COMPARISON OF THE PHARMACODYNAMICS AND PHARMACOKINETICS OF AN INFUSION OF CIS-ATRACURIUM (51W89) OR ATRACURIUM IN CRITICALLY ILL PATIENTS UNDERGOING MECHANICAL VENTILATION IN AN INTENSIVE THERAPY UNIT

Citation
Ah. Boyd et al., COMPARISON OF THE PHARMACODYNAMICS AND PHARMACOKINETICS OF AN INFUSION OF CIS-ATRACURIUM (51W89) OR ATRACURIUM IN CRITICALLY ILL PATIENTS UNDERGOING MECHANICAL VENTILATION IN AN INTENSIVE THERAPY UNIT, British Journal of Anaesthesia, 76(3), 1996, pp. 382-388
Citations number
26
Categorie Soggetti
Anesthesiology
ISSN journal
00070912
Volume
76
Issue
3
Year of publication
1996
Pages
382 - 388
Database
ISI
SICI code
0007-0912(1996)76:3<382:COTPAP>2.0.ZU;2-D
Abstract
We have studied 12 critically ill, sedated patients who required a neu romuscular blocking drug to assist mechanical ventilation in an intens ive care unit. Patients were randomized to receive an infusion of cis- atracurium 0.18 mg kg(-1) h(-1) (group 1, n = 6) or atracurium 0.6 mg kg(-1) h(-1) (group 2, n = 6) preceded, if necessary, by a bolus dose of 2x ED(95) of the same drug (cis-atracurium 0.1 mg kg(-1) or atracur ium 0.5 mg kg(-1)). Neuromuscular block was monitored using an acceler ograph and the infusion rate adjusted regularly so that it was possibl e to detect the first response to train-of-four (TOF) stimulation of t he ulnar nerve at the wrist. Blood samples were obtained for estimatio n of plasma cis-atracurium and laudanosine concentrations (group 1) or the three groups of atracurium isomers and laudanosine (group 2). The re was no apparent haemodynamic or allergic response to either drug. T he mean infusion time in group 1 was 37.6 h and in group 2, 27.5 h. On termination of the infusion, the time for the TOF ratio to reach 0.7 was similar in the two groups (group 1 = 60 min; group 2 = 62 min). Th e mean infusion rate of cis-atracurium was 0.19 mg kg(-1) h(-1) and of atracurium 0.47 mg kg(-1) h(-1) (expressed as mg of bis-cation): cis- atracurium was 2.5 times more potent than atracurium. Using the NONMEM program, a single compartment pharmacokinetic model was fitted to the plasma concentrations of cis-atracurium and the cis-cis, cis-trans an d trans-trans isomers of atracurium. The mean population pharmacokinet ic values for cis-atracurium were: volume of distribution (V) = 21 900 (SEM 416) mt; clearance (Cl) = 549 (79) mi min(-1); half-life (T-1/2) = 27.6 (3.6) min; and for the three groups of atracurium isomers were : cis-cis, V = 15100 (720) ml, Cl = 449 (42) ml min(-1), T-1/2 = 23.4 (1.2) min; cis-trans, V = 18000 (667) ml, Cl = 1070 (43) ml min(-1), T -1/2 = 11.7 (0.1); trans-trans, V = 13100 (1280) ml, Cl = 1560 (55) ml min(-1), T-1/2 = 5.8 (0.4) min. Plasma laudanosine concentrations wer e lower in the cis-atracurium (peak value 1.3 mu g ml(-1)) than in the atracurium (maximum 4.4 mu g ml(-1)) group.