Effect Of CPB On Plasma Concentration Of TCI Propofol

BackgroundBy the developing of cardiac operation and cardiopulmonary bypass (CPB), and renovating the concept of anesthetic, the"fast trucks"(FTCS) cardiac anesthesia was going to be a better way for patients were suffering cardiac disease (CD)these two decades.Then after 1996, the popular parameter that was about propofol target controlled infusion (TCI) had been tried on the CD patients by Barvais[1] ,the TCI was popularize on cardiac surgery. TCI was a better way that based on pharmacokinetics and pharmacodynamics, and it was regulated by computer as blood drug level had changed.And propofol was used in various kinds surgery operations as being of short half-life and adjusting easily.The TCI of propofol was a wonderful event for contemporary anesthesiology.But there were many effect during CPB,just as hemodilution , hypothermia and organ perfusion and so on,it was not suited CPB anesthesia.Then hemodilution and hypothermia are the significant factors.So we picked the factors to study for CPB anesthesia.ObjectiveTo investigate the effect of acute hypervolemic hemodilution (AHH) and hypothermia on plasma concentration of TCI propofol under monitoring by BIS , and find out a safe anesthesia scheme guiding the clinic cardiovascular"fast trucks"anesthesia.MethodsThe study is composed of three parts:1. Nucleodur C18 was packed in the analytical column,the mobile phase consisted of acetonitrile :water: trifluoroacetic acid (65: 35: 0. 1)and the flow rate was 1. 4 m1/min.The fluorescence detective wave length wereλex=276nm,λem=310nm.2. Effect of CPB-induced acute hemodilution on plasma concentration of TCI propofolFourteen ASAⅡ～Ⅳpatients aged 48.2±12.0 years and weighted 40～75 kg, were subjected to bicuspid valve and aortic valve replacement.. The vital signs of the patients,including MAP ,HR,P,CVP, ECG,ETCO2, SPO2 NT(temperature of nasal cavity) and RT (rectal temperature) were continuously monitored before and during the anesthesia.The radial artery and right internal jugular vein were cannulated before induction of anesthesia for MAP and CVP monitoring. TCI of propofol was performed in all the patients after induction of anesthesia . The target plasma concentration (Cp) of propofol was set at 2μg/ml by Diprifusor TCI system. At the beginning of CPB, 4% gelofusine was infused simultaneously. Arterial blood samples were taken before hemodilution(T0), and at 3 min(T1),8 min(T2),15 min(T3) after it for determination of plasma concentration(Cm) of propofol by HPLC. Hct,Hb, AST,ALT,Cr and BUN were also determined at the same time .3. Effect of CPB-induced acute hypothermia on plasma concentration of TCI propofolThirteen ASAⅡ～Ⅳpatients aged 48.2±12.0 years and weighted 40～75 kg ,were subjected to bicuspid valve and aortic valve replacement. The vital signs of the patients,including MAP ,HR,P,CVP, ECG,ETCO2, SPO2 NT(temperature of nasal cavity) and RT (rectal temperature) were continuously monitored before and during the anesthesia.The radial artery and right internal jugular vein were cannulated before induction of anesthesia for MAP and CVP monitoring. TCI of propofol was performed in all the patients after induction of anesthesia . The target plasma concentration (Cp) of propofol was set at 2μg/ml by Diprifusor TCI system.Then the temperature was reduced after CPB15 min , ice cap and cooling the temperature of operating room. The rectal temperature was to 32℃in 20 min after CPB. Arterial blood samples were taken at36℃34℃, 32℃, 30℃and 28℃for determining the plasma concentration of propofol(measured concentration) by HPLC. Hct,Hb, AST,ALT,Cr and BUN were also determined at the same time .Results1. The standard curve equation was C=0.183X+5.04×10-3(R2=0.9999,n=8),the linear range was 0.1～10μg/ml,the recovery was 95.80%～104.92%.Intra-day and inter-day precision(RSD%)were all less than 10% significantly.The limit of detection was0.1μg/ml.2. After hemodilution, Hb was significantly reduced from initial (139.86±19.90)g/L to (82.71±12.86) g/L and Hct from (40.62±4.09)% to (25.14±3.82)%, respectively ( P﹤0.01). The Cm was obviously lower at T1, T2 and T3 than that at T0 (P<0.05).There was no significant difference in Cm among T1, T2 and T3 ( P>0.05).And AST,ALT,Cr and BUN was no significant difference after hemodilution.3. After hypothermia in the course of CPB , no difference was found in Hb and Hct at 34℃and down to 28℃(P﹥0.05),the ratio of Cm / Cps rose gradually with lowering of rectal temperature and it reached the top value at 28℃;during this period AST,ALT,Cr and BUN were all normal.Conclusions1. The RP-HPLC method is simple, sensitive and accurate for monitoring propofol concentration in clinical plasma samples.2. AHH in CPB decreases the blood concentration of propofol obviously. And it turnes down dramastically at T1. Before AHH, Cm is higher than Cp, but Cm is lower than Cp after AHH. The Cp needs to be increased during AHH of CPB in order to keep a proper depth of anesthesia.3. Hypothermia in CPB increases the Cm / Cps of propofol obviously. It is better to down-regulate the target concentration of propofol proportionally for safety when TCI is practised .