C.A. Lien British Journal of Anaesthesia

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Development and potential clinical impact of ultra-short acting neuromuscular blocking agents† C.A. Lien British Journal of Anaesthesia Volume 107, Pages i60-i71 (December 2011) DOI: 10.1093/bja/aer341 Copyright © 2011 The Author(s) Terms and Conditions

Fig 1 The impact of increasing the dose of neuromuscular blocking agents on time to onset of 100% NMB. In the doses studied, the onset of rocuronium and cisatracurium is shortened as dose increased. The magnitude of the decrease becomes smaller as the dose of cisatracurium is increased. Doubling the dose from one to two times the ED95 shortens the onset by 2.4 min and doubling it again to four times the ED95 shortens it further by 2.5 min. Doubling it again to eight times the ED95 only shortens the onset by 0.8 min to1.9 min. The onset of vecuronium is shortened from 3.8 to 1.8 min as the dose increased from two to four times the ED95. The onset is not shortened further with additional increases in dose. Similarly, the onset of gantacurium is shortened from 2.6 to 1.7 min by increasing the dose from one to two times the ED95. Additional increases in dose do not significantly shorten the onset. British Journal of Anaesthesia 2011 107, i60-i71DOI: (10.1093/bja/aer341) Copyright © 2011 The Author(s) Terms and Conditions

Fig 2 The chemical structure of gantacurium, an asymmetric chlorofumarate. It contains six chiral centres. Like cisatracurium, gantacurium exists as only one stereoisomer'in contrast to atracurium and mivacurium, both of which are mixtures of stereoisomers. British Journal of Anaesthesia 2011 107, i60-i71DOI: (10.1093/bja/aer341) Copyright © 2011 The Author(s) Terms and Conditions

Fig 3 The inactivation of gantacurium occurs by two different pathways. At pH 7.4 and temperature 37°C, the more rapid of these is adduction of cysteine to the olefinic double bond. The adduct then slowly undergoes hydrolysis. The second, slower means of breakdown is alkaline hydrolysis. British Journal of Anaesthesia 2011 107, i60-i71DOI: (10.1093/bja/aer341) Copyright © 2011 The Author(s) Terms and Conditions

Fig 4 The chemical structure of CW 002, an olefinic (double-bonded) isoquinolinium diester compound. British Journal of Anaesthesia 2011 107, i60-i71DOI: (10.1093/bja/aer341) Copyright © 2011 The Author(s) Terms and Conditions