title: Influence of acute normovolemic hemodilution on the pharmacokinetics of Cisatracurium Besylate.
abstract: BACKGROUND
  Acute normovolemic hemodilution (ANH) is an efficacious blood conservation strategy for avoiding or reducing allogeneic blood transfusion. In a previous publication, on a different cohort of patients, we demonstrated that cisatracurium's potency and duration of action were not influenced by ANH, but we could not establish which role, if any, pharmacokinetics played.
  
  
  METHODS
  Forty patients were randomly allocated to the ANH or control groups. Patients received cisatracurium single 100 µg kg-1 bolus dose, serial arterial blood samples were collected and assayed for pharmacokinetic analysis.
  
  
  RESULTS
  Central and steady state apparent volumes of distribution (V1, Vdss) and slope factor (γ) were larger, effect-compartment concentration at 50% neuromuscular block was lower in the ANH (90.8±41.6 mL kg-1, 159.1±39.2 mL kg-1, 6.0±0.9 and 136.4±29.1 ng·mL-1) compared with the control group (65.5±26.1 mL kg-1, 134.8±31.8 mL kg-1, 5.5±0.8 and 158.5±26.0 ng·mL-1) respectively. Elimination half-life (t1/2 β) and mean residence time (MRT) were longer in the ANH (37.2±20.9, 23.5±13.2 min) than the control group (26.8±9.8, 16.9±6.2 min), albeit not statistically significant (P=0.051, P=0.051). There were no significant differences in distribution half-life (t1/2 α), effect-compartment equilibration rate-constant (keo), central and total clearances (Clc, Cl) between the ANH (2.4±1.2 min, 0.070±0.013 min-1, 6.1±1.9 mL kg-1 min-1 and 7.7±2.3 mL kg-1 min-1) and control group (1.9±1.2 min, 0.063±0.008 min-1, 7.0±1.8 mL kg-1 min-1 and 8.5±2.1 mL kg-1 min-1) respectively.
  
  
  CONCLUSIONS
  ANH altered some pharmacokinetic parameters such as significantly larger volumes of distribution. Other parameters such as elimination half-life were considerably longer albeit not statistically significant.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria - ashraf.dahaba@medunigraz.at.
authors.forename: A A
authors.initials: AA
authors.lastname: Dahaba
authors.forename: I
authors.initials: I
authors.lastname: Suljevic
authors.forename: K
authors.initials: K
authors.lastname: Oettl
authors.forename: Z
authors.initials: Z
authors.lastname: Xiao
authors.forename: H
authors.initials: H
authors.lastname: Dong
authors.forename: L
authors.initials: L
authors.lastname: Xiong
authors.forename: G
authors.initials: G
authors.lastname: Reibnegger
mesh_terms: D000328:Adult; D001279:Atracurium / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006438:Hemodilution / Q000379:methods; D006801:Humans; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000493:pharmacokinetics*
chemical_list: D009466:Neuromuscular Blocking Agents; D001279:Atracurium; C101584:cisatracurium