OBJECTIVE:To study the clinical pharmacokinetics of Midazolam.METHODS:Fourteen patients undergoing general anesthesia with Midazolam in combination with remifentanil and isoflurane were enrolled in our study.The midazolam was administered by constant-rate infusion of 20 ?g?kg-1?min-1 for 20 min.The sampling of radial artery blood samples(3 mL/sample)were schedule before the infusion and at 1,3,5,7,10,15 and 20 min after the initiation of infusion and at 5,15,30,45 min and 1,2,4,6,12,18,24 h following the completion of midazolam.The plasma midazolam concentrations were determined by RP-HPLC.The pharmacokinetic analysis was performed using DAS2.1.1 program.RESULTS:The concentration-time curves of midazolam were best described by a simple three-compartment open model in which the weight coefficient was 1 and the typical pharmacokinetics parameters of midazolam were as follows:t1/2?=9.584 2 min,t1/2?=85.367 7 min,t1/2?=339.736 5 min,V1(the distribution volume of central compartment)=0.182 1 L?kg-1,CL=119.434 4 mL?h-1?kg-1,K10=0.045 8 min-1,K12=0.086 3 min-1,K21=0.017 5 min-1,K13=0.013 3 min-1,K31=0.002 4 min-1.CONCLUSION:t1/2?,t1/2?,t1/2? and CL were in line with those reported in the literature abroad,but V1 is on the lower side and it is easy for the medication to reach a balance.However,the rapid clearance of midazolam is more in line with the pharmacokinetic parameters of the Chinese subjects.

Objective To evaluate the effects of fentanyl and lidocaine on hypnotic effect of propofol in total intravenous anesthesia(TIVA) Methods One hundred and sixty ASAI Ⅲ patients(86 male,74 female) aged (55 0?12 4)yr,weighing (58 0?9 8)kg,scheduled for elective surgery were randomly divided into propofol group(group P,n=30), propofol fentanyl group(group PF,n=52) and propofol lidocaine group (group PL,n=78) Patients with kidney and liver dysfunction, hypertension, neurological and mental disease were excluded All patients were premedicated with intramuscular phenobarbital 0 1g and atropine 0 5mg BP,HR,SpO 2 and BIS were continuously monitored The patients were anesthetized by TIVA with TCI The target plasma concentration for fentanyl was 2?g/L(group PF) and for lidocaine 4mg/L(group PL) The initial target plasma concentration of propofol was set at 1mg/L When pre set concentration was reached, target propofol plasma concentration was increased by increments of 0 5mg/L until loss of consciousness Blood samples were taken before anesthesia(T 0), loss of consciousness(T 1), immediately after intubation(T 2), at skin incision(T 3), 5 and 10 min after skin incision(T 4,T 5), when TIVA was ended (T 6) and when the patient waked up(T 7) for determination of plasma concentrations of propofol, fentanyl and lidocaine Results ED 90 and ED 50 of propofol for loss of consciousness were lower in group PF and PL than those in group P but the difference was of no statistical significance (P

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.

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.

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

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.

This paper introduces such information of a LCD graphic display system based on SED1335 as its hardware link with the singlechip computer Atmega128 and the design of system display software. With a simple, compact and stable circuit, this system can be applied to portable medical signal monitoring and controlling equipments.

Objective To explore the correlation of patient-controlled sedation of dexmedetomidine and Narcotrend values. Methods Forty patients with lower limb surgery were enrolled. Until CSEA block fixed , the electronic pump ran the patient-controlled sedation of dexmedetomidine. The parameter of electronic pump was set as follows: load dose 2 mL + background dose 1.5 mL/h + single dose 0.5 mL + locktime 20 s. The heart rate , mean arterial pressure, pressing times, effective times, OAA/S sedation scores and NI values were determined. Results At T4 point, the patients reached appropriate sedation. At T4 ~ T9 OAA/S scores kept 3 to 4. From T5 point, NI values showed significant decrease. After the T7 point. OAA/S scores and NI values reached the plateau time of (7.5 ± 1.8) min and (13.1 ± 3.4) min, OAA/S scores of 1, 2, 3, 4, respectively, corresponding roughly with NI values 95 to 100, 90 to 94, 65 to 89, 40 to 64. The correlation coefficient was 0.58. The time of NI values significant decreased in the younger group and in the elderly group, with (10.2 ± 1.6) min and (14.4 ± 2.2) min. In T5~ T9 point, NI values of the younger group were significantly lower than those in the elderly group. Conclusion Relevant relationships are observed between dexmedetomidine patient-controlled sedation depth and the narcotrend values under CSEA.

OBJECTIVE:To study the accuracy of infusion of Midazoloam with plasma concentration as target. METHODS:The parameters of Midazoloam obtained from our researches were inputted into target-controlled infusion(TCI) system with C language. The clinical anesthesia of 12 patients undergoing selective operations was completed with plasma concentration as target-controlled infusion. Predicted value of plasma concentration of Midazoloam was compared with measured value. Parameters of Midazoloam sample were calculated such as performance error(PE),absolute performance error(absPE),median performance error(MDPE),median absolute performance error(MDAPE),constancy error(CE),absolute constancy error(absCE),median constancy error(MDCE) and median absolute constancy error(MDACE). RESULTS:PE,absPE,MDPE and MDAPE of plasma concentration were -2.57%,14.16%,-3.28% and 15.34%,respectively. CE,absCE,MDCE and MDACE were 0.06%,1.42%,0.03% and 1.21%,respectively. The measured values were in indirect relationship with predicated values(r=0.986,P

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.