| [Objectives] Since propofol has been used in clinical anesthesia, many scientists investigated its pharmacodynamic and pharmacokinetic aspects. However, influence of hypovolemia and hypervolemic hemodilu-tion on the amplitude of plasma propofol concentration has not yet been fully investigated during continuous propofol infusion, and they were a practical problem that an anesthesiologist often faced to. Therefore, an experimental research on pigs were taken place to discuss following fields: 1) Efficacy of the development of hypovolemic shock on the plasma propofol concentration; 2 ) Efficacy of different stages of hypovolemic shock on plasma propofol concentration; 3) Correlation between blood volume lost and plasma propofol concentration; 4) Efficacy of hypovole- mic shock on the clearance and metabolism of propofol by liver; 5)Efficacy of hypervolemic hemodilution on myocar-dial function and analysis of feasibility; 6)Efficacy of hypervolemic hemodilution on plasma propofol concentration; 7)Efficacy of hypervolemic hemodilution on plasma incremental effect; 8)Efficacy of hypervolemic hemodilution on the balance of supply and consumption of oxygen.Even the high performance liquid chromatography (HPLC) was one of the sophisticated method for measurement of propofol in human plasma concentration, it showed an obvious limitation for measurement of propofol plasma concentration in large animals during the pre-experiment.HPLC measuring conditions should be adjusted and evaluated for the proper measurment of propofol plasma concentration in pigs.This experimental study can be summarized in three parts. Part 1: Establishment of measuring.method for propofol concentration. Part 2: Efficacy of hypovolemic shock against plasma propofol concentration. Part 3: Efficacy of hypervolemic hemodilution on plasma volume and plasma propofol concentration.[ Methods ] In part 1 ,in order to avoid the malpractice which occurred in pre-experimental study, such as emulsifying affection, prolonged extracting time, low absolute extracting rate and instability, adjustment of detecting conditions were taken place and mobile phase changed for a better formation of peaks. Observation of aether and ethanol triethylamine as substitutes for other extract organic and alky organic solutions, and addtion of β -cyclodextrin in mobile phase consisted of methyl hydrate and water. Electrophoretic separation for propofol was also been established, including pH value of buffering solution and its subdivision and working voltage.In Part 2, after a stable propofol plasma concentration was achieved by continuous propofol infusion, and stepwise bleeding of each ten percentage blood volume was taken every 30 min, thereafter, to the point of circulatory collapse. Systemic vascular resistance(SVR) and heart rate(HR) were counted for shock compensatory indicators; mean arterial pressure lower 50mmHg and could not insist on consideration as circulatory collapse; difference between arterial and hepatic vein concentrations of propofol reflects the clearance ability of propofol in liver indirectly and the arterial propofol concentration was detected during all the procedure against hypovolemic shock.In Part 3,The less interruption of new colloid solutions against the coagulating system may gives further space to increase the colloid solution volume during hypervolemic hemodilution. 6% hetastarch wasinfused in 30 minutes with 30ml/kg dosage (common clinical was between 15~20 ml/kg dosage), for stimulation of the hypervolemic hemodilution in clinical practice. Cardiovascular function was evaluated by pulmonary artery catheter; posthypervolemic plasma volume changes was estimated by hematocrit dynamic changes; the posthypervolemic supply and consumption balance of oxygen and arterial propofol concentration were also observed.[Results] In Part 1, Propofol in pigs plasma was extracted with Aether and thymol was used as the internal standard, ethanol triethylamine was employed as substitute for the extraction in organic solutions, β -cyclodextrin in mobile phase consi... |
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