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BJA Advance Access published online on July 27, 2006
British Journal of Anaesthesia, doi:10.1093/bja/ael207
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© The Board of Management and Trustees of the British Journal of Anaesthesia 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted June 7, 2006

Clinical Investigation

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

A. A. Dahaba 1 *, S. I. Perelman 2, D. M. Moskowitz 2, H. L. Bennett 2, A. Shander 2, K. Oettl 3, G. Reibnegger 3, and H. Metzler 1

1 Department of Anaesthesiology and Intensive Care Medicine, Graz Medical University, Graz, Austria
2 Department of Anesthesiology, Critical Care Medicine, Pain Management and Hyperbaric Medicine, Englewood Hospital and Medical Center, Englewood, NJ, USA
3 Institute of Medical Chemistry and Pregl Laboratory, Graz Medical University, Graz, Austria

* To whom correspondence should be addressed.
A. A. Dahaba, E-mail: ashraf.dahaba{at}meduni-graz.at


  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 kg-1, 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 In the pharmacokinetics groups, serial arterial blood samples were withdrawn for rocuronium assay after a single dose of rocuronium 600 µg kg-1.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 dose95 (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 kg-1 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 min-1, 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.

Keywords: complications, acute normovolaemic haemodilution; neuromuscular block, rocuronium.
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