Objective To determine the population pharmacokinetics of intravenous etomidate infusion in adult patients.Methods Twenty-nine ASA Ⅰ or Ⅱ patients of both sexes aged 25-82 yr weighing 45-80 kg received contant-rate infusion of etomidate at 60 μg· kg-1 · min-1 until BIS value dropped to ≤ 40.Arterial blood samples were obtained from radial artery for determination of plasma etomidate concentration before,at 1,3,5 min of continuous etomidate infusion and at 1,3,5,7,10,20,30,45,75,120,180,240,300 and 360 min after termination of etomidate infusion.Population pharmacokinetic model was established by using the software package NONMEM.Population pharmacokinetic parameters were calculated according to etomidate concentrations and covariates including age,height,bodyweight,sex,liver-kidney function etc.using software package NONMEM.Results Pharmacokinetics of etomidate was best described by a three-compartment pharmacokinetic model with age as a covariate affecting systemic clearance (CL1).The typical parameters were:V1 =4.7 L,V2 =11 L,V3 =123L,CL1 =1.28-0.0119 × (Age (yr)-55) L/min,CL2 =1.25 L/min and CL3 =1.08 L/min respectively.Context-sensitive half-time increased with age and steady-state infusion time.Conclusion Pharmacokinetics of etomidate is best described by a three-compartment pharmacokinetic model with age as a covariate affecting systemic clearance (CL1).

Objective To compare the pharmacokinetic profile of propofol administered by target-controlled infusion (TCI) during anesthesia in patients with and without obstructive jaundice. Methods Twenty-four ASAⅠorⅡpatients aged 40-65 yrs weighing 50-75 kg undergoing elective surgery under general anesthesia were divided into 3 groups (n = 8 each) : group A control (serum total bilirubin 171.1?mol?L-1) . Each group received propofol by TCI using Graseby 3500 infusion pump, based on pharmacokinetic parameter set published by Marsh. The target plasma concentration of propofol was set at 3?g?ml-1 . TCI of propofol was started from the induction of anesthesia and maintained until the end of the surgery. Arterial blood samples were taken at 0.5, 1, 2, 4, 6, 8 min after TCI of propofol was started and every 15 min during maintenance of anesthesia and at 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 90, 120, 180, 240 and 300 min after TCI was terminated. Plasma concentrations of propofol were determined by high-performance liquid chromatography (HPLC) with fluorescence detector. NONMEM was used to analyze the pharmacokinetic parameters. Results The 3 groups were comparable with respect to sex ratio, age and body weight. The pharmacokinetic profile of propofol given by TCI was best described by three-compartment open pharmacokinetic model in the majority of patients and by two-compartment open pharmacokinetic model in a few patients. There were no significant differences in the pharmacokinetic profile of propofol among the 3 groups. Conclusion Obstructive jaundice does not affect the pharmacokinetics of propofol.

0.05) . AEP index increased sharply from 42 to 67 when the patients regained consciousness (OAA/S increased from 2 to 3) but BIS increased gradually from 64 to 72 indicating that AEP index had better discriminatory performance. OAA/S correlated fairly well with BIS , AEP index and target-controlled concentration of propofol and r was 0.781, 0.684 and - 0.580 respectively. Conclusions Both AEP index and BIS can predict fairly well the level of sedation but AEP index prooes to be better in distinguishing conscious from unconscious.

Objective To evaluate the accuracy of target-controlled infusion (TCI) of propofol using pharmacokinetic parameters reported by Marsh to predict plasma propofol concentration in Chinese. MethodsTwenty-two ASA I - II patients were divided into two groups: group Y aged65 yr ( n = 11). Patients with liver, kidney or cardiovascular diseases were excluded. The patients were premedicated with pethidine 50mg and phenobarhital 0.1 g im. Radial artery and internal jugular vein(IJV) were cannulated. The pharmacokinetic parameters incorporated in the Graseby 3500 pump we used were: V1=228 ml-kg-1 , K10 =0.119 min-1 ,K12=0.112 min-1, K2l=0.055min-1 , K13 =0.0419 min-1 ,K31 =0.0033 min-1. Target concentration was started with 2ug-ml-1 and increased at increment of 1ugml-1 until loss of consciousness. The patient was then intubated. When target concentration of propofol was increased, the concentration of inhalation anesthetic was reduced to maintain hemodynamic stability. When target concentration of propofol was increased, arterial blood sample was taken 1-3 times for determination of plasma propofol concentration measured by HPLC (Agilent 1100) . Then blood samples every 10-15 min. For each sample prediction error(PE) and constancy error(CE) were calculated. For each patient median prediction error(MDPE), median absolute prediction error(MDAPE) . Median absolute constancy error (MDACE) and median constancy error (MDCE) were calculated.ResultsThere was remarkable initial overshot. PE and absolute PE were 63.3 % and 66.2 % in group E and 62.1 % and 62.7% in group Y. CE and absolute CE were -0.3% and 12.7% in group E and 0.6% and 13.5% in group Y. The median value of MDPE ( = the median value of MDAPE) was 78.1 % in group E and 66.1% in group Y. The median value of MDCE was 0.2% (group E) and 0.8% (group Y) and MDACE was 12.5% (group E) and 13.5% (group Y) . The measured concentrations were significantly linearly correlated with the premedicated concentrations. Conclusion TCI system with propofolpharmacokinetic parameters reported by Marsh can lead to initial overshot and underestimate the measured plasma propofol concentration but it can maintain a stable plasma concentration

Objective To evaluate the efficacy of epidural block combined with general anesthesia for elderly upper abdominal surgery Methods Thirty-four elderly patients ,scheduled for elective upper abdominal surgery, ASA grade Ⅰ-Ⅱ, were divided randomly into study group (groupⅠ) and control group (group Ⅱ) In both groups anesthesia was induced with introvenous diazepam 0 1mg?kg -1, fentanyl 5?g?kg -1, etomidate 3mg?kg -1, atracurium 0 2 mg?kg -1 and succinylcholine 2 mg?kg -1, and was maintained with intravenous infusion of propofol 4-10ml/h and/or inhalation of 1% isoflurane and intermittent bolus of atracurium In groupⅠ epidural block was performed before induction Hemodynamics was measured with impendence cardiography and electroencephagram were monitored and intraoperative awareness, postoperative restlessness and anesthetic dosage were recorded, also the concentrations of plasma vasopressin and blood glucose were determined at pre-operation, incision and the end of surgery Results In group Ⅰ MAP,CO,HR incresed slightly during intubation, incision and extubation, and systemic vascular resistance (SVR) decreased during operation , but SVR was increased abruptly after extubation in group Ⅱ There were unsignificant changes in thoracic fluid index(TFI), stroke volume(SV), ejection volume index(EVI), EVI/TFI ratio in both groups during whole procedures SEF was recovered more earlier in group Ⅰthan that of in group Ⅱ after extubation The vasopressin and glucose levels increased significantly after-extubation compared with those before operation in group Ⅱ Conclusions The epidural block combined with general anesthesia can be more effectvely and safely applied to elderly upper abdominal surgery

Objective To evaluate the blood-saving effect of acute hypervolemic hemodilution (AHH) with 6％ hydroxyethyl starch 130/0.4 (HES 130/0.4) in preschool children.Methods Forty ASA Ⅰ patients,aged 3-6 yr,weighing 11.5-22.5 kg,with body height of 78-120 cm,scheduled for orthopedic or general surgeries,were divided into 2 groups by drawing lots:group AHH (n =20) and group control (n =20).6％HES 130/0.4 10 ml/kg was infused over 30 min at a rate of 0.3 ml·kg-1 · min-1 through the internal jugular vein before surgery in group AHH.The fluid balance,blood loss,urine output and blood transfusion during operation were recorded.The blood routine,liver and kidney function and coagulation function (prothrombin time (PT),activated partial thromboplastin time (APTT),fibrinogen (Fib)) were measured before AHH (T0) and at 0,4 and 24 h after AHH (T1-3).Hypokalemia,hypocalcemia and prolongation of PT and APTT during surgery,and pulmonary edema,heart failure and abnormal bleeding from the site in the wound during the perioperative period were recorded.Results The two groups were comparable with regard to the volume of multiple electrolyte solution consumed,blood loss,parameters of liver and kidney function,platelet count and incidences of hypokalemia and hypocalcemia (P ＞ 0.05).The urine output was significantly increased,Hct at T1 and Fib at T1,2 were significantly decreased,PT and APTT were prolonged,and the percentage of patients without allogeneic blood transfusion and incidences of prolongation of PT and APTT were significantly increased in group AHH as compared with group C (P ＜ 0.05).No pulmonary edema,heart failure and abnormal bleeding were found during the perioperative period.Conclusion AHH with 6％ HES 130/0.4 10 ml/kg provides better blood-saving effect in preschool children,has little effect on the internal environment,but prolongs the coagulation time and exerts effect on coagulation function to some extent.

Objective To establish the pharmacodynamic model of sevoflurane with bispectral index (BIS) as the effective index in pediatric patients.Methods Thirteen ASA physical status Ⅰ or Ⅱ pediatric patients,aged 4-9 yr,weighing 12-39 kg,undergoing non-cardiac surgery,were selected in the study.The pediatric patients sequentially inhaled 1％,5 ％ and 1％ sevoflurane via a face mask and each concentration was inhaled for 15 min.BIS value,HR,BP and SpO2 were automatically recorded every 10 s.Based on nonlinear mixed effect modeling,the population pharmacodynamic model of sevoflurane was established using NONMEM software.The effect of age on the pharmacodynamic parameters was evaluated using a stepwise forward addition then backward elimination modeling approach.The standard for model improvement was defined as a decrease in the value of the objective function by more than 3.84.Results Twelve pediatric patients,aged 4.0-8.5 yr,weighing 12.8-38.0 kg,with body height of 92-135 cm,were enrolled in this study and the data which were enrolled comprised 2964 effective concentration-time-BIS points.The model was not improved significantly with any covariates (age,body height,and body weight) introduced (P ＞ 0.05).The estimated parameters of the final pharmacodynamic model of sevoflurane were as follows:ke0 =O.516/min ; EC50 (BIS50) =2.11％ ; γ =2.46 ; E0 =74.6 ; EMAx =11.2.Conclusion The pharmacodynamic model of sevoflurane is successfully established with BIS as the effective index in pediatric patients,and the analysis for each parameter of the model indicates that the sensitivity to sevoflurane is lower,but the blood-brain equilibration time of the drug is shorter and the onset and recovery are faster in children than in adults.

Objective To evaluate the pharmacodynamics of oral chloral hydrate sedation for echocardiography in pediatric patients with congenital heart disease (CHD).Methods Two hundred ASA physical status Ⅱ-Ⅳ pediatric patients with CHD, aged 5-620 days,scheduled for elective echocardiography,were enrolled in the study.The dose of oral chloral hydrate was set at 50 mg/kg in the first pediatric patient.The oral dosage was determined by up-and-down sequential experiment.Each time the oral dose increased/decreased by 10％ in the next pediatric patient.The pharmacodynamics was analyzed based on the dose-response model to determine the 50％ effective dose (ED50),95％ effective dose (ED95) and 95％ confidence interval (95％ CI) of chloral hydrate for sedation.The covariates (age,gender,time period of administration,fasting time,sleeping at 2 h before sedation,premature and cyanotic CHD) were introduced into the dose-response model,and the effect of each covariate on the pharmacodynamics of chloral hydrate sedation was evaluated.Results The ED50 of chloral hydrate for sedation during echocardiography was 42.2 mg/kg (95 ％ CI 40.2-44.2 mg/kg), ED95 was 67.4 mg/kg (95％ CI 53.7-81.1 mg/kg) in the pediatric patients with CHD.Each covariate provided no effect on the pharmacodynamics of chloral hydrate sedation (P ＞ 0.05).When fasting time and premature were introduced into the dose-response model,95％ CI of the slope of dose-response curve included 0.When age which was stratified was introduced into the dose-response model,it was difficult to fit or the data seriously deviated from the clinical data.Conclusion The ED50 and ED95 of chloral hydrate for sedation during echocardiography were 42.2 mg/kg (95％ CI 40.2-44.2 mg/kg) and 67.4 mg/kg (95％CI 53.7-81.1 mg/kg),respectively,in the pediatric patients with CHD.Gender,time period of administration,sleeping before sedation and cyanotic CHD do not affect the pharmacodynamics of oral chloral hydrate sedation,while the effect of age,fasting time and premature needs further determination.

Objective To investigate the effect of preoperative oral midazolam on emergence agitation after sevoflurane anesthesia in children.Methods Sixty children,34 males,26 females, aged 2-7 years,ASA grade Ⅰ or Ⅱ,receiving sevoflurane for tonsillectomy/adenoidectomy were ran-domly divided into low dose midazolam group (group M1),high dose midazolam group (group M2) and control group (group C)(n=20 each).The 5 ml mixture of midazolam 0.5 mg/kg,0.75 mg/kg and 10% glucose was taken orally 30 min before anesthesia in group M1 and group M2,respectively. While 5 ml of 10% glucose was given in group C.Anesthesia was induced with inhalation of 8%sevoflurane and maintained with intravenous infusion of remifentanil and inhalation of sevoflurane. Scores of parental separation anxiety scale(PSAS),pediatric anesthesia emergence delirium scale (PAED scale),FLACC scale were compared.Times to extubation and discharge from PACU were al-so recorded.Results Group C showed significantly higher incidence of separation anxiety(P <0.05). The incidence of emergence agitation,peak PAED scores,FLACC scores,time to extubation were similar among three groups.Discharge time from PACU was longer in group M2 (P < 0.05). Conclusion Preoperative oral midazolam 0.5 mg/kg or 0.75 mg/kg can effectively reduce parental separation anxiety.This,however,dose not result in a reduced incidence of emergence agitation after sevoflurane anesthesia.Midazolam 0.75 mg/kg can extend the discharge time from PACU.

Objective To evaluate the accuracy of ultrasonographic measurement of the subglottic airway diameter in selecting the cuffed endotracheal tube (ETT) size for the pediatric patients with congenital heart disease.Methods Sixty pediatric patients of both sexes with congenital heart disease,of American Society of Anesthesiologists physical status Ⅱ-Ⅳ,aged 1 month-7 yr,undergoing elective open heart surgery,were included in this study.The subglottic airway diameter was measured by bedside ultrasonography after induction of anesthesia.The outer diameter of the cuffed ETT was determined according to the subglottic airway diameter.The air leak test was performed after intubation to determine whether or not the ETT size selected based on ultrasonography was appropriate.When the difference between the inner diameter of the finally selected ETT and the result calculated by the Motoyama formula was less than 0.2 mm,the ETT size selected based on the Motoyama formula was considered appropriate.The agreement and correlation between the subglottic airway diameter measured by age-based formula and ultrasonography and the outer diameter of the actually selected ETT were analyzed using Bland-Altman plot and Passing-Bablok regression analysis.Results The accurate rate of the ETT selected based on the ultrasonic measurement and Motoyama formula were 80％ and 55％,respectively,and there was significant difference (P＜0.05).Conclusion Ultrasonographic measurement of the subglottic airway diameter produces higher accuracy than the classical Motoyama formula in selecting the cuffed ETT size for the pediatric patients with congenital heart disease.