British Journal of Anaesthesia, Vol 76, Issue 3 382-388, Copyright © 1996 by The Board of Management and Trustees of the British Journal of Anaesthesia
A. H. Boyd, N. B. Eastwood, CJR. Parker and J. M. Hunter
We have studied 12 critically ill, sedated patients who required a
neuromuscular blocking drug to assist mechanical ventilation in an
intensive 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 2 x ED95 of
the same drug (cis-atracurium 0.1 mg kg-1 or atracurium 0.5 mg kg-1).
Neuromuscular block was monitored using an accelerograph and the infusion
rate adjusted regularly so that it was possible to detect the first
response to train-of-four (TOF) stimulation of the ulnar nerve at the
wrist. Blood samples were obtained for estimation of plasma cis-atracurium
and laudanosine concentrations (group 1) or the three groups of atracurium
isomers and laudanosine (group 2). There was no apparent haemodynamic or
allergic response to either drug. The 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). The 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 and trans-trans isomers of atracurium. The mean population
pharmacokinetic values for cis-atracurium were: volume of distribution (V)
= 21,900 (SEM 416) ml; clearance (Cl) = 549 (79) ml min-1; half-life (T1/2)
= 27.6 (3.6) min; and for the three groups of atracurium isomers were:
cis-cis, V = 15,100 (720) ml, Cl = 449 (42) ml min-1, T1/2 = 23.4 (1.2)
min; cis-trans, V = 18,000 (667) ml, Cl = 1070 (43) ml min-1, T1/2 = 11.7
(0.1); trans-trans, V = 13,100 (1280) ml, Cl = 1560 (55) ml min-1, T1/2 =
5.8 (0.4) min. Plasma laudanosine concentrations were lower in the
cis-atracurium (peak value 1.3 micrograms ml-1) than in the atracurium
(maximum 4.4 micrograms ml-1) group.
CLINICAL INVESTIGATIONS
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
University Department of Anaesthesia, Royal Liverpool University Hospital, Prescot Street, Liverpool L69 3BX
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