitos da ventilação artificial. Conclusão: O dado sugeri que o uso de bloqueadores neuromusculares associado à ventilação artificial pode reduzir a PaCO2 em cirurgias torácicas em suínos.

Background: Swine have been used as animal models in experimental surgeries. In order to determine possible alterations in the physiological parameters caused by inhalation anesthesia and balanced anesthesia in swine undergoing lateral thoracoscopy, 14 animals weighing 15 to 20 kg were used. The animals were divided into two groups, group I (inhalation anesthesia) and group II (balanced anesthesia). Methods: Both groups received preanesthetic medication (atropine sulphate and midazolam). In group I, anesthesia was induced by the administration of thiopental sodium. Anesthesia was maintained by administering oxygen and isoflurane. In group II, anesthesia was induced by an association between fentanyl and midazolam, followed by thiopental sodium and pancuronium. Then the animals were mechanically ventilated. Anesthesia was maintained with isoflurane and continuous administration of fentanyl and pancuronium every 20 minutes. Cardiocirculatory variables, respiratory and body temperature were measured every 15 minutes during 60 minutes of anesthesia. Results: PaO2 (in mmHg) of group II at T0 presented a significant reduction from 415.43 ± 47.35 to 332.06 ± 55.81, which may be explained by the occurrence of apnea caused by the use of pancuronium. PaCO2 of group II presented a significant reduction at all times measured. Mean values (in mmHg) of the four times in group I and group II were 35.33 ± 8.67 and 24.20 ± 10.98, respectively, which may be explained by reduced muscle metabolism and decreased CO2 production due to the useof pancuronium associated with the effect of artificial ventilation. Conclusion: We concluded that the use of neuromuscular blockers associated with artificial ventilation may reduce the concentrations of PaCO2 in thoracic surgeries in swine.

Influence of stimulus frequency on blockade induced by pancuronium and rocuronium: study on rats phrenic nerve-diaphragm preparation / Influência da freqüência de estímulos no bloqueio neuromuscular produzido pelo pancurônio e rocurônio. Estudo em preparação nervo frênico-diafragma de ratos

PURPOSE: To evaluate the influence of two stimulation frequencies on the installation of neuromuscular blockade produced by pancuronium and rocuronium on the rat diaphragm. METHODS: Diaphragms were submitted to an indirect frequency stimulation of 0.1 and 1Hz (Groups I and II, respectively). Subgroups were formed (n=5) according to the neuromuscular blocker employed (pancuronium-2µg/ml and rocuronium-4µg/ml). The twitch height depression was evaluated at 5, 15 and 30 minutes after adding the neuromuscular blocker. RESULTS: The decrease in twitch height was greater (p<0.01) with a frequency of 1Hz at all time periods studied both in preparations that are blocked with pancuronium and in those that are blocked with rocuronium. CONCLUSION: The frequency of stimulation interferes significantly with the installation of neuromuscular blockade produced by pancuronium and rocuronium, since the reduction in amplitude of the rat diaphragm response was greater for 1Hz frequencies, at all periods studied(AU)

OBJETIVO: Avaliar a influência de duas freqüências de estimulação na instalação do bloqueio neuromuscular induzido por pancurônio e rocurônio em diafragma de ratos. MÉTODOS: Os diafragmas foram submetidos a uma freqüência de estimulação indireta de 0.1 e 1Hz (Grupos I e II, respectivamente). Os animais foram divididos em subgrupos (n=5) de acordo com o bloqueador neuromuscular a ser utilizado (pancurônio-2µg/mL e rocurônio-4µg/mL). A amplitude das respostas musculares foi avaliada 5, 15 e 30 minutos após a adição do bloqueador neuromuscular à preparação. RESULTS: A redução na intensidade da contração foi maior (p<0.01) com a freqüência de 1Hz em todos os tempos avaliados para as preparações contendo pancurônio e rocurônio CONCLUSION: A freqüência de estímulo interfere significativamente na instalação do bloquio neuromuscular produzido por pancurônio e rocurônio, uma vez que a redução na amplitude da resposta do diafragma foi maior para a freqüência de 1Hz em todos os períodos estudados(AU)

Influence of stimulus frequency on blockade induced by pancuronium and rocuronium: study on rats phrenic nerve-diaphragm preparation

PURPOSE: To evaluate the influence of two stimulation frequencies on the installation of neuromuscular blockade produced by pancuronium and rocuronium on the rat diaphragm. METHODS: Diaphragms were submitted to an indirect frequency stimulation of 0.1 and 1Hz (Groups I and II, respectively). Subgroups were formed (n=5) according to the neuromuscular blocker employed (pancuronium-2µg/ml and rocuronium-4µg/ml). The twitch height depression was evaluated at 5, 15 and 30 minutes after adding the neuromuscular blocker. RESULTS: The decrease in twitch height was greater (p<0.01) with a frequency of 1Hz at all time periods studied both in preparations that are blocked with pancuronium and in those that are blocked with rocuronium. CONCLUSION: The frequency of stimulation interferes significantly with the installation of neuromuscular blockade produced by pancuronium and rocuronium, since the reduction in amplitude of the rat diaphragm response was greater for 1Hz frequencies, at all periods studied.

OBJETIVO: Avaliar a influência de duas freqüências de estimulação na instalação do bloqueio neuromuscular induzido por pancurônio e rocurônio em diafragma de ratos. MÉTODOS: Os diafragmas foram submetidos a uma freqüência de estimulação indireta de 0.1 e 1Hz (Grupos I e II, respectivamente). Os animais foram divididos em subgrupos (n=5) de acordo com o bloqueador neuromuscular a ser utilizado (pancurônio-2µg/mL e rocurônio-4µg/mL). A amplitude das respostas musculares foi avaliada 5, 15 e 30 minutos após a adição do bloqueador neuromuscular à preparação. RESULTS: A redução na intensidade da contração foi maior (p<0.01) com a freqüência de 1Hz em todos os tempos avaliados para as preparações contendo pancurônio e rocurônio CONCLUSION: A freqüência de estímulo interfere significativamente na instalação do bloquio neuromuscular produzido por pancurônio e rocurônio, uma vez que a redução na amplitude da resposta do diafragma foi maior para a freqüência de 1Hz em todos os períodos estudados.

Influence of stimulus frequency on blockade induced by pancuronium and rocuronium: study on rats phrenic nerve-diaphragm preparation.

PURPOSE: To evaluate the influence of two stimulation frequencies on the installation of neuromuscular blockade produced by pancuronium and rocuronium on the rat diaphragm. METHODS: Diaphragms were submitted to an indirect frequency stimulation of 0.1 and 1 Hz (Groups I and II, respectively). Subgroups were formed (n=5) according to the neuromuscular blocker employed (pancuronium-2 microg/ml and rocuronium-4 microg/ml). The twitch height depression was evaluated at 5, 15 and 30 minutes after adding the neuromuscular blocker. RESULTS: The decrease in twitch height was greater (p<0.01) with a frequency of 1 Hz at all time periods studied both in preparations that are blocked with pancuronium and in those that are blocked with rocuronium. CONCLUSION: The frequency of stimulation interferes significantly with the installation of neuromuscular blockade produced by pancuronium and rocuronium, since the reduction in amplitude of the rat diaphragm response was greater for 1 Hz frequencies, at all periods studied.

Incidencia de bloqueo neuromuscular residual al ingreso en la unidad de recuperación postanestésica / Incidence of residual neuromuscular block when entering post-anesthesia recovery unit

Introducción: Se denomina bloqueo neuromuscular residual a la condición clínica determinada por la persistencia de los efectos farmacológicos de los bloqueantes neuromusculares no despolarizantes. El objetivo de este estudio fue cuantificar la incidencia de bloqueo neuromuscular residual al ingreso en la unidad de recuperación postanestésica (URPA) tras la administración de atracurio o pancuronio durante el acto anestésico. Pacientes y métodos: Diseño prospectivo observacional, con un muestreo no probabilístico, consecutivo intencional. Se definió bloqueo neuromuscular residual como la presencia de una relación T4/T1 < 0.9 medida en el aductor del pulgar por acelerometría (TOF-GUARD-Organon Teknika). Se estudiaron 140 pacientes sometidos a anestesia general para cirugía programada que habían recibido como BNMND atracurio (n = 125) o pancuronio (n = 15). Resultados: Considerando la definición tradicional (T4/T1 < 0.7), el 13 por ciento de los pacientes (18 de 140) presentó bloqueo neuromuscular residual. Considerando la definición actual (T4/T1 < 0,9), el 49 por ciento de los pacientes (69/140) presentó bloqueo neuromuscular residual. Para ambas definiciones, la incidencia de bloqueo neuromuscular residual al ingreso en la URPA fue significativamente mayor para el pancuronio (53 y 93 por ciento) que para el atracurio (8 y 44 por ciento), respectivamente (p < 0.00005). Se había administrado en quirófano antiacetilcolinesterásicos al 47 por ciento del total de los pacientes observados (66 de 140): 42 por ciento de los pacientes del grupo atracurio (53 de 125) y 87 por ciento del grupo pancuronio (13 de 15). De los 74 pacientes que no recibieron antiacetilcolinesterásicos, 34 (46 por ciento del subgrupo) presentaron bloqueo neuromuscular residual, en tanto que entre los 66 pacientes que sí recibieron la reversión del bloqueo neuromuscular, 35 (53 por ciento del subgrupo) también presentaron bloqueo neuromuscular residual. Estos niveles de incidencia entre los que

Incidencia de bloqueo neuromuscular residual al ingreso en la unidad de recuperación postanestésica / Incidence of residual neuromuscular block when entering post-anesthesia recovery unit

Introducción: Se denomina bloqueo neuromuscular residual a la condición clínica determinada por la persistencia de los efectos farmacológicos de los bloqueantes neuromusculares no despolarizantes. El objetivo de este estudio fue cuantificar la incidencia de bloqueo neuromuscular residual al ingreso en la unidad de recuperación postanestésica (URPA) tras la administración de atracurio o pancuronio durante el acto anestésico. Pacientes y métodos: Diseño prospectivo observacional, con un muestreo no probabilístico, consecutivo intencional. Se definió bloqueo neuromuscular residual como la presencia de una relación T4/T1 < 0.9 medida en el aductor del pulgar por acelerometría (TOF-GUARD-Organon Teknika). Se estudiaron 140 pacientes sometidos a anestesia general para cirugía programada que habían recibido como BNMND atracurio (n = 125) o pancuronio (n = 15). Resultados: Considerando la definición tradicional (T4/T1 < 0.7), el 13 por ciento de los pacientes (18 de 140) presentó bloqueo neuromuscular residual. Considerando la definición actual (T4/T1 < 0,9), el 49 por ciento de los pacientes (69/140) presentó bloqueo neuromuscular residual. Para ambas definiciones, la incidencia de bloqueo neuromuscular residual al ingreso en la URPA fue significativamente mayor para el pancuronio (53 y 93 por ciento) que para el atracurio (8 y 44 por ciento), respectivamente (p < 0.00005). Se había administrado en quirófano antiacetilcolinesterásicos al 47 por ciento del total de los pacientes observados (66 de 140): 42 por ciento de los pacientes del grupo atracurio (53 de 125) y 87 por ciento del grupo pancuronio (13 de 15). De los 74 pacientes que no recibieron antiacetilcolinesterásicos, 34 (46 por ciento del subgrupo) presentaron bloqueo neuromuscular residual, en tanto que entre los 66 pacientes que sí recibieron la reversión del bloqueo neuromuscular, 35 (53 por ciento del subgrupo) también presentaron bloqueo neuromuscular residual. Estos niveles de incidencia entre los que

Incidencia de bloqueo neuromuscular residual al ingreso en la unidad de recuperación postanestésica / Incidence of residual neuromuscular block when entering post-anesthesia recovery unit

Introducción: Se denomina bloqueo neuromuscular residual a la condición clínica determinada por la persistencia de los efectos farmacológicos de los bloqueantes neuromusculares no despolarizantes. El objetivo de este estudio fue cuantificar la incidencia de bloqueo neuromuscular residual al ingreso en la unidad de recuperación postanestésica (URPA) tras la administración de atracurio o pancuronio durante el acto anestésico. Pacientes y métodos: Diseño prospectivo observacional, con un muestreo no probabilístico, consecutivo intencional. Se definió bloqueo neuromuscular residual como la presencia de una relación T4/T1 < 0.9 medida en el aductor del pulgar por acelerometría (TOF-GUARD-Organon Teknika). Se estudiaron 140 pacientes sometidos a anestesia general para cirugía programada que habían recibido como BNMND atracurio (n = 125) o pancuronio (n = 15). Resultados: Considerando la definición tradicional (T4/T1 < 0.7), el 13 por ciento de los pacientes (18 de 140) presentó bloqueo neuromuscular residual. Considerando la definición actual (T4/T1 < 0,9), el 49 por ciento de los pacientes (69/140) presentó bloqueo neuromuscular residual. Para ambas definiciones, la incidencia de bloqueo neuromuscular residual al ingreso en la URPA fue significativamente mayor para el pancuronio (53 y 93 por ciento) que para el atracurio (8 y 44 por ciento), respectivamente (p < 0.00005). Se había administrado en quirófano antiacetilcolinesterásicos al 47 por ciento del total de los pacientes observados (66 de 140): 42 por ciento de los pacientes del grupo atracurio (53 de 125) y 87 por ciento del grupo pancuronio (13 de 15). De los 74 pacientes que no recibieron antiacetilcolinesterásicos, 34 (46 por ciento del subgrupo) presentaron bloqueo neuromuscular residual, en tanto que entre los 66 pacientes que sí recibieron la reversión del bloqueo neuromuscular, 35 (53 por ciento del subgrupo) también presentaron bloqueo neuromuscular residual. Estos niveles de incidencia entre los que

Similar preoperative hemodynamic response to pancuronium and rocuronium in high-risk cardiac surgical patients.

AIM: Rocuronium may be a good alternative to pancuronium in cardiac surgical patients. We evaluate the hemodynamic response to rocuronium and pancuronium administered to cardiac surgical patients. METHODS: A single-blind, randomized clinical trial was carried out at the National Institute of Cardiology in Mexico. Twenty-two patients older than 18 years, NYHA class III-IV, and scheduled to undergo an elective cardiovascular surgical procedure were enrolled. Patients were randomly allocated to receive an i.v. bolus dose of either pancuronium 100 microg/kg or rocuronium 600 microg/kg. Peripheral arterial (radial) and venous cannulations and insertion of a multi-lumen pulmonary artery flotation catheter through the right internal jugular vein were carried out under local anesthesia. Anesthetic induction with an i.v. bolus dose of fentanyl 700 microg and diazepam 20 mg was performed and thereafter the neuromuscular blocking agent was administered. Ventilation with O2 100% was performed until a TOF < or =5% was observed and tracheal intubation was performed. After intubation, patients were maintained with O2 10 mL/kg administered by means of a pulmonary ventilator at a pressure of 20-25 cm H2O. The basal, pre-laryngoscopy, post-intubation, and pre-operative recording of a set of cardiovascular parameters were obtained. RESULTS: No differences (P>0.05) in the hemodynamic response were observed between pancuronium and rocuronium nor during the different evaluation times in each group. CONCLUSIONS: Rocuronium can be a safe alternative to pancuronium for patients requiring cardiac surgical procedures.

Comienzo bifásico de acción de la succinilcolina / Biphasic onset of succinylcholines action

Introducción: Anteriormente hemos descrito y comprobado los cambios de velocidad durante la instalación del bloqueo neuromuscular producido por el rocuronio. El propósito de la presente investigación es estudiar el período de comienzo de acción de la succinilcolina utilizando los índices diseñados en aquella oportunidad y basados en la relación entre el bloqueo fraccionado y el tiempo de instalación, que permiten determinar su velocidad y rapidez. Material y métodos: Después de su consentimiento, dos grupos iguales de pacientes (n = 20 c/u) sin contraindicación aparente para su empleo fueron intubados directamente con succinilcolina o precurarizados con rapacuronio. Por electromiografía se determinaron los tiempos para alcanzar un bloqueo del 80 por ciento, el efecto final y el máximo bloqueo. Utilizando los índices respectivos se calcularon la rapidez (seg/por ciento) y velocidad (por ciento/seg). Resultados: La precurarización con rapacuronio alargó el tiempo para alcanzar un bloqueo del 80 por ciento y el máximo efecto, disminuyendo este último. La velocidad y rapidez inicial fueron mayores que al final y menores en el grupo precurarizado. Conclusión: Los resultados obtenidos aplicando esta metodología indican que la succinilcolina, lo mismo que el rocuronio y el vecuronio, tiene un tiempo de comienzo bifásico con una fase inicial casi cuatro veces más rápida y veloz que la final. La precurarización con rapacuronio alarga el tiempo parcial y total de instalación del efecto de la succinilcolina; no modifica su carácter bifásico pero vuelve exageradamente lenta su fase final. Se comenta la posibilidad de hacer uso de la brevedad inicial de su acción para realizar una intubación traqueal precoz, ya que con el efecto periférico mostrado la relajación laríngea debe ser completa. Se hacen especulaciones sobre las supuestas causas responsables de esta peculiar manera de instalarse el bloqueo neuromuscular. (AU)

Extubación postoperatoria inmediata (ultra fast-track) en cirugía coronaria sin circulación extracorpórea / Immediate postoperative extubation (ultra fast-track) after coronary surgery without cardiopulmonary bypass

Antecedentes: La ventilación en el postoperatorio es una práctica rutinaria en los pacientes sometidos a cirugía de revascularización miocárdica. En los últimos años, junto con la incorporación de la cirugía de revascularización miocárdica (CRM) sin circulación extracorpórea (sin CEC), hemos adoptado como objetivo la extubación en el quirófano, es decir, al finalizar la cirugía. Objetivos: Extubación inmediata en quirófano (ultra fast-track (UFT)) utilizando anestesia general; secundariamente, analizar la curva de aprendizaje durante el período de estudio. Lugar de aplicación: Institución privada. Diseño: Estudio retrospectivo, casuístico, observacional. Población: 209 pacientes sometidos a CRM sin CEC durante el período que va de julio de 2002 a abril de 2003. Se incluyeron todos los pacientes en forma consecutiva, sin criterios de exclusión. Método: Anestesia general balanceada intravenosa e inhalatoria. Se evaluaron las características preoperatorias, las condiciones necesarias para la extubación, el número de pacientes extubados y el de no extubados, y sus causas. Los pacientes fueron divididos en dos grupos: G02 = 2002 (110 pacientes) y G03 = 2003 (99 pacientes). Resultados: De las condiciones preoperatorias, hubo diferencia estadísticamente significativa entre G02 y G03, con mayor severidad para este último en tabaquismo (p = 0.007), clase funcional III-IV (p = 0.009) y función ventricular moderada-severa (p = 0.021). Hubo tendencia, pero sin significación estadística, también hacia G03 en cirugía no electiva, balón de contrapulsación intra aórtico, diabetes y reoperación. Se extubó el 81 por ciento de los pacientes en el quirófano, un 71 por ciento del período 02 y 92 por ciento del periodo 03. Los no extubados obedecieron a: falta de conciencia 13 (11/2), inestabilidad hemodinámica 13 (7/6), cambios eléctricos 3 (3/0), sangrado 3 (3/0), respiratorias 3 (3/0) y conversión a CEC 5 (5/0). Las complicaciones fueron: respiratorias: 4.8 por ciento, distress: 0.9 por ciento, IAM 2.9 por ciento y mortalidad 3.8 por ciento. La estadía en UTI fue de 1 día y la estadía total 5 días. Conclusión: Es posible realizar la extubación en quirófano para cirugía de revascularización miocárdica sin circulación extracorpórea utilizando anestesia general balanceada, ajustándola a la técnica de UFT. También la curva de aprendizaje ha influido favorablemente en los resultados. (AU)

Comienzo bifásico de acción de la succinilcolina / Biphasic onset of succinylcholine's action

Introducción: Anteriormente hemos descrito y comprobado los cambios de velocidad durante la instalación del bloqueo neuromuscular producido por el rocuronio. El propósito de la presente investigación es estudiar el período de comienzo de acción de la succinilcolina utilizando los índices diseñados en aquella oportunidad y basados en la relación entre el bloqueo fraccionado y el tiempo de instalación, que permiten determinar su velocidad y rapidez. Material y métodos: Después de su consentimiento, dos grupos iguales de pacientes (n = 20 c/u) sin contraindicación aparente para su empleo fueron intubados directamente con succinilcolina o precurarizados con rapacuronio. Por electromiografía se determinaron los tiempos para alcanzar un bloqueo del 80 por ciento, el efecto final y el máximo bloqueo. Utilizando los índices respectivos se calcularon la rapidez (seg/por ciento) y velocidad (por ciento/seg). Resultados: La precurarización con rapacuronio alargó el tiempo para alcanzar un bloqueo del 80 por ciento y el máximo efecto, disminuyendo este último. La velocidad y rapidez inicial fueron mayores que al final y menores en el grupo precurarizado. Conclusión: Los resultados obtenidos aplicando esta metodología indican que la succinilcolina, lo mismo que el rocuronio y el vecuronio, tiene un tiempo de comienzo bifásico con una fase inicial casi cuatro veces más rápida y veloz que la final. La precurarización con rapacuronio alarga el tiempo parcial y total de instalación del efecto de la succinilcolina; no modifica su carácter bifásico pero vuelve exageradamente lenta su fase final. Se comenta la posibilidad de hacer uso de la brevedad inicial de su acción para realizar una intubación traqueal precoz, ya que con el efecto periférico mostrado la relajación laríngea debe ser completa. Se hacen especulaciones sobre las supuestas causas responsables de esta peculiar manera de instalarse el bloqueo neuromuscular.