Effects of Cisatracurium on Cardiovascular System and Histamine Release in Comparison to Atracurium and Pipecuronium

Background: Cardiovascular stability is considered desirable in an ideal muscle relaxant. Cisatracurium is a recently introduced neuromuscular blocker. It is an isomer of atracurium and is said to be of weaker autonomic effects and it does not release histamine. The aim of this work is to evaluate the hemodynamic change profile and assessment of histamine release associated with cisatracurium administration in both young adults and elderly patients, both experimentally and clinically in comparison with the parent drug atracurium and with a cardiovascular stable relaxant pipecuronium. Materials and methods: The clinical study was done on 120 patients who were assigned into two groups according to their age. Each group was further subdivided into three subgroups (n=20) who randomly received only one of the three neuromuscular blockers; pipecuronium, atracurium and cisatracurium. The hemodynamic changes over time were measured and manifestations of histamine release were assessed. The experimental study was done to study the effect of gradually increasing doses of pipecuronium, atracurium, and cisatracurium on isolated rabbit heart and the possible histamine release. Results: In the clinical study, there were neither clinically nor statistically significant cardiovascular changes in the mean heart rate or in the mean values of (systolic, diastolic and mean) blood pressure following cisatracurium or pipecuronium in both age groups. In contrast, atracurium showed an elevation in the mean HR in one age group (young adults and a reduction in the mean values of systolic, diastolic and mean) blood pressure in the eldery group in comparison to the other groups. 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 patients receiving pipecuronium, these signs were comletely absent. In the experimental study cisatracurium in a dose = 32xED50 resulted in apparent increase in the contraction of the ventricles. Atracurium in a lesser dose = l 6x ED50 produced a similar effect. These responses were abolished completely after the injection of H-2 antagonist. UP to = 64 x ED50 of pipecuronium failed to produce any chang in ventricular contraction. Conclusion: Cisatracurium in the clinically used doses, appears to have much less or may be devoid of histamine release than atracurium and so it has a cardiovascular stability as pipecuronum.