Effect of acute hypervolemic hemodilution on the pharmacoklnetics of propofol by target -controlled infusion / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effect of acute hypervolemic hemodilution (AHHD) on pharmacokinetics of propofol given by target-controlled infusion (TCI). Methods Thirty-six ASA Ⅰ-Ⅱpatients (18 male, 18 female) undergoing elective surgery were randomized to one of two groups control group (n = 18) and AHHD group ( n = 18). The patients were premedicated with atropine 0.007-0.01mg?kg-1 and phenobarbital 1-2mg?kg-1 i.m. . Radial artery and right internal jugular vein were cannulated before induction of anesthesia. Anesthesia was induced with TCI of propofol. The target plasma propofol concentration was set at 3 ?g?ml-1. When the patients lost consciousness, fentanyl 2?g? kg-1 was given i.v. and tracheal intubation was facilitated by vecuronium 0. 1 mg?kg-1 . Ten minutes after tracheal intubation an additional dose of fentanyl 2 ?g?kg-1 and vecuronium 0.08 mg?kg-1 was given i.v.. TCI of propofol continued for 1 hour. In AHHD group lactated Ringer's solution 10 ml?kg-1 was infused over 30 min before induction of anesthesia. 10 min after TCI propofol was started, 6 % HES 20 ml ?kg-1 was infused within 30 min. In control group the patients received only lactated Ringer's solution 10 ml? kg-1 . All fluid infused was prewarmed to 35℃ Arterial blood samples were taken before and 2,5, 10, 20, 30, 40, 50 and 60 min after TCI propofol was started and 2.5, 5, 10, 15, 20, 30 min after termination of TCI propofol for determination of blood concentration of propofol by gas-chromatography-mass spectrometry (GC-MS) . The TCI system consisted of Graseby 3500 infusion pump controlled by Stelpump 1.07 software, which included Tackley pharmacokinetic parameters. Results The demographic data including sex, age, body weight and amount of propofol consumed were comparable between the two groups. The pharmacokinetic profile of propofol given by TCI was best described by a two-compartment open model during AHHD. The pharmacokinetic parameters tor the final model; K10 was0.116, K12 0.0907 and K210.024mm-1 ; V, was 0.311 and V2 0.446L?kg-1 ; Cl1 was 33.31 and Cl2 16.65 ml?min-1?kg-1 respectively. V1 and V2 were significandy larger, and transfer and clearance rates were significantly higher in AHHD group than those in control group. At the end of AHHD, Hb decreased by 31.0% and Hct by 31.3%; total plasma protein decreased by 30.1% and plasma albumin by 25.7% as compared with the baseline values before AHHD. Conclusion AHHD has significant effect on pharmacokinetics of propofol. Less propofol is bound to plasma protein and duration of action is relatively shorter. During AHHD the target plasma propofol concentration should be increased to some extent to achieve the same depth of anesthesia.