The Effect Of Acute Normovolemic Hemodilution On The Pharmacokinetics Of Propofol By Target-controlled Infusion

Objective: To investigate the effect of acute normovolemic hemodi-lution (ANHD) on the pharmacokinetics of propofol given by target-controlled infusion (TCI). Method: Thirty-five ASA I - II patients (20-60 years old, 45-70 kg) scheduled for non-cardiac surgical operations and expected to experience surgical blood loss of more than 1000 ml were randomly divided into two groups: ANHD group (n=17) and control group (n=18). In ANHD group hemodilution was performed after induction of general anesthesia. The volume of blood withdrawn was estimated by Gross's formula. Hemodilution was achieved by drainage of autologous blood and simultaneously intravenous infusion of an equal volume (1:1) of 6% HES and half volume (0.5:1) of Ringer's solution to maintain intravascular volume. Ten minutes after ANHD, TCI of propofol was started. The target plasma propofol concentration was set at 3 ug.ml^-1. TCI of propofol continued for 60 minutes. Arterial blood samples were taken before and 2, 5, 10, 20, 30, 40, 50 and 60 min after TCI propofol was started and 20, 40, 60, 90, 120 min after termination of TCI propofol for determination of the blood concentration of propofol by gas-chromatography-mass spectrometry (GC-MS). If significant surgical blood loss occurred or it was 30 min before the end of the operation, the transfusion of blood obtained by hemodilution could begin. Pharmacokinetic parameters were calculated and assessed with NONMEM software. Results: The pharmacokinetics of propofol by TCI was best described mathematically by a two-compartment open model in ANHD group. The pharmacokinetic parameters for the final model: V₁was 0.331 Lkg'1 in ANHD group and 0.205 L ? kg"1 in control group. Compared with the control group, Vi in ANHD group increased by 51.71%.Ki2 was 0.091mm'1 in ANHD group and 0.064 min"1 in control group. Kn in ANHD group increased by 42.19% compared with the control group. CLi, CL2 were 33.31 mlmin'^kg"1 and 16.65 mlmin"lkgl in ANHD group. They were 22.76 ml ? min"1 ? kg"1 and 13.24 ml ?min"1 "kg^in control group. CLi and CL2 in ANHD group increased by 46.35% and 25.76% respectively compared with the control group. The rest pharmacokinetic parameters were not statistically different between the two groups. After ANHD hematocrit (Hct) decreased from (39.41 ± 3.95) % to (25.53 + 1.94) %, and hemoglobin (Hb) decreased from (133.46+13.21) g-L'1 to (86.47 + 8.62) g-L"1 in ANHD group. Hct and Hb descended by 35.22% and 35.21% respectively compared with basic levels (before ANHD). Conclusions: (1) ANHD has effect on the pharmacokinetics of propofol given by TCI: Vi, K12, CLi, and CL2 increase. (2) During ANHD, the target plasma concentration of propofol given by TCI should be increased. (3) The duration of action of propofol decreases because its plasma concentration descends below the effective concentration quickly resulting from its higher clearance during ANHD.