( EVALUATION OF THE NEUROMUSCULAR BLOCKADE CHARACTERISTICS OF CISATRACURIUM IN COMPARISON TO ATRACURIUM AND PIPECURONIUM ( PHARMACOLOGICAl AND CliNICAL STUDIES

Abstract

The introduction of Cisatracurium (51W89), a purified preparation of one of the isomers of atracurium, may represent an advance in the development of the class benzylisoquinolinium muscle relaxants. The ED50 (dose producing about 50% reduction in the contraction of the gastrocnemius muscle in the chloralose

anesthetized cats) of cisatracurium was 45!-lg/kg, that of atracurium was 125 tg/kg, and 7!-lg/kg for pipecuronium. Cisatracurium was more potent than atracurium but less potent than pipecuronium and the three drugs were easily reversed by neostigmine. Cisatracurium and pipecuronium are devoid of both ganglion blocking and a-adrenergic blocking actions and did not alter the blood pressure even with doses up to 16 x E050 (7201-'g/kg and 112 1-'g/kg respectively). However atracurium in Oa dose of 8xE050 (1000 tgikg) produced slight ganglion blocking effect, but had neither effect on n-adrencrgic receptors nor the blood pressure of the chloralose anesthetized cats. Cisatracurium, pipecuronium and atracurium produced non­ depolarizing neuromuscular block. When they were administered at 2xED95, the mean onset time although was longer in the elderly patierts than in young patients, yet it

had no statistical significance in cisatracurium and pipecuronium groups. The mean onset time of cisatracurium was intermediate between pipecuronium and atracurium in both age groups (1&11), with a very highly significant dilference between (cisatracurium & pipecuronium) and (cisa\racurium & atrcurium) mean times in both age groups. The mean duration of action of cisatracurium approaches the duration of action of atracurium with respect to age but is comparable to that of pipecuronium which had a • significant longer duration of action specially in the elderly group of. patients. The reversal time of cisatracurium was similar to atracurium but significantly shorter than pipecuronium. Cisatracurium, similar to pipecuronium showed non significant alteration in the hemodynamic profiles of patients in both age groups until 40 minutes of administration. In contrast. atracurium showed an elevation in the mean heart rate/min in one age group (young adults) and a reduction in the means of the systolic. diastolic and mean blood pressures in the other group (the elderly) following its administration. These changes seem to be due to the histamine release induced by atracurium which also caused other signs of histamine release in the form of local rashes in the arm of injection. face & neck and chest wall and/or increased airway pressure. These results of (histamine release signs). shown with the atracurium­ receiving patients were comparable and statistically significant from those of the nearly absent signs in the cisatracurium-receiving patients. In the patients receiving pipecuronium these signs were completely absent. Thus with the clinically used doses of cisatracurium. it appears to be much less or devoid of histamine release than atracurium, while pipecuronium is devoid of histamine release. Cisatracurium is the first neuromuscular blocking agent that combines both the organ-independent elimination of atracurium and the cardiovascular stability of pipecuronium.