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 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.

Efficacy and safety of propofol target-controlled infusion combined with butorphanol for sedated colonoscopy

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.

Propofol sedation in routine endoscopy:A case series comparing target controlled infusion vs manually controlled bolus concept

BACKGROUND Many studies have addressed safety and effectiveness of non-anaesthesiologist propofol sedation(NAPS)for gastrointestinal(GI)endoscopy Target controlled infusion(TCI)is claimed to provide an optimal sedation regimen by avoiding under-or oversedation.AIM To assess safety and performance of propofol TCI sedation in comparison with nurse-administered bolus-sedation.METHODS Fouty-five patients undergoing endoscopy under TCI propofol sedation were prospectively included from November 2016 to May 2017 and compared to 87 patients retrospectively included that underwent endoscopy with NAPS.Patients were matched for age and endoscopic procedure.We recorded time of sedation and endoscopy,dosage of medication and adverse events.RESULTS There was a significant reduction in dose per time of propofol administered in the TCI group,compared to the NAPS group(8.2±2.7 mg/min vs 9.3±3.4 mg/min;P=0.046).The time needed to provide adequate sedation levels was slightly but significantly lower in the control group(5.3±2.7 min vs 7.7±3.3 min;P<0.001),nonetheless the total endoscopy time was similar in both groups.No differences between TCI and bolus-sedation was observed for mean total-dosage of propofol rate as well as adverse events.CONCLUSION This study indicates that sedation using TCI for GI endoscopy reduces the dose of propofol necessary per minute of endoscopy.This may translate into less adverse events.However,further and randomized trials need to confirm this trend.

Efficacy of Bispectral index-monitored closed-loop targeted-controlled infusion of propofol for laparoscopic radical operation for gastric cancer

Objective:To discuss the efficacy of Bispectral index (BIS)-monitored closed-loop targeted-controlled infusion of propofol for laparoscopic radical operation for gastric cancer.Methods:A total of 106 patients with primary gastric cancer who underwent laparoscopic radical operation for gastric cancer in our hospital between August 2015 and February 2018 were chosen as the research subjects and divided into the control group (n=53) and the observation group (n=53) according to the different anesthesia methods. Control group of patients received BIS-monitored manually adjusted targeted-controlled infusion concentration of propofol, and observation group of patients received BIS-monitored closed-loop targeted-controlled infusion of propofol. The differences in hemodynamic index levels as well as serum contents of inflammatory factors and stress hormones were compared between the two groups of patients before anesthesia (T0), 30 min after surgery started (T1) and 30 min before surgery ended (T2).Results:At T0, the differences in hemodynamic index levels as well as serum contents of inflammatory factors and stress hormones were not statistically significant between the two groups. At T1 and T2, hemodynamic indexes MAP and HR levels of observation group were lower than those of control group at the corresponding time points;serum inflammatory factors sICAM-1, IL-1β, IL-8 and TNF-α contents were lower than those of control group at the corresponding time points;serum stress hormones Cor, T4 and glucagon contents were lower than those of control group at the corresponding time points.Conclusion: BIS-monitored closed-loop targeted-controlled infusion of propofol can effectively stabilize the intraoperative hemodynamics and inhibit the systemic inflammatory stress response in patients with laparoscopic radical operation for gastric cancer.

Effect of propofol infusion at different rate on liver blood flow and oxygen metabolism in rabbit

To evaluate the effect of propofol infusion on hepatic blood flow(HBF) and oxygen delivery and consumption in rabbit.Methods Thirty adult male rabbits weighing 1.6～2.4 kg were randomly allocated into 3 groups:group Ⅰ high dose propofol (HP) (n=11);group Ⅱ low dose propofol(HP) (n=10) and group Ⅲ control group (C)(n=9).The rabbits were anesthetized with intravenous 3% pentobarbital 45 mg·kg -1 and mechanically ventilated (VT=10 ml·kg -1 RR=40 bpm,I∶E=1∶2) after tracheal intubation.ECG,urinary output and rectal temperature were continuously monitored.Portal vein and hepatic artery were dissected and exposed for measurement of blood flow using electromagnetic flowmeter.Catheters were inserted into carotied artery,portal vein and hepatic vein via the mesenteric vein and right femoral vein for collection of blood samples.After the circulation was stabilized for 30 min,propofol infusion was started at a rate of 1.2 mg·kg -1 ·min -1 (HP) or 0.4 mg·kg -1 ·min -1 (LP).In control group normal saline was infused instead of propofol.Portal venous and hepatic arterial blood flow were continuously measured.Blood samples were obtained from carotid artery,portal vein and hepatic vein before (baseline )and at 30,50,70 and 90 min of propofol infusion for determination of Hb,SO2,PO2 and PCO2.The hepatic O2 delivery (DO2) and consumption (VO2) were calculated.Results The three groups were comparable with respect to body weight,duration of operation,the volume of fluid infused and blood loss and urinary output.HBF was significantly higher at 30～90 min of propofol infusion in HP group than in C group,meanwhile DO2 and VO2 in HP group were significantly higher during propofol infusion than the baseline value before infusion and those in C group.However,there was no significant difference in DO2/VO2 ratio between HP and C group.Conclusion High dose propofol infusion improves liver blood flow and O2 delivery but it also increases hepatic O2 comsumption.However the balance between hepatic O2 supply/demand remains unchanged.9 refs,2 tabs.

Relationship between depth of anesthesia and effect-site concentration of propofol during induction with the target-controlled infusion technique in elderly patients

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.

Comparison of C50 for Propofol-remifentanil Target-controlled Infusion and Bispectral Index at Loss of Consciousness and Response to Painful Stimulus in Elderly and Young Patients

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.

Concentrations of propofol in cerebral spinal fluid: target-controlled infusion

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.

Population Pharmacokinetics of Propofol Administered by TCI in Chinese Elderly Patients

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.

Pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese surgical patients

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.

Two-stage analysis of pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese patients

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.

Predictive performance of'Diprifusor'TCI system in patients during upper abdominal surgery under propofol/fentanyl anesthesia

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.

A New Pharmacokinetic Model of Propofol for Japanese Patients

Target-controlled infusion (TCI) of propofol is used for general anesthesia. However, the only pharmacokinetic parameter commercially used for Japanese patients is weight, and pharmacokinetic models are based on European physical attributes. Drug metabolism also differs in races. This study aimed to identify optimal continuous doses of propofol for Japanese patients and to create a simulated pharmacokinetic (PK) model. Thirty Japanese patients were enrolled. Patients received a constant infusion of 9 mg/kg/h of propofol. Arterial blood samples were collected and the time course of plasma propofol concentrations was modeled using the nonlinear mixed effects model (NONMEM) three-compartmental PK model. We validated the model by intravenously injecting 10 patients with a TCI driver system programmed with the NONMEM model. Our model’s performance was evaluated using the median prediction error (MDPE), median absolute prediction error (MDAPE), and Wobble. We analyzed 320 blood samples for model building and 160 samples for validating our new model. The calculated parameters for the three-compartmental PK model were volume [V1, 3.58;V2, 13.0 + 0.49 × (Age—64);and V3, 186] and elimination clearance [CL1, 0.77 + (WT—54) × 0.04 + (HT—158) × 0.03;CL2, 0.89 + 0.12 × (Age—64);and CL3, 0.98 × exp ((Age—64)/10)]. The new model improved MDPE, MDAPE, and Wobble values (11.5% ± 43.8%, 14.3% ± 33.0%, and 25.0% ± 21.3%, respectively). We created a new pharmacokinetic model for Japanese patients, which is more accurate than the three existing models applied to Japanese populations. Electronic document is a “live” template. The various components of your paper [title, text, heads, etc.] are already defined on the style sheet, as illustrated by the portions given in this document.

Effects of Glucose Load on Catabolism during Propofol-Based Anesthesia with Remifentanil in Patients with Diabetes Mellitus: A Prospective Randomized Trial

Background: Perioperative exacerbation of hyperglycemia and insulin resistance is associated with increased complications in patients with diabetes mellitus. We recently reported that glucose load during anesthesia with sevoflurane suppressed lipid catabolism in diabetic patients. In contrast to inhaled anesthetics, propofol solution contains triglycerides, which can be an energy source during surgery. However, the clinical relevance of glucose load under propofol-based anesthesia in diabetic patients is unknown. Therefore, we investigated the effect of intraoperative glucose load on catabolism during propofol-based anesthesia in patients with diabetes mellitus. Methods: Twenty-three patients with diabetes mellitus undergoing elective surgery with propofol-remifentanil-based anesthesia were randomly assigned to receive a glucose load (1.5 mg/kg/ min) or not. Plasma levels of glucose, insulin, cortisol, catecholamines, acetoacetic acid, free fatty acids, ketone bodies, 3-hydroxybutyric acid, and 3-methylhistidine/creatinine, used as a marker for protein catabolism, were measured at the start of surgery and 3 h later. Results: Glucose and insulin levels were significantly higher in patients who received a glucose load than in those who did not. Nonetheless, the levels of cortisol and catecholamines were unchanged during surgery. Similarly, the difference in the levels of markers for lipid as well as protein catabolism was not significant between the groups at 3 h after the start of surgery. Conclusions: Changes in lipid as well as protein catabolism were not altered by glucose load in diabetic patients under propofol-based anesthesia with remifentanil. Our study suggested that continuous infusion of propofol at a clinical dose is sufficient to reduce the requirement for glucose infusion during surgery in patients with diabetes.

老年髋关节置换术中实施丙泊酚闭环靶控输注麻醉的效果及对患者术后谵妄风险的影响

目的研究老年髋关节置换术中实施丙泊酚闭环靶控输注麻醉的效果及对术后谵妄风险的影响。方法回顾性选取2020年1月至2023年1月入安庆市第一人民医院接受治疗的90例髋关节骨折老年患者,择期行髋关节置换术。参考麻醉方式不同分为A组、B组和C组,每组各30例。A组给予丙泊酚闭环靶控持续输注麻醉,B组给予丙泊酚开环靶控持续输注麻醉,C组给予丙泊酚人工持续输注麻醉。比较3组患者的术中相关指标(麻醉时间、手术时间以及拔管时间)、麻醉相关指标(术中丙泊酚总计用量、术中维持泵调节次数)、血流动力学变化[麻醉诱导开始(T_(0))、插管(T_(1))、手术开始(T_(2))、手术结束(T_(3))、拔管(T_(4))的平均动脉压、心率以及脑电双频指数(BIS)值]情况、术后恢复情况及术后谵妄发生情况。结果(1)术中指标:3组患者麻醉时间、手术时间以及拔管时间比较,差异均无统计学意义(P>0.05)。(2)麻醉相关指标:A组患者术中丙泊酚总计用量、术中维持泵调节次数均明显低于B、C组,差异均有统计学意义(P<0.05);B组患者单位麻醉时间内丙泊酚用量、单位手术时间内丙泊酚用量均明显高于A、C组,差异均有统计学意义(P<0.05)。(3)血流动力学:A组T_(2)、T_(3)时平均动脉压均高于B组、C组,A组T_(4)时的平均动脉压更加接近于T_(0);3组患者不同时刻心率差异无统计学意义(P>0.05);A组T_(2)、T_(3)时BIS值均低于B组、C组,差异均有统计学意义(P<0.05)。(4)术后恢复情况:A组患者PACU停滞时间、自主呼吸恢复时间、指令反应恢复时间均明显低于B、C组,差异均有统计学意义(P<0.05)。(5)术后谵妄:A组患者术后谵妄发生率为16.67%,显著低于B、C组(40.00%、46.67%),差异均有统计学意义(P<0.05)。结论老年髋关节置换术中采用丙泊酚靶控输注麻醉可减少丙泊酚用量,术中生命体征更加平稳,可降低人工操作次数,术后麻醉苏醒更快,且术后谵妄发生率也更低,是老年患者首选的麻醉方案。

Effect of midazolam and propofol on cytokine balance in patients undergoing cardiac valve replacement

Objective To compare the effect of midazolam and propofol on cytokine balance in patients undergoing cardiac June 2003 Vol12 No2 valve replacement under CPB. Methods Twenty NYHA class II - 333 patients with rheumatic heart disease scheduled for elective cardiac valve replacement under CPB were randomy divided into 2 groups: midazolam group (M, n = 10) and propofol group (P, n = 10). Patients with preoperative hepatic and renal dysfunctions were premedicated intramuscular morphine 0. 1 mg · kg-1 and oral diazepam 0.1 mg·kg-1 . Anesthesia was induced withmidazolam 0. 06 -0.1 mg· kg-1 (group M) or propofol1.0-1.5 mg·kg-1 (gropu P) and scopolamine 0.6 mg, fentanyl 4-10 μg · kg-1, vecuronium 0. 1 mg · kg-1 and lidocaine 1. 5 mg·kg-1,and maintained with intermittent iv boluses of midazolam 0. 04 - 0.1 mg· kg-1(group M) or propofol intravenous infusion at a rate of 3 - 5 mg· kg-1 · h-1 supplemented with intermittent boluses of fentanyl and vecuronium. PETCO2 was maintained at 30 -40 mmHg during

艾司氯胺酮和丙泊酚在宫腔镜手术中的药效学相互作用

目的采用响应曲面法分析艾司氯胺酮和丙泊酚在宫腔镜手术中的药效学相互作用。方法选择择期行宫腔镜手术患者45例,年龄18~64岁,BMI 18.5~28.0 kg/m^(2),ASAⅠ或Ⅱ级。选择不同血浆药物浓度的艾司氯胺酮(0、0.1、0.2、0.3、0.4、0.5、0.6、0.7、0.8μg/ml)复合丙泊酚靶控输注,术中维持艾司氯胺酮的血浆药物浓度不变,阶梯式增加丙泊酚的血浆药物浓度。评估扩张宫颈引起的体动反应。采用响应曲面模型分析艾司氯胺酮与丙泊酚的药效学相互作用。结果艾司氯胺酮(0~0.8μg/ml)与丙泊酚(1.0~7.0μg/ml)相互作用的三维响应曲面显示,两者抑制扩张宫颈引起的体动反应方面具有相加作用。抑制扩张宫颈引起的体动反应的艾司氯胺酮半数有效浓度(EC_(50))为0.61μg/ml(95%CI 0.41~0.81μg/ml),丙泊酚EC_(50)为4.69μg/ml(95%CI 3.17~6.21μg/ml)。结论响应曲面法可以定性和定量地分析艾司氯胺酮和丙泊酚的药效学相互作用规律,在抑制扩张宫颈引起的体动反应上,艾司氯胺酮和丙泊酚具有相加作用。

丙泊酚微量泵输注联合前锯肌平面阻滞对老年胃癌根治术患者麻醉药物用量、术后谵妄及躁动影响

目的探讨丙泊酚微量泵输注联合前锯肌平面阻滞对老年胃癌根治术患者麻醉药物用量、术后谵妄及躁动影响。方法前瞻性选取2021年1月至2023年12月临汾市人民医院收治的80例老年胃癌患者作为研究对象,按照抽签法分为观察组与对照组,每组各40例。所有患者均择期实施胃癌根治术治疗,对照组患者实施单纯全身静脉麻醉,术中采取丙泊酚微量泵注维持麻醉,观察组在对照组基础上增加前锯肌平面阻滞。对比两组麻醉效果,麻醉前(T1)、麻醉后2 min(T2)、手术开始即刻(T3)及手术结束即刻(T4)平均动脉压、血氧饱和度及心率水平变化,对比两组麻醉药物总用量,术后1、6及12 h疼痛及镇静情况,最后对比其谵妄及躁动发生率。结果观察组麻醉效果Ⅰ级患者比率为65.00%,高于对照组(37.50%),观察组麻醉效果Ⅲ级患者比率为2.50%,低于对照组(15.00%),差异均有统计学意义(P<0.05)。观察组T2、T3、T4时MAP水平分别为(80.94±6.26)、(83.37±6.52)、(92.39±5.18)mmHg,均高于对照组[(74.33±4.85)、(76.21±4.42)、(83.72±11.22)mmHg],观察组T2、T3时血氧饱和度分别为(98.84±1.67)%、(98.95±1.56)%,均高于对照组[(93.52±2.52)%、(93.12±1.53)%],观察组T2时心率为(80.36±9.27)次/min,低于对照组[(86.28±7.22)次/min],差异均有统计学意义(P<0.05)。两组患者瑞芬太尼用量比较,差异无统计学意义(P>0.05),观察组患者舒芬太尼、丙泊酚用量分别为(43.32±5.12)μg、(251.63±42.52)mg,均明显低于对照组[(46.02±7.25)μg、(281.68±56.12)mg],差异均有统计学意义(P<0.05)。观察组术后1、6、12 h Ramsay评分(1.62±0.28)、(1.08±0.15)、(0.73±0.16)级,均低于对照组[(2.81±0.31)、(1.52±0.12)、(1.03±0.12)级];观察组术后1、6、12 h VAS评分(3.41±1.23)、(2.44±0.21)、(2.17±0.31)分,均低于对照组[(4.39±1.38)、(3.57±0.11)、(3.03±0.25)分],差异均有统计学意义(P<0.05)。观察组术后谵妄及躁动发生率分别为5.00%、2.50%,均明显低于对照组(22.50%、17.50%),差异均有统计学意义(P<0.05)。结论丙泊酚微量泵输注联合前锯肌平面阻滞可提升老年胃癌根治术患者麻醉效果,稳定术中生命体征,减少麻醉药物用量,同时可提升术后镇痛及镇静效果,降低躁动及谵妄发生率。

BIS指导下丙泊酚联合瑞芬太尼靶控输注对老年髋关节置换患者术中丙泊酚用量和术后谵妄发生率的影响

目的:探讨脑电双频指数(BIS)指导下丙泊酚联合瑞芬太尼靶控输注(TCI)对老年髋关节置换患者术中丙泊酚用量和术后谵妄发生率的影响。方法:回顾性分析老年髋部骨折患者的病例资料,依据患者接受的麻醉方式不同分为两组,即接受BIS指导下丙泊酚联合瑞芬太尼TCI麻醉的髋关节置换患者纳入观察组,接受BIS指导下丙泊酚联合瑞芬太尼持续静脉泵入的同类患者纳入对照组,建立二元Logistics回归分析,构建倾向性评分匹配模型分析得出观察组获取56例病例资料,对照组获取49例病例资料,组间差异无统计学意义(P>0.05)。观察两组不同时间点[入室后(T_(0))、麻醉后(T_(1))、骨水泥后(T_(2))、术毕(T_(3))、出室后(T_(4))、术后3h(T_(5))及术后5h(T_(6))时刻]的平均动脉压(MAP)、心率(HR)、手术一般情况、丙泊酚用量、BIS值维持情况,对比两组不同时间点(术前及术后1h、6h、1d、3d、7d时刻)谵妄评分[谵妄量表分析系统(CAM-CR)],记录两组术后谵妄发生率,比较两组不同时间点(术前及术后1d)的血糖(Glu)及血浆肾上腺素(E)、皮质醇(Cor)水平变化。结果:观察组在T_(1)时刻MAP值相比T_(0)时刻有显著性降低(P<0.05),两组均在T_(2)时刻MAP值相比T_(0)时刻有显著性降低(P<0.05),其中对照组在T_(5)、T_(6)及T_(7)时刻HR值相比T_(4)时刻出现显著性降低(P<0.05);两组手术时间、麻醉时间及术中出血量对比均差异无统计学意义(P>0.05),观察组丙泊酚用量显著少于对照组(P<0.05),观察组BIS值目标范围维持时间比显著高于对照组(P<0.05),观察组苏醒时间、气管拔管时间及定向力恢复时间显著短于对照组(P<0.05);术后1h、6h、1d、3d、7d,两组CAM-CR评分可见先升高后降低,均显著高于术前(P<0.05),观察组术后1h、6h、1d、3d的CAM-CR评分均显著低于对照组(P<0.05),两组术后7d的上述评分较术前和组间同时间点对比均差异无统计学意义(P>0.05);观察组的术后谵妄发生率为5.36%,显著低于对照组的18.37%(P<0.05);术后1d,两组Glu及血浆E、Cor水平相比术前出现显著性升高(P<0.05),但观察组显著低于对照组(P<0.05)。结论:BIS指导下丙泊酚联合瑞芬太尼TCI应用于老年髋关节置换患者术中能稳定血流动力学,改善围手术期指标,并减少丙泊酚用量,改善BIS值维持情况,并促进患者麻醉恢复,减少术后谵妄发生风险,同时能减轻机体应激反应。