Analysis And Investigation Of Influencing Factors Of Cardiopulmonary Bypass On Propofol Concentration

Background: Cardiopulmonary bypass is one of the necessary technologies for open heart surgery. But many factors including hemodilution, temperature, sorts of oxygenator, all kinds of drugs in priming fluid and ultrafiltration could affect the plasma concentration of propofol. The author would investigate these influencing factors from in vitro and in vivo to supply proper remedy for clinical anesthesia.Objective: 1) To investigate the effect of AHHD and ANHD on the propofol concentration and to evaluate the performance of target controlled infusion (TCI) for propofol; 2) To investigate the influence of oxygenator, temperature, drug and CPB time on propofol concentration; 3) To investigate the effect of domestic extracorporeal circuit on plasma concentration of propofol during target controlled infusion and to evaluate the performance of target controlled infusion (TCI) for propofol; 4) To investigate the effect of CPB on the propofol concentration and to assess both clinical effects and inflammatory mediator removal by high-volume, zero-fluid balance ultrafiltration (Z-BUF) during CPB.Methods: 1) Fifty four patients, ASAⅠ-Ⅱ, scheduled for operations were randomly divided into three groups. In AHHD group (n=18), Lactated Ringer's solution (RL) 10 ml·kg-1 was infused over 60min before induction of anesthesia. 10min after TCI propofol was started, AHHD was performed by 6% HES (hydroxyethylstarch 200/0.5) 20ml·kg-1. In ANHD group (n=18), autologous blood was removed from arterial line and stored in units of about 500mL with CPDA-l-stabilizer until the hematocrit (Hct) fell to 26%. Simultaneously, an equal amount of RL and 6% HES was given via a peripheral venous line. The process of ANHD lasted for 30min. After 10min of stabilization of ANHD, TCI propofol was started. In the control group, patients did not receive hemodilution during TCI. A single constant target plasma propofol concentration was 3μg·ml–1 as infusion with varied speeds, lasting 1hour. Arterial blood samples were taken at 0, 2, 5, 10, 20, 30, 40, 50, 60, 80, 100, 120, 150, 180min after TCI for determination of blood concentration of propofol by gas chromatography-mass spectrometry; 2) The oxygenator, temperature, drug and CPB time were taken as four experiment factors. Repeated measurement design was used. There were three kinds of oxygenators: Polystan membrane oxygenator, domestic membrane oxygenator and domestic bubble oxygenator. The temperature of the circulating solution was maintained at 28℃or 35℃with a heat exchanger. Oxygenator, a reservoir, silicone and polyvinylchloride tubings and arterial filter were comprised extracorporeal circuits. 20mg propofol were added to 2000ml priming solution with or without drug. The extracorporeal circuits ran 60min. Propofol concentration was then measured at before CPB, after CPB1, 5, 10, 20, 40, 60min by reverse high performance liquid chromatography (HPLC); 3) 60 adult patients with single valve disease or double valve diseases receiving valve replacement were randomly assigned to three groups: domestic bulb oxygenator group, domestic membrane oxygenator group and Polystan membrane group, each group comprising 20 cases. After intubation all patients were performed propofol TCI and 1h later were performed cardiopulmonary bypass (CPB). 3ml blood sample were taken before CPB, during CPB 1, 5, 10, 20, 40, 60min and after CPB 5, 10min for measurement propofol plasma concentration by reverse high performance liquid chromatography (HPLC); 4) Forty patients undergoing cardiac surgery were randomly assigned to Z-BUF or a control group. Z-BUF was performed after CPB started 1min and lasted 40min. 3ml blood sample were taken before CPB, during CPB 1, 5, 10, 20, 40min for measurement propofol plasma concentration by reverse high performance liquid chromatography (HPLC). Interleukin (IL) -6, IL-10, tumor necrosis factorα(TNF-α) and cTnI were determined in duplication by enzyme-linked immunosorbent assay before CPB, after CPB, 2h, 6h, 24h after operation. To be comparable, the concentration values were corrected for hemodilution.Results: 1) The measured propofol concentrations of the AHHD and ANHD group were significantly lower than the control group at different time-site during TCI (P<0.05) and the biggest drop was 38.5% in AHHD group and 40.0% in ANHD group. But there was no statistically significant difference between AHHD and ANHD on propofol concentration. The median performance error (MDPE) and median absolute performance error (MDAPE) were -7.12% and 21.23% in AHHD group and -8.83% and 22.98% in ANHD group, respectively; 2) There was a statistically significant difference in temperature (P=0.042) and CPB time (P=0.001) on propofol concentration, respectively. There was no statistically significant difference in oxygenator (P=0.052) and drugs (P=0.337) on propofol concentration, respectively. The effect of domestic bubble oxygenator on propofol concentration was smaller than Polystan membrane oxygenator and domestic membrane oxygenator. The propofol concentration in 28℃was higher than in 35℃. The oxygenator and CPB time interacted on propofol concentration. The propofol concentration significantly effected at different time-site during CPB 40min (P <0.05); 3) Propofol concentration decreased obviously after CPB in three groups: domestic bulb oxygenator group decreased 22.6%, domestic membrane oxygenator group 28.7% and Polystan membrane group 31.1%. 20min later propofol concentration of domestic and Polystan membrane oxygenator group recovered to the level before CPB value, but domestic bulb oxygenator group took 40min. There was no statistically significant difference between the three groups (P=0.681). The median performance error (MDPE) , median absolute performance error (MDAPE), wobble, and divergence of target-controlled infusion system were 21%, 29%, 21%, and–0.06%/h, respectively; 4) Ultrafiltration volume was 35 ml·kg-1 in the Z-BUF group. The propofol concentration decreased by 38.5% at CPB 5min and there was statistically significant difference between the two groups (P<0.0001). No statistically significant difference was found between the two groups in Entropy (P=0.5583). In the Z-BUF group, IL-6, IL-10, TNF-αand cTnI were significantly removed and eight patients (40%) needed supplement heparin.Conclusions: 1) AHHD and ANHD affected the measured concentrations, but there was no statistically significant difference between AHHD and ANHD on propofol concentration. TCI lowered estimated firstly and then overestimated significantly the measured concentrations and propofol TCI may be fitted to patients with AHHD and ANHD; 2) CPB time and temperature affected propofol concentration respectively. The effect of domestic bubble oxygenator on propofol concentration was smaller than Polystan membrane oxygenator and domestic membrane oxygenator. The propofol concentration in 28℃was higher than in 35℃; 3) The effect of CPB on propofol concentration was significant within CPB 20min. The domestic bulb oxygenator group decreased 22.6%, domestic membrane oxygenator group 28.7% and Polystan membrane group 31.1%. There was no statistically significant difference in three oxygenators. The MDPE and wobble of target-controlled infusion system under cardiopulmonary bypass were high; 4) Ultrafiltration volume, 35 ml·kg-1, Z-BUF could significantly remove inflammatory mediator and cTnI, and decreased propofol concentration by 30%～38%.