Influence of acute normovolaemic haemodilution on the dose-response relationship, time-course of action and pharmacokinetics of rocuronium bromide

Abstract

Background. Acute normovolaemic haemodilution (ANH) is an effective strategy for avoiding or reducing allogeneic blood transfusion. We aimed to study its effect on the pharmacological profile of rocuronium. Methods. In two study centres, 28 patients undergoing major surgery with ANH were matched with 28 control patients. In the dose-response groups, using the mechanomyograph, neuromuscular block of six consecutive incremental doses of rocuronium 50 μg kg-1, followed by 300 μg kg1, was evaluated. In the pharmacokinetics groups, serial arterial blood samples were withdrawn for rocuronium assay after a single dose of rocuronium 600 μg kg-1. Results. ANH resulted in a shift to the left of rocuronium dose-response curve. Rocuronium effective dose 95 (ED95) was 26% lower (P<0.05) in the ANH group [283.4 (92.0) μg kg-1] compared with the control group [383.5 (127.3) μg kg-1]. Times from administration of last incremental dose until 25% of first response of train-of-four (TOF) recovery (Dur25) and 0.8 TOF ratio recovery (Dur0.8) were 28% longer in the ANH group [39.9 (8.4), 66.7 (14.2) min] compared with the control group [31.1 (6.6), 52.1 (15.8) min] (P<0.01, P<0.05), respectively. Volume of distribution was higher (P<0.01), central clearance was lower (P<0.05) and terminal elimination half-life was longer (P<0.0001) in the ANH group [234.97 (47.11) ml kg-1, 4.70 (0.94) ml kg1 min-1, 77.29 (12.25) min] compared with the control group [181.22 (35.73) ml kg-1, 5.71 (1.29) ml kg-1 min1, 56.86 (10.05) min, respectively]. Conclusion. ANH resulted in prolongation of rocuronium time-course of action, thus careful monitoring of neuromuscular block is recommended in patients who undergo ANH. © Copyright 2006 Oxford University Press.