Influence of different local anesthetics on atracurium neuromuscular blockade on rats / Influência de diferentes anestésicos locais no bloqueio neuromuscular produzido pelo atracúrio em ratos

Abstract Introduction: The association between local anesthetics (LA) and neuromuscular blocking (NMB) drugs in clinical practice, and the possibility of interaction between these drugs has been investigated. LAs act on neuromuscular transmission in a dose-dependent manner and may potentiate the effects of NMB drugs. Objective: The aim of this study was to evaluate, in an experimental model, the effect of lidocaine and racemic bupivacaine on neuromuscular transmission and the influence on neuromuscular blockade produced by atracurium. Methods: Male Wistar rats, weighing from 250 to 300 g were used. The preparation was set up based on a technique proposed by Bülbring. Groups were formed (n = 5) according to the drug studied: lidocaine 20 µg.mL−1 (Group I); racemic bupivacaine 5 µg.mL−1 (Group II); atracurium 20 µg.mL−1 (Group III); atracurium 20 µg.mL−1 in a preparation previously exposed to lidocaine 20 µg.mL−1 and racemic bupivacaine 5 µg.mL−1, Groups IV and V, respectively. The following parameters were assessed: 1) Amplitude of hemi diaphragmatic response to indirect stimulation before and 60 minutes after addition of the drugs; 2) Membrane potentials (MP) and miniature endplate potentials (MEPPs). Results: Lidocaine and racemic bupivacaine alone did not alter the amplitude of muscle response. With previous use of lidocaine and racemic bupivacaine, the neuromuscular blockade (%) induced by atracurium was 86.66 ± 12.48 and 100, respectively, with a significant difference (p = 0.003), in comparison to the blockade produced by atracurium alone (55.7 ± 11.22). These drugs did not alter membrane potential. Lidocaine initially increased the frequency of MEPPs, followed by blockade. With the use of bupivacaine, the blockade was progressive. Conclusions: Lidocaine and racemic bupivacaine had a presynaptic effect expressed by alterations in MEPPs, which may explain the interaction and potentiation of NMB produced by atracurium.

Resumo Introdução: A associação de anestésicos locais (AL) com bloqueadores neuromusculares (BNM) na prática clínica e a possibilidade de interação entre esses fármacos têm sido investigadas. Objetivo: Avaliar, em modelo experimental, o efeito da lidocaína e da bupivacaína racêmica na transmissão neuromuscular e sua influência no bloqueio neuromuscular produzido pelo atracúrio. Método: Ratos machos da linhagem Wistar, peso entre 250 e 300 g. A preparação foi feita de acordo com a técnica proposta por Bulbring. Grupos (n = 5) de acordo com o fármaco em estudo: lidocaína 20 µg.mL-1 (Grupo I); bupivacaína racêmica 5 µg.mL-1 (Grupo II); atracúrio 20 µg.mL-1 (Grupo III); atracúrio 20 µg.mL-1 em preparação previamente exposta a lidocaína 20 µg.mL-1 e bupivacaína racêmica 5 µg.mL-1, Grupos IV e V, respectivamente. Foram avaliados: 1) A amplitude das respostas do hemidiafragma à estimulação indireta antes e 60 minutos após a adição dos fármacos; 2) Os potenciais de membrana (PM) e os potenciais de placa terminal em miniatura (PPTM). Resultados: Os AL, isoladamente, não alteraram a amplitude das respostas musculares. Com o uso prévio dos AL, o bloqueio neuromuscular (%) do atracúrio foi 86,66 ± 12,48 e 100, respectivamente, com diferença significante (p= 0,003) em relação ao produzido pelo atracúrio isoladamente (55,7 ± 11,22). Não alteraram o PM. A lidocaína inicialmente aumentou a frequência dos PPTM, seguido de bloqueio; com a bupivacaína, o bloqueio foi progressivo. Conclusão: A lidocaína e a bupivacaína racêmica apresentaram efeito pré-sináptico expresso por alterações nos PPTM, podem justificar a potencialização do bloqueio neuromuscular produzido pelo atracúrio.

Bloqueadores neuromusculares en infusión continua en anestesia general endovenosa total / Neuromuscular blocking drugs in continuous infusion in total intravenous general anesthesia

Introducción: La administración de agentes anestésicos de forma endovenosa dio inicio a una nueva modalidad que implicó la administración de anestésicos en forma de infusiones continuas. Objetivo: Actualizar la información sobre la función de los bloqueadores neuromusculares cuando se administran en infusión continua en anestesia general endovenosa total. Desarrollo: Los bloqueadores neuromusculares se pueden administrar en infusión continua para mantener una concentración plasmática estable y lograr una adecuada relajación del paciente durante el procedimiento quirúrgico, así como una recuperación más rápida y segura de forma espontánea, basándose en el inicio de acción del fármaco utilizado, pero fundamentalmente del alcance de su efecto máximo. A pesar de ello es importante administrar una dosis de carga inicial que deben oscilar entre 2 y 3 DE 95 (dosis efectiva para disminuir la respuesta al estímulo en 95 por ciento de su valor inicial) y continuar con la administración en infusión continúa como parte del mantenimiento de la anestesia. Conclusiones: Independientemente de los diferentes criterios entre autores, la mayoría coinciden que las infusiones continuas logran mantener mayor estabilidad en sangre y por ende, menor dosis de bloqueadores neuromuscular, menores tiempos reales de reversión y menos efectos adversos(AU)

Introduction: The administration of anesthetic agents intravenously started a new modality that involved the administration of anesthetics in the form of continuous infusions. Objective: To update the information on the function of neuromuscular blocking drugs when administered in continuous infusion in total intravenous general anesthesia. Development: Neuromuscular blocking drugs can be administered in continuous infusion to maintain a stable plasma concentration and achieve adequate relaxation of the patient during the surgical procedure, as well as a faster and safer spontaneous recovery, based on the action onset of the drug used, but fundamentally on its maximum effect. Despite this, it is important to administer an initial loading dose that must range from 2 to 3 DE 95 (effective dose to decrease the response to the stimulus in 95 percent of its initial value) and continue with the administration in continuous infusion as part of the maintenance of anesthesia. Conclusions: Regardless the different criteria among authors, most agree that continuous infusions are effective in maintaining greater blood stability and, therefore, lower doses of neuromuscular blocking drugs, shorter real reversal times and fewer adverse effects(AU)

Interacción farmacológica de los bloqueadores neuromusculares con fármacos de uso anestesiológico / Neuromuscular-blocking drugs interaction with drugs used in anesthesiology

Introducción: Se entiende por interacción farmacológica la capacidad que tiene un fármaco de alterar los efectos farmacológicos de otro que se administre simultáneamente. Objetivo: Realizar una revisión actualizada de la interacción farmacológica de los bloqueadores neuromusculares con fármacos de uso frecuente en el ámbito anestesiológico. Desarrollo: Los mecanismos de interacción medicamentosa son variados y se complican cuando se trata de modificaciones sobre las propiedades farmacocinéticas y farmacodinámicas de cada medicamento. Los bloqueadores neuromusculares (BNM) son fármacos que se utilizan para relajar la musculatura estriada y garantizar la intubación traqueal, la ventilación y producir un plano quirúrgico suficiente para que el cirujano pueda realizar de forma adecuada el procedimiento quirúrgico. Muchos medicamentos interactúan con los BNM y con frecuencia potencian el efecto relajante muscular. Esto resulta de importancia clínica en el caso de antibióticos, anestésicos inhalatorios, litio y ciclosporina. Conclusiones: El anestesiólogo moderno debe tener suficientes conocimientos teóricos sobre las diferentes interacciones medicamentosas que se pueden presentar en el perioperatorio. Los bloqueadores neuromusculares pueden interactuar con fármacos de uso común por los pacientes o por el anestesiólogo, por lo que es necesario el diagnóstico precoz y el tratamiento adecuado para evitar las complicaciones(AU)

Introduction: Drug interaction is understood as the ability of a drug for altering the pharmacological effects of another simultaneously administered. Objective: To carry out an updated review about the drug interaction of neuromuscular-blocking drugs with others frequently used in the anesthesiological field. Findings: The mechanisms of drug interaction are varied and are complicated in cases of modifications on the pharmacokinetical and pharmacodynamical properties of each medicine. Neuromuscular-blocking drugs (NMBs) are used to relax the striated musculature and to ensure tracheal intubation, ventilation. They produce a sufficient surgical plane in order for the surgeon to perform the surgical procedure properly. Many medications interact with NMBs and often potentiate the muscle relaxant effect. This is of clinical importance in the case of antibiotics, inhalational anesthetics, lithium and cyclosporine. Conclusions: Modern anesthesiologists must have sufficient theoretical knowledge about different drug interactions that may occur during the perioperative period. Neuromuscular-blocking drugs can interact with others commonly used by patients or by the anesthesiologists, a reason why early diagnosis and appropriate treatment are necessary to avoid complications(AU)

Anafilaxias y reacciones alérgicas durante cirugías y procedimientos médicos / Anaphylaxis and allergic reactions during surgery and medical procedures

Las reacciones anafilácticas intraoperatorias son impredecibles, infrecuentes y pueden poner en riesgo al paciente. Tienen una incidencia de 1/10 000 a 1/20 000 produciéndose en la mayoría de los casos por bloqueantes musculares, látex y antibióticos. No hay estadística de las reacciones alérgicas sistémicas durante otros procedimientos médicos. El estudio diagnóstico posterior a una reacción es complejo debiendo incluir toda la medicación utilizada en el procedimiento. En este estudio retrospectivo describimos 15 pacientes, de los cuales 10 tuvieron reacciones anafilácticas en un procedimiento quirúrgico, 2 en endoscopías y 1 en una ecografía transvaginal. Los dos pacientes restantes presentaron una reacción alérgica sistémica durante una ecografía transvaginal y un procedimiento odontológico. Estudiamos los pacientes con toda la medicación utilizada, incluimos látex y, eventualmente, los detergentes y desinfectantes, de haber sido empleados. Tres de las 10 cirugías no pudieron realizarse por desarrollarse la reacción durante la inducción anestésica, en cinco casos debieron interrumpirse y solo en dos se terminaron. Las reacciones posteriores a endoscopías fueron severas, requiriendo internación en terapia intensiva; las reacciones en ecografías transvaginales y procedimientos odontológicos fueron asistidas en emergencias. Los agentes causales en las cirugías incluyeron bloqueantes musculares, látex, cefalosporina, azul patente y ranitidina; en endoscopías el agente causal fue el orto-ftalaldehído (OPA), en las ecografías transvaginales el látex y en el procedimiento odontológico la amoxicilina. El objetivo de este artículo es describir la etiología de las reacciones alérgicas sistémicas y anafilácticas intraoperatorias y en procedimientos médicos, recalcando su gravedad y la necesidad de su identificación.

Anaphylaxis during anesthesia is an unpredictable, severe, and rare reaction. It has an incidence of 1/10 000 to 1/20 000 surgeries. In most series, the responsible drugs include neuromuscular blocking agents, latex, or antibiotics. The frequency and etiology of systemic allergic reactions in other medical procedures are largely unknown. The identification of responsible drugs of anaphylaxis is a complex task, requiring testing of all medications and substances used during surgery. We describe our experience in a retrospective study of 15 patients. Ten subjects developed anaphylaxis during surgery, two in endoscopic studies and one in a trans-vaginal ultrasound. The remaining two subjects, one in a trans-vaginal ultrasound and another during a dental procedure had a systemic allergic reaction. We studied all patients with all medications administered during the procedures, including latex and detergents and disinfectants. Three surgeries had to be suspended at induction of anesthesia, five were stopped incomplete and two were completed. Both patients that presented a reaction during endoscopy required intensive care unit admission and the rest were observed in a Hospital. The responsible drugs during surgery anaphylaxis were neuromuscular blocking agents, latex, patent blue, and ranitidine. Ortho-phthalaldehyde (OPA) was identified during endoscopic studies; latex was responsible in transvaginal ultrasounds; and amoxicillin in the dental procedure. The aim of the present article is to review our experience studying allergic systemic reactions and anaphylaxis during general anesthesia and medical procedures, emphasizing the severity of these reactions and the need for causative drug identification.