The effects of intra-cerebroventricular administered rocuronium on the central nervous system of rats and determination of its epileptic seizure-inducing dose / Efeitos da administração intracerebroventricular de rocurônio sobre o sistema nervoso central de ratos e determinação da dose indutora de crise epiléptica

Abstract Background: The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. Methods: A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n = 6), Group 1/10 (n = 6), and Group 1/100 (n = 6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. Results: The rocuronium bromide seizure threshold value was found to be 0.056 ± 0.009 µmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286 µmoL/kg-1. A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. Conclusions: This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures.

Resumo Justificativa: O objetivo deste estudo foi investigar os efeitos do brometo de rocurônio administrado intracerebroventricularmente sobre o sistema nervoso central, determinar a dose do limiar convulsivo de rocurônio em ratos e investigar os efeitos de rocurônio no sistema nervoso central em diluições de 1/5, 1/10 e 1/100 da dose do limiar convulsivo determinada. Métodos: Uma cânula permanente foi colocada no ventrículo lateral do cérebro dos animais. O estudo foi projetado em duas fases. Na primeira, a dose do limiar convulsivo do brometo de rocurônio foi determinada. Na segunda, o Grupo R 1/5 (n = 6), o Grupo 1/10 (n = 6) e Grupo 1/100 (n = 6) foram formados com doses de 1/5, 1/10 e 1/100, respectivamente, da dose do limiar convulsivo de brometo de rocurônio obtida. Resultados: Descobrimos que o valor do limiar convulsivo de brometo de rocurônio é 0,056 ± 0,009 µmoL. O limiar convulsivo, como uma função do peso corporal dos ratos, foi calculado como 0,286 µmoL/kg-1. Uma dose de 1/5 da dose do limiar convulsivo causou principalmente abertura postural dos membros e tremores em todo o corpo, enquanto uma dose de 1/10 da dose do limiar convulsivo causou agitação e tremores. Uma dose de 1/100 da dose do limiar convulsivo foi associada à diminuição da atividade locomotora. Conclusões: Este estudo mostrou que o brometo de rocurônio tem efeitos deletérios relacionados com a dose sobre o sistema nervoso central e pode produzir efeitos excitatórios dependentes da dose e convulsões.

Effects of conventional vs high-dose rocuronium on the QTc interval during anesthesia induction and intubation in patients undergoing coronary artery surgery: a randomized, double-blind, parallel trial

Myocardial ischemia, as well as the induction agents used in anesthesia, may cause corrected QT interval (QTc) prolongation. The objective of this randomized, double-blind trial was to determine the effects of high- vs conventional-dose bolus rocuronium on QTc duration and the incidence of dysrhythmias following anesthesia induction and intubation. Fifty patients about to undergo coronary artery surgery were randomly allocated to receive conventional-dose (0.6 mg/kg, group C, n=25) or high-dose (1.2 mg/kg, group H, n=25) rocuronium after induction with etomidate and fentanyl. QTc, heart rate, and mean arterial pressure were recorded before induction (T0), after induction (T1), after rocuronium (just before laryngoscopy; T2), 2 min after intubation (T3), and 5 min after intubation (T4). The occurrence of dysrhythmias was recorded. In both groups, QTc was significantly longer at T3 than at baseline [475 vs 429 ms in group C (P=0.001), and 459 vs 434 ms in group H (P=0.005)]. The incidence of dysrhythmias in group C (28%) and in group H (24%) was similar. The QTc after high-dose rocuronium was not significantly longer than after conventional-dose rocuronium in patients about to undergo coronary artery surgery who were induced with etomidate and fentanyl. In both groups, compared with baseline, QTc was most prolonged at 2 min after intubation, suggesting that QTc prolongation may be due to the nociceptive stimulus of intubation.

Rocuronio en obesos: ¿debe dosificarse por peso real o por peso ideal? / Rocuronium in obese: should be dosed by actual weight or ideal weight?

El aumento universal en la prevalencia de obesidad ha causado que los anestesiólogos se vean frecuentemente enfrentados a anestesiar pacientes obesos. Pese a esto aún existen dudas respecto a cómo dosificar las drogas en estos pacientes. La literatura recomienda dosificar el rocuronio en obesos en base al peso ideal (IBW, iniciales del inglés Ideal Body Weight) pero esta sugerencia está basada más bien en la prudencia que en la evidencia. Se decidió explorar con análisis de sobrevida (análisis tiempo-evento), la duración del rocuronio en obesos al ser dosificado por peso ideal (IBW) y por peso real (TBW, iniciales del inglés de peso corporal total). Al administrar el rocuronio en base al peso real (TBW) se observó una prolongación en su duración de acción con un acortamiento de su latencia en relación con la dosificación en base al peso ideal (IBW). Hubo una marcada prolongación de la duración de acción y el índice de recuperación tanto al dosificar por peso real como peso ideal. Debido a esta sensibilidad aumentada al rocuronio en pacientes obesos recomendamos dosificarlo en base al peso ideal, excepto si se necesita intubar rápidamente...

The universal increase in prevalence of obesity has caused that anesthesiologist are frequently encountered with anesthetizing obese patients. There stills exists doubt on how to dosage drugs to these patients. Literature recommends dosing rocuronium in the obese based on ideal weight (IBW), being this suggestion based more on prudence than on evidence. Randomized control trial was designed for obese patients scheduled for bariatric surgery to study the pharmacodynamics of rocuronium in this population. Patients were randomly assigned into two groups: rocuronium dosage 0.6 mg•kg-1 for real weight (TBW) or rocuronium dosage of 0.6mg•kg-1 for ideal weight (IBW). Ideal weight was calculated according to Lemmens formula. The reference group was the dosage based on IBW. Previous calibration, evaluating the first twitch of train-of-four (T1), we registered onset time, clinical duration, recovery index, level of muscle relaxation to which the first reinforcement was administered and clinical duration of rocuronium reinforcement. A total of 100 patients were part of the study: 54 in group TBW and 46 in group IBW. When administering rocuronium based on real weight (TBW) a prolongation in clinical duration was found: Medium (IQR*); 79.5 (67 - 105) minutes versus 44.5(33 - 63.5 minutes) in the IBW group (p < 0.001) with a decrease in latency in the TBW group 120 (90-150secs.) versus the IBW group 180 (120 - 270 secs.) (p < 0.001). There were no differences in the recovery index between both levels of dosing. There was a marked prolongation of both clinical duration and recovery index in both groups, as supported in some literature. Based on the evidence, we recommend to dose rocuronium in obese patients based on ideal weight, with the exception of cases were quick intubation is required...

Uso del sugammadex para la reversión del bloqueo neuromuscular de larga duración con rocuronio: bolos vs infusión continua / Use of sugammadex for reversal of neuromuscular blockade of long duration with rocuronium: bolus vs continuous infusion

Introducción: El bloqueo neuromuscular residual es causa de complicaciones postoperatorias. Objetivo: Identificar la eficacia del sugammadex para revertir el bloqueo neuromuscular con rocuronio, en procederes de larga duración, cuando éste se administra en forma de bolos versus infusión continua. Método: Se realizó un estudio descriptivo exploratorio en una serie de 10 pacientes para tratamiento quirúrgico de más de dos horas, de forma electiva con anestesia general en el Hospital General Universitario de Alicante, España, entre los meses de noviembre y diciembre del 2010. La inducción y el mantenimiento del bloqueo neuromuscular se realizaron mediante bolos (B) o infusión continua (IC), quedando los pacientes divididos en dos grupos. Se compararon los grupos según el tiempo de recuperación mediante la prueba de U-Mann Whitney. Resultados: Existió homogeneidad entre los grupos en cuanto a edad, peso corporal y estado físico según la ASA II – III. La mediana del tiempo quirúrgico para el grupo B fue de 3:55 horas versus 4:20 horas en el grupo de infusión continua. Para alcanzar el cociente T4/T1 > 90%, la mediana del tiempo de recuperación fue de 75.0 minutos para el grupo IC, mientras en el grupo que se utilizaron bolos se observó un tiempo de 140.0 minutos; las diferencias entre ambos grupos resultaron ser estadísticamente significativas (p = 0,008). Conclusiones: La reversión del bloqueo neuromuscular de larga duración inducido por rocuronio fue más rápida cuando el sugammadex se administró en infusión continua en nuestro grupo de pacientes.

Comparison of the variability of the onset and recovery from neuromuscular blockade with cisatracurium versus rocuronium in elderly patients under total intravenous anesthesia

This study was designed to compare the variability of the onset and offset of the effect of two neuromuscular blocking drugs with different elimination pathways in adult and elderly patients during total intravenous anesthesia (TIVA). After Ethics Committee approval and patients’ informed consent, the drugs were compared in 40 adult and 40 elderly patients scheduled for elective surgery under TIVA with tracheal intubation who were randomized to receive a single bolus dose of 0.15 mg/kg cisatracurium or 0.9 mg/kg rocuronium. The time of onset of maximum depression, duration of action, and recovery index time were measured and recorded for each patient and variability is reported as means ± standard deviation. Time of onset was significantly shorter for rocuronium than cisatracurium for the adult and elderly groups (P = 0.000), but the variability of cisatracurium was significantly greater compared with rocuronium for the same age groups (93.25 vs 37.01 s in the adult group and 64.56 vs 33.75 s in the elderly group; P = 0.000). The duration of the effect in the elderly group receiving rocuronium was significantly longer than in the elderly group receiving cisatracurium, and the variability of the duration was significantly greater in the rocuronium group than in the cisatracurium group. Mean time of recovery was significantly longer for the elderly group receiving rocuronium than for the elderly group receiving cisatracurium (P = 0.022), and variability was also greater (P = 0.002). Both drugs favored good intubating conditions. In conclusion, cisatracurium showed less variability in these parameters than rocuronium, especially in the elderly, a fact that may be of particular clinical interest.

Pretreatment with lignocaine: effects on pain of rocuronium injection and withdrawal movements of the arm

To assess the frequency of pain and withdrawal movements after injection of rocuronium and effects of pre-treatment with lignocaine. Double blind study. This study was of six months duration and was carried out from March 2004 to September 2004. Combined Military Hospital Kharian. One hundred and twenty unpremedicated patients with ASA grade I and II, aged between 18-60 years and of both sexes were enrolled in the study. Patients were randomly divided into two groups of 60 patients each. After induction of anaesthesia with thiopentone, patients in group A received 3 ml of lignocaine plain while those in group B, received 3 ml of normal saline as pre-treatment before injection of rocuronium. Their effects on pain on injection and withdrawal movements of the arm were studied. Out of total of 120 patients, only 17 patients [14%] developed withdrawal movements of the arm or wrist. In Group A, who received lignocaine plain before rocuronium injection, only 3 patients out of 60 patients had withdrawal movements while in Group B, who received normal saline as pre-treatment fourteen out of 60 patients developed withdrawal movements of the arm or wrist. Only one patient belonging to Group B experienced pain. Pretreatment with lignocaine plain greatly reduces the chances of withdrawal movements and pain on injection of rocuronium

Influência de anestésicos locais sobre o bloqueio neuromuscular produzido pelo rocurônio: ação da lidocaína e da mistura enantiomérica em excesso de 50 por cento de bupivacaína na junção neuromuscular / Influencia de anestésicos locales sobre el bloqueo neuromuscular producido por el rocuronio: acción de la lidocaína y de la mezcla enantiomérica en exceso de 50 por ciento de bupivacaína en la junción neuromuscular / Influence of local anesthetics on the neuromuscular blockade produced by rocuronium: effects of lidocaine and 50 percent enantiomeric excess bupivacaine on the neuromuscular junction

Justificativa e objetivos: Os efeitos dos anestésicos locais (AL) na transmissão neuromuscular e sua influência no bloqueio neuromuscular produzido por bloqueadores neuromusculares competitivos são ainda alvo de pouca investigação. O objetivo do estudo foi avaliar in vitro os efeitos da lidocaína e da mistura enantiomérica em excesso de 50 por cento de bupivacaína (S75-R25) no bloqueio neuromuscular...

Background and objetives: 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 percent enantiomeric excess bupivacaine (S75-R25) on the neuromuscular blockade produced by rocuronium...

Justificativa y objetivos: Los efectos de los anestésicos locales (AL), en la transmisión neuromuscular y su influencia en el bloqueo neuromuscular producido por bloqueadores neuromusculares competitivos, todavía no se ha investigado lo suficiente. El objetivo del estudio, fue evaluar in vitro los efectos de la lidocaína y de la mezcla enantiomérica en exceso de 50 por ciento de bupivacaína (S75-R25) en el bloqueo neuromuscular...

The use of rocuronium in giant Amazon turtle Podocnemis expansa (Schweigger, 1812) (Testudines, Podocnemididae) / Uso do rocurônio em tartaruga da Amazônia Podocnemis expansa (Schweigger, 1812) (Testudines, Podocnemididae)

PURPOSE: To determine whether rocuronium would provide safe, short-term immobilization in Podocnemis expansa. METHODS: Twenty P. expansa, weighing on average 1.59 ± 0.28 kg, were subjected to two protocols: G1 0.25 mg/kg IM of rocuronium and 0.07 mg/kg IM of neostigmine, while G2 received 0.50 mg/kg IM of rocuronium and 0.07 mg/kg IM of neostigmine. The drugs were applied, respectively, in the left and right thoracic members. Assessments were made of the anesthetic parameters of respiratory frequency, heartbeat, righting reflex, cloacal relaxation, palpebral and pupilar reflexes, easy handling, muscle relaxation, locomotion, response to pain stimuli in the right thoracic members, pelvic members and tail, ambient humidity and temperature. RESULTS: They were not found statistical differences between the dosages for the majority of the assessments. G1 was as efficient as G2. A consistent neuromuscular blockade effect was recorded 12 ± 4.21 minutes in G1 and G2. All the animals were recovered in 150 minutes. CONCLUSIONS: Administration of rocuronium at dose of 0.25 to 0.5 mg/kg IM is a safe and effective adjunct to clinical proceedings or pre-anesthetics in P. expansa. Because rocuronium does not provide any analgesic or sedative effects, the duration of neuromuscular blockade without anesthesia should be minimized to avoid undue stress.

OBJETIVO: Determinar se o rocurônio promove imobilização segura e de curta duração em Podocnemis expansa. MÉTODOS: Vinte P. expansa com média de peso 1,59 ± 0,28 kg, foram submetidas a dois protocolos: G1 recebeu rocurônio 0,25 mg/kg IM e neostigmina 0,07 mg/kg IM enquanto G2 rocurônio 0,50 mg/kg IM e neostigmina 0,07 mg/kg IM, aplicados no membro torácico esquerdo e direito, respectivamente. Observaram-se os parâmetros anestésicos: freqüência respiratória e cardíaca, reflexo de endireitamento, relaxamento do esfíncter da cloaca, reflexo palpebral e pupilar, facilidade de manipulação, relaxamento muscular, locomoção, resposta aos estímulos dolorosos no membro torácico direito, nos membros pelvinos e na cauda, temperatura e umidade ambiental. RESULTADOS: Não foram encontradas diferenças estatísticas entre as doses para a maioria dos parâmetros e o G1 foi tão eficiente quanto o G2. Um bloqueio neuromuscular consistente foi observado aos 12 ± 4,21 minutos tanto no G1 como no G2. A recuperação de todos os animais ocorreu em até 150 minutos. CONCLUSÕES: Administração de rocurônio nas doses 0,25 e 0,50 mg/kg IM é segura e efetiva para os procedimentos clínicos ou pré-anestésicos em P. expansa. Como o rocurônio não produz efeitos sedativos ou analgésicos, a duração do bloqueio neuromuscular sem anestesia deverá ser minimizado para evitar estresse.

Corrección de la curva dosis-respuesta acumulativa de atracurio y rocuronio / Correction of the cumulative dose-response to atracurium and rocurionium

Introducción: La curva dosis-respuesta acumulativa es un método práctico para evaluar las dosis efectivas de atracurio y rocuronio. Debido a sus características farmacocinéticas, los resultados de dicha curva subestiman la potencia de ambos fármacos en comparación con los que resultan de la administración de dosis únicas. El objetivo de la presente investigación es corregir aquella técnica y hacer las dos estadísticamente equivalentes. Material y métodos: En dos grupos de pacientes electivos se utilizó atracurio o rocuronio para calcular sus potencias por el método de las dosis únicas (n = 45 c/u) o acumulativas (n = 11 c/u). El efecto de cada dosis se determinó por electromiografía, y después de sus transformaciones logaritmo-probits, considerando gamma como la relación probit/log, se obtuvieron las DE 50 y 90 resolviendo la ecuación de Hill para cada sujeto. La técnica acumulativa se corrigió al utilizar las cifras actuales para las dosis y sus efectos, en lugar de los valores acumulativos a partir de la segunda administración. Resultados: Las DE 50 de las técnicas de dosis única, acumulativa y corregida fueron: 172 ± 73, 264 ± 52 y 162 ± 81 mcg/kg respectivamente, cuando se utilizó rocuronio, y 141 ± 61, 193 ± 53 y 141 ± 70 respectivamente, cuando se utilizó atracurio. En el caso de las DE 90' los valores fueron 233 ± 98, 327 ± 65, 254 ± 126 y 222 ± 96, 279 ± 77 y 254 ± 126, en el mismo orden. No se detectaron diferencias significativas entre los métodos de dosis única y corregida, mientras que los valores de las dosis acumulativas fueron significativamente mayores. Discusión y conclusiones: En las condiciones de la presente investigación, una sencilla corrección del método acumulativo reproduce razonable y estadísticamente la potencia del atracurio y del rocuronio evaluada por las dosis únicas.

Introduction: The cumulative dose-response curve is a practical method to evaluate the effective doses of atracurium and rocuronium. When compared with those obtained by single administrations, the resulting figures underestimate their potency due to pharmacokinetic features. The purpose of this trial is to correct the cumulative technique and to make both statistically equivalent. Material & Methods: Single (n = 45 e/a) or cumulative (n = 11 e/a) doses of atracurium or rocuronium were administered to elective patients and maximal effect assessed by electromyography. A regression line was obtained after log dose-probit effect transformation, and considering gamma as the probit/log ratio, ED 50 and 90 were calculated resolving the Hill equation for each patient. The cumulative technique was corrected by using actual figures instead of cumulative ones, starting at second administration. Results: ED 50 were 172 ± 73, 264 ± 52 y 162 ± 81 mcg/kg as single, cumulative dose or corrected respectively for rocuronium and 141 ± 61, 193 ± 53 y 141 ± 70 for atracurium. ED 90 was 233 ± 98,327 ± 65, 254 ± 126, 222 ± 96, 279 ± 77 y 254 ± 126 in the same order. Non-significant differences between single dose and corrected method were noticed. Cumulative values were significantly larger. Conclusion: In keeping with the conditions of the present trial, a simple correction made to the cumulative method reasonably and statistically reproduces atracurium and rocuronium potencies evaluated by single dose-responses technique.

Introdução: A curva dose-resposta acumulativa é um método prático de avaliação das doses efetivas de atracúrio e rocuronio. Dada suas características farmacocinéticas, os resultados dessa curva subestimam a potência de ambos fármacos em comparação com os resultados decorrentes da administração de dose únicas. O objetivo da presente pesquisa é corrigir aquela técnica e tornar as duas estatisticamente equivalentes. Material e métodos: Dois grupos de pacientes eletivos receberam atracúrio ou rocurônio com o objetivo de calcular as potências destes fármacos pelo método das doses únicas (n = 45 c/u) ou acumulativas (n = 11 c/u). Foi determinado o efeito de cada dose por eletromiografia, e por transformação log-probits (considerando gama a relação probit/log), obtiveram-se as DE 50 e 90 resolvendo a equação de Hill para cada sujeito. A técnica acumulativa foi corrigida utilizando as cifras atuais para doses e seus efeitos, em lugar dos valores acumulativos, a partir da segunda administração. Resultados: As DE 50 das técnicas de dose única, acumulativa e corrigida foram: 172 ± 73, 264 ± 52 e 162 ± 81 mcg/kg, respectivamente, quando se utilizou rocurônio, e 141 ± 61, 193 ± 53 e 141 ± 70, respectivamente, quando se utilizou atracúrio. No caso das DE 90' os valores foram 233 ± 98, 327 ± 65, 254 ± 126 e 222 ± 96, 279 ± 77 e 254 ± 126, na mesmo ordem. Não foram observadas diferenças significativas entre os métodos (de dose única e corrigida), ao passo que os valores das doses acumulativas foram significativamente maiores. Discussão e conclusões: Nas condições da presente pesquisa, uma simples correção do método acumulativo reproduz de forma razoável e estatisticamente as potências do atracúrio e rocuronio avaliadas por doses únicas.

Antihistamine Pretreatment to Reduce Incidence of Withdrawal Movement After Rocuronium Injection

The purpose of this study was to determine the effectiveness of antihistamine therapy for withdrawal movements caused by rocuronium injection. One hundred seventy one ASA I-II adults undergoing elective surgery were randomly assigned to one of two groups. Patients in the control group (Group C) were premedicated with 2 mL normal saline, and those in the antihistamine group (Group A) were pre-medicated with 2 mL (45.5 mg) pheniramine maleate. After the administration of thiopental sodium 5 mg/kg, rocuronium 0.6 mg/kg was injected. Withdrawal movements were assessed using a four-grade scale. The administration of antihistamine reveals lower grade of withdrawal movement after rocuronium injection.

A Comparison of the Effect of Lidocaine or Sodium Bicarbonate Mixed with Rocuronium on Withdrawal Movement, Mean Arterial Pressure and Heart Rate during Rocuronium Injection

PURPOSE: This study was performed to find out the effects of lidocaine or 8.4% sodium bicarbonate mixed with rocuronium on mean arterial pressure, heart rate and withdrawal movement. METHODS: Data collection was performed from December 15, 2006 through May 31, 2007. Seventy-five patients with American Society Anesthesiologist (ASA) physical status I & II, under general anesthesia, were randomly assigned to 1 of 3 groups: R group (RG) received rocuronium 0.6 mg/kg; RL group (RLG), rocuronium 0.6 mg/kg mixed with 2 mL of 2% lidocaine; RS group (RSG), rocuronium 0.6 mg/kg with the same volume of 8.4% sodium bicarbonate. Mean arterial pressure, heart rate and withdrawal movement were observed from its injection until 5 min after endotracheal intubation. RESULTS: The incidence of withdrawal movement with its corresponding injections was 72%, 40% and 4% in RG, RLG and RSG, respectively (p<.001). Score of withdrawal movement was the lowest in RSG of all groups (p<.001). While mean arterial pressure (p=.011) in RSG decreased significantly, and heart rate (p=.003) in RG increased more with its injection than before induction of anesthesia. CONCLUSION: Administration of the equivalent volume of 8.4% sodium bicarbonate with rocuronium is more effective than that of lidocaine with rocuronium compared with rocuronium only, in preventing withdrawal movement and in stabilizing mean arterial pressure and heart rate.

Precurarización con rocuronio y d-tubocurarina: otra perspectiva / Precurarization with rocuronium and d-tubocurarine

Objetivo: Estudiar la precurarización de la succinilcolina utilizando d-tubocurarina y rocuronio introduciendo los métodos restrictivo, conceptos de velocidad de acción y recuperación y una nueva semiología para evaluar las fasciculaciones. Material y método: Se administraron succinilcolina (1 mg x Kg-1) (n =21) sola o precedida por rocuronio o d-tubocurarina (60 ó 50 ug x Kg-1) (n =21 c/u), determinándose: la fase inicial de comienzo hasta 80 por ciento de bloqueo, tiempo de comienzo, máximo efecto, duración clínica, tiempo de reversión espontánea entre 10 por ciento y 25 por ciento y 25 por ciento a 50 por ciento. Se calculó la velocidad de acción (inicial, final y global) como la relación tiempo/bloqueo fraccionado y la velocidad de recuperación. El método restrictivo fue empleado para el estudio del tiempo de comienzo, utilizando un rango restringido de bloqueo. Las fasciculaciones fueron evaluadas por su intensidad en seis regiones anatómicas por cuatro observadores imparciales e independientes y las medias de sus valoraciones utilizadas para analizarlas. Resultados: Aparentemente ambos desfasciculantes prolongan la fase inicial, tiempo de comienzo y velocidad de la succinilcolina, pero el método restrictivo únicamente lo confirmó para el tiempo de comienzo y la velocidad global. La velocidad inicial fue más rápida que la final. El rocuronio redujo el efecto y la duración clínica e incrementó la velocidad de recuperación de la succinilcolina. Las fasciculaciones fueron más frecuentes e intensas en el tronco y miembro superior izquierdo, pero los precurarizantes las redujeron tanto en intensidad como localización Discusión: La precurarización no modifica la fase inicial de comienzo, surgiendo la posibilidad de practicar una intubación temprana. Debido al acortamiento que provoca la precurarización con rocuronio se hace evidente la necesidad precoz de nuevas dosis de relajantes.

Objective: To study the precurarization of succinylcholine with d-tubocurarine and rocuronium, using the restrictive method, speed of action and recovery principles and a particular evaluation for fasciculations Material & Methods: Patients received succinylcholine (1 mg x Kg-1) (n =21) either alone or preceded by d-tubocurarine or rocuronium (60 ó 50 micron g x Kg-1) (n =21 e/a), and the following clinical measurements were made: earlyphase of onset time (up to 80 percent blockade), onset time, maximal block, clinical duration and recovery time between 10 percent and 25 percent and 25 percent to 50 percent. Speed of action (initial, final and global)as the ratio between time and fractional blockade and speed of recovery, were calculated. Restrictive method was used for the study of the entire onset time on patients included in a limited range of final block. Intensity of fasciculations was evaluated by four independent observers blind to the drugs used in six anatomical regions and their mean values used for analysis. Results: Apparently, precurarizing drugs prolonged initial phase, onset time and reduced speed for succinylcholine, but only onset time and global speed were confirmed by restrictive method. After rocuronium, maximal effect as well as clinical duration of succinylcholine werereduced and speed of recovery increased. Fasciculations were more frequent and intense at the trunk and left upper arm, but precurarization reduced both intensity and localization prevalence. Discussion: As lack of changes on the initial phase of onset time for succinylcholine inducedby precurarization was noticed, an early tracheal intubation could be contemplated. Due to reduction on clinical duration after rocuronium,new doses of muscle relaxants are sooner necessary. The present method for evaluation of fasciculations shows how far they are spread and how effective precurarization was, given rise to doubts on previous results.

Neuromuscular blockade in cardiac surgery: an update for clinicians.

There have been great advancements in cardiac surgery over the last two decades; the widespread use of off-pump aortocoronary bypass surgery, minimally invasive cardiac surgery, and robotic surgery have also changed the face of cardiac anaesthesia. The concept of "Fast-track anaesthesia" demands the use of nondepolarising neuromuscular blocking drugs with short duration of action, combining the ability to provide (if necessary) sufficiently profound neuromuscular blockade during surgery and immediate re-establishment of normal neuromuscular transmission at the end of surgery. Postoperative residual muscle paralysis is one of the major hurdles for immediate or early extubation after cardiac surgery. Nondepolarising neuromuscular blocking drugs for cardiac surgery should therefore be easy to titrate, of rapid onset and short duration of action with a pathway of elimination independent from hepatic or renal dysfunction, and should equally not affect haemodynamic stability. The difference between repetitive bolus application and continuous infusion is outlined in this review, with the pharmacodynamic and pharmacokinetic characteristics of vecuronium, pancuronium, rocuronium, and cisatracurium. Kinemyography and acceleromyography are the most important currently used neuromuscular monitoring methods. Whereas monitoring at the adductor pollicis muscle is appropriate at the end of surgery, monitoring of the corrugator supercilii muscle better reflects neuromuscular blockade at more central, profound muscles, such as the diaphragm, larynx, or thoraco-abdominal muscles. In conclusion, cisatracurium or rocuronium is recommended for neuromuscular blockade in modern cardiac surgery.

Estudo comparativo entre uma e duas doses efetivas (DE95) de rocurônio para a intubação traqueal / A comparative study between one and two effective doses (ED95) of rocuronium for tracheal intubation

JUSTIFICATIVA E OBJETIVOS: Os bloqueadores neuromusculares (BNM) são fármacos utilizados para produzir relaxamento da musculatura esquelética e facilitar a intubação traqueal (IT). A literatura descreve como sendo necessárias duas doses efetivas (DE95) o ideal para a IT. O rocurônio é um BNM não-despolarizante do tipo esteróide, sintético e de duração intermediária. O objetivo desse estudo foi avaliar e comparar as condições de intubação traqueal (IT), utilizando uma e duas doses efetivas (DE95) do rocurônio, seguindo os critérios da Conferência de Consenso de Copenhague. MÉTODO: Foram avaliados 60 pacientes divididos aleatoriamente em dois grupos de 30, de ambos os sexos, idades entre 20 e 60 anos, estado físico ASA I e II, Mallampati 1 e 2, índice de massa corporal (IMC) < 35, submetidos a anestesia geral. No Grupo 1 (G1) foi administrado 0,3 mg.kg-1 (1 DE95) e no Grupo 2 (G2), 0,6 mg.kg-1 DE95 (2 DE95) de rocurônio. Os parâmetros para a avaliação da IT foram baseados nos critérios da Conferência de Consenso de Copenhague (Good Clinical Research Practice): laringoscopia, cordas vocais (posição e movimentação), reação à inserção do tubo e/ou a insuflação do balonete (movimento dos membros e tosse). RESULTADOS: Todas as intubações foram consideradas excelentes ou boas (aceitáveis), não havendo, portanto, nenhum caso em que não se logrou êxito ou que tenha sido classificado como ruim (inaceitável). Os resultados da análise estatística não foram significativos. Portanto, não houve diferença clínica significativa em nenhum dos parâmetros avaliados. CONCLUSÕES: O rocurônio tanto na dose de 0,3 mg.kg-1 quanto na de 0,6 mg.kg-1 DE95 proporcionou condições clinicamente aceitáveis de IT nos procedimentos eletivos.

BACKGROUND AND OBJECTIVES: Neuromuscular blockers (NMB) are used to induce relaxation of skeletal muscles and facilitate tracheal intubation (TI). According to the literature, two effective doses (ED95) of NMB are ideal for TI. Rocuronium is a steroid-type, synthetic, non-depolarizing neuromuscular blocker of medium duration. The objective of this study was to evaluate and compare the conditions of tracheal intubation with one and two effective doses (ED95) of rocuronium, following the criteria of the Copenhagen Consensus Conference. METHODS: Sixty patients of both genders, ages 20 to 60 years, physical status ASA I and II, Mallampati 1 and 2, body mass index (BMI) < 35, who underwent general anesthesia, randomly divided in two groups of 30 patients, were evaluated. Group 1 (G1) received 0.3 mg.kg-1 of rocuronium (1 ED95), and Group 2 (G2) received 0.6 mg.kg-1 (2 DE95). Parameters used to evaluate TI were based on the criteria of the Copenhagen Consensus Conference (Good Clinical Research Practice): laryngoscopy, vocal cords (position and movements), reaction to the insertion of the tube and/or filling of the cuff (movements of limbs and cough). RESULTS: All intubations were considered excellent or good (acceptable); therefore, there were no cases of failure or any intubation considered bad (unacceptable). The results of the statistical analysis were not significant. Consequently, we did not observe any clinically significant differences in the parameters evaluated. CONCLUSIONS: Both doses of rocuronium, 0.3 mg.kg-1 and 0.6 mg.kg-1 ED95, provided clinically satisfactory parameters of TI in elective procedures.

JUSTIFICATIVA Y OBJETIVOS: Los bloqueadores neuromusculares (BNM) son fármacos utilizados para producir el relajamiento de la musculatura esquelética y facilitar la intubación traqueal (IT). La literatura describe que son necesarias de los dosis efectivas (DE95) lo ideal para la IT. El rocuronio es un BNM no despolarizador del tipo esteroide, sintético y de duración intermedia. El objetivo de este estudio fue evaluar y comparar las condiciones de intubación traqueal (IT), utilizando una y de los dosis efectivas (DE95) del rocuronio, secundando los criterios de la Conferencia de Consenso de Copenhague. MÉTODO: Se estudiaron 60 pacientes divididos aleatoriamente en 2 grupos de 30, de ambos sexos, edades entre 20 y 60 años, estado físico ASA I y II, Mallampati 1 y 2, índice de masa corporal (IMC) < 35, sometidos a anestesia general. En el Grupo 1 (G1) se administró 0,3 mg.kg-1 (1 DE95) y en el Grupo 2 (G2) 0,6 mg.kg-1 DE95 (2 DE95) de rocuronio. Los parámetros para la evaluación de la IT fueron en base a los criterios de la Conferencia de Consenso de Copenhague (Good Clinical Research Practice): Laringoscopia, cuerdas vocales (posición y movimiento), reacción a la inserción del tubo y/o a la insuflación del globo (movimiento de los miembros y tos). RESULTADOS: Todas las intubaciones se consideraron excelentes o buenas boas (aceptables), y no hubo ningún caso en que no se logró el éxito o que no haya sido clasificado como malo (inaceptable). Los resultados del análisis estadístico no arrojaron nada de importante. Por tanto, no hubo diferencia clínica significativa en ninguno de los parámetros evaluados. CONCLUSIONES: El rocuronio tanto en la dosis de 0,3 mg.kg-1 como en la de 0,6 mg.kg-1 DE95 proporcionó condiciones clínicamente aceptables de IT en los procedimientos de elección.

Remifentanil Prevents Withdrawal Movements Caused by Intravenous Injection of Rocuronium

PURPOSE: The incidence of pain induced withdrawal movement following intravenous injection of rocuronium is high. This randomized, double-blind, placebo-controlled study was designed to evaluate the effect of pretreatment of remifentanil on the withdrawal movements due to intravenous injection of rocuronium during anesthetic induction. MATERIALS AND METHODS: Ninety adult female patients undergoing thyroidectomy were randomly allocated to three groups. Each patient intravenously received one of three solutions of equal volume (4 mL): normal saline (Group I, n=30), 0.5 microgram/kg remifentanil (Group II, n=30) or 1 microgram/kg remifentanil (Group III, n=30). Thirty seconds after remifentanil administration, anesthesia was induced with 5 mg/kg IV thiopental. Twenty seconds after thiopental injection, 0.6 mg/kg IV rocuronium was administered (injection rate of 0.5 mL/sec) and patients' withdrawal movements were assessed. Mean arterial pressure (MAP) and heart rate were assessed on arrival in the operation room, before the tracheal intubation and immediately, 1 and 2 min after the tracheal intubation. RESULTS: The incidence of withdrawal movements was significantly lower in both of the remifentanil groups (3 and 0% in Group II and III, respectively) than in the saline group (70%). Remifentanil attenuated the increase of heart rate and MAP immediately and 1 min after the tracheal intubation. CONCLUSION: The pretreatment with 0.5 and 1.0 microgram/kg remifentanil of bolus doses prevented the withdrawal movements caused by rocuronium injection, and effectively blunted cardiovascular activation following tracheal intubation.

Influência da lidocaína no bloqueio neuromuscular produzido pelo rocurônio: estudo em preparação nervo frênico-diafragma de rato / Influence of lidocaine on the neuromuscular block produced by rocuronium: study in rat phrenic-diaphragmatic nerve preparation

JUSTIFICATIVA E OBJETIVOS: O mecanismo de ação dos anestésicos locais (AL) na junção neuromuscular motivou a realização de vários estudos. Em baixas doses eles não interferem na transmissão neuromuscular, mas em altas doses podem comprometer a transmissão neuromuscular e potencializar os efeitos de bloqueadores neuromusculares. O objetivo do estudo foi avaliar, em diafragma de rato, a interação da lidocaína com o rocurônio através da influência no grau de bloqueio neuromuscular. MÉTODO: Foram utilizados ratos, com peso entre 250 e 300 g. A preparação foi feita de acordo com a técnica descrita por Bulbring. Formaram-se grupos (n = 5) de acordo com a droga em estudo: lidocaína - 20 µg.mL-1 (Grupo I); rocurônio - 4 µg.mL-1 (Grupo II) e rocurônio - 4 µg.mL-1 com lidocaína - 20 µg.mL-1 (Grupo III). Foram avaliadas: 1) a amplitude das respostas do músculo diafragma à estimulação indireta, antes e 60 minutos após a adição da lidocaína e do bloqueador neuromuscular; 2) os potenciais de membrana (PM) e potenciais de placa terminal em miniatura (PPTM); 3) a eficácia da neostigmina e 4-aminopiridina na reversão do bloqueio neuromuscular. RESULTADOS: A lidocaína isoladamente não alterou a amplitude das respostas musculares. Com o uso prévio de lidocaína o bloqueio neuromuscular do rocurônio foi de 82,8 por cento ± 1,91 por cento, com diferença significativa (p = 0,0079) em relação ao grupo com rocurônio isolado (57,8 por cento ± 1,9 por cento). O bloqueio foi parcial e totalmente revertido pela neostigmina e 4-aminopiridina, respectivamente. A lidocaína não alterou o potencial de membrana e ocasionou aumento inicial na freqüência dos PPTM, seguido de bloqueio. CONCLUSÕES: A lidocaína potencializou o bloqueio neuromuscular produzido pelo rocurônio. As alterações do PPTM identificam ação pré-sináptica. O antagonismo completo da 4-aminopiridina sugere componente pré-sináptico, idéia que é suportada pelo antagonismo parcial pela neostigmina.

Correlación entre la concentración molar del rocuronio y su tiempo de comienzo o velocidad de acción / Correlation between molar concentration of rocuroniom and its time of onset or speed of action

Objetivo: Estudiar la correlación entre dosis subparalizantes de rocuronio con el tiempo de comienzo y utilizarla para su predicción. Material y método: Cinco grupos de pacientes recibieron 0.34, 0.68, 1, 1.38 o 2.8 x DE50 de rocuronio, y se determinó el máximo efecto, el tiempo para alcanzarlo (TC), las concentraciones molares (µM/kg) y la velocidad de acción (VA), relación entre tiempo y efecto o viceversa de cada dosis. Para la correlación, los valores se convirtieron en logaritmos (log) o raíz cuadrada (V2). De la línea de regresión se obtuvieron la fórmula, R al cuadrado y la significación estadística. Resultados: La correlación entre log µM/kg con Tc y VA (seg/por ciento o por ciento/seg) se tradujo en los siguientes resultados: R2= 0.972,0.845 y 0.845, y una p= 0.001, 0.027 y 0.027, respectivamente. Al resolver las fórmulas de regresión se puedo predecir el TC y VA. Cuando los valores se transforman en V al cuadrado los resultados fueron similares. Discusión: El TC de un bloqueante neuromuscular está ligado a su efecto, y la permeabilidad al tamaño de sus moléculas o µM/kg, la cual a su vez es función de la dosis. El estudio no comprueba la similitud propuesta del TC entre las bajas dosis de los relajantes musculares. Los resultados demuestran que existe una alta y significativa correlación entre la µM/kg de las dosis subparalíticas de rocuronio con las tres formas de estudiar el período de comienzo. También pone en evidencia que a través de la misma correlación es posible hacer predicciones sobre los parámetros de comienzo.

The Relationship of the Anthropometric Variables to the Infusion Rate of Rocuronium in the Elderly

We have determined the infusion rates of rocuronium in the elderly and young adult patients during sevoflurane and nitrous oxide anesthesia. The correlation of some anthropometric predictors with infusion rate of rocuronium was also investigated for both elderly and young adult. Participating patients were assigned to one of two groups: 1) young adult patients aged 20 to 50 years (n = 30) ; 2) elderly patients aged over 65 years (n = 30). The anthropometric variables such as height, weight, ratio of weight to body surface area, subscapularis and suprailiac skin folds, body surface area, body mass index and % ideal body weight were evaluated as predictors for infusion rate. The infusion rate in elderly patients was significantly less compared with that in young adult patients (p < 0.05). In elderly patients, no anthropometric predictor was related to the infusion rate of rocuronium. This suggests that the infusion rate of rocuronium for an elderly patient needs to be individualized by monitoring neuromuscular transmission to avoid excessive dose.

Can lidocaine reduce succinylcholine induced postoperative myalgia?

This study was undertaken to determine the effect of lidocaine pretreatment on reduction of succinylcholine-induced myalgia in patients undergoing general anesthesia for gynecological surgery. One hundred and thirty-five patients were assigned to one of three groups in a prospective, double blind, randomized manner. Group PS, the control group, received normal saline and succinylcholine 1.5 mg x kg(-1); Group LS, lidocaine 1.5 mg x kg(-1) and succinylcholine 1.5 mg x kg(-1); Group PR, normal saline and rocuronium 0.6 mg x kg(-1). Morphine 0.1 mg x kg(-1) iv was given for premedication and all patients were monitored with a noninvasive blood pressure monitor, ECG and pulse oximetry. Anesthesia was induced with 5 mg.kg(-1) thiopental iv. followed by succinylcholine (Group PS, LS) or rocuronium (Group PR) for tracheal intubation. Following administration of these agents, the presence, and degree of fasciculation were assessed visually on a four point scale by one investigator who was blinded to the drug administered. The blood pressure and heart rate of each patient were monitored on nine occasions. Twenty-four hours later, any myalgia experienced was assessed according to a structured questionaire and graded by a four point scale by one investigator blinded to the intraoperative management. The results indicate that muscle fasciculation was not found in Group PR while the patients in Group LS had a lower incidence of muscle fasciculation than those in Group PS (p < 0.001). At 24 h, the incidence of myalgia was higher in Group PS than in Group LS and PR (p < 0.05). A correlation was not found between the incidence of myalgia and the occurrence of muscle fasciculation. The changes in systolic and diastolic blood pressure and heart rate were not significant among the three groups. In conclusion, where succinylcholine is used, lidocaine is proven to be the useful pretreatment agent for the reduction of postoperative myalgia.

Intubating conditions after three different doses of rocuronium in the elderly.

This randomized controlled trial study evaluated the intubating conditions at 1 minute after 0.3, 0.6 and 0.9 mg/kg of rocuronium in 60 Thai elderly patients who enrolled for elective surgery under general anesthesia with fentanyl, thiopental and halothane at King Chulalongkorn Memorial Hospital. Excellent or good conditions were observed in 50 per cent (p<0.05) at rocuronium 0.3 mg/kg, compared with 95 and 85 per cent at 0.6 and 0.9 mg/kg of rocuronium, respectively but the excellent conditions were 5 (p<0.05), 30 and 45 per cent from each dose. Therefore, rocuronium 0.6 or 0.9 mg/kg should be adequate for intubation in elective, elderly patients but was inadequate for emergency case. In addition, rocuronium 0.3 mg/kg is insufficient for intubation at 1 minute in this age group. No serious side effects of the drug nor complications were found in this study.