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British Journal of Anaesthesia, 2002, Vol. 88, No. 4 555-562
© 2002 The Board of Management and Trustees of the British Journal of Anaesthesia

Laboratory Investigations

Does ester hydrolysis change the in vitro degradation rate of cisatracurium and atracurium?

M. Weindlmayr-Goettel*,1, H. Gilly1,2 and H. G. Kress1,2

1Department (B) of Anaesthesiology and General Intensive Care, University of Vienna, Waehringer-Guertel 18–20, A-1090 Vienna and 2L. Boltzmann-Institute of Experimental Anaesthesiology and Research in Intensive Care Medicine, Vienna, Austria*Corresponding author

Background. We assessed the role of ester hydrolysis as an additional degradation mechanism to Hofmann elimination in the breakdown of cisatracurium and atracurium.

Methods. Cisatracurium and atracurium were incubated in phosphate buffer (pH 7.4, 37°C) with and without the addition of carboxylesterase. Control measurements with an added esterase inhibitor were performed separately. Cisatracurium/atracurium and their degradation products, laudanosine and monoquaternary acid, were analysed using high-pressure liquid chromatography.

Results. Degradation of cisatracurium and atracurium proceeded exponentially, and after addition of carboxylesterase, no significant differences in the degradation rates were found. Neither an increase in carboxylesterase activity nor the addition of esterase inhibitor showed any effect. However, areas under the peaks of the chromatogram representing monoquaternary acid increased during incubation with esterase.

Conclusion. The rate-limiting step in the degradation of cisatracurium/atracurium is Hofmann elimination. Ester hydrolysis is involved in the second degradation step that forms monoquaternary acid, but its contribution to the total elimination rate is negligible.

Br J Anaesth 2002; 88: 555–62


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