BACKGROUND Propofol is a short-acting,rapid-recovering anesthetic widely used in sedated colonoscopy for the early detection,diagnosis and treatment of colon diseases.However,the use of propofol alone may require high...BACKGROUND Propofol is a short-acting,rapid-recovering anesthetic widely used in sedated colonoscopy for the early detection,diagnosis and treatment of colon diseases.However,the use of propofol alone may require high doses to achieve the induction of anesthesia in sedated colonoscopy,which has been associated with anesthesia-related adverse events(AEs),including hypoxemia,sinus bradycardia,and hypotension.Therefore,propofol co-administrated with other anesthetics has been proposed to reduce the required dose of propofol,enhance the efficacy,and improve the satisfaction of patients receiving colonoscopy under sedation.AIM To evaluate the efficacy and safety of propofol target-controlled infusion(TCI)in combination with butorphanol for sedation during colonoscopy.METHODS In this controlled clinical trial,a total of 106 patients,who were scheduled for sedated colonoscopy,were prospectively recruited and assigned into three groups to receive different doses of butorphanol before propofol TCI:Low-dose butorphanol group(5μg/kg,group B1),high-dose butorphanol group(10μg/kg,group B2),and control group(normal saline,group C).Anesthesia was achieved by propofol TCI.The primary outcome was the median effective concentration(EC50)of propofol TCI,which was measured using the up-and-down sequential method.The secondary outcomes included AEs in perianesthesia and recovery characteristics.RESULTS The EC50 of propofol for TCI was 3.03μg/mL[95%confidence interval(CI):2.83-3.23μg/mL]in group B2,3.41μg/mL(95%CI:3.20-3.62μg/mL)in group B1,and 4.05μg/mL(95%CI:3.78-4.34μg/mL)in group C.The amount of propofol necessary for anesthesia was 132 mg[interquartile range(IQR),125-144.75 mg]in group B2 and 142 mg(IQR,135-154 mg)in group B1.Furthermore,the awakening concentration was 1.1μg/mL(IQR,0.9-1.2μg/mL)in group B2 and 1.2μg/mL(IQR,1.025-1.5μg/mL)in group B1.Notably,the propofol TCI plus butorphanol groups(groups B1 and B2)had a lower incidence of anesthesia AEs,when compared to group C.Furthermore,no significant differences were observed in the rates of AEs in perianesthesia,including hypoxemia,sinus bradycardia,hypotension,nausea and vomiting,and vertigo,among group C,group B1 and group B2.CONCLUSION The combined use with butorphanol reduces the EC50 of propofol TCI for anesthesia.The decrease in propofol might contribute to the reduced anesthesia-related AEs in patients undergoing sedated colonoscopy.展开更多
This study aimed to establish a new propofol target-controlled infusion（TCI） model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and ...This study aimed to establish a new propofol target-controlled infusion（TCI） model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol（10 mg/kg） was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using Win Nonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index（NI） versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/m L, while 12.52±0.69 μg/m L at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant（ke0） was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/m L（95% CI, 10.25–13.67）. Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.展开更多
Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirty-two patients with ASA Ⅰ - Ⅱ , 65 - 82 years old, undergoing selective lower abdominal op...Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirty-two patients with ASA Ⅰ - Ⅱ , 65 - 82 years old, undergoing selective lower abdominal operation were studied. Propofol was administered by target-controlled infusion with Marsh parameter. The target plasma concentration was 3 μg＇ mL^-1. Radial arterial blood samples were collected and analyzed by reversed phase HPLC with fluorescence detection. Population pharmacokinetic modeling was performed using NONMEM. Inter-individual variability and intra-individual variability of propofol were estimated for clearances and volumes of distribution. The effects of age, body weight, lean body mass, gender, height, hemoglobin, total protein, albumin, creatinine, alanine aminotrans ferase （ALT）, and aspartate aminotransferase （AST） were investigated. The effects of coadministered opioid drugs were also studied. Results The pharmacokinetics of propofol in the Chinese elderly patients was best described by a three-compartment open model. Lean body mass was found to be a covariate for system clearance at significant level （ P 〈 0.005）. The clearance decreased linearly with age as well （ P 〈 0. 005）. The apparent volume of distribution for deep peripheral compartment （V3） was influenced by gender. Elderly female patients showed a higher value for V3. Conclusion The pharmacokinetics of propofol administered by TCI in Chinese elderly patients can be well described by a three-compartment open model. Inclusion of age, lean body mass and gender as covariates significantly improved the model. To ensure the accuracy and precision of target-controlled infusion, the population pharmacokinetic model applied to the individual patient should be adjusted reasonably.展开更多
Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in...Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in Chinese surgical patients. Methods The pharmacokinetics of sufentanil was investigated in 12 adult patients, aged 23-76 years, scheduled for prolonged surgery under general anesthesia. Anesthetic induction was carried out with propofol, rocuronium and TCI administered sufentanil aiming for target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI lasted for 30 minutes. Frequent arterial blood samples （1.5 ml） were drawn during and up to 24 hours after sufentanil TCI. Plasma sufentanil concentrations were measured by liquid chromatography-tandem mass spectrometry; limit of sensitivity of mass spectrometry was 5 pg/ml. The data were analyzed with the nonlinear mixed-effect model program. Results The pharmacokinetics of TCI administered sufentanil were optimally described by a three-compartment model with the following parameters： the central volume of distribution （V1） = 5.4 L, the volume of distribution at steady-state （Vdss） = 195.4 L, systemic clearance （CI1） = 1.10 L/min, and elimination half-life （t1/2 Y） = 271.8 minutes. Both age and gender affected the pharmacokinetic parameters. The rapid distribution clearance （012） was negatively correlated with patient age, and the volume of slowly equilibrating compartment （V3） was positively correlated with age. The Cl2 and the volume of rapidly equilibrating compartment （V2） were influenced by gender with male patients showing higher values of Cl2 and V2 than female patients. There was no relationship of body weight, lean body mass, plasma albumin, or target effect-site concentration of sufentanil with any of the pharmacokinetic parameters studied. Conclusions The pharmacokinetics of TCI administered sufentanil in Chinese patients can be adequately described by a three-compartment model. Pharmacokinetics adjusted to the individual patient should improve the accuracy of TCI systems.展开更多
Background There are few studies to assess whether the effect-site concentration of propofol can predict anesthetic depth during the target-controlled infusion （TCI） induction in elderly patients. This study aimed t...Background There are few studies to assess whether the effect-site concentration of propofol can predict anesthetic depth during the target-controlled infusion （TCI） induction in elderly patients. This study aimed to evaluate the relationship between effect-site concentration of propofol and depth of anesthesia during the TCI induction in elderly patients. Methods Ninety patients （60-80 years） with an American Society of Anesthesiologists （ASA） physical status of 1-3, undergoing scheduled abdominal and thoracic surgery under general anesthesia were randomly allocated into one of three groups, Group S1, S2 and S3 （30 patients in each group）. The patients in Group S1 received propofol with a target plasma concentration of 4.0 pg/ml; patients in Group S2 received propofol with an initial target plasma concentrations of 2.0 IJg/ml that was raised to 4.0 pg/ml 3 minutes later; patients in Group S3 received an infused scheme of 3 steps; starting from a target plasma concentration of 2.0 pg/ml that was increased stepwised by 1 pg/ml until a target plasma concentration of 4.0 pg/ml was achieved, the interval between the two steps was 3 minutes. When an Observer＇s Assessment of Alertness/Sedation （OANS） score of 1 was achieved, remifentanil （effect-site concentration （Ce） of 4.0 ng/ml） and rocuronium 0.9 mg/kg were administered. Tracheal intubation was started 2 minutes after rocuronium injection. Changes of propofol Ce, blood pressure （BP）, heart rate （HR）, and bispectral index （BIS） were recorded. Results When an OAA/S score of 1 was achieved, Ce of propofol were （1.7±0.4） pg/ml, （1.9±0.3） pg/ml, （1.9±0.4） pg/ml and the BIS values were 64±5, 65±8, and 62±8 in Groups S1, S2 and S3. Before intubation, Ce of propofol was （2.8±0.2） pg/ml, （2.8±0.3） pg/ml, （2.7±0.3） pg/ml, and the BIS values were 48±7, 51±7, and 47±5 in Groups S1, S2 and S3. By linear regression analysis, a significant correlation between Ce of propofol and BIS values was found （r=-0.580, P 〈0.01）. Systolic blood pressure （SBP） before intubation was significantly lower in Group S1 than in Groups S2 and S3. SBP and HR after intubation in the three groups were significantly increased when compared with pre-intubation values, but they did not exceed baseline values Conclusions During the TCI induction, Ce of propofol with （1.9±0.3） pg/ml may make the elderly patients unconscious. When remifentanil with a Ce of 4.0 ng/ml is added a Ce of propofol with （2.8±0.3） pg/ml is suitable for intubation. The Ce of propofol has a close correlation with the BIS values. Also, a two-step TCI technique seems to be a more suitable method of anesthesia induction in elderly patients compared with the no-stepwise TCI technique and three-step TCI technique.展开更多
Background Sufentanil is a suitable choice for target-controlled infusion （TCI） because of its shorter context-sensitive half-time. The current study was to estimate the pharmacokinetics of sufentanil TCI in Chinese...Background Sufentanil is a suitable choice for target-controlled infusion （TCI） because of its shorter context-sensitive half-time. The current study was to estimate the pharmacokinetics of sufentanil TCI in Chinese patients using the two-stage analysis. Methods Twelve adult patients with American Society of Anesthesiologists （ASA） physical status I or II undergoing elective surgery under general anesthesia were included. Anesthesia was induced with propofol, rocuronium and sufentanil administered by TCI lasting for 30 minutes, with target effect-site concentration of sufentanil 4 or 6 ng/ml. Frequent arterial blood samples （1.5 ml） were taken during and up to 24 hours after sufentanil TCI. Before the end of surgery, another arterial blood sample （1.0 ml） was drawn for the blood-gas analysis. Plasma sufentanil concentrations were determined by liquid chromatography-tandem mass spectrometry （limit of quantitation was 5 pg/ml）. The data were analyzed with the two-stage approach, linear regression and correlation analysis. Results The pharmacokinetics of sufentanil TCI were adequately described by a three-compartment model. The variables were derived as follows： the volume of central compartment （V1） was 5.4 L, volume of distribution at steady-state （Vdss） was 222.6 L, metabolic clearance （CI1） was 0.84 L/min and elimination half-life （t~/2y） was 389 minutes. Patients＇ age, gender and PaCO2 correlated significantly with the pharmacokinetic parameters. The Vdss, volume of slowly equilibrating compartment （V3） and t1/2 y increased, and rapid distribution clearance （012） decreased with increasing patient age. Male patients had larger values of Vdss, volume of rapidly equilibrating compartment （V2） and V3 than female patients. The Vdss and V3 increased with higher PaCO2 values. There were no significant correlations between the pharmacokinetic variables and body weight, height, lean body mass, plasma albumin, sufentanil dose, duration of surgery, pH or base excess of blood （BE-B）. Conclusions The pharmacokinetics of sufentanil TCI in Chinese patients can be optimally described by a three-compartment model. The pharmacokinetic analysis technique may affect the pharmacokinetic parameters and correlations.展开更多
Objective:To evaluate the predictive performance of‘Diprifusor’TCI(target-controlled infusion)system for its betterapplication in clinical anesthesia.Methods:The predictive performance of a‘Diprifusor’TCI system w...Objective:To evaluate the predictive performance of‘Diprifusor’TCI(target-controlled infusion)system for its betterapplication in clinical anesthesia.Methods:The predictive performance of a‘Diprifusor’TCI system was investigated in 27Chinese patients(16 males and 11 females)during upper abdominal surgery under total intravenous anesthesia(TIVA)withpropofol/fentanyl.Measnred arterial propofol concentrations were compared with the values predicted by the TCI infusion system.Performance was determined by the median performance error(MDPE),the median absolute performance error(MDAPE),thedivergence(the percentage change of the absolute PE with time),and the wobble(the median absolute deviation of each PE fromthe MDPE).Results:The median(range)values of 14.9%(-21.6%～42.9%)for MDPE,23.3%(6.9%～62.5%)for MDAPE,-1.9%h^(-1)(-32.7%～23.0% h^(-1))for divergence,and 18.9%(4.2%～59.6%)for wobble were obtained from 227 samples from all patients.For the studied population,the PE did not increase with time but with increasing target propofol concentration,particularly fol-lowing induction.Conclusions:The control of depth of anaesthesia was good in all patients undergoing upper abdominal surgicaloperation and the predictive performance of the‘Diprifusor’target controlled mthsion system was considered acceptable forclinical purposes.But the relatively bigger wobble showed that the pharmacokinetic model is not so suitable and requires im-provement.展开更多
Background：In this prospective randomized study,we compared the predicted blood and effect-site C50 for propofol and remifentanil target-controlled infusion （TCI） and the bispectral index （BIS） values at loss of ...Background：In this prospective randomized study,we compared the predicted blood and effect-site C50 for propofol and remifentanil target-controlled infusion （TCI） and the bispectral index （BIS） values at loss of consciousness （LOC） and response to a standard noxious painful stimulus （LOS） in elderly and young patients,respectively.We hypothesized that the elderly patients will require lower target concentration of both propofol and remifentanil at above two clinical end-points.Methods：There were 80 American Society of Anesthesiologists （ASA） physical status Ⅰ Ⅱ unpremedicated patients enrolled in this study,they were divided into elderly group （age ≥65 years,n =40） and young group （aged 18-54 years,n =40）.Propofol was initially given to a predicted blood concentration of 1.2 μg/ml and thereafter increased by 0.3 μg/ml every 30 s until Observer＇s Assessment of Alertness and Sedation score was 1.The propofol level was kept constant,and remifentanil was given to provide a predict blood concentration of 2.0 ng/ml,and then increased by 0.3 ng/ml every 30 s until loss of response to a tetanic stimulus.BIS （version 3.22,BIS Quattro sensor） was also recorded.Results：In elderly group,the propofol effect-site C50 at LOC of was 1.5 （1.4-1.6） μg/ml,was significantly lower than that of young group,which was 2.2 （2.1-2.3） μg/ml,the remifentanil effect-site C50 at LOS was 3.5 （3.3-3.7） ng/ml in elderly patients,was similar with 3.7 （3.6-3.8） ng/ml in young patients.Fifty percent of patients lost consciousness at a BIS value of 57.3 （56.4-58.1）,was similar with that of young group,which was 55.2 （54.0-56.3）.Conclusion：In elderly patients,the predicted blood and effect-site concentrations of propofol at LOC were lower than that of young patients.At same sedation status,predicted blood and effect-site concentrations of remifentanil required at LOS were similar in elderly and young patients.BIS were not affected by age.Low-propofol/high-opioid may be optional TCI strategy for elderly patients.展开更多
Background Although the performance of target-controlled infusion (TCI) have been studied extensively, the accuracy and safety of a TCI system that targets the effect site remains to be demonstrated. This study was to...Background Although the performance of target-controlled infusion (TCI) have been studied extensively, the accuracy and safety of a TCI system that targets the effect site remains to be demonstrated. This study was to investigate the relations of TCI of propofol to its concentrations in cerebral spinal fluid (CSF), the effect-site concentrations and bispectral index (BIS).Methods Twelve mongrel dogs were used for investigations. The target effect-site concentration was set at 3μg/ml and the infusion was lasted for 15 minutes. CSF and blood samples were then collected and propofol concentrations were determined by using high performance liquid chromatography with fluorescence detection. BIS and hemodynamic data were monitored continuously.Results The predicted plasma concentrations were generally overestimated. Median performance error (MDPE) and absolute median performance error (MDAPE) were -10.0% and 29.9% respectively. Propofol CSF concentrations were much lower than its effect-site concentrations. Changes in BIS were consistent with propofol concentrations in CSF, both of which changed direction at 5 minutes while the effect-site concentrations relatively lagged behind. Better correlation ( r2 = 0. 9195) was found between BIS and CSF concentrations, when compared with that between BIS and effect-site concentrations (r2=0. 554).Conclusion With 1% enflurane inhaled, the inconsistency of drug effect to the effect-site concentrations may result from inaccuracy of pharmacokinetic parameters. CSF may show effect-site concentrations more accurately than plasma when using target effect-site concentration infusion.展开更多
文摘BACKGROUND Propofol is a short-acting,rapid-recovering anesthetic widely used in sedated colonoscopy for the early detection,diagnosis and treatment of colon diseases.However,the use of propofol alone may require high doses to achieve the induction of anesthesia in sedated colonoscopy,which has been associated with anesthesia-related adverse events(AEs),including hypoxemia,sinus bradycardia,and hypotension.Therefore,propofol co-administrated with other anesthetics has been proposed to reduce the required dose of propofol,enhance the efficacy,and improve the satisfaction of patients receiving colonoscopy under sedation.AIM To evaluate the efficacy and safety of propofol target-controlled infusion(TCI)in combination with butorphanol for sedation during colonoscopy.METHODS In this controlled clinical trial,a total of 106 patients,who were scheduled for sedated colonoscopy,were prospectively recruited and assigned into three groups to receive different doses of butorphanol before propofol TCI:Low-dose butorphanol group(5μg/kg,group B1),high-dose butorphanol group(10μg/kg,group B2),and control group(normal saline,group C).Anesthesia was achieved by propofol TCI.The primary outcome was the median effective concentration(EC50)of propofol TCI,which was measured using the up-and-down sequential method.The secondary outcomes included AEs in perianesthesia and recovery characteristics.RESULTS The EC50 of propofol for TCI was 3.03μg/mL[95%confidence interval(CI):2.83-3.23μg/mL]in group B2,3.41μg/mL(95%CI:3.20-3.62μg/mL)in group B1,and 4.05μg/mL(95%CI:3.78-4.34μg/mL)in group C.The amount of propofol necessary for anesthesia was 132 mg[interquartile range(IQR),125-144.75 mg]in group B2 and 142 mg(IQR,135-154 mg)in group B1.Furthermore,the awakening concentration was 1.1μg/mL(IQR,0.9-1.2μg/mL)in group B2 and 1.2μg/mL(IQR,1.025-1.5μg/mL)in group B1.Notably,the propofol TCI plus butorphanol groups(groups B1 and B2)had a lower incidence of anesthesia AEs,when compared to group C.Furthermore,no significant differences were observed in the rates of AEs in perianesthesia,including hypoxemia,sinus bradycardia,hypotension,nausea and vomiting,and vertigo,among group C,group B1 and group B2.CONCLUSION The combined use with butorphanol reduces the EC50 of propofol TCI for anesthesia.The decrease in propofol might contribute to the reduced anesthesia-related AEs in patients undergoing sedated colonoscopy.
基金supported by a grant from Shenzhen Baoan Hospital Affiliated to Southern Medical University
文摘This study aimed to establish a new propofol target-controlled infusion（TCI） model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol（10 mg/kg） was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using Win Nonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index（NI） versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/m L, while 12.52±0.69 μg/m L at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant（ke0） was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/m L（95% CI, 10.25–13.67）. Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.
文摘Aim To investigate the population pharmacokinetics of propofol administered by TCI in Chinese elderly patients. Methods Thirty-two patients with ASA Ⅰ - Ⅱ , 65 - 82 years old, undergoing selective lower abdominal operation were studied. Propofol was administered by target-controlled infusion with Marsh parameter. The target plasma concentration was 3 μg＇ mL^-1. Radial arterial blood samples were collected and analyzed by reversed phase HPLC with fluorescence detection. Population pharmacokinetic modeling was performed using NONMEM. Inter-individual variability and intra-individual variability of propofol were estimated for clearances and volumes of distribution. The effects of age, body weight, lean body mass, gender, height, hemoglobin, total protein, albumin, creatinine, alanine aminotrans ferase （ALT）, and aspartate aminotransferase （AST） were investigated. The effects of coadministered opioid drugs were also studied. Results The pharmacokinetics of propofol in the Chinese elderly patients was best described by a three-compartment open model. Lean body mass was found to be a covariate for system clearance at significant level （ P 〈 0.005）. The clearance decreased linearly with age as well （ P 〈 0. 005）. The apparent volume of distribution for deep peripheral compartment （V3） was influenced by gender. Elderly female patients showed a higher value for V3. Conclusion The pharmacokinetics of propofol administered by TCI in Chinese elderly patients can be well described by a three-compartment open model. Inclusion of age, lean body mass and gender as covariates significantly improved the model. To ensure the accuracy and precision of target-controlled infusion, the population pharmacokinetic model applied to the individual patient should be adjusted reasonably.
文摘Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in Chinese surgical patients. Methods The pharmacokinetics of sufentanil was investigated in 12 adult patients, aged 23-76 years, scheduled for prolonged surgery under general anesthesia. Anesthetic induction was carried out with propofol, rocuronium and TCI administered sufentanil aiming for target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI lasted for 30 minutes. Frequent arterial blood samples （1.5 ml） were drawn during and up to 24 hours after sufentanil TCI. Plasma sufentanil concentrations were measured by liquid chromatography-tandem mass spectrometry; limit of sensitivity of mass spectrometry was 5 pg/ml. The data were analyzed with the nonlinear mixed-effect model program. Results The pharmacokinetics of TCI administered sufentanil were optimally described by a three-compartment model with the following parameters： the central volume of distribution （V1） = 5.4 L, the volume of distribution at steady-state （Vdss） = 195.4 L, systemic clearance （CI1） = 1.10 L/min, and elimination half-life （t1/2 Y） = 271.8 minutes. Both age and gender affected the pharmacokinetic parameters. The rapid distribution clearance （012） was negatively correlated with patient age, and the volume of slowly equilibrating compartment （V3） was positively correlated with age. The Cl2 and the volume of rapidly equilibrating compartment （V2） were influenced by gender with male patients showing higher values of Cl2 and V2 than female patients. There was no relationship of body weight, lean body mass, plasma albumin, or target effect-site concentration of sufentanil with any of the pharmacokinetic parameters studied. Conclusions The pharmacokinetics of TCI administered sufentanil in Chinese patients can be adequately described by a three-compartment model. Pharmacokinetics adjusted to the individual patient should improve the accuracy of TCI systems.
文摘Background There are few studies to assess whether the effect-site concentration of propofol can predict anesthetic depth during the target-controlled infusion （TCI） induction in elderly patients. This study aimed to evaluate the relationship between effect-site concentration of propofol and depth of anesthesia during the TCI induction in elderly patients. Methods Ninety patients （60-80 years） with an American Society of Anesthesiologists （ASA） physical status of 1-3, undergoing scheduled abdominal and thoracic surgery under general anesthesia were randomly allocated into one of three groups, Group S1, S2 and S3 （30 patients in each group）. The patients in Group S1 received propofol with a target plasma concentration of 4.0 pg/ml; patients in Group S2 received propofol with an initial target plasma concentrations of 2.0 IJg/ml that was raised to 4.0 pg/ml 3 minutes later; patients in Group S3 received an infused scheme of 3 steps; starting from a target plasma concentration of 2.0 pg/ml that was increased stepwised by 1 pg/ml until a target plasma concentration of 4.0 pg/ml was achieved, the interval between the two steps was 3 minutes. When an Observer＇s Assessment of Alertness/Sedation （OANS） score of 1 was achieved, remifentanil （effect-site concentration （Ce） of 4.0 ng/ml） and rocuronium 0.9 mg/kg were administered. Tracheal intubation was started 2 minutes after rocuronium injection. Changes of propofol Ce, blood pressure （BP）, heart rate （HR）, and bispectral index （BIS） were recorded. Results When an OAA/S score of 1 was achieved, Ce of propofol were （1.7±0.4） pg/ml, （1.9±0.3） pg/ml, （1.9±0.4） pg/ml and the BIS values were 64±5, 65±8, and 62±8 in Groups S1, S2 and S3. Before intubation, Ce of propofol was （2.8±0.2） pg/ml, （2.8±0.3） pg/ml, （2.7±0.3） pg/ml, and the BIS values were 48±7, 51±7, and 47±5 in Groups S1, S2 and S3. By linear regression analysis, a significant correlation between Ce of propofol and BIS values was found （r=-0.580, P 〈0.01）. Systolic blood pressure （SBP） before intubation was significantly lower in Group S1 than in Groups S2 and S3. SBP and HR after intubation in the three groups were significantly increased when compared with pre-intubation values, but they did not exceed baseline values Conclusions During the TCI induction, Ce of propofol with （1.9±0.3） pg/ml may make the elderly patients unconscious. When remifentanil with a Ce of 4.0 ng/ml is added a Ce of propofol with （2.8±0.3） pg/ml is suitable for intubation. The Ce of propofol has a close correlation with the BIS values. Also, a two-step TCI technique seems to be a more suitable method of anesthesia induction in elderly patients compared with the no-stepwise TCI technique and three-step TCI technique.
文摘Background Sufentanil is a suitable choice for target-controlled infusion （TCI） because of its shorter context-sensitive half-time. The current study was to estimate the pharmacokinetics of sufentanil TCI in Chinese patients using the two-stage analysis. Methods Twelve adult patients with American Society of Anesthesiologists （ASA） physical status I or II undergoing elective surgery under general anesthesia were included. Anesthesia was induced with propofol, rocuronium and sufentanil administered by TCI lasting for 30 minutes, with target effect-site concentration of sufentanil 4 or 6 ng/ml. Frequent arterial blood samples （1.5 ml） were taken during and up to 24 hours after sufentanil TCI. Before the end of surgery, another arterial blood sample （1.0 ml） was drawn for the blood-gas analysis. Plasma sufentanil concentrations were determined by liquid chromatography-tandem mass spectrometry （limit of quantitation was 5 pg/ml）. The data were analyzed with the two-stage approach, linear regression and correlation analysis. Results The pharmacokinetics of sufentanil TCI were adequately described by a three-compartment model. The variables were derived as follows： the volume of central compartment （V1） was 5.4 L, volume of distribution at steady-state （Vdss） was 222.6 L, metabolic clearance （CI1） was 0.84 L/min and elimination half-life （t~/2y） was 389 minutes. Patients＇ age, gender and PaCO2 correlated significantly with the pharmacokinetic parameters. The Vdss, volume of slowly equilibrating compartment （V3） and t1/2 y increased, and rapid distribution clearance （012） decreased with increasing patient age. Male patients had larger values of Vdss, volume of rapidly equilibrating compartment （V2） and V3 than female patients. The Vdss and V3 increased with higher PaCO2 values. There were no significant correlations between the pharmacokinetic variables and body weight, height, lean body mass, plasma albumin, sufentanil dose, duration of surgery, pH or base excess of blood （BE-B）. Conclusions The pharmacokinetics of sufentanil TCI in Chinese patients can be optimally described by a three-compartment model. The pharmacokinetic analysis technique may affect the pharmacokinetic parameters and correlations.
文摘Objective:To evaluate the predictive performance of‘Diprifusor’TCI(target-controlled infusion)system for its betterapplication in clinical anesthesia.Methods:The predictive performance of a‘Diprifusor’TCI system was investigated in 27Chinese patients(16 males and 11 females)during upper abdominal surgery under total intravenous anesthesia(TIVA)withpropofol/fentanyl.Measnred arterial propofol concentrations were compared with the values predicted by the TCI infusion system.Performance was determined by the median performance error(MDPE),the median absolute performance error(MDAPE),thedivergence(the percentage change of the absolute PE with time),and the wobble(the median absolute deviation of each PE fromthe MDPE).Results:The median(range)values of 14.9%(-21.6%～42.9%)for MDPE,23.3%(6.9%～62.5%)for MDAPE,-1.9%h^(-1)(-32.7%～23.0% h^(-1))for divergence,and 18.9%(4.2%～59.6%)for wobble were obtained from 227 samples from all patients.For the studied population,the PE did not increase with time but with increasing target propofol concentration,particularly fol-lowing induction.Conclusions:The control of depth of anaesthesia was good in all patients undergoing upper abdominal surgicaloperation and the predictive performance of the‘Diprifusor’target controlled mthsion system was considered acceptable forclinical purposes.But the relatively bigger wobble showed that the pharmacokinetic model is not so suitable and requires im-provement.
文摘Background：In this prospective randomized study,we compared the predicted blood and effect-site C50 for propofol and remifentanil target-controlled infusion （TCI） and the bispectral index （BIS） values at loss of consciousness （LOC） and response to a standard noxious painful stimulus （LOS） in elderly and young patients,respectively.We hypothesized that the elderly patients will require lower target concentration of both propofol and remifentanil at above two clinical end-points.Methods：There were 80 American Society of Anesthesiologists （ASA） physical status Ⅰ Ⅱ unpremedicated patients enrolled in this study,they were divided into elderly group （age ≥65 years,n =40） and young group （aged 18-54 years,n =40）.Propofol was initially given to a predicted blood concentration of 1.2 μg/ml and thereafter increased by 0.3 μg/ml every 30 s until Observer＇s Assessment of Alertness and Sedation score was 1.The propofol level was kept constant,and remifentanil was given to provide a predict blood concentration of 2.0 ng/ml,and then increased by 0.3 ng/ml every 30 s until loss of response to a tetanic stimulus.BIS （version 3.22,BIS Quattro sensor） was also recorded.Results：In elderly group,the propofol effect-site C50 at LOC of was 1.5 （1.4-1.6） μg/ml,was significantly lower than that of young group,which was 2.2 （2.1-2.3） μg/ml,the remifentanil effect-site C50 at LOS was 3.5 （3.3-3.7） ng/ml in elderly patients,was similar with 3.7 （3.6-3.8） ng/ml in young patients.Fifty percent of patients lost consciousness at a BIS value of 57.3 （56.4-58.1）,was similar with that of young group,which was 55.2 （54.0-56.3）.Conclusion：In elderly patients,the predicted blood and effect-site concentrations of propofol at LOC were lower than that of young patients.At same sedation status,predicted blood and effect-site concentrations of remifentanil required at LOS were similar in elderly and young patients.BIS were not affected by age.Low-propofol/high-opioid may be optional TCI strategy for elderly patients.
基金This study was supported by a grant from the Chinese Ministry of Education (No. 9805).
文摘Background Although the performance of target-controlled infusion (TCI) have been studied extensively, the accuracy and safety of a TCI system that targets the effect site remains to be demonstrated. This study was to investigate the relations of TCI of propofol to its concentrations in cerebral spinal fluid (CSF), the effect-site concentrations and bispectral index (BIS).Methods Twelve mongrel dogs were used for investigations. The target effect-site concentration was set at 3μg/ml and the infusion was lasted for 15 minutes. CSF and blood samples were then collected and propofol concentrations were determined by using high performance liquid chromatography with fluorescence detection. BIS and hemodynamic data were monitored continuously.Results The predicted plasma concentrations were generally overestimated. Median performance error (MDPE) and absolute median performance error (MDAPE) were -10.0% and 29.9% respectively. Propofol CSF concentrations were much lower than its effect-site concentrations. Changes in BIS were consistent with propofol concentrations in CSF, both of which changed direction at 5 minutes while the effect-site concentrations relatively lagged behind. Better correlation ( r2 = 0. 9195) was found between BIS and CSF concentrations, when compared with that between BIS and effect-site concentrations (r2=0. 554).Conclusion With 1% enflurane inhaled, the inconsistency of drug effect to the effect-site concentrations may result from inaccuracy of pharmacokinetic parameters. CSF may show effect-site concentrations more accurately than plasma when using target effect-site concentration infusion.
