The chronotropic effect of acetylcholine in the presence of vecuronium and atracurium A study in the isolated perfused rabbit heart

The bradycardia produced by 1 microgram acetylcholine in the isolated perfused rabbit heart, in the presence of vecuronium and atracurium, was studied and compared with control. Vecuronium at a concentration of 2.5 micrograms/litre and atracurium 6 micrograms/litre did not enhance the negative chronotropic effect of acetylcholine. Atracurium produced a statistically significant inhibition of the negative chronotropic effect of acetylcholine.     

Atracurium and vecuronium interaction with gentamicin and tobramycin

Drug interactions between the aminoglycosides (tobramycin and gentamicin) and atracurium and vecuronium were studied prospectively in 44 patients. Twenty-two patients had therapeutic serum levels of tobramycin or gentamicin and 22 served as controls. Onset time, clinical duration, and time to spontaneous recovery of T4/T1 ratio of 0.70 after atracurium or vecuronium injection were measured. No statistically significant differences were found in onset time, but clinical duration and time to recovery were significantly longer in patients receiving tobramycin or gentamicin and paralyzed with vecuronium than for controls (P less than 0.01 for clinical duration and P less than 0.0005 for recovery). The neuromuscular block produced by atracurium was not significantly influenced by the presence of therapeutic serum levels of tobramycin or gentamicin. We conclude that for patients treated with these antibiotics, atracurium may present some advantages over vecuronium when a prolonged block is not desired.     

Reactivity and toxicity of atracurium and its metabolitesin vitro

Cytotoxicity of atracurium and of its metabolites was tested in vitro.Exposure of isolated rat hepatocytes to atracurium produced cellular damage evidenced by extrusion of an intracellular enzyme, lactate dehydrogenase (LDH), into the incubation medium. Leakage of LDH was directly related to the concentration of atracurium in the medium (250 to 800 μM). If the spontaneous degradation of atracurium (presumably via Hofmann elimination) was first carried out in vitroand the degradation products subsequently added to the isolated hepatocytes, the leakage of LDH was also dose-dependent but larger than that observed after the addition of the parent drug. When l-cysteine was admixed to the products of the spontaneous degradation of atracurium prior to their addition to the liver cells, no leakage of LDH was observed. The results are compatible with the working hypothesis that atracurium itself and, even more so, acrylates formed in Hofmann elimination of atracurium, are reactive toward nucleophiles and damage the cells by alkylating nucleophiles present in cellular membranes. Antecedent covalent binding of acrylates to the nucleophile cysteine, i.e., the formation of acrylatecysteine adducts, saturated the reactive capacity of acrylates for nucleophiles and thus prevented the reactive metabolites from alkylating the endogenous nucleophiles. Possible clinical consequences resulting from in vivogeneration of reactive metabolites are not clear at the present time but are projected to be related to (a) the dose of atracurium administered, (b) the amount of acrylates generated, (c) the functional importance of the endogenous nucleophiles alkylated, and (d) the pathway and the speed of detoxification of atracurium and its metabolites.     

Acute quadriparesis in an asthmatic treated with atracurium

An 18-yr-old male asthmatic was paralyzed with atracurium for a period of seven days to facilitate mechanical pulmonary ventilation. After withdrawal of the muscle relaxant, train-of-four neuromuscular monitoring demonstrated rapid recovery of normal function. Three days later he developed acute quadriparesis without respiratory compromise. Electrophysiological studies showed normal conduction velocities, low compound muscle action potential amplitudes and evidence of denervation. Most cases of post-ventilatory weakness in the ICU involve the use of vecuronium and pancuronium. It has been suggested that the steroid nucleus in these muscle relaxants may be responsible. Our patient developed generalised weakness after treatment with atracurium, a benzylisoquinolinium muscle relaxant. Thus, it appears that the steroid nucleus of vecuronium and pancuronium is not essential in causing post-ventilatory weakness.     

罗库溴铵、阿曲库铵和琥珀酰胆碱三药肌松作用的对照研究

全麻下组Ⅰ以罗库溴铵０ ．６ ｍｇ／ｋｇ 静注,组Ⅱ以阿曲库铵０ ．５ ｍｇ／ｋｇ 静注,组Ⅲ以琥珀酰胆碱１ ．５ ｍｇ／ｋｇ 静注。结果：气管插管条件,以琥珀酰胆碱组肌松作用最好,而罗库溴铵和阿曲库铵肌松作用相似;罗库溴铵组肌松起效时间、临床恢复时间和无反应时间分别为８６ ．２５ ±２７ ．１３ｓ 、２９ ．９０ ±６ ．２５ ｍｉｎ 和２０ ．８４ ±７ ．９５ ｍｉｎ ,介于其它两药之间。说明,罗库溴铵可为临床提供较好的气管插管条件,且无琥珀酰胆碱的诸多副作用。     

Continuous infusions of atracurium and vecuronium,compared with intermittent boluses of pancuronium: dose requirements and reversal

This study was designed to determine the effect of prolonged infusion on the ease of reversal of atracurium and vecuronium, and whether factors which potentiate the block delayed reversal. In phase one, 40 patients were randomized (double blind) to determine the steady state conditions for atracurium and vecuronium. Fourteen atracurium patients and 17 vecuronium patients were evaluable. The unblinded second phase involved the steady state conditions using halothane or isoflurane and atracurium infusions. The infusion required for 95% twitch depression (TD95) for atracurium was 7.6 +/- 1.1 micrograms.kg-1 x min-1. The requirement for vecuronium changes with time: TD95 at 30 min was 1.01 +/- 0.16, at 60 min 0.89 +/- 0.12 and after 90 min 0.85 +/- 0.17 micrograms.kg-1 x min-1 (P < 0.05). The mean TD95 was 0.94 +/- 0.23 micrograms.kg-1 x min-1. Multivariate regression analysis of the infusion data revealed a vecuronium model predicting TD95 by the duration of infusion (P < 0.05) and weight (P = 0.05). Atracurium TD95 was predicted by age (P = 0.05). The addition of an inhalation agent to atracurium reduced the infusion rate by 2.01 +/- 0.28 micrograms.kg-1 x min-1 (P = 0.0001) for each increase in MAC. The mean reversal times for atracurium with three different anaesthetics and for vecuronium were not different. Reversal of pancuronium blockade, from less profound twitch depression (86.4 vs 95%) took twice as long as for atracurium and vecuronium for which the following predictors were identified: age, weight, duration of infusion, level of blockade, and type of anaesthetic, using a stepwise regression model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Residual curarization in the neonate after Caesarean section

The transplacental transfer and the neonatal effects of atracurium 0.3 mg.kg-1 (ED95) were compared with those of d-tubocurarine at the usual clinical dose of 0.3 mg.kg-1 (ED90) in 46 patients undergoing elective Caesarean section. The atracurium group (25 patients) was similar to the d-tubocurarine group (21 patients) as far as age, parity and time intervals between precurarization, induction, skin incision, muscle relaxant administration, hysterotomy and birth. The transplacental transfer of atracurium was lower than that of d-tubocurarine, with a feto-maternal ratio of 9 +/- 3% for atracurium and 12 +/- 5% for d-tubocurarine (P less than 0.05). The transplacental transfer of laudanosine was low at 14 +/- 5%, with blood levels of 0.101 +/- 0.032 microM.L-1 in the umbilical vein. Newborns in the two groups were comparable in terms of Apgar scores at one, five and ten minutes, as well as for NACS scores (neurological and adaptive capacity scoring test) at two and 24 hours after birth. However, at 15 min after birth, only 55% of newborns in whom the mothers received atracurium had a normal NACS score (greater than or equal to 35/40) compared with 83% of newborns in whom the mothers received d-tubocurarine (P less than 0.05). Further analysis of the five variables related to active muscle tone revealed that the modal score for active extension of the neck of newborns from the atracurium group was lower than for newborns from the d-tubocurarine group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Priming with atracurium efficiently suppresses etomidate-induced myoclonus

IntroductionEtomidate is a hypnotic drug widely used as an intravenous anesthetic induction agent. The incidence of etomidate-induced myoclonus has been reported as much as 50–80% after induction making it an undesirable drug for induction.ObjectiveOur aim is to use a priming dose of atracurium to suppress etomidate-induced myoclonus during induction of anesthesia.MethodsIn a double-blinded clinical trial 80 patients were randomly given either atracurium (20% of ED95 × kg) or saline as a priming agent. Then, induction of anesthesia was performed using 0.4 mg/kg etomidate. Age, weight, body mass index, bispectral index (BIS) monitor, and duration and grade of myoclonus were recorded.ResultsThe demographic characteristics, age, body mass index, BIS score, and weight were not significantly different between the atracurium (ATRA) priming group and control groups. The binomial regression model showed that BMI was an independent predictor variable for myoclonus (OR: 2.1, CI 95%: 1.7–7.5, p = 0.032). In this model, adjusted odds ratios (OR) of myoclonus (multivariate logistic regression analysis) in the control group was 6.6 (95% CI: 1.5–9.7, p = 0.013).ConclusionLow-dose atracurium priming could effectively suppress etomidate-induced myoclonus.     

Atracurium is associated with postoperative residual curarization

Background. Residual paralysis following the use of neuromuscularblocking drugs remains a clinical problem. As part of departmentalquality assurance, we examined the degree of postoperative residualcurarization (PORC) following atracurium. Methods. Forty patients undergoing general anaesthesia involvingatracurium were studied. Quantitative neuromuscular monitoring(mechanomyography, Myograph 2000, Biometer, Denmark) was performedby assessing the response to supramaximal train-of-four (TOF)stimulation of the ulnar nerve. Anaesthesia was provided bynon-participating clinicians who were blinded to the study data.A TOF ratio