Pharmacokinetics and pharmacodynamics of cisatracurium in patients undergoing surgery with two hemodilution methods

Abstract

Objective: To investigate the pharmacokinetics and pharmacodynamics of cisatracurium in patients undergoing surgery under acute normovolemic hemodilution (ANH) and acute hypervolemic hemodilution (AHH).

Methods: Ninety patients with orthopedic surgery were divided into ANH, AHH and control groups, which received hemodilution by hydroxyethyl starch 130/0.4 transfusion, Voluven transfusion and regular transfusion and infusion during surgery, respectively. Each group was divided into 3 sub-groups, administrated with cisatracurium at dosage of 0.1, 0.2 and 0.3mg/kg respectively. The changes in plasma protein, pH and electrolytes from the hemodilution beginning to surgery finish were monitored. Before and after cisatracurium administration, the phamocodynamic indicators of muscle relaxant were observed, and the plasma drug concentration was measured.

Results: After hemodilution or regular transfusion, all three groups experienced a distinct drop in total plasma protein, albumin and pH. Compared with control group, the plasma concentrations of both K⁺ and Ca²⁺ in ANH and AHH groups significantly dropped (P<0.05), and those in each group after administration of cisatracurium also dropped, compared with before (P<0.05). After administration with cisatracurium, the onset time of muscle relaxation in AHH group was extended notably, compared with AHH and control groups (P<0.05), with no distinct difference of residual pharmacodynamics parameters (P>0.05). In the same hemodilution or regular infusion, with increase of drug dosage, the onset time of muscle relaxation was shortened, and the period of no response to train-of-four stimulation, muscle relaxation blockade duration and action time of muscle relaxation blockade in body were extended (P<0.05).

Conclusion: When using cisatracurium under AHH, the dosage should be increased appropriately, while it need not be adjusted under ANH.

Keywords: Cisatracurium; Hemodilution; Pharmacodynamics; Pharmacokinetics.