Neuromuscular blocking agents provide muscle relaxation for a great variety of surgical procedures with light planes of general anaesthesia. Besides having a significant impact in the development of anaesthesia and surgery, these agents continue to play an important role as pharmacological tools in the elucidation of the physiological and pharmacological regulation of neuromuscular transmission and the morphofunctional organisation of the neuromuscular junction. In the daily practice of anaesthesia, muscle relaxants are considered to be safe drugs with predictable, straightforward pharmacological actions. However, the use of relaxants constitutes a deliberate encroachment on respiration, one of the most important physiological mechanisms. The pharmacokinetic behaviour of this class of agents is little influenced by age or anaesthetic agents; however, hepatic or renal disease may profoundly alter their excretion pattern, resulting in prolonged duration of neuromuscular blockade. Biotransformation plays an important role in the total elimination of recently introduced compounds. Consequently, knowledge of the disposition pharmacokinetics, excretion and biotransformation of this class of drugs is indispensable for their rational choice for various surgical procedures. In this review, the known pharmacokinetics of standard compounds (introduced before 1980) are briefly summarised and new information generated by the development of vecuronium, rocuronium, pipecuronium (steroidal agents) and atracurium, mivacurium, doxacurium (benzylisoquinolinium esters) is discussed in more detail.

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A modification of the isolated arm technique was applied in 10 females under opioid-based i.v. anaesthesia for comparison of the offset of an atracurium-induced neuromuscular block in an isolated arm to an arm with maintained circulation. The neuromuscular blocking effect of a bolus dose of atracurium 0.5 mg.kg-1 was measured bilaterally using the integrated adductor pollicis EMG response (integrated T1 EMG response in % of baseline value and T4/T1 ratio) after bilateral ulnar nerve train-of-four (TOF) stimulation. At 10% T1 recovery, one arm was isolated from the general circulation for 20 min by means of a tourniquet cuff (isolated arm), while normal circulation was maintained in the other arm (control arm). In both arms, the TOF response, peripheral skin temperature, mixed peripheral venous pH and plasma concentrations of atracurium and laudanosine were then measured and compared. Core and peripheral skin temperatures in both arms remained stable and normal throughout the study, and mixed peripheral venous pH stayed within physiological limits in both arms in all subjects. In the isolated arm, recovery of the neuromuscular block was markedly delayed compared to the control arm, the integrated EMG T1 response and TOF ratio being significantly reduced in the isolated arm after 20 min of isolation. The decline in plasma concentration of atracurium was less in the isolated arm than in the control arm, whereas laudanosine levels increased in the isolated and decreased in the control arm. Normal peripheral circulation is of major importance for termination of an atracurium-induced neuromuscular block.(ABSTRACT TRUNCATED AT 250 WORDS)

1 A new in vivo experimental method is described whereby the neuromuscular blocking effects of muscle relaxants can be investigated on the intrinsic laryngeal muscles of anaesthetized cats. The peripheral tibialis anterior muscle preparation is employed in the same animal to compare the blocking effect on both preparations. 2 The intrinsic laryngeal muscles react with different sensitivities to the neuromuscular blocking agents when compared to the tibialis anterior muscle. 3 The neuromuscular response in both muscle preparations is similar with steroidal agents but appeared to be different after suxamethonium or isoquinoline analogues. 4 It is concluded that this preparation may become a useful tool for studying new muscle relaxants developed to facilitate rapid intubation conditions.