Pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese surgical patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>The pharmacokinetics of TCI administered sufentanil were optimally described by a three-compartment model with the following parameters: the central volume of distribution (V(1))=5.4 L, the volume of distribution at steady-state (Vdss)=195.4 L, systemic clearance (Cl(1))=1.10 L/min, and elimination half-life (t(1/2) gamma)=271.8 minutes. Both age and gender affected the pharmacokinetic parameters. The rapid distribution clearance (Cl(2)) was negatively correlated with patient age, and the volume of slowly equilibrating compartment (V(3)) was positively correlated with age. The Cl(2) and the volume of rapidly equilibrating compartment (V(2)) were influenced by gender with male patients showing higher values of Cl(2) and V(2) 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.</p><p><b>CONCLUSIONS</b>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.</p>

Two-stage analysis of pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>The pharmacokinetics of sufentanil TCI were adequately described by a three-compartment model. The variables were derived as follows: the volume of central compartment (V(1)) was 5.4 L, volume of distribution at steady-state (Vdss) was 222.6 L, metabolic clearance (Cl(1)) was 0.84 L/min and elimination half-life (t(1/2Y)) was 389 minutes. Patients' age, gender and PaCO2 correlated significantly with the pharmacokinetic parameters. The Vdss, volume of slowly equilibrating compartment (V(3)) and t(1/2Y) increased, and rapid distribution clearance (Cl(2)) decreased with increasing patient age. Male patients had larger values of Vdss, volume of rapidly equilibrating compartment (V(2)) and V(3) than female patients. The Vdss and V(3) 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).</p><p><b>CONCLUSIONS</b>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.</p>

Clinical evaluation of target controlled infusion system for sufentanil administration / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sufentanil target controlled infusion (TCI) provides stable analgesia, better hemodynamic control than a bolus injection of intravenous anesthetics, anticipated recovery and improved quality of anesthesia during perioperative period. This study evaluated the accuracy and feasibility of TCI system for sufentanil at high concentrations in Chinese surgical patients.</p><p><b>METHODS</b>Twelve low risk adult patients undergoing elective surgery under general anesthesia were included in this study. Sufentanil was administered with a specific TCI system incorporating the population pharmacokinetic data of sufentanil previously reported, using a target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI duration was 30 minutes. Frequent arterial blood samples were taken during and up to 24 hours after sufentanil TCI for determination of plasma sufentanil concentrations by liquid chromatography-mass spectrometry/mass spectrometry. The changes of circulatory system function during the procedure, recovery profile and adverse effects were recorded. Measured plasma sufentanil concentrations were compared with the values predicted by the TCI system. The bias (median performance error, MDPE), precision (median absolute performance error, MDAPE) and wobble (variability of performance error) of the sufentanil TCI system were determined.</p><p><b>RESULTS</b>All patients had stable cardiovascular variables during induction and maintenance of anesthesia. Time to eye opening and extubation were (5.6 + or - 1.7) minutes when TCI set to 4 ng/ml and (7.2 + or - 2.3) minutes when set to 6 ng/ml. There was no episode of agitation, muscle rigidity or intraoperative awareness. The bias (MDPE), precision (MDAPE) and wobble of the sufentanil TCI system were -3.7%, 18.9% and 19.6% respectively during TCI, and the MDPE, MDAPE and wobble were -29.1%, 31.7% and 15.0% respectively after TCI (up to 8 hours).</p><p><b>CONCLUSIONS</b>The TCI system programmed for sufentanil at 4 or 6 ng/ml was considered acceptable for clinical use in low risk Chinese surgical patients. But the relatively larger MDPE and MDAPE after TCI suggest improvements of the pharmacokinetic model are needed.</p>