ABSTRACT
This paper presents a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extending power and easy manipulation. It has been used in the clinical anesthesia.
Subject(s)
Humans , Anesthesia, Intravenous , Methods , Anesthetics, Intravenous , Pharmacokinetics , Drug Delivery Systems , Methods , Drug Therapy, Computer-Assisted , Methods , Monitoring, Intraoperative , MethodsABSTRACT
OBJECTIVE To establish an assay for the simultaneous determination of propofol and lidocaine in human plasma using reversed-phase high performance liquid chromatography（RP-HPLC）.METHODS With thymol and bupivacaine as the internal standards for propofol and lidocaine respectively,the extraction was performed with cyclohexane.The organic layer was evaporated and the residue was redissolved by mobile phase.The concentrations of propofol and lidocaine were assayed on a hypersil BDS C18 column with a mobile phase consisting of acetonitrile-methanol-water（10∶60∶30）（including 0.14% n-butyamine 0.1% acetic acid）at a flow rate of 1 mL*min-1 and detected at 220 nm during 1～7 min and at 273 nm during 7～16 min.RESULTS The linearity between concentrations and peak area ratio was obtained from 0.1 μg*mL-1 to 25.6 μg*mL-1（r=0.998，r=0.9995）.The detection limits were 0.1 μg*mL-1 for propofol and 0.05 μg*mL-1 for lidocaine.The within-day and between-day variation coefficients were less than 5%(n=5).The average recoveries were 93.33%,99.4% and 90%,95.67% respectively.CONCLUSION The method was found to be rapid,accurate and precise.It is suitable for clinical pharmacokinetic and pharmacodynamic study.
ABSTRACT
Objective: To perform target-controlled infusion (TCI) in total intravenous anesthesia (TIVA) of propofol and fentanyl. Method: Using effect compartment modeling, computer controlled infusion(the computer software was developed by Coezee and Pina) was performed during induction and maintenance of anesthesia in two groups of adult patients. The target predicted concentration of theoretical effect-site compartment for propofol was 4?g/ml and for fentanyl was 2?g/ml. The plasma concentration (Cm) of propofol was determined by fluorospectrophotometry and Cm of fentanyl was measured with radioimmunoassay. Result: The mean Cm from 0 to 120 min showed that excessive dose of propofol was administered, MDAPE=25%,however the mean Cm of fentanyl was lower than the target level obviously,MDAPE=35.5% in first group. After an imitative calculation,another pharmacokinetic (PK) parameter sets of propofol and fentanyl were selected in the second group,MDAPE=15.5% for propofol and MDAPE=37. 75% for fentanyl. Conclusion: The concentrations of propofol and fentanyl in the effect site compartment can be achieved rapidly by using the effect compartment control algorithm. The PK parameter,described by different authors influences the accuracy of TCI administration.
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Objective To study the influence of age on the pharmacodynamics of propofol including the relationship between plasma concentrations of propofol and the time of loss of consciousness or return of consciousness.Methods Forty-two ASAⅠ-Ⅱ patients were assigned to one of three age groups: group A: age ranged from 18-34 yr(n=14); group B:35-60 yr(n=15); and group C: 61-90 yr(n=13). Once spinal anesthesia was completed, propofol infusion at the rate of 0.5 mg?kg -1?min -1(group A) or 0.4 mg?kg -1?min -1(group B and C )was started until burst suppression of EEG lasting 3s was observed. Venous blood samples were taken at 1, 2, 4, 8,10, 15, 30, 45,60,90,120 and 240 min after the start of propofol infusion for the determination of plasma propofol concentrations. The influence of age on relationship between propofol plasme concentration and loss of consciousness or return of consciousness was analyzed by non-linear regression. The relationships between age and time of loss of consciousness,duration of sleep,the total dose of propofol,the plasma concentration at the time of loss of consciousness or return of consiousness were determined by linear regression.Results As compared with those in group A and B,the time of loss of consciousness and the total dose of propofol required decreased markedly in group C. The observation showed increased sensitivity to propofol in elderly patients. The EC50 values for loss of consciousness were 2.86 (at age of 25 yr),2.26 (at 50yr), and 1.78 (at 75yr) ?g?ml -1,and the EC50 values for return of consciousness of 1.76 (at 25 yr),1.45(at 50yr),1.11(at 75yr)?g?ml -1 respectively.Conclusions Elderly patients are more sensitive to propofol than younger people in terms of hypnosis and EEG effects.
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Objective To study the influence of lidocaine on the propofol concentration effect relationships for loss of eyelash reflex and loss of consciousness,hemodynamic function Methods Thirty eight patients were randomly allocated to receiving a computer controlled infusion of lidocaine at target concentration of 0?g?ml -1 (group A,n=9),1 25?g?ml -1 (group B,n=7), 2 5?g?ml -1 (group C,n=7), 5?g?ml -1 (group D,n=8),or 7?g?ml -1 (group E,n=7) respectively While the target concentration of lidocaine was kept stable, propofol was administrated with a computer controlled infusion at an initial target concentration of 0 5 1?g?ml -1 , which was increased every time by 0 5?g?ml -1 until loss of consciousness Plasma concentrations of lidocaine and propofol were measured with high performance liquid chromatography Results 50% of patients lost eyelash reflex and consciousness at plasma propofol concentrations(Cp50) of 1 78 and 3 17?g?ml -1 in the absence of lidocaine In the presence of plasma lidocaine concentration of 1 25 4 3 ?g?ml -1 ,the Cp50 for loss of eyelash reflex was reduced by 42 1% There was a linear regression relationship between plasma lidocaine concentrations from 0 to 7?g?ml -1 and the Cp50 for loss of consciousness (r=-0 69 ) Conclusions The Chinese Cp50 for loss of eyelash reflex and consciousness are lower than those reported abroad Plasma lidocaine concentration at 4?g?ml -1 can potentiate properly the potency of propofol on the sedation and hypnosis during anesthesia induction
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To study the effects of fentanyl on the MAC of sevoflurane. Method: One hundred and sixteen patients were given continuous infusion of fentanyl with CACI-pump (computer-assisted continuous infusion)to maintain different target plasma concentrations (Ct), meanwhile inhaled sevoflurane. All patients were randomly divided into seven groups receiving sevoflurane in oxygen with fentanyl target plasma concentration of 0?g/L (n=16), 0.5?g/L(n=20), 1?g/L(n=18), 2?g/L(n=16), 3?g/L(n=18), 4?g/L(n= 14) or 6?g/L(n= 14). Plasma concentraion of fentanyl was measured with radioimmunoassay. MAC determination, in response to the stimulus of skin incision, was made using the "up-down" method and logistic regression. Result: The MAC of sevoflurane from group 1 to group 7 were 1.94%, 1.89%, 1.55%, 1.29%, 1.09%, 0.86% and 0.35% respectively. Conclusion: We verify the MAC of sevoflurane, which is reduced by increasing plasma fentanyl concentration.