Target-controlled Infusion System Research Articles

Development of extended pharmacokinetic models for propofol based on measured blood and brain concentrations

Propofol’s pharmacokinetics have been extensively studied using human blood samples and applied to target-controlled infusion systems; however, information on its concentration in the brain remains scarce. Therefore, this study aimed to simultaneously measure propofol plasma and brain concentrations in patients who underwent awake craniotomy and establish new pharmacokinetic model. Fifty-seven patients with brain tumors or brain lesions who underwent awake craniotomy were sequentially assigned to model-building and validating groups. Plasma and brain (lobectomy or uncapping margins) samples were collected at five time-points. The concentration of propofol was measured using high-performance liquid chromatography. Population pharmacokinetic analysis was conducted through a nonlinear mixed-effects modeling program using a first-order conditional estimation method with interactions. Propofol’s brain concentrations were higher than its plasma concentrations. The measured brain concentrations were higher than the effect site concentrations using the previous models. Extended models were constructed based on measured concentrations by incorporating the brain/plasma partition coefficient (Kp value). Extended models showed good predictive accuracy for brain concentrations in the validating group. The Kp value functioned as a factor explaining retention in the brain. Our new pharmacokinetic models and Kp value can predict propofol’s brain and plasma concentrations, contributing to safer and more stable anesthesia.

External validation of the modified Marsh and Schnider models for medium-chain triglyceride propofol in target-controlled infusion anesthesia

BackgroundPropofol formulated with medium- and long-chain triglycerides (MCT/LCT propofol) has rapidly replaced propofol formulated with long-chain triglycerides (LCT propofol). Despite this shift, the modified Marsh and Schnider pharmacokinetic models developed using LCT propofol are still widely used for target-controlled infusion (TCI) of propofol. This study aimed to validate the external applicability of these models by evaluating their predictive performance during TCI of MCT/LCT propofol in general anesthesia.MethodsAdult patients (n = 48) undergoing elective surgery received MCT/LCT propofol via a TCI system using either the modified Marsh or Schnider models. Blood samples were collected at various target propofol concentrations and at specific time points, including the loss of consciousness and the recovery of consciousness (13 samples per patient). The actual plasma concentration of propofol was determined using high-performance liquid chromatography. The predictive performance of each pharmacokinetic model was assessed by calculating four parameters: inaccuracy, bias, divergence, and wobble.ResultsBoth the modified Marsh and Schnider models demonstrated predictive performances within clinically acceptable ranges for MCT/LCT propofol. The inaccuracy values were 24.4% for the modified Marsh model and 26.9% for the Schnider model. Both models showed an overall positive bias, 16.4% for the modified Marsh model and 16.6% for the Schnider model. The predictive performance of MCT/LCT propofol was comparable to that of LCT propofol, suggesting formulation changes might exert only a minor impact on the reliability of the TCI system during general anesthesia. Additionally, both models exhibited higher bias and inaccuracy at target concentrations ranging from 3.5 ~ 5 ug/ml than at concentrations between 2 ~ 3 ug/ml.ConclusionsThe modified Marsh and Schnider models, initially developed for LCT propofol, remain clinically acceptable for TCI with MCT/LCT propofol.Trial registrationThis study was registered at the Clinical Research Information Service of the Korean National Institute of Health (https://cris.nih.go.kr; registration number: KCT0002191; 06/01/2017).

Robotic Anesthesia: A Vision for 2050.

The last 2 decades have brought important developments in anesthetic technology, including robotic anesthesia. Anesthesiologists titrate the administration of pharmacological agents to the patients' physiology and the needs of surgery, using a variety of sophisticated equipment (we use the term "pilots of the human biosphere"). In anesthesia, increased safety seems coupled with increased technology and innovation. This article gives an overview of the technological developments over the past decades, both in terms of pharmacological and mechanical robots, which have laid the groundwork for robotic anesthesia: target-controlled drug infusion systems, closed-loop administration of anesthesia and sedation, mechanical robots for intubation, and the latest development in the world of communication with the arrival of artificial intelligence (AI)-derived chatbots are presented.

External validation of a pharmacokinetic model for target-controlled infusion of cefazolin as a prophylactic antibiotic.

This study aimed to evaluate the predictive performance of previously constructed cefazolin pharmacokinetic models and determine whether cefazolin administration via the target-controlled infusion (TCI) method may be possible in clinical practice. Twenty-five gastrectomy patients receiving cefazolin as a prophylactic antibiotic were enrolled. Two grams of cefazolin was dissolved in 50 mL of normal saline to give a concentration of 40 mg mL-1 . Before skin incision, cefazolin was administered using a TCI syringe pump, and its administration continued until the end of surgery. The target total plasma concentration was set to 100 μg mL-1 . Total and unbound plasma concentrations of cefazolin were measured in three arterial blood samples collected at 30, 60 and 120 min after the start of cefazolin administration. The predictive performance of the TCI system was evaluated using four measures: inaccuracy, divergence, bias and wobble. Total (n = 75) and unbound (n = 75) plasma concentration measurements from 25 patients were included in the analysis. The pooled median (95% confidence interval) biases and inaccuracies were 6.3 (4.0-8.5) and 10.5 (8.6-12.4) for the total concentration model and -10.3 (-16.8 to -3.7) and 22.4 (18.2-26.7) for the unbound concentration model, respectively. All unbound concentrations were above 10μg mL-1 . Administration of cefazolin by the TCI method showed a clinically acceptable performance. Applying the TCI method by setting the total concentration as the target concentration rather than the unbound concentration is effective in maintaining a constant target concentration of cefazolin.

Propofol TCI or sevoflurane anesthesia without muscle relaxant for thoracoscopic thymectomy in myasthenia gravis patients: a prospective, observational study

BackgroundMyasthenia gravis (MG) patients interact unpredictably with anesthetic agents, including neuromuscular blocking agents. Here, we investigate the effectiveness of general anesthesia without muscle relaxants using either propofol via target-controlled infusion systems (TCI) or sevoflurane in MG patients undergoing thoracoscopic thymectomy.MethodsThis prospective, open-label, observational study was conducted in a university hospital. We included 90 myasthenic patients undergoing thoracoscopic thymectomy with general anesthesia. Patients received induction and maintenance anesthesia with propofol TCI (group P, n = 45) or induction with propofol 2–3 mg.kg−1 and maintenance anesthesia with sevoflurane (group S, n = 45). In both groups, the procedure was performed under the guidance of entropy with sufentanil but not a muscle relaxant. Intubation conditions, hemodynamic changes, respiratory function, neuromuscular transmission, arterial blood gas, and complications were evaluated.ResultsAll patients achieved good intubation conditions. Hemodynamic instability was more frequent in group S than in group P, mostly in the induction stage, and was controllable. The reduction in the intraoperative train-of-four ratio from baseline at 30 min, 60 min, and 90 min in group S was 10.3%, 14.2%, and 14.3%, respectively, significantly higher than that in group P (6.8%, 7.2%, and 8.4%, respectively), which completely recovered at the end of the surgery. All patients were extubated in the operating room without complications. No other significant differences between the groups were observed.ConclusionsAnesthesia with propofol TCI or sevoflurane without muscle relaxants in MG patients offered safe and effective conditions for thoracoscopic thymectomy. Sevoflurane achieved higher levels of intraoperative muscular relaxation than propofol TCI. Postoperative neuromuscular function was not affected by these anesthetics.

The efficacy of non-anesthesiologist-administered propofol sedation with a target-controlled infusion system during double-balloon endoscopic retrograde cholangiopancreatography

BackgroundThe sedation method used during double-balloon endoscopic retrograde cholangiopancreatography (DB-ERCP) differs among countries and/or facilities, and there is no established method. This study aimed to evaluate the efficacy of non-anesthesiologist-administered propofol (NAAP) sedation using a target-controlled infusion (TCI) system during DB-ERCP.MethodsThis retrospective study was conducted between May 2017 and December 2020 at an academic center. One hundred and fifty-six consecutive patients who underwent DB-ERCP were sedated by gastroenterologists using diazepam (n = 77) or propofol with a TCI system (n = 79), depending on the period. The primary endpoint was a comparison of poor sedation rates between the two groups. Poor sedation was defined as a condition requiring the use of other sedative agents or discontinuation of the procedure. Secondary endpoints were sedation-related adverse events and risk factors for poor sedation.ResultsPoor sedation occurred significantly more often in the diazepam sedation group (diazepam sedation, n = 12 [16%] vs. propofol sedation, n = 1 [1%]; P = 0.001). Vigorous body movements (3 or 4) (diazepam sedation, n = 40 [52%] vs. propofol sedation, n = 28 [35%]; P = 0.038) and hypoxemia (< 85%) (diazepam sedation, n = 7 [9%] vs. propofol sedation, n = 1 [1%]; P = 0.027) occurred significantly more often in the diazepam sedation group. In the multivariate analysis, age < 70 years old (OR, 10.26; 95% CI, 1.57–66.98; P = 0.015), BMI ≥ 25 kg/m2 (OR, 11.96; 95% CI, 1.67–85.69; P = 0.014), and propofol sedation (OR, 0.06; 95% CI, 0.01–0.58; P = 0.015) were associated factors for poor sedation.ConclusionsNAAP sedation with the TCI system during DB-ERCP was safer and more effective than diazepam sedation.

Remimazolam-remifentanil causes less postoperative nausea and vomiting than remimazolam-alfentanil during hysteroscopy: a single-centre randomized controlled trial

BackgroundAlthough the operation time of hysteroscopy is short, the incidence of postoperative nausea and vomiting is high. The aim of this study was to compare the incidence of postoperative nausea and vomiting in hysteroscopy when remimazolam is combined with remifentanil or alfentanil.MethodsWe conducted a randomized, controlled, double-blind trial. Patients undergoing hysteroscopy were recruited and randomly assigned to either the remimazolam-remifentanil (Group RR) or the remimazolam-alfentanil group (Group RA). All patients in the two groups were started with an induction dose of remimazolam besylate 0.2 mg/kg and then maintained with a dosage of 1.0 mg/kg/h. After induction with remimazolam besylate, in Group RR, remifentanil was infused using a target-controlled infusion system with a target concentration of 1.5 ng/ml and titrated throughout the procedure. In Group RA, infusion of alfentanil was started with an initial bolus dose of 20 µg/kg over 30 s and then maintained at an initial rate of 0.16 µg/kg/min. The primary observation outcome was the incidence rate of postoperative nausea and vomiting. The secondary observation outcomes were the time to awakening, the length of stay in the PACU, the total remimazolam dose and adverse effects, such as low SpO2, bradycardia, hypotension and body movement.ResultsA total of 204 patients were successfully included in this study. The incidence of postoperative nausea and vomiting in Group RR (2/102, 2.0%) was significantly lower than that in Group RA (12/102, 11.8%) (p < 0.05). There was no significant difference in the incidence of adverse events, such as low SpO2, bradycardia, hypotension and body movement, between Groups RR and RA (p > 0.05).ConclusionsRemimazolam-remifentanil causes less postoperative nausea and vomiting than remimazolam-alfentanil in hysteroscopy.Trial registrationClinical trial registration number: ChiCTR2100044177. Full date of the first registration: 12/03/2021.

Comparison of recovery profiles in target-controlled infusions (TCI) versus manually controlled infusions for total intravenous anesthesia (TIVA) in laparoscopic surgeries. A randomized controlled trial.

Considerable importance has been attached to early recovery and discharge readiness after surgeries. Many centers use total intravenous anesthesia (TIVA) as their anesthesia technique of choice. Target-controlled infusions (TCI) have been proposed as a method to precisely deliver continuous infusions of propofol and opioids as compared to the traditionally used manual-controlled infusion (MCI) methods. However, TCI has also been shown to result in the administration of larger doses of propofol which could cause delayed emergence and recovery from anesthesia. Studies involving TCI have focused mainly on its effects on anesthesia induction but not much literature is available on recovery profiles of patients on TCI. This study was designed to compare the effect of conventionally used MCI methods versus the target-controlled infusion (TCI) method of administering TIVA on recovery characteristics in patients undergoing laparoscopic surgery. This was a prospective randomized interventional study on 54 patients. Our primary objective was to compare the rates of recovery from anesthesia as judged by four parameters. Time to return of spontaneous ventilation, time to respond to verbal commands, time to extubation, and time to shift patient out of the operating room after stoppage of propofol infusion. As secondary objectives, intraoperative average bispectral index (BIS) values and total anesthetic drugs (propofol and fentanyl) consumption were also compared. We noted that for laparoscopic surgeries lasting less than 4 hours, both MCI and TCI techniques of TIVA have comparable rates of recovery after the stoppage of propofol infusion. Total consumption of propofol and fentanyl was also similar; however, with the use of the TCI method of TIVA, better depth of anesthesia as evidenced by lower average BIS levels was noted. Recovery rates after TIVA using a target-controlled infusion (TCI) system are similar to BIS-guided MCIs in patients undergoing laparoscopic surgery lasting less than 4 hours. TCI resulted in better depths of anesthesia though per kg/min consumption of propofol was found to be more.

A Transformer-Based Prediction Method for Depth of Anesthesia During Target-Controlled Infusion of Propofol and Remifentanil.

Accurately predicting anesthetic effects is essential for target-controlled infusion systems. The traditional (PK-PD) models for Bispectral index (BIS) prediction require manual selection of model parameters, which can be challenging in clinical settings. Recently proposed deep learning methods can only capture general trends and may not predict abrupt changes in BIS. To address these issues, we propose a transformer-based method for predicting the depth of anesthesia (DOA) using drug infusions of propofol and remifentanil. Our method employs long short-term memory (LSTM) and gate residual network (GRN) networks to improve the efficiency of feature fusion and applies an attention mechanism to discover the interactions between the drugs. We also use label distribution smoothing and reweighting losses to address data imbalance. Experimental results show that our proposed method outperforms traditional PK-PD models and previous deep learning methods, effectively predicting anesthetic depth under sudden and deep anesthesia conditions.

Effects of different depth of anesthesia on perioperative inflammatory reaction and hospital outcomes in elderly patients undergoing laparoscopic radical gastrectomy

BackgroundTo investigate the effect of different depth of anesthesia on inflammatory factors and hospital outcomes in elderly patients undergoing laparoscopic radical gastrectomy for gastric cancer, in order to select an appropriate depth of anesthesia to improve the prognosis of patients undergoing surgery and improve the quality of life of patients.MethodsA total of 80 elderly patients aged 65 and above who underwent laparoscopic radical gastrectomy in our hospital were by convenience sampling and randomly divided into two groups : 55 groups ( group H ) and 45 groups ( group L ), 40 cases in each group. The depth of anesthesia was maintained using a closed-loop target-controlled infusion system: the EEG bispectral index was set to 55 in the H group and 45 in the L group. Venous blood samples were collected 2 h (T2), 24 h (T3) and 72 h (T4) after the start of surgery. The intraoperative dosage of propofol and remifentanil, operation duration, postoperative PACU stay time, intraoperative consciousness occurrence, postoperative hospital stay and postoperative pulmonary inflammatory events were recorded.ResultsThe patient characteristic of the two groups had no statistical difference and were comparable (P > 0.05). The intraoperative dosage of propofol in group H was lower than that in group L (P < 0.05). Compared with the L group, the plasma IL-6 and IL-10 concentrations in the H group were significantly increased at T2 (P < 0.05), and the plasma IL-10 concentration was significantly increased at T4 (P < 0.05). The plasma concentrations of IL-6 and IL-10 were higher in both groups at T2, T3 and T4 than at T1, while at T4, the concentration of TNF-α in group H was higher than at T1 (P < 0.05).ConclusionWhen the BIS value of the depth of anesthesia is 45, the perioperative release of inflammatory factors in elderly patients with laparoscopic radical gastrectomy for gastric cancer is less than BIS 55, and does not affect the prognosis.

Influence of body fatness on propofol requirements for loss of consciousness in target-controlled infusion: A STROBE-compliant study.

This prospective observational study evaluated the effects of body fat on the pharmacologic effect of propofol. Hundred patients aged 18 to 75 years who were scheduled to undergo orthopedic surgery under regional block were enrolled. All participants underwent bioelectrical impedance analysis and were allocated into 2 groups: the high and normal adiposity group, according to percent body fat. Following successful regional block, propofol was incrementally infused until loss of consciousness (LOC) with a target-controlled infusion pump. The effect-site concentration of propofol at LOC and the total infused dose of propofol per total body weight until LOC were recorded. At the end of the surgery, the infusion of propofol was stopped. The elapsed time to recovery of consciousness (ROC) and the effect-site concentration at ROC were recorded. These pharmacologic data were compared between 2 groups. The effect-site concentration of propofol at LOC (µg/mL) was significantly lower in the high adiposity group than in the normal group in both sexes (3.5 ± 0.4 vs 3.9 ± 0.6; P = .020 in males, and 3.4 [interquartile range: 2.9–3.5] vs 3.8 [interquartile range: 3.3–3.9]; P = .006 in females). Total dose per total body weight until LOC (mg/kg) were also significantly lower in the high adiposity group than in the normal group. There was no significant difference in the data related to ROC. The pharmacologic effects of propofol may be affected by the composition of body components. The concentration of propofol using a target-controlled infusion system may be diminished in patients with a high proportion of body fat.

Pediatric TCI: A new pharmacokinetic-pharmacodynamic theory proposal-part one

New theoretical research of pharmacokinetic-pharmacodynamics constants for anaesthetic drugs are discussed in this report. Our study aims to set up a new algorithm to be validate and eventually insert in a new theoretical software. The algorithm will be installed in a new Target Controlled Infusion (TCI) System dedicated to neonatal and paediatric anaesthesia and especially for patients weighing less than 30 kgs, so for dynamics rapid cells growth and or elderly patients suffering of rapid dynamic death cells. TCI systems used for the management of paediatric and neonatal anaesthesia, i.e. Paedfusor TCI by Absalom-Lal-Kenny et al (2005), needed further investigation for their use in younger patients. There is a lack of body functioning and pharmacological data in the paediatric and neonatal population that need to be integrated in a new program to be installed in computer-driven anaesthesia systems. A new theoretical pathway and speculation about the approach to applied pharmacology is compulsory. But as new theoretical “pharmacodynamics-pharmacokinetic” (PK/PD) concept and covariates choices are required to be settled in the systems; a new scientific approach is required. Our theoretical speculations and practical mathematical proposal takes into consideration different covariate factors and is based not only on the theoretical consideration that drove to “Gepts thricompartimental equation” concept, but would like to considers the aid of “allometry” growth pharmacological laws and equations and insert the concepts in a sort of “Quantic Pharmacology” new research pathway. We want to argue if the way we look at such a complex approach is correct, and if it could be applicable, and better defines and use novel data to improve the “Gepts” equation related to the neonatal-paediatric-elderly age range.

Development and optimization of a fentanyl pharmacokinetic model for target-controlled infusion in anaesthetized dogs

ObjectiveTo investigate pharmacokinetics (PK) of fentanyl administered by target-controlled infusion (TCI), and to develop a PK model optimized by covariates for TCI in anaesthetized dogs. Study designProspective clinical study. AnimalsA group of 20 client-owned dogs with spinal pain undergoing anaesthesia for magnetic resonance imaging. MethodsFentanyl was administered as an infusion to 20 anaesthetized dogs using a TCI system incorporating a previously described fentanyl two-compartment PK. Arterial blood samples were collected at specific time points during the infusion and over 60 minutes post-infusion for measurement of fentanyl plasma concentrations. The predictive performance of the Sano PK model was assessed by comparing predicted and measured plasma concentrations. A population PK analysis was then performed using a nonlinear mixed-effect modelling approach, allowing inter- and intra-individual variability estimation. Finally, a quantitative stepwise evaluation of the influence of various covariates such as weight, body condition score, size, size-related age, sex and type of premedication on the PK model was considered. ResultsOverall predictive performance of the Sano PK set of variables was not clinically acceptable in anaesthetized dogs. Fentanyl PK was best described by a three-compartment model. Weight and sex were found to affect the volume of distribution of the central compartment. Addition of these two covariate/variable associations resulted in a reduction of the objective function value (OFV) from –340.18 to –448.34, and of the median population weighted residual and the median population absolute weighted residual from 16.1% and 38.6% to 3.9% and 20.3%, respectively. Fentanyl infusions at measured concentrations up to 5.4 ng mL–1 in sevoflurane-anaesthetized dogs resulted in stable anaesthesia and smooth recoveries without complications. Conclusions and clinical relevanceA population three-compartment PK model for fentanyl TCI in anaesthetized dogs was developed. Weight and sex have been detected and incorporated as significant covariates.

To ascertain the plasma concentration of propofol to achieve bispectral index-guided sedation using a target-controlled infusion in patients undergoing elective surgeries under neuraxial anaesthesia.

Sedation improves patient satisfaction, comfort and acceptance of regional anaesthesia. Propofol using bispectral index (BIS)/target-controlled infusion (TCI) system can be an optimal method of sedation, as it combines objective measurement of sedation using BIS along with maintenance of a steady plasma concentration of propofol with the TCI device. The aim of this study was to ascertain the dose and safety of propofol using BIS/TCI system for sedation in patients undergoing surgeries under neuraxial anaesthesia. One hundred and seven adult patients, undergoing elective surgical procedures under spinal or combined spinal epidural anaesthesia, were recruited. Propofol infusion was started with TCI at an initial target plasma concentration (Cpt) of 1.2 μg/mL, and after equilibration between Cpt and effect site concentration (Ce), propofol was then adjusted in increments and/or decrements of 0.2 μg/mL in order to maintain a BIS value between 60 and 80. The average time to reach BIS = 80 after starting infusion was 7.32 ± 3.13 minutes. The objective was to calculate mean Cpt value maintaining BIS between 60 and 80 and to observe recovery time and complications. Mean Cpt value was 1.13 ± 0.17 mg/mL with 95% confidence interval (1.10-1.16 μg/mL). In 85% of patients, a BIS value of 60-80 was maintained at Cpt ≤ 1.2 μg/mL. No patient had severe complications requiring stoppage of infusion. Propofol sedation using BIS/TCI system can provide safe and convenient sedation during neuraxial anaesthesia at very low plasma concentration, Cpt ≤ 1.2 μg/mL in majority of patients. There were no periprocedural complications, and recovery was rapid.

A single-center pilot study comparing dexmedetomidine continuous infusion versus propofol TCI for drug-induced sleep endoscopy (DISE)

Background: Drug-induced sleep endoscopy (DISE) has become a routine diagnostic tool to assess the upper airway in obstructive sleep apnea patients, enabling effective diagnosis and appropriate treatment of the obstruction site. A number of protocols with different drugs and availability of target-controlled infusion (TCI) systems have been reported and published, making comparisons between studies difficult. In recent years, dexmedetomidine has claimed a role as a potential alternative to propofol for DISE sedation. In a real-life study we compared the effects of dexmedetomidine continuous infusion or propofol-TCI in patients undergoing DISE on time to reach adequate observation conditions, cardio-respiratory parameters, and recovery. Methods: Pilot prospective, randomized not blinded, single center study. A total of 28 patients scheduled to have DISE were randomly assigned to either group P (N=14; propofol-TCI, initial propofol effect-site target concentration 2.0 µg/mL, increased by 0.3 µg/mL every 2 min) or group D (N=14; dexmedetomidine bolus 1 µg/kg over 10 min, followed by infusion at 0.7 µg/kg/h). Hemodynamic and respiratory variables (including SpO2 nadir), time to reach the observation window and overall DISE duration were recorded. Results: A total of 28 patients were enrolled and completed the study: the cohort included 26 males (92.85%) and 2 females (7.14%). The mean age was 45.4±11.1 years [interquartile (IQ), 25.0–65.0], body mass index 30.5±3.4 kg/m2 (IQ, 21.0–36.0), and apnea-hypopnea index 36.9±21.1 events/hour (IQ, 7.8–95.0). There were no statistically significant differences between the 2 groups in baseline apnea-hypopnea index, oxygen desaturation index, Epworth Sleepiness Scale score, preprocedural SpO2 nadir, age, sex, or body mass index. Compared with group P, group D showed significant differences in SpO2 (higher nadir during DISE, 87.09±5.4% vs. 75.0±11.0; P&lt;0.001) and heart rate (80.4±8.9 vs. 62.8±6.6; P&lt;0.001). While group D had longer duration of endoscopic examination times and emergence time from sedation, the grading of site of obstructions were similar in the 2 groups. Conclusions: Dexmedetomidine seems a limited, if viable, clinical alternative for DISE when propofol is contraindicated or not available: while causing higher SpO2 nadirs compared with propofol, it has a slow onset and longer recovery time, increasing total procedural time. Studies with greater patient numbers are needed to confirm these observations.

Effects of dopamine, norepinephrine or phenylephrine on the prevention of hypotension in isoflurane-anesthetized cats administered vatinoxan or vatinoxan and dexmedetomidine

ObjectiveTo determine the dose of phenylephrine, norepinephrine and dopamine necessary to maintain mean arterial pressure (MAP) within 70–80 mmHg during administration of isoflurane, isoflurane and vatinoxan and isoflurane, vatinoxan and dexmedetomidine at three plasma concentrations. Study designRandomized crossover experimental study. AnimalsA group of five adult healthy neutered male cats. MethodsInstrumentation occurred during anesthesia with isoflurane in oxygen. Isoflurane end-tidal concentration was set to 1.25 × minimum alveolar concentration (MAC). Phenylephrine, norepinephrine or dopamine was administered to maintain MAP 70–80 mmHg. A target-controlled infusion system was used to administer vatinoxan at a target plasma concentration of 1 μg mL–1 and three dexmedetomidine concentrations (5, 10 and 20 ng mL–1). Isoflurane concentration was altered to maintain an equivalent 1.25 MAC. Heart rate, arterial blood pressure, central venous pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, body temperature, arterial and mixed venous blood gas, cardiac output and drug concentrations were measured at baseline (isoflurane alone), during vatinoxan administration, and during administration of vatinoxan and dexmedetomidine at the three target concentrations. ResultsMAP < 70 mmHg was observed with vatinoxan alone and in the dopamine treatment with dexmedetomidine concentrations ≤ 10 ng mL–1. Norepinephrine and phenylephrine maintained MAP 70–80 mmHg during vatinoxan and dexmedetomidine ≤ 10 ng mL–1. As the target dexmedetomidine concentration increased, the dose of norepinephrine and phenylephrine needed to maintain MAP 70–80 mmHg decreased; no treatment was necessary to maintain MAP > 70 mmHg at the 20 ng mL–1 target dexmedetomidine concentration in most cats. Conclusions and clinical relevanceNorepinephrine and phenylephrine, but not dopamine, are effective to prevent hypotension in isoflurane-anesthetized cats administered dexmedetomidine and vatinoxan.

Efficacy and safety of remimazolam besylate versus propofol during hysteroscopy: single-centre randomized controlled trial

BackgroundRemimazolam besylate is a newer benzodiazepine with characteristics of quick onset of effects, short maintenance and recovery times without accumulation in tissues. This trial was conducted to confirm the efficacy and safety of remimazolam besylate versus propofol during hysteroscopy.MethodsPatients undergoing hysteroscopy were randomly assigned to either the remimazolam (Group R) or the propofol group (Group P). Group R was administered an induction dose of 0.2 mg/kg and a maintenance dosage of 1.0 mg/kg/h. In Group P, propofol was started at 1.5–2.0 mg/kg and then maintained at 3.0–6.0 mg/kg/h. After remimazolam besylate or propofol induction, remifentanil was infused using a target-controlled infusion system with a target concentration of 1.5 ng/ml and titrated during the procedure. The incidence rates of injection pain, low oxygen saturation (SpO2) and adverse effects in both groups were compared.ResultsEighty-two patients were included in this study. The incidence of adverse events in Group R (3.7%) was significantly lower than that in Group P (36.6%) (p < 0.001). The incidence of injection pain in Group P (80.5%) was much higher than that in Group R (2.4%) (p < 0.001). The incidence of other adverse events, such as low SpO2, bradycardia, and hypotension in Group R was lower than that in Group P (p < 0.05).ConclusionsRemimazolam besylate proves to be a safer alternative for anesthesia during hysteroscopy. Moreover, adverse events caused by propofol, such as low SpO2 and injection pain, are largely avoided.Trial registrationThis study was approved by the Clinical Research Ethics Committee of Mengcheng County No. 1 People’s Hospital (2020MYL20003) and registered at http://www.chictr.org.cn (15/09/2020, ChiCTR-2000038252). The study protocol followed the CONSORT guidelines. The study protocol was performed in the relevant guidelines.

Stability of BIS with Schnider or modified Marsh effect-site targeted infusions : as you like it, or much ado about nothing?

Although commercial target-controlled infusion (TCI) systems have been available since the late 1990s1 and have facilitated safe and accurate administration of propofol in more than 90 countries,2 there remain areas of uncertainty and controversy.3

Analysis of influence factors of pharmacodynamics of propofol with target-controlled infusion during anesthetic recovery period.

To explore the pharmacodynamic (PD) characteristics of propofol during anesthetic recovery period with target-controlled infusion (TCI), and to identify the clinical variables related to the PD parameters. 20 patients scheduled for otolaryngology surgery were enrolled. After the surgery was finished, target effect site concentration was gradually decreased, blood samples were measured at 7 time points and the differences between the target and measured plasma concentration were compared. Observer's assessment of alertness/sedation (OAA/S) and Narcotrend index (NI) were used as two PD indicators by fitting sigmoid Emax model. Correlations between PD parameter and clinical variables were evaluated. Performance of the TCI system showed a positive bias at the end of the anesthesia sedation period and a negative bias in the anesthetic recovery period. PD parameters (EC50, r) calculated with OAA/S and NI were significantly different, EC50 of OAA/S was lower than EC50 of NI (1.53 ± 0.70 vs. 2.16 ± 0.99 µg/mL), r of OAA/S was higher than r of NI (57.07 ± 56.39 vs. 4.35 ± 4.42). Propofol dosage and hemodynamic parameters were significantly correlated with EC50 (OAA/S), lean body weight and gender were significantly correlated with EC50 (NI). NI provided a more stable and adequate assessment of the depth of anesthesia than OAA/S, and the influence factors should be taken into account for precise dosing.

Bispectral index monitoring of the clinical effects of propofol closed-loop target-controlled infusion: Systematic review and meta-analysis of randomized controlled trials.

Background:To investigate whether closed-loop systems under bispectral index anesthesia depth monitoring can reduce the intraoperative propofol dosage.Methods:All randomized controlled trials (RCTs) on reducing propofol dosage under closed-loop systems were collected, and the literature was screened out, the abstracts and full texts were carefully read, and the references were tracked, data extraction and quality evaluation were conducted on the included research, and the RevMan5.3 software was used for meta-analysis. The main results were propofol and the incidence of adverse reactions such as hypertensive hypotension and postoperative cognitive dysfunction. A total of 879 cases were included in 8 articles, including 450 occurrences in the closed-loop system group and 429 cases in the open-loop system group.Results:Compared with manual control, closed-loop systems under bispectral index anesthesia depth monitoring reduced the dose of propofol (MD: −0.62, 95% CI: −1.08–−0.16, P = .008), with heterogeneity (I2 = 80%). Closed-loop systems significantly reduced the incidence of abnormal blood pressure (MD: −0.02, 95%CI: −0.05–0.01, P = .15, I2 = 74%) and postoperative cognitive dysfunction (MD: −0.08, 95% CI: −0.14 −0.01, P = .02, I2 = 94%).Conclusion:Bispectral index monitoring of propofol closed-loop target-controlled infusion system can reduce the amount of propofol, reduce the incidence of adverse reactions such as hypertensive or hypotension and postoperative cognitive dysfunction.