Plasma Propofol Concentrations Research Articles

Cascaded PID controller for anaesthesia delivery.

The technologies for continuous measurement of the anaesthetic agents circulating in body fluids are not mature yet, though some preliminary prototypes exist already. We present a control algorithm that based on the real measurement of propofol plasma concentration may adjust the delivery rate. This opens a possibility for a safer anesthesia when the technologies for online measurement of drug concentration will be mature enough to be combined with our model.

Target-controlled versus fractionated propofol sedation in flexible bronchoscopy: A randomized noninferiority trial.

Fractionated propofol administration (FPA) in flexible bronchoscopy (FB) may lead to oversedation and an increased risk of adverse events, because a stable plasma concentration of propofol is not maintainable. The purpose of this randomized noninferiority trial was to evaluate whether target-controlled infusion (TCI) of propofol is noninferior to FPA in terms of safety in FB. Coprimary outcomes were the mean lowest arterial oxygen saturation (SpO2 ) during FB and the number of propofol dose adjustments in relation to procedure duration. Secondary outcomes were the number of occasions with SpO2 < 90% and/or oxygen desaturations of >4% from baseline, number of occasions with systolic blood pressure < 90 mm Hg, cough frequency, cumulative propofol dose, recovery time, maximum transcutaneous CO2 , mean SpO2 and O2 delivery during FB. Seventy-seven patients were included. TCI was noninferior to FPA in terms of mean (standard deviation) lowest SpO2 during the procedure (88.3% (5.4%) vs 86.9% (7.3%)) and required fewer dose adjustments (0.04/min vs 0.28/min, P < 0.001) but a higher cumulative propofol dose (264 vs 194 mg, P = 0.003). All other secondary outcomes were comparable between the groups. We suggest that TCI of propofol is a favourable sedation technique for FB with equal safety issues and fewer dose adjustments compared with FPA.

Propofol target-controlled infusion modeling in rabbits: Pharmacokinetic and pharmacodynamic analysis.

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 WinNonlin 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/mL, while 12.52±0.69 μg/mL 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/mL (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.

A membrane separator interface for mass-spectrometric analysis of desflurane, propofol, and fentanyl in blood plasma and cerebrospinal fluid

An easy-to-operate mass-spectrometric membrane separator interface, which is intended for measuring the concentrations of anesthetic preparations in biological fluids (blood plasma and cerebrospinal fluid), is described. Biological fluids are sampled during balanced inhalation (desflurane, fentanyl) anesthesia and total intravenous (desflurane, propofol) anesthesia. In the design of the mass-spectrometer interface, a hydrophobic membrane that separates anesthetic preparations from biological fluids is used: inhalation anesthetic desflurane, hypnotic propofol, and analgetic fentanyl. It was revealed that the membrane does not degrade during multiple (up to 30 cycles) measurements. The possibility of using the interface for measuring the absolute concentrations of desflurane and propofol in blood plasma and cerebrospinal fluid when studying the properties and degree of degradation of the blood–brain barrier in the in situ mode.

Evaluation and optimisation of propofol pharmacokinetic parameters in cats for target-controlled infusion

The aim of this study was to develop and evaluate a pharmacokinetic model-driven infusion of propofol in premedicated cats. In a first step, propofol (10 mg/kg) was administered intravenously over...

Obesity Does Not Affect Propofol Pharmacokinetics During Hypothermic Cardiopulmonary Bypass.

Because of the lack of data regarding the impact of obesity on propofol pharmacokinetics in patients undergoing cardiac surgery using hypothermic cardiopulmonary bypass (CPB), the authors sought to explore propofol pharmacokinetics and develop a predictive pharmacokinetic model that characterizes and predicts propofol pharmacokinetics in this population. A prospective, observational study. A teaching hospital. The study comprised 17 obese and 17 control (nonobese) patients undergoing hypothermic CPB. None. Patients mainly underwent valve surgery. On initiation of hypothermic CPB (28°C-32°C), patients received a propofol (1%) bolus (1 mg/kg) immediately followed by a 2 mg/kg/h infusion. Blood samples were withdrawn at the following times: before dosing; 1, 3, 5, and 7 minutes after the propofol bolus dose; every 20 minutes during infusion; just before discontinuation of the infusion; and at 1, 3, 5, 7, 10, 20, 30, and 60 minutes after discontinuation of the infusion. The plasma propofol concentration was determined using high-performance liquid chromatography, and then data were imported into Monolix (Lixoft, Antony, France) for population pharmacokinetic modeling and pharmacokinetic parameters estimation. A 2-compartment pharmacokinetic model with age as a covariate on the peripheral volume of distribution (V2) best described the pooled data. The pooled data was internally evaluated successfully to describe and predict propofol pharmacokinetics in the addressed population. Propofol clearance, intercompartmental clearance, and central volume of distribution were 805 mL/min, 1140 mL/min and 18.8 L, respectively. V2 was calculated as 9.86×exp.(1.88×[age/40]) L. Propofol pharmacokinetic parameters were similar in obese and nonobese patients undergoing hypothermic CPB. Age was the major determinant of propofol V2 in the obese population.

Comparison of cerebral oxygenation inpatients undergoing gynecological laparoscopic surgery under sevoflurane- versus propofol-based anesthesia

Objective To compare the cerebral oxygenation in the patients undergoing gynecological laparoscopic surgery under sevoflurane- versus propofol-based anesthesia. Methods Fifty adult patients, aged 18-56 yr, weighing 55-72 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with hemoglobin≥110 g/L, undergoing elective gynecological laparoscopic surgery under general anesthesia, were equally and randomly divided into sevoflurane group(group S)and propofol group(group P)using a random number table.Anesthesia was induced with iv midazolam 0.04 mg/kg, sufentanil 1.5-2.0 μg/kg, rocuronium 0.9 mg/kg, and propofol 1.5-2.0 mg/kg.Anesthesia was maintained with inhalation of sevoflurane(2.0%-2.6%)in group S, or with target-controlled infusion of propofol(plasma concentration 2.5-4.0 μg/ml)in group P. The concentrations of sevoflurane and propofol were adjusted to maintain bispectral index value at 40-50.In both groups, remifentanil was given by target-controlled infusion(target plasma concentration 2 ng/ml), and vecuronium 0.06-0.08 mg/kg was injected intermittently to maintain muscle relaxation.The regional cerebral oxygen saturation(rSO2)was recorded after induction and at 10 min before pneumoperitoneum(T1), at 10 min of pneumoperitoneum in the Trendelenburg position(T2), and at 10 min after the end of pneumoperitoneum(T3). The occurrence of cerebral oxygen desaturation was recorded during surgery. Results The rSO2 was significantly higher at T2, 3 in group S than in group P(P 0.05), and the rSO2 was significantly decreased at T2, 3 in group P(P<0.05). The incidence of cerebral oxygen desaturation was 12% in group P, and cerebral oxygen desaturation was not detected in group S. Conclusion Sevoflurane-based anesthesia produces no effect on rSO2, however, propofol-based anesthesia can decrease rSO2 in the patients undergoing gynecological laparoscopic surgery, and sevoflurane-based anesthesia is more suitable for gynecological laparoscopic surgery. Key words: Anesthetics, inhalation; Propofol; Laparoscopy; Brain; Oxygen

Evidence of Different Propofol Pharmacokinetics under Short and Prolonged Infusion Times in Rabbits.

Propofol is an anaesthetic widely used in both human beings and animals. However, the characterization of propofol pharmacokinetics (PK) is not well understood when long-term infusions are used. The main objective of this study was to explore the PK behaviour of propofol in a rabbit model during short and prolonged propofol infusions and to develop an internally validated PK model, for propofol dose individualization in the rabbit for future use. Population 1 (P1) was constituted by seven New Zealand rabbits and was used to characterize the PK profile of propofol at short infusions. Animals were anaesthetized with a bolus of 20 mg/kg, followed by an infusion rate of 50 mg/kg/hr of propofol at 1%, which was then maintained for 30 min. A second rabbit population (P2, n = 7) was sedated according to reflexes responses and Index of Consciousness values, for 20 consecutive hours using propofol 2% aiming at characterizing propofol behaviour at long-term infusions. Clinical data and blood samples were collected at specific time-points in both populations. Propofol plasma concentrations were determined by gas chromatography/ion trap mass spectrometry. The NONMEM VII software was used to evaluate the relationships between dose and plasma concentrations. A linear two-compartment model with different central compartment volume and plasma clearance (separately modelled in the two populations) was the one that best described propofol concentrations. The time course of propofol plasma concentrations was well characterized by the PK model developed, which simultaneously accounts for propofol short- and long-term infusions and can be used to optimize future PK studies in rabbits.

Effects of Dexmedetomidine on motor- and somatosensory-evoked potentials in patients with thoracic spinal cord tumor: a randomized controlled trial.

BackgroundWe hypothesized that the addition of dexmedetomidine in a clinically relevant dose to propofol-remifentanil anesthesia regimen does not exert an adverse effect on motor-evoked potentials (MEP) and somatosensory-evoked potentials (SSEP) in adult patients undergoing thoracic spinal cord tumor resection.MethodsSeventy-one adult patients were randomized into three groups. Propofol group (n = 25): propofol-remifentanil regimenand the dosage was adjusted to maintain the bispectral index (BIS) between 40 and 50. DP adjusted group (n = 23): Dexmedetomidine (0.5 μg/kg loading dose infused over 10 min followed by a constant infusion of 0.5 μg/kg/h) was added to the propofol-remifentanil regimen and propofol was adjusted to maintain BIS between 40 and 50. DP unadjusted group (n = 23): Dexmedetomidine (administer as DP adjusted group) was added to the propofol-remifentanil regimen and propofol was not adjusted. All patients received MEP, SSEP and BIS monitoring.ResultsThere were no significant changes in the amplitude and latency of MEP and SSEP among different groups (P > 0.05). The estimated propofol plasma concentration in DP adjusted group (2.7 ± 0.3 μg/ml) was significantly lower than in propofol group (3.1 ± 0.2 μg/ml) and DP unadjusted group (3.1 ± 0.2 μg/ml) (P = 0.000). BIS in DP unadjusted group (35 ± 5) was significantly lower than in propofol group (44 ± 3) (P = 0.000).ConclusionsThe addition of dexmedetomidine to propofol-remifentanil regimen does not exert an adverse effect on MEP and SSEP monitoring in adult patients undergoing thoracic spinal cord tumor resection.Trial registrationThe study was registered with the Chinese Clinical Trial Registry on January 31st, 2014. The reference number was ChiCTR-TRC-14004229.

Pharmacodynamic response modelling of arterial blood pressure in adult volunteers during propofol anaesthesia

Concentration effect relationships are commonly described with a direct response model as for example the sigmoid E(max) model with one effect compartment as site of action. In this study we investigated whether models with more than one effect site, or indirect response, or counter-regulatory response models may be more appropriate for modelling the propofol effect on arterial blood pressure. Nine young healthy volunteers received propofol as target controlled infusion with predefined increasing and decreasing plasma target concentrations. Propofol concentrations were determined from arterial blood samples. Arterial blood pressure was measured invasively at radial artery site. Pharmacokinetic/-pharmacodynamic modelling was performed by population analysis with MONOLIX, testing different direct, indirect and counter-regulatory response models. Propofol plasma concentrations were well described by a three-compartment model. The propofol effect on arterial blood pressure was best described by a direct sigmoid E(max) model with two effect site compartments. Two effect sites were needed to describe the propofol effect on arterial blood pressure. This may reflect different pathways of arterial blood pressure response to propofol.

The relationship between the Bispectral Index (BIS) and the Observer Alertness of Sedation Scale (OASS) scores during propofol sedation with and without ketamine: a randomized, double blinded, placebo controlled clinical trial.

Prior studies have examined the static effect of intravenous ketamine on the BIS Index for sedation but it remains unknown if the BIS Index is a reliable method to track sedation levels in the presence of ketamine. The major objective of the current investigation was to compare the BIS Vista Index ability to track varying depths of sedation as determined by OASS scores in a standardized anesthetic regimen with and without ketamine. The study was a randomized, double blinded clinical trial. Patients undergoing breast surgery under sedation with propofol were randomized to receive ketamine (1.5μgkgmin(-1)) or saline. Infusion data was used to estimate propofol plasma concentrations (Cp). The main outcome of interest was the correlation between the BIS Vista Index with the OASS score. Twenty subjects were recruited and fifteen completed the study. Four hundred fifty-five paired data points were included in the analysis. Model performance (Nagelkerke R(2)) of the multinomial logistic regression model was 0.57 with the c-statistic of 0.87 (95% CI 0.82-0.91). Compared to awake the odds ratio for BIS values predicting moderate sedation in the saline/propofol group 1.19 (95% CI 1.12-1.25) but only 1.06 (95% CI 1.02-1.1) in the ketamine/propofol group (P=0.001). There was no difference in the odds for BIS values to predict deep sedation between groups (P=0.14). The BIS monitor can be used to monitor sedation level even when ketamine is used with propofol as part of the sedation regimen. However, ketamine reduces the value of the BIS in predicting moderate sedation levels.

手术病人丙泊酚的血药浓度测定及靶控输注系统评价

手术病人丙泊酚的血药浓度测定及靶控输注系统评价

Performance of target-controlled infusion of propofol using two different pharmacokinetic models in open heart surgery - a randomised controlled study

We compared the performance of a propofol target-controlled infusion (TCI) using Marsh versus PGIMER models in patients undergoing open heart surgery, in terms of measured plasma levels of propofol and objective pharmacodynamic effect. Twenty-three, ASA II/III adult patients aged 18-65 years and scheduled for elective open heart surgery received Marsh or PGIMER (Postgraduate Institute of Medical Education and Research) pharmacokinetic models of TCI for the induction and maintenance of anaesthesia with propofol in a randomized, active-controlled, non-inferiority trial. The plasma levels of propofol were measured at specified time points before, during and after bypass. The performances of both the models were similar, as determined by the error (%) in maintaining the target plasma concentrations: MDPE of -5.0 (-12.0, 5.0) in the PGIMER group vs -6.4 (-7.7 to 0.5) in the Marsh group and MDAPE of 9.1 (5, 15) in the PGIMER group vs 8 (6.7, 10.1) in the Marsh group. These values indicate that both models over-predicted the plasma propofol concentration. The new pharmacokinetic model based on data from Indian patients is comparable in performance to the commercially available Marsh pharmacokinetic model.

Attenuation of high-frequency (50-200 Hz) thalamocortical EEG rhythms by propofol in rats is more pronounced for the thalamus than for the cortex.

BackgroundThalamocortical EEG rhythms in gamma (30-80 Hz) and high-gamma (80-200 Hz) ranges have been linked to arousal and conscious processes. To test the hypothesis that general anesthetics attenuate these rhythms, we characterized the concentration-effect relationship of propofol on the spectral power of these rhythms. In view of the ongoing debate about cortex versus thalamus as the primary site of anesthetic action for unconsciousness, we also compared the relative sensitivity of cortex and thalamus to this effect propofol.MethodsAdult male Long-Evans rats were chronically implanted with electrodes in somatosensory (barrel) cortex and ventroposteromedial thalamus. Propofol was delivered by a computer-controlled infusion using real-time pharmacokinetic modeling to obtain the desired plasma concentration. Spectral power was assessed during baseline, at four stable propofol plasma-concentrations (0, 3,6,9,12 μg/ml) and during recovery over four frequency ranges (30-50, 51-75, 76-125, 126-200 Hz). Unconsciousness was defined as complete loss of righting reflex. Multiple regression was used to model the change of power (after logarithmic transformation) as a function of propofol concentration and recording site.ResultsUnconsciousness occurred at the 9 μg/ml concentration in all animals. Propofol caused a robust linear concentration-dependent attenuation of cortical power in the 76-200 Hz range and of thalamic power in the 51-200 Hz range. In all instances the concentration-effect slope for the thalamus was markedly steeper than for the cortex. Furthermore the lowest concentration causing unconsciousness significantly reduced cortical power in the 126-200 Hz range and thalamic power in the 51-200 Hz range.ConclusionsPropofol causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 51-200 Hz range and this effect is far more pronounced for the thalamus, where the attenuation provides a robust correlate of the hypnotic action of propofol.

Efficacy of high performance liquid chromatography for simultaneous determination of propofol and remifentanil concentrations in human plasma

Objective To evaluate the efficacy of high performance liquid chromatography(HPLC)for simultaneous determination of propofol and remifentanil concentrations in human plasma. Methods Methods Eighteen healthy volunteers of both sexes, aged 18-45 yr, weighing 52-81 kg, were enrolled in the study.Venous blood samples were collected, and the concentrations of propofol and remifentanil in human plasma were detected simultaneously by HPLC.The internal standard was thymol.Potassium dihydrogen phosphate 0.1 mol/L was added to the plasma and then the plasma samples were extracted with extract liquor(ethyl acetate∶hexane=4∶1, V/V). The analytical column was ZORBAX Eclipse XDB-C18(4.6 mm×250 mm, 5 μm). The mobile phase was methano∶0.02 mol/L NaH2PO4∶acetonitrile, the flow rate was 1.0 ml/min, the detection wavelength was 210 nm within 1-7 min, and 266 nm within 7-16 min, and the sample size was 20 μl.Linear regression analysis was performed by using the least-squares method.The specimens of the blood with the final concentration of remifentanil 1.00, 5.00 and 20.00 ng/ml and propofol 0.50, 2.00 and 10.00 μg/ml were obtained to determine the recovery, precision and stability. Results Linear regression equation of remifentanil was C=12.853 5Ai/As+ 0.084 8(R2=0.999 4), and this system showed a good linear relationship with the concentration of remifentanil ranged 0.5-40.0 ng/ml.Linear regression equation of propofol was C=8.554 3Ai/As+ 0.029 1(R2=0.998 6), and this system showed a good linear relationship with the concentration of propofol ranged 0.2-20.0 μg/ml.For both propofol and remifentanil concentrations, the relative recovery was within the range of 85%-115%, the absolute recovery was larger than 75%, and the relative standard deviation of intra- and inter-day precision and stability was less than 5%.The method was proved to meet the requirements of biological sample analysis. Conclusion For HPLC method established in this trial, the determination is sensitive, reproducible, rapid and simple, and it can be used for simultaneous determination of propofol and remifentanil concentrations in human plasma and for clinical pharmacokinetic research. Key words: Chromatography, high pressure liquid; Propofol; Piperidines; Plasma concentration

Online breath analysis of propofol during anesthesia: clinical application of membrane inlet-ion mobility spectrometry.

Breath analysis of propofol is a potential noninvasive method for approximating the plasma propofol concentration. There have been various reported techniques for measuring the exhaled propofol concentration at steady state; however, the propofol concentration undergoes marked changes during clinical anesthesia. Therefore, this study investigated the use of membrane inlet-ion mobility spectrometry (MI-IMS) to monitor exhaled propofol discontinuously and continuously during propofol anesthesia. The study included 19 patients of American Society of Anesthesiologists physical status I or II. In experiment I (discontinuous study), breath and blood samples were collected discontinuously, with stable target propofol concentrations of 2.8 μg/ml, 3.2 μg/ml, 3.5 μg/ml, and 3.8 μg/ml. In experiment II (continuous study), propofol concentration was maintained at 3.5 μg/ml after induction, and exhaled breath was collected continuously every 3 min during propofol infusion. Relationships of the exhaled propofol concentration with the plasma propofol concentration, measured by high-performance liquid chromatography and the continuously measured bispectral (BIS) index were investigated. Comparison of the exhaled and plasma propofol concentrations revealed a bias ± precision of 2.1% ± 14.6% (95% limits of agreement: - 26.5-30.7%) in experiment I and - 10.4% ± 13.2 (- 36.3-15.4%) in experiment II. In both experiments, exhaled propofol concentrations measured by MI-IMS were consistent with, the propofol effect represented by the BIS index. MI-IMS may be a suitable method to predict plasma propofol concentration online during propofol anesthesia. Monitoring exhaled propofol may improve the safety of propofol anesthesia.

Comparison of Pharmacokinetic Models for Hypnosis Control Based on Effect-Site Propofol Concentration to Maintain Appropriate Hypnosis

This paper studies an appropriate pharmacokinetic (PK) model for hypnosis control based on effect-site anesthetic concentration. For maintaining hypnosis, methods to keep plasma or effect-site concentration of propofol, an anesthetic drug, calculated using PK models at a target level are often used. In order to realize a desirable hypnosis control by such methods an accurate estimation of propofol concentration corresponding to the threshold of unconsciousness is critical. Since time variation of the calculated propofol concentration depends on the PK model, the performance of maintaining hypnosis also depends on it. In this paper, we compare the existing PK models of propofol focusing on sensitivity and specificity for detecting consciousness during anesthesia by a criterion based on cal ulated propofol concentration and measured aepEX, a hypnosis index. The results show that Barr model provides the highest sensitivity and specificity, and that Marsh, modified Marsh, and Schnider models, which are often used in target controlled infusion systems give fairly high sensitivity and specificity.

Gas chromatograph–surface acoustic wave for quick real-time assessment of blood/exhaled gas ratio of propofol in humans

Although pilot studies have reported that exhaled propofol concentrations can reflect intraoperative plasma propofol concentrations in an individual, the blood/exhaled partial pressure ratio RBE varies between patients, and the relevant factors have not yet been clearly addressed. No efficient method has been reported for the quick evaluation of RBE and its association with inter-individual variables. We proposed a novel method that uses a surface acoustic wave (SAW) sensor combined with a fast gas chromatograph (GC) to simultaneously detect propofol concentrations in blood and exhaled gas in 28 patients who were receiving propofol i.v. A two-compartment pharmacokinetic (PK) model was established to simulate propofol concentrations in exhaled gas and blood after a bolus injection. Simulated propofol concentrations for exhaled gas and blood were used in a linear regression model to evaluate RBE. The fast GC-SAW system showed reliability and efficiency for simultaneous quantitative determination of propofol in blood (correlation coefficient R(2)=0.994, P<0.01) and exhaled gas (R(2)=0.991, P<0.01). The evaluation of RBE takes <50 min for a patient. The distribution of RBE in 28 patients showed inter-individual differences in RBE (median 1.27; inter-quartile range 1.07-1.59). Fast GC-SAW, which analyses samples in seconds, can perform both rapid monitoring of exhaled propofol concentrations and fast analysis of blood propofol concentrations. The proposed method allows early determination of the coefficient RBE in individuals. Further studies are required to quantify the distribution of RBE in a larger cohort and assess the effect of other potential factors. ChiCTR-ONC-13003291.

The effect of epidural lidocaine administration on sedation of propofol general anesthesia: a randomized trial

Study ObjectiveTo examine the influence of epidural and intravenous (IV) lidocaine, and height of the epidural sensory block, on the dose of propofol required for induction of general anesthesia. DesignRandomized controlled study. SettingUniversity hospital. Patients66 adult, ASA physical status 1 and 2 patients, aged 25 to 65 years, undergoing elective abdominal surgery. InterventionsPatients were randomized to 4 groups: the epidural saline control group (Group C; L2-L3 puncture, epidural and IV saline), the IV lidocaine group (Group IV; L2-L3 puncture, saline epidural, IV lidocaine 1 mg/kg), the lumbar epidural lidocaine group (Group EL; L2-L3 puncture, 1.5% lidocaine epidural, IV saline), and the thoracic epidural lidocaine group (Group ET; T9-T10 puncture, 1.5%lidocaine epidural, IV saline). Two minutes after the beginning of the infusion of IV lidocaine or saline, propofol anesthesia was initiated. MeasurementsMean arterial blood pressure (MAP), heart rate (HR), and sensory block height were monitored. The induction dose of propofol, its estimated effect-site concentration (Ce), and plasma concentration were measured at various time points. Finally, we recorded the time taken for the bispectral index (BIS) to decrease to 60, the plasma concentration of lidocaine at induction, and the occurrence of adverse events. The induction time (when BIS reached 60) also was recorded. Main ResultsThe induction propofol dose, Ce, and plasma concentration of propofol when BIS equaled 60 were significantly lower in Group IV, Group EL, and Group ET than Group C. The above parameters in Group ET (T9 - T10 puncture) were significantly less than in Group EL (L2 - L3 puncture). The induction doses of propofol and plasma concentration of propofol and lidocaine were significantly higher in Group IV than in Groups EL or ET. ConclusionsEpidural and IV lidocaine reduce the dose of propofol required to induce general anesthesia. Administration of lidocaine via the epidural route reduces anesthetic requirements more so than the IV route. Propofol requirements were further reduced in patients with higher sensory epidural block.

High-performance liquid chromatographic determination of propofol in human plasma: comparison of different heteroscedastic calibration curve models.

The aim of this study was to select the best calibration model for determination of propofol plasma concentration by high-performance liquid chromatography method. Determination of propofol in plasma after deproteinization with acetonitrile containing thymol (as internal standard) was carried out on a C18 column with a mixture of acetonitrile and trifluoroacetic acid 0.1% (60:40) as mobile phase which delivered at the flow rate of 1.2 mL/minute . Fluorescence detection was done at the excitation and emission wavelengths of 276 and 310 nm, respectively. After fitting different equations to the calibration data using weighted regression, the adequacy of models were assessed by lack-of-fit test, significance of all model parameters, adjusted coefficient of determination (R(2) adjusted) and by measuring the predictive performance with median relative prediction error and median absolute relative prediction error of the validation data set. The best model was a linear equation without intercept with median relative prediction error and median absolute relative prediction error of 4.0 and 9.4%, respectively in the range of 10-5000 ng/mL. The method showed good accuracy and precision. The presented statistical framework could be used to choose the best model for heteroscedastic calibration data for analytes like propofol with wide range of expected concentration.