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.

Effects of neuromuscular blocking agents on central respiratory chemosensitivity in newborn rats

Neuromuscular blocking agents suppress central respiratory activity through their inhibitory effects on preinspiratory neurons and the synaptic drive from preinspiratory neurons to inspiratory neurons. Central CO2-chemosensitive areas, which partly consist of CO2-excited neurons, in the rostral ventrolateral medulla are thought to provide tonic drive to the central respiratory network and involve cholinergic mechanisms, which led us to hypothesize that neuromuscular blocking agents can inhibit CO2-excited neurons and attenuate respiratory CO2 responsiveness. To test this hypothesis, we used isolated brainstem-spinal cord preparations from newborn rats. The increase of C4 burst frequency induced by a hypercapnic superfusate, i.e. respiratory CO2 responsiveness, was suppressed by the application of neuromuscular blocking agents, either d-tubocurarine (10, 100M) or vecuronium (100M). These agents (40M) also induced hyperpolarization and decreases in firing frequency of CO2-excited neurons in the rostral ventrolateral medulla. Our results demonstrate that neuromuscular blocking agents inhibit CO2-excited tonic firing neurons and attenuate respiratory CO2 responsiveness.

Pharmacological evaluation of muscle relaxant potency of mivacurium chloride against standard non-depolarizing muscle relaxant D. tubocurarin

The study was designed to evaluate potency of neuromuscular blocking activity of mivacurium chloride on the preparation of isolated frog's rectus abdominis muscle in contrast to that of the standard non - depolarizing muscle relaxant d- tubocurarin. The contractile response of the muscle was recorded in response to Acetylcholine [0.1 microg / ml] followed by addition of mivacurium to the bath Fluid and d- tubocurarin in a logarithmic increasing doses [1 mic/ ml- 16 mic/ml]. The percentage of inhibition by d-tubocurarin was more marked than that of mivacurium

Androgen regulation of the nicotinic acetylcholine receptor-ionic channel in a hormone-dependent skeletal muscle

The trophic influence of testosterone on the nicotinic acetylcholine receptor-ionic channel (AChR) was studied in the levator ani (LA) muscle of adult malr rats (120 days) intact (C) or gonadectomized when 90 days old (G). In the indirectly elicited muscle twitch, the LA from G rats was less sensitive to d-tubocurarine (0.1-1µM) than control muscles (IC25:C = 0.30µM,G=0.46µM). In G rats, the amplitude of neurally evoked endplate currents (EPC) was reduced by 70%, but the EPC time constant was not changed. Maximal junctional binding of [125I] alfa-bungarotoxin in the LA(C: 72.5 ñ 13.2 amol/endplate) was reduced by 18.8-fold in LA from G rats, with no change of the association rate constant (C: 5.64 ñ 1.29 10**6 M-1 min**-1). The results indicate that testosterone deprivation reduces the junctional AChR density in the rat LA without modifying the binding properties of the receptor

neuromuscular blocking effect of full and half equipotent doses of d-tubocurarine and vecuronium combinations versus d-tubocurarine alone

This study was carried out on 30 patients [17 males and 13 females] undergoing elective surgical procedures under general anaesthesia. No patient had neuromuscular [NM], renal, cardiovascular, respiratory or hepatic diseases. All patients were premedicated with 10 mg of diazepam orally and 1 mg of atropine intramuscular 1 hour pre-operatively. Anaesthesia was induced with thiopental 4-5 mg/kg, while the equipment for monitoring the neuromuscular function [The Myograph 2000-Biometer], being attached to the patient. Succinuyl-choline in a dose of 1 mg/Kg was used to facilitate tracheal intubation Anaesthesia was maintained with nitrous oxide [N2O] in oxygen [7:3 L/min] and 0.5% Halothane with increments of 20 mg pethidine given if needed. After stabilization of twitch response of train-of-four [TOF], the muscle relaxant under study was given and patients were classified into 3 groups. The first group received 0.3 mg/Kg of d-Tubocurarine [dtc], the second group received 0.03 mg/Kg of dtc plus 0.005 mg/Kg of vecuronium [Vecu.] The third group received 0.015 mg/Kg of dtc plus 0.0025 mg/Kg of vecu. At the end of the surgical procedure, spontaneous recovery was allowed to occur and the residual blockade was antagonized. The onset times and 5% to 25% recovery times were estimated. This study was carried out to evaluate the NM blocking effect of combinations of dtc and vecu. in full and half equipotent doses of each drug versus dtc alone. It was found that full equipotent doses of dtc plus vec. can produce 95% depression of NM function as dtc alone; while Half equipotent doses can not produce more than 60% depression of NM function and all patients received the combinations of the two drugs recovered significantly more quickly than patients received dtc alone

Efeitos cardiovasculares dos relaxantes neuromusculares / Cardiovascular effects of neuromuscular relaxants

O autor faz uma revisäo das açöes farmacológicas dos relaxantes neuromusculares sobre o sistema cardiovascular. Os mecanismos básicos pelos quais os relaxantes neuromusculares induzem efeitos cardiovasculares säo sumarizados. Entre estes incluem a liberaçäo de histamina, bloqueio ganglionar, bloqueio dos receptores muscarínicos no sistema cardiovascular e a recaptaçäo das catecolaminas a nível neural. Consideraçöes sobre os mais recentes agentes, atracúrio e vecurônio, säo feitas, especialmente quanto aos seus efeitos hemodinâmicos

Effects of neuromuscular blocking agents on arterial blood pressure in the rat.

Gallamine triethiodide pancuronium bromide or d-tubocurarine was infused intravenously at different rates in urethane anaesthetized rats. When given in neuromuscular blocking doses gallamine triethiodide produced significant hypotension if the rate of infusion exceeded 2 mg/min whereas neither pancuronium bromide nor d-tubocurarine produced a marked change in blood pressure in neuromuscular blocking doses.

The effect of imipramine on isolated skeletal muscle preparations.

Imipramine (2-10 microng/ml) noncompetitively inhibited acetylcholine responses of the frog rectus abdominis muscle, and markedly inhibited the contracture produced by carbachol and succinylcholine without affecting the contracture produced by KCl, caffeine, and chlorpromazine. The twitch responses to indirect and direct stimulation of the rat phrenic nerve-diaphragm and the frog sciatic nerve-gastrocnemius were first augmented and then depressed markedly and irreversibly by imipramine (5-20 microng/ml). The indirect stimulation was inhibited earlier and to a greater degree than the direct stimulation. The blockade in the nerve-sartorius developed and progressed quickly without prior augmented responses, and with a parallel time course for indirect and direct stimulation. On the frog rectus, physostigmine antagonised whereas d-tubocurarine and CaCl2 increased the imipramine-induced inhibition. In the nerve muscle preparations, physostigmine, CaCl2 and KCl did not affect the neuromuscular blockade produced by imipramine; tubocurarine (0.05 microng/ml) markedly increased the blocking effect of imipramine (20 microng/ml) on the rat phrenic nerve-diaphragm. The results have been discussed in relation to the memberane stabilizing and the calcium releasing actions of imipramine.