Backgroud Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The goal of this study was to study the population pharmacokinetics of remifentanil in the diffe...Backgroud Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The goal of this study was to study the population pharmacokinetics of remifentanil in the different phases of orthotopic liver transplantation （OLT） and the influence of relevant factors.Methods Thirteen adult patients undergoing OLT were enrolled. A single bolus infusion of remifentanil 5 IJg/kg was administered during the preanhepatic, anhepatic and neohepatic phases of OLT. Arterial blood samples of 1.5 ml were collected at 0 （baseline）, 1, 2, 3, 5, 7, 10, 15, 20, 25, 30, 45, 60 and 90 minutes after drug administration. Remifentanil concentration was assayed by high-performance liquid chromatography/mass spectrometry/mass spectrometry （HPLC/MS/MS）. Population pharmacokinetic modeling was performed using nonlinear mixed-effects modeling （NONMEM）.Results The pharmacokinetics of remifentanil in patients undergoing OLT was best described by a two-compartment open model. The pharmacokinetic parameters were not influenced by age, gender, operative phase, blood temperature, rehydration volume, or blood loss volume during sampling. The volume of distribution in the central compartment （V1） and the volume of distribution in the peripheral compartment （V2） were influenced by body weight.Conclusions The population pharmacokinetics of remifentanil in patients undergoing OLT can be well described by a two-compartment open model. The functional status of the liver does not significantly affect the pharmacokinetics of remifentanil, but the body weight is an influential factor of V1 and V2.展开更多
Background Recently, the combination of sevoflurane and remifentanil has been widely used in general anesthesia. In this study, we investigated the sevoflurane-remifentanil pharmacodynamic interactions at clinical con...Background Recently, the combination of sevoflurane and remifentanil has been widely used in general anesthesia. In this study, we investigated the sevoflurane-remifentanil pharmacodynamic interactions at clinical concentrations using the observer＇s assessment of alertness/sedation （OAA/S） and the bispectral index （BIS） by response surface analysis. Methods Totally 65 American Society of Anesthesiologists （ASA） I patients age 20 to 50 years old were included in this study. Patients were randomly assigned to be anesthetized with different target end-tidal sevoflurane concentrations that ranged from 0.2% to 3.4% in increments of 0.2%. The end-tidal sevoflurane concentration was maintained constant throughout the study. Remifentanil was infused with a target controlled infusion （TCI） system at increasing step-wise concentrations from 1 ng/ml to 10 ng/ml. The values of OAA/S and BIS at different sevoflurane-remifentanil concentration combinations were measured. The pharmacodynamic interactions between sevoflurane and remifentanil were analyzed by a response surface method. The three-dimensional response surfaces were constructed with Minitab Software. Model parameters were estimated with NONMEM program. Results Sevoflurane and remifentanil acted synergistically on OANS. Sevoflurane alone could produce OANS 〈1 at a minimal alveolar concentration （MAC） of 0.93%. When used in combination with remifentanil at 1, 3, 6, and 10 ng/ml, the corresponding sevoflurane MACs were reduced to 0.79%, 0.58%, 0.48%, and 0.38%, with reductions of 17.2%, 37.6%, 48.4%, and 62.0% from baseline, respectively. In patients administered remifentanil alone, the OANS score was 〉3 even when the remifentanil concentration reached 10 ng/ml. BIS was closely associated with the sevoflurane concentration and the remifentanil concentration did not noticeably influence the relationship between the sevoflurane concentration and BIS. A sevoflurane concentration of （1.04＋0.19）% to （1.81＋0.21）% could maintain a BIS between 60 and 40. Conclusions The response surface method can analyze the pharmacodynamic interactions between remifentanil and sevoflurane qualitatively and quantitatively. Within the range of our study （remifentanil 〈10 ng/ml, sevoflurane 〈3.4%）, the two drugs produced synergistic effects on OAA/S but had no interactive effect on BIS. A guideline of BIS between 40 and 60 may cause excessive anesthesia when opioids are used to maintain anesthesia.展开更多
Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult...Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model （NONMEM）, and to investigate the influence of relevant factors in adult patients. Methods Fourteen ASA Ⅰ-Ⅱ patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration （Cpt） was 2.0 μg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T1 scale was blocked by 90%-95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry （LC-MS/MS）. The population pharmacokinetics analysis was performed using NONMEM program. Results The pharmacokinetics of TCI rocuronium in adult patients was best described by a three-comparment model. Pharmacokintic parameters were clearance （CL）1=0.205 L/min, CL2=0.324 L/min, CL3=0.0292 L/min, volumes of distribution （V）1=4.00 L, V2=2.28 L, V3=4.26 L, Vdss=10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V1 and CL1 were negatively correlated with patient age. CL1 was positively correlated with weight. Conclusions No pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters.展开更多
文摘Backgroud Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The goal of this study was to study the population pharmacokinetics of remifentanil in the different phases of orthotopic liver transplantation （OLT） and the influence of relevant factors.Methods Thirteen adult patients undergoing OLT were enrolled. A single bolus infusion of remifentanil 5 IJg/kg was administered during the preanhepatic, anhepatic and neohepatic phases of OLT. Arterial blood samples of 1.5 ml were collected at 0 （baseline）, 1, 2, 3, 5, 7, 10, 15, 20, 25, 30, 45, 60 and 90 minutes after drug administration. Remifentanil concentration was assayed by high-performance liquid chromatography/mass spectrometry/mass spectrometry （HPLC/MS/MS）. Population pharmacokinetic modeling was performed using nonlinear mixed-effects modeling （NONMEM）.Results The pharmacokinetics of remifentanil in patients undergoing OLT was best described by a two-compartment open model. The pharmacokinetic parameters were not influenced by age, gender, operative phase, blood temperature, rehydration volume, or blood loss volume during sampling. The volume of distribution in the central compartment （V1） and the volume of distribution in the peripheral compartment （V2） were influenced by body weight.Conclusions The population pharmacokinetics of remifentanil in patients undergoing OLT can be well described by a two-compartment open model. The functional status of the liver does not significantly affect the pharmacokinetics of remifentanil, but the body weight is an influential factor of V1 and V2.
基金The National Natural Science Foundation Youth Fund of China
文摘Background Recently, the combination of sevoflurane and remifentanil has been widely used in general anesthesia. In this study, we investigated the sevoflurane-remifentanil pharmacodynamic interactions at clinical concentrations using the observer＇s assessment of alertness/sedation （OAA/S） and the bispectral index （BIS） by response surface analysis. Methods Totally 65 American Society of Anesthesiologists （ASA） I patients age 20 to 50 years old were included in this study. Patients were randomly assigned to be anesthetized with different target end-tidal sevoflurane concentrations that ranged from 0.2% to 3.4% in increments of 0.2%. The end-tidal sevoflurane concentration was maintained constant throughout the study. Remifentanil was infused with a target controlled infusion （TCI） system at increasing step-wise concentrations from 1 ng/ml to 10 ng/ml. The values of OAA/S and BIS at different sevoflurane-remifentanil concentration combinations were measured. The pharmacodynamic interactions between sevoflurane and remifentanil were analyzed by a response surface method. The three-dimensional response surfaces were constructed with Minitab Software. Model parameters were estimated with NONMEM program. Results Sevoflurane and remifentanil acted synergistically on OANS. Sevoflurane alone could produce OANS 〈1 at a minimal alveolar concentration （MAC） of 0.93%. When used in combination with remifentanil at 1, 3, 6, and 10 ng/ml, the corresponding sevoflurane MACs were reduced to 0.79%, 0.58%, 0.48%, and 0.38%, with reductions of 17.2%, 37.6%, 48.4%, and 62.0% from baseline, respectively. In patients administered remifentanil alone, the OANS score was 〉3 even when the remifentanil concentration reached 10 ng/ml. BIS was closely associated with the sevoflurane concentration and the remifentanil concentration did not noticeably influence the relationship between the sevoflurane concentration and BIS. A sevoflurane concentration of （1.04＋0.19）% to （1.81＋0.21）% could maintain a BIS between 60 and 40. Conclusions The response surface method can analyze the pharmacodynamic interactions between remifentanil and sevoflurane qualitatively and quantitatively. Within the range of our study （remifentanil 〈10 ng/ml, sevoflurane 〈3.4%）, the two drugs produced synergistic effects on OAA/S but had no interactive effect on BIS. A guideline of BIS between 40 and 60 may cause excessive anesthesia when opioids are used to maintain anesthesia.
文摘Background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model （NONMEM）, and to investigate the influence of relevant factors in adult patients. Methods Fourteen ASA Ⅰ-Ⅱ patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration （Cpt） was 2.0 μg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T1 scale was blocked by 90%-95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry （LC-MS/MS）. The population pharmacokinetics analysis was performed using NONMEM program. Results The pharmacokinetics of TCI rocuronium in adult patients was best described by a three-comparment model. Pharmacokintic parameters were clearance （CL）1=0.205 L/min, CL2=0.324 L/min, CL3=0.0292 L/min, volumes of distribution （V）1=4.00 L, V2=2.28 L, V3=4.26 L, Vdss=10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V1 and CL1 were negatively correlated with patient age. CL1 was positively correlated with weight. Conclusions No pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters.
