Efeitos hemodinâmicos do atracúrio e do cisatracúrio e o uso de difenidramina e cimetidina

Abstract

Atracurium, a benzylisoquinoline compound, is a non-depolarizing blocker of neuromuscular cholinergic receptors 5 . It is composed by a mixture of ten optical and geometrical isomers 5,6 . The incidence of atracurium-related hypotension is low, but it has been considered the etiologic factor in 18% of the episodes of anaphylaxis during anesthesia 2 . In doses higher than three times its ED 95 in humans, this drug can cause severe hypotension 5,6 . Cisatracurium, one of the 10 isomers of atracurium, has a similar profile, since evidence that isomers have a different behavior on the release of histamine does not exist 3 . The objective of the present study was to compare the hemodynamic effects of the intravenous administration of different doses of atracurium and cisatracurium in rats, and to investigate whether histamine receptor blockers, H1 (diphenhydramine) and H2 (cimetidine), protect against those hemodynamic changes. The use of diphenhydramine and cimetidine as H1 and H2 antagonists, respectively, was based on literature reports suggesting that those substances could block atracurium-induced hemodynamic actions 7,8 . METHODSAll experimental protocols used in the present study were approved by the Ethics on Animal Use Commission of the Health Sciences Center of the Universidade Federal do Rio de Janeiro (CCS-UFRJ). This study was undertaken in three steps: 1) In vivo assessment of the neuromuscular blockadeWistar Rats of both genders, weighing 300 to 450 g, were used to determine the dose necessary to promote neuromuscular blockade in rats. Animals were anesthetized with 50 mg.kg -1 of intraperitoneal sodium pentothal. The animals were intubated and the lungs were ventilated with room air with an automatic Harvard ventilator for small animals. To achieve adequate respiratory conditions, tidal volume was maintained at 10 ml.kg -1 and a respiratory rate of 50 bpm (breaths per minute). To investigate the in vivo effects of NMBs, the technique described by Brown et al. in 1936 9 was used. The sciatic nerve of one of the paws was surgically dissected and stimulated with a pair of platinum electrodes connected to a Grass S88 stimulator. The tendon of the gastrocnemius muscle was fixed to the Grass FT03 transducer with a metallic string and contractions were recorded on paper with a quill. The voltage of the stimuli and muscle stretching were adjusted to obtain maximal muscular contractions, i.e., until stimuli frequency that promoted maximal muscular contraction were achieved, which was 0.2 Hz. Thus, supramaximal stimuli were evoked to assess the neuromuscular function under the effects of the intravenous administration of atracurium or cisatracurium. Train-of-four (TOF) stimuli of 2 Hz were used to determine the occupation rate of nicotinic receptors in the muscle and to evaluate the neuromuscular function in experimental animal models, since the relationship between