The Effects of d-Tubocurarine, Pancuronium and Atracurium on the Responses of Gastrocnemius and Soleus Muscles in the Cat

In vivo, the effects of d-tubocurarine (0.20 mg kg-1), pancuronium (0.015 mg kg-1) and atracurium (0.15 mg kg-1) on the responses of the indirectly stimulated cat gastrocnemius (fast) and soleus (slow) muscles to a twitch, train-of-four and tetanic stimuli were studied. The soleus muscle demonstrated a greater degree of fade than the gastrocnemius in response to tetanic stimuli (50 Hz). There was no difference between the responses of the two muscles to twitch or train-of-four stimuli with any of the drugs. Recovery of train-of-four ratio occurred more rapidly than did the tetanic fade ratio. At a time when train-of-four ratio exceeded 0.7, tetanic fade was still evident, especially in the soleus muscle.     

Tetanic fade during neuromuscular blockade produced by atracurium in the rat diaphragm preparation

In the present investigation, we studied and measured the phenomenon of tetanic fade and peak tetanic tension depression in the rat diaphragm preparation in the presence of a blocking concentration of atracurium (e.g., 10 μmol.l^-1). Atracurium (10 μmol.l^-1) produced a pronounced tetanic fade (i.e., 47–69% reduction of total sustained tetanic tension) at a time (15 s) when it reduced the peak tetanic tension by only 25%. The time course for total tetanic fade was 30–35 s, whereas the time taken for complete peak tetanic tension depression was 3-3.5 min, suggesting that the two effects were produced via different mechanisms, involving presynaptic and postsynaptic mechanism. It was concluded that atracurium produces a profound tetanic fade, with respect to its effect on twitch or tetanic tension, suggesting that the drug is a potent neuromuscular blocker, with rapid onset of blockade.     

Pharmacokinetics and pharmacodynamics of the benzylisoquinolinium muscle relaxants

The benzylisoquinolinium class of drugs comprises atracurium, 51W89, doxacurium, and mivacurium. Atracurium can be used as a pharmacokinetic benchmark; it has at least two distinct metabolic pathways, of which Hofmann elimination and ester hydrolysis are the most significant. The relative importance of each of these two routes is still a matter of speculation, and this, coupled with the fact that atracurium is a mixture of 10 isomers, has led to the development of many innovative pharmacokinetic modelling concepts. 51W89 is a cis-cis -isomer of atracurium and probably has a pharmacokinetic profile very similar to that of atracurium. Doxacurium, a long-acting benzylisoquinolinium, has a small apparent volume of distribution and an elimination half-time similar to that of pancuronium, and is excreted by the kidneys. Mivacurium is a short-acting benzylisoquinolinium that is rapidly hydrolysed by plasma cholinesterases. Two isomers of mivacurium are very similar, whereas the third isomer differs greatly in both pharmacological activity and elimination half-time, so that analysis requires complex pharmacokinetic methods.     

The use of neuromuscular blocking drugs in intensive care practice

Critically ill patients represent a very different population from that of the operating theatre, but much of our knowledge of many of the neuromuscular blocking drugs is derived from intraoperative use. The diversity of clinical-practice and case-mix differences in intensive care are probably responsible for the absence of a formal consensus about the use of neuromuscular blocking drugs in the intensive care unit (ICU). Various surveys suggest that these drugs are used comparatively infrequently, but we do not know whether current usage is either safe or appropriate. In addition to the adverse effects which inevitably accompany prolonged paralysis and immobility, the steroidal relaxants, pancuronium and vecuronium, have also been associated with myopathy. This seems to be aggravated by concurrent use of pharmacologic doses of corticosteroids or the aminoglycoside antibiotics. Neither the mechanism nor the validity of the association with steroidal relaxants is known at present. Muscle dysfunction is a common feature of critical illness, and it is possible that neuromuscular blocking drugs interfere with muscle repair and regrowth. Patients with multiple organ failure present a particular challenge both because of the extent of tissue injury and because drug clearance via the liver or kidneys is generally impaired.     

阿曲库铵和罗库溴铵量-效关系和恢复时相的比较

目的：对比观察阿曲库铵和罗库溴铵的量-效关系和恢复时相特征。方法：选择60例ASAⅠ级，年龄18～50岁，施择期整形外科手术的患者，随机平均分成阿曲库铵组和罗库溴铵组。用60％NO2-O2-硫喷妥钠-芬太尼维持麻醉；通过加速度仪监测神经肌肉功能，采用TOF刺激方式，以T1抑制的百分比为研究指标。采用累计给药方法建立阿曲库铵和罗库溴铵的量撤关系曲线。结果：根据量-效关系曲线，阿曲库铵和罗库溴铵的作用强度比率为1：1．2，两药的ED90、ED90和ED90均有显著性差别。应用等效剂量（1．5×ED95）后，两药的高峰时间、临床作用时间和体内作用时间具有显著性差别，但恢复时间无显著性差别。结论：阿曲库铵和罗库溴铵均是弱效能的中效非去极化肌肉松弛药。与阿曲库铵相比，罗库溴铵的作用强度大约弱20％。而且作用时间较短。