title: 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 microg kg(-1), followed by 300 microg kg(-1), was evaluated. In the pharmacokinetics groups, serial arterial blood samples were withdrawn for rocuronium assay after a single dose of rocuronium 600 microg kg(-1).
  
  
  RESULTS
  ANH resulted in a shift to the left of rocuronium dose-response curve. Rocuronium effective dose(95) (ED(95)) was 26% lower (P<0.05) in the ANH group [283.4 (92.0) microg kg(-1)] compared with the control group [383.5 (127.3) microg kg(-1)]. Times from administration of last incremental dose until 25% of first response of train-of-four (TOF) recovery (Dur(25)) and 0.8 TOF ratio recovery (Dur(0.8)) 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].
  
  
  CONCLUSIONS
  ANH resulted in prolongation of rocuronium time-course of action, thus careful monitoring of neuromuscular block is recommended in patients who undergo ANH.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Graz Medical University, Graz, Austria. ashraf.dahaba@meduni-graz.at
authors.forename: A A
authors.initials: AA
authors.lastname: Dahaba
authors.forename: S I
authors.initials: SI
authors.lastname: Perelman
authors.forename: D M
authors.initials: DM
authors.lastname: Moskowitz
authors.forename: H L
authors.initials: HL
authors.lastname: Bennett
authors.forename: A
authors.initials: A
authors.lastname: Shander
authors.forename: K
authors.initials: K
authors.lastname: Oettl
authors.forename: G
authors.initials: G
authors.lastname: Reibnegger
authors.forename: H
authors.initials: H
authors.lastname: Metzler
mesh_terms: D000368:Aged; D000732:Androstanols / Q000097:blood / Q000494:pharmacology*; D000768:Anesthesia, General; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006438:Hemodilution; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D008297:Male; D008875:Middle Aged; D009469:Neuromuscular Junction / Q000187:drug effects; D003473:Neuromuscular Nondepolarizing Agents / Q000097:blood / Q000494:pharmacology*; D011446:Prospective Studies; D000077123:Rocuronium
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D000077123:Rocuronium