Comparison of the negative effect of remimazolam and propofol on cardiac contractility: Analysis of a randomised parallel-group trial and a preclinical ex vivo study.

Remimazolam is a newly developed ultra-short-acting benzodiazepine that exerts sedative effects. This study aimed to clarify the effects of remimazolam on cardiac contractility. In a randomised-parallel group trial, haemodynamic parameters were compared between propofol (n = 11) and remimazolam (n = 12) groups during the induction of general anaesthesia in patients undergoing non-cardiac surgery. In a preclinical study, the direct effects of remimazolam on cardiac contractility were also evaluated using isolated rat hearts. RNA sequence data obtained from rat and human hearts were analysed to assess the expression patterns of the cardiac γ-aminobutyric acid type A (GABAA ) receptor subunits. In a clinical study, the proportional change of the maximum rate of arterial pressure rise was milder during the study period in the remimazolam group (propofol: -52.6 [10.2] (mean [standard deviation])% vs. remimazolam: -39.7% [10.5%], p = 0.007). In a preclinical study, remimazolam did not exert a negative effect on left ventricle developed pressure, whereas propofol did exert a negative effect after bolus administration of a high dose (propofol: -26.9% [3.5%] vs. remimazolam: -1.1 [6.9%], p < 0.001). Analysis of the RNA sequence revealed a lack of γ subunits, which are part of the major benzodiazepine binding site of the GABAA receptor, in rat and human hearts. These results indicate that remimazolam does not have a direct negative effect on cardiac contractility, which might contribute to its milder effect on cardiac contractility during the induction of general anaesthesia. The expression patterns of cardiac GABAA receptor subunits might be associated with the unique pharmacokinetics of benzodiazepines in the heart.

Impact of wrist-ankle acupuncture on propofol dosage under the dual monitoring of density spectrum array and anesthesia consciousness index in elderly patients undergoing urologic surgery: a sham-controlled randomized clinical trial.

Background: Propofol is a widely used intravenous anesthetic in clinic. However, it is easy to cause serious circulatory fluctuation in elderly patients, so the dose should be reduced as appropriate. Studies have shown that wrist-ankle acupuncture (WAA) can reduce the dosage of propofol in patients undergoing painless endoscopy. Unfortunately, there is no report on whether WAA will reduce the dosage of propofol when used for anesthesia in elderly patients. The purpose of this study is to observe the effect of WAA on propofol dosage in elderly patients, and to provide a new method for maintaining circulatory stability in elderly patients under general anesthesia. Methods: From October 2022 to December 2022, Hebei Provincial Hospital of Traditional Chinese Medicine was selected. Forty-four elderly patients undergoing general anesthesia in urology department were randomly divided into two groups according to the complete random method with WAA group, consisting of 22 individuals, and non-WAA (NWAA) group, also consisting of 22 individuals. Both groups were treated with WAA or false needle acupuncture at the same site before anesthesia, respectively, and the needle was kept until the operation was finished. During the operation, the dosage of propofol was adjusted according to the depth of field monitoring density spectrum array (DSA) and anesthesia consciousness index (Ai) with anesthesia monitor. Results: A total of 44 patients participated in this study, and all of them completed the experiment. There were no significant difference in sex, age, height, weight, duration of anesthesia, liver and kidney function, score of Fried frailty scale, activity of daily living (ADL), age-adjusted Charlson comorbidity index (aCCI) and mini-cognitive test (Mini-Cog) between the two groups (P>0.05), but the total dose of propofol (WAA =121.5, NWAA =170.5) mg and maintenance dose (WAA =1.02±0.55, NWAA =1.76±0.67) mg/kg/h, utilization rate of vasoactive drugs during operation, recovery time after anesthesia (WAA =2, NWAA =3) min and surgeon satisfaction (WAA =9, NWAA =8.5) had significant differences (P<0.05). Conclusions: Compared with NWAA group, WAA group could reduce the dosage of propofol in anesthesia for elderly patients with exocrine secretion and was beneficial to circulatory stability. Trial Registration: Chinese Clinical Trial Registry (ID: ChiCTR2100054132).

Electroacupuncture Pretreatment Attenuates Learning Memory Impairment Induced by Repeated Propofol Exposure and Modulates Hippocampal Synaptic Plasticity in Rats.

Background: Recurrent propofol anesthesia in the peak of neurodevelopment may lead to learning-memory decline. This study aimed to examine the efficacy of electroacupuncture pretreatment in ameliorating the aforementioned learning memory deficits and to explore its underlying mechanisms in a rat model of repeated propofol exposure. Methods: 10-day-old Sprague Dawley rats were randomly assigned to five groups: the control, fat emulsion, propofol, electroacupuncture pretreatment and electroacupuncture pretreatment combined with propofol groups. The electroacupuncture pretreatment involved three consecutive daily sessions, while propofol was received intraperitoneally once daily for five days. Following the modeling period, the rats' learning-memory performance was assessed using the New Novel Arm Y-maze, New Object Recognition, and Morris Water Maze. The Nissl staining method was used to observe the development of hippocampal neurons, while Golgi staining was employed to observe hippocampal synaptic development. Results: The electroacupuncture pretreatment significantly attenuated the learning and memory impairment induced by recurring propofol exposure in rats. Additionally, it facilitated the development of hippocampal neurons and synaptic plasticity in the hippocampus. Immunofluorescence and Western Blot analyses were conducted to detect the expression of proteins related to apoptosis, learning memory, and synaptic plasticity. In the propofol group, the pro-apoptotic factors Caspase-3 and Bax was up-regulated, while the anti-apoptotic factor Bcl-2 was down-regulated, as compared to the blank group. Additionally, the phosphorylated cAMP-response element binding protein (pCREB), brain-derived neurotrophic factor (BDNF), synaptophysin, and growth associated protein-43 (GAP-43) was significantly decreased. In contrast, the electroacupuncture pretreatment combined with propofol group exhibited decreased the Caspase-3 and Bax and increased the Bcl-2, as compared to the propofol group, meanwhile, the pCREB, BDNF, Synaptophysin and GAP-43 was increased. Conclusion: Our findings indicate that electroacupuncture pretreatment can alleviate the learning and memory impairment induced by recurring propofol exposure in rats. This is achieved by enhancing hippocampal synaptic plasticity, activating the pCREB/BDNF pathway and inhibiting neuronal apoptosis.

Erector spinae plane block versus local infiltration anaesthesia for transforaminal percutaneous endoscopic discectomy: A prospective randomised controlled trial.

BACKGROUND: Around 60%-80% of the population suffers from back pain, making it one of the most common health complaints. Transforaminal percutaneous endoscopic discectomy (TPED) is an effective treatment for low back pain that can be performed using different anaesthesia techniques. Our primary objective was to test the hypothesis that bilateral Erector spinae plane block (ESP) plus sedation is equally effective as traditional local infiltration anaesthesia plus sedation in TPED. MATERIALS AND METHODS: Fifty-two patients undergoing TPED were randomly assigned to 2 groups: G1 - intravenous sedation with local infiltration anaesthesia; G2 - intravenous sedation with bilateral ESP. PRIMARY OUTCOME: volume of fentanyl and propofol administered during surgery. SECONDARY OUTCOMES: adverse events during sedation reported using the World Society of Intravenous Anaesthesia (SIVA) adverse sedation event tool, level of postoperative sedation measured on the Richmond Agitation-Sedation Scale (RASS), intensity of postoperative pain on a visual analogue scale (VAS), mechanical pain threshold (MPT) measured with von Frey monofilaments on both lower extremities, patient satisfaction with analgesia on 5-point Likert scale. RESULTS: Volume of fentanyl, propofol, and level of postoperative sedation was significantly lower in G2 (p < 0.001). There was no difference between groups in intensity of pain, patient satisfaction with analgesia, and mechanical pain threshold after surgery. There were no adverse events in G2, but in G1 2 patients presented minimal risk descriptors, 5 presented minor risk descriptors, and 1 presented sentinel risk descriptors that required additional medication or rescue ventilation. CONCLUSIONS: The ESP was equal to local infiltration anaesthesia in terms of intensity of pain, mechanical pain threshold after surgery, and patient satisfaction; however, ESP reduced the volume of intraoperative fentanyl and propofol, thereby reducing the adverse effects of sedation.

Sedative-sparing effect of acupuncture in gastrointestinal endoscopy: systematic review and meta-analysis.

Objective: This study aimed to perform a systematic review and meta-analysis to identify the efficacy of acupuncture therapy (including manual acupuncture and electroacupuncture) performed before or during gastrointestinal endoscopy with propofol as the main sedative, compared with placebo, sham acupuncture, or no additional treatment other than the same sedation. Methods: A systematic search was performed through PubMed, Embase, Web of Science, Cochrane Library, Chinese Biomedical Databases (CBM), Wanfang database, China National Knowledge Infrastructure (CNKI), SinoMed, and Chinese Scientific Journal Database (VIP) to collect randomized controlled trials published before 5 November 2022. Bias assessment of the included RCTs was performed according to Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Stata16.0 software was used to perform statistical analysis, sensitivity analysis, and publication bias analysis. The primary outcome was sedative consumption, and the secondary outcomes included the incidence of adverse events and wake-up time. Results: A total of 10 studies with 1331 participants were included. The results showed that sedative consumption [mean difference (MD) = -29.32, 95% CI (-36.13, -22.50), P < 0.001], wake-up time [MD = -3.87, 95% CI (-5.43, -2.31), P < 0.001] and the incidence of adverse events including hypotension, nausea and vomiting, and coughing (P < 0.05) were significantly lower in the intervention group than in the control group. Conclusion: Acupuncture combined with sedation reduces sedative consumption and wake-up time compared with sedation alone in gastrointestinal endoscopy; this combined approach allows patients to regain consciousness more quickly after examination and lower the risk of adverse effects. However, with the limited quantity and quality of relevant clinical studies, caution must be applied until more high-quality clinical studies verify and refine the conclusions. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier: CRD42022370422.

Administration of lipid emulsion reduced the hypnotic potency of propofol more than that of thiamylal in mice.

Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal. Male adult mice (ddY) were intravenously administered 10 ml/kg propofol or thiamylal diluted with physiological saline, 10% soybean oil, or 20% soybean oil. The 50% effective dose (ED50) for achieving hypnosis was calculated using probit analysis. To investigate the volume effect, 0, 10, or 20 ml/kg of saline or soybean oil was administered, either simultaneously or beforehand. Next, a two- or three-fold dose of the anesthetics was administered and the durations of anesthesia were measured. Finally, at 30 s after the first injection, supplemental soybean oil was administered. The mean (± SE) ED50 values of propofol and thiamylal were 5.79 mg/kg (0.61) and 8.83 mg/kg (0.84), respectively. Lipid dilution increased the ED50 values of both anesthetics. After injection of a dose two-fold the ED50 value, the respective mean (± SD) durations of anesthesia were 125 ± 35 s and 102 ± 38 s. Supplemental administration of soybean oil significantly shortened the duration of anesthesia of propofol, but not that of thiamylal. The results indicate that administration of a lipid emulsion vitiated the anesthetic effect of propofol by reducing the non-emulsified free fraction in the aqueous phase, which may elucidate the lipid resuscitation likely caused by the lipid sink mechanism.

Prevention of pain on injection of propofol using ice gel pack versus pre-treatment with lignocaine: a randomized controlled trial.

PURPOSE: Regardless of the positive attributes of propofol, it is frequently associated with pain on injection. We compared the efficacy of topical cold thermotherapy using an ice gel pack with intravenous lignocaine pre-treatment for reducing pain on propofol injection. METHODS: This single-blinded randomized controlled trial was conducted in 200 American Society of Anesthesiologists physical status I, II, and III patients scheduled for elective/emergency surgery under general anesthesia. The patients were randomized into two groups: the Thermotherapy group- receiving an ice gel pack proximal to the intravenous cannula for 1 min, or the Lignocaine group-receiving 0.5 mg/kg of lignocaine administered intravenously, with occlusion proximal to the site of the intravenous cannula for 30 s. The primary objective was to compare the overall incidence of pain after propofol injection. The secondary objectives included the incidence of discomfort on the application of an ice gel pack, comparison of dose of propofol needed for induction, and hemodynamic changes at induction, between the two groups. RESULTS: Fourteen patients in the lignocaine group and 15 patients in the thermotherapy group reported pain. The incidence of pain and the distribution of pain scores were comparable among groups (p = 1.00). Patients of the lignocaine group required significantly less amount of propofol for induction as compared to the thermotherapy group (p = 0.001). CONCLUSION: Topical thermotherapy using an ice gel pack was not found superior to lignocaine pre-treatment in alleviating pain on injection of propofol injection. However, topical cold therapy using an ice pack remains a non-pharmacological technique that is easily available, reproducible, and cost-effective. Further studies are required to prove its equivalence to lignocaine pre-treatment. TRIAL REGISTRATION: CTRI (CTRI/2021/04/032950).

Propofol disrupts alpha dynamics in functionally distinct thalamocortical networks during loss of consciousness.

During propofol-induced general anesthesia, alpha rhythms measured using electroencephalography undergo a striking shift from posterior to anterior, termed anteriorization, where the ubiquitous waking alpha is lost and a frontal alpha emerges. The functional significance of alpha anteriorization and the precise brain regions contributing to the phenomenon are a mystery. While posterior alpha is thought to be generated by thalamocortical circuits connecting nuclei of the sensory thalamus with their cortical partners, the thalamic origins of the propofol-induced alpha remain poorly understood. Here, we used human intracranial recordings to identify regions in sensory cortices where propofol attenuates a coherent alpha network, distinct from those in the frontal cortex where it amplifies coherent alpha and beta activities. We then performed diffusion tractography between these identified regions and individual thalamic nuclei to show that the opposing dynamics of anteriorization occur within two distinct thalamocortical networks. We found that propofol disrupted a posterior alpha network structurally connected with nuclei in the sensory and sensory associational regions of the thalamus. At the same time, propofol induced a coherent alpha oscillation within prefrontal cortical areas that were connected with thalamic nuclei involved in cognition, such as the mediodorsal nucleus. The cortical and thalamic anatomy involved, as well as their known functional roles, suggests multiple means by which propofol dismantles sensory and cognitive processes to achieve loss of consciousness.

Paraventricular thalamus controls consciousness transitions during propofol anaesthesia in mice.

BACKGROUND: The neuronal mechanisms underlying propofol-induced modulation of consciousness are poorly understood. Neuroimaging studies suggest a potential role for non-specific thalamic nuclei in propofol-induced loss of consciousness. We investigated the contribution of the paraventricular thalamus (PVT), a midline thalamic nucleus that has been implicated in arousal control and general anaesthesia with inhaled anaesthetics, to loss and recovery of consciousness during propofol anaesthesia. METHODS: Polysomnographic recordings and righting reflex test were used to determine the transitions of loss and recovery of righting reflex, used as a measure of consciousness in mice, during propofol anaesthesia in mice under conditions mimicking clinical propofol administration. PVT neuronal activities were monitored using fibre photometry and regulated using optogenetic and chemogenetic methods. RESULTS: Population activities of PVT glutamatergic neurones began to decrease before propofol-induced loss of consciousness and rapidly increased to a peak at the onset of recovery of consciousness. Chemogenetic inhibition of PVT calretinin-expressing (PVTCR) neurones shortened onset (from 176 [35] to 127 [26] s; P=0.001) and prolonged return (from 1568 [611] to 3126 [1616] s; P=0.002) of righting reflex. Conversely, chemogenetic activation of PVTCR neurones exerted opposite effects. Furthermore, optogenetic silencing of PVTCR neurones accelerated transitions to loss of consciousness (from 205 [35] to 158 [44] s; P=0.027) and slowed transitions to recovery of consciousness (from 230 [78] to 370 [99] s; P=0.041). During a steady period of unconsciousness maintained with continuous propofol infusion, brief optical activation of PVTCR neurones restored cortical activity and arousal with a latency of about 5 s. CONCLUSIONS: The paraventricular thalamus contributes to the control of consciousness transitions in propofol anaesthesia in mice. This provides a potential neuroanatomical target for controlling consciousness to reduce anaesthetic dose requirements and side effects.

The Development and Optimization of Lipid-Based Self-Nanoemulsifying Drug Delivery Systems for the Intravenous Delivery of Propofol.

PURPOSE: Propofol is a relatively short-acting potent anesthetic lipophilic drug used during short surgical procedures. Despite the success of propofol intravenous emulsions, drawbacks to such formulations include inherent emulsion instability, the lack of a safe vehicle to prevent sepsis, and concern regarding hyperlipidemia-related side effects. The aim of the current investigation was to develop a novel, lipid-based self-nanoemulsifying drug delivery system (SNEDDS) for propofol with improved stability and anesthetic activity for human use. METHODS: A series of SNEDDS formulations were developed using naturally obtained medium-chain/long-chain mono-, di-, and triglycerides, glyceryl monocaprylate, and water-soluble cosolvents with hydrogenated castor oil constructing ternary phase diagrams for propofol. The developed SNEDDS formulations were characterized using visual observation, particle size analysis, zeta potential, transmission electron microscopy, equilibrium solubility, in vitro dynamic dispersion and stability, and in vivo sleeping disorder studies in rats. The in vivo bioavailability of the SNEDDSs in rats was also studied to compare the representative formulations with the marketed product Diprivan®. RESULTS: Medium-chain triglycerides (M810) with mono-diglycerides (CMCM) as an oil blend and hydrogenated castor oil (KHS15) as a surfactant were selected as key ingredients in ternary phase diagram studies. The nanoemulsifying regions were identified from the studies and a number of SNEDDSs were formulated. Results from the characterization studies demonstrated the formation of efficient nanosized particles (28-45 nm globule size, 0.10-0.20 PDI) in the optimized SNEDDS with a drug loading of 50 mg/g, which is almost 500-fold higher than free propofol. TEM analysis showed the formation of spherical and homogeneous nanoparticles of less than 50 nm. The dissolution rate of the representative SNEDDS was faster than raw propofol and able to maintain 99% propofol in aqueous solution for around 24 h. The optimized liquid SNEDDS formulation was found to be thermodynamically stable. The intravenous administration of the SNEDDS in male Wistar rats induced a sleeping time of 73-88 min. The mean plasma concentrations after the IV administration of propofol nano-formulations PF2-SNEDDS and PF8-SNEDDS were 1348.07 ± 27.31 and 1138.66 ± 44.97 µg/mL, as compared to 891.44 ± 26.05 µg/mL (p = 0.05) observed after the IV administration of raw propofol. CONCLUSION: Propofol-loaded SNEDDS formulations could be a potential pharmaceutical product with improved stability, bioavailability, and anesthetic activity.

The effect of age on electroencephalogram measures of anesthesia hypnosis: A comparison of BIS, Alpha Power, Lempel-Ziv complexity and permutation entropy during propofol induction.

Background: Improving anesthesia administration for elderly population is of particular importance because they undergo considerably more surgical procedures and are at the most risk of suffering from anesthesia-related complications. Intraoperative brain monitors electroencephalogram (EEG) have proved useful in the general population, however, in elderly subjects this is contentious. Probably because these monitors do not account for the natural differences in EEG signals between young and older patients. In this study we attempted to systematically characterize the age-dependence of different EEG measures of anesthesia hypnosis. Methods: We recorded EEG from 30 patients with a wide age range (19-99 years old) and analyzed four different proposed indexes of depth of hypnosis before, during and after loss of behavioral response due to slow propofol infusion during anesthetic induction. We analyzed Bispectral Index (BIS), Alpha Power and two entropy-related EEG measures, Lempel-Ziv complexity (LZc), and permutation entropy (PE) using mixed-effect analysis of variances (ANOVAs). We evaluated their possible age biases and their trajectories during propofol induction. Results: All measures were dependent on anesthesia stages. BIS, LZc, and PE presented lower values at increasing anesthetic dosage. Inversely, Alpha Power increased with increasing propofol at low doses, however this relation was reversed at greater effect-site propofol concentrations. Significant group differences between elderly patients (>65 years) and young patients were observed for BIS, Alpha Power, and LZc, but not for PE. Conclusion: BIS, Alpha Power, and LZc show important age-related biases during slow propofol induction. These should be considered when interpreting and designing EEG monitors for clinical settings. Interestingly, PE did not present significant age differences, which makes it a promising candidate as an age-independent measure of hypnotic depth to be used in future monitor development.

The Effect of Relaxation Therapy on Hypoxia During Intravenous Propofol Anesthesia in Patients With Pre-operative Anxiety: A Prospective Randomized Controlled Trial.

Background: This study aimed to investigate the effect of relaxation therapy on hypoxia during intravenous propofol anesthesia in patients with pre-operative anxiety. Methods: Two-hundred and eighty patients were randomly categorized in the experimental group (relaxation therapy group) and control group. The Spielberger State-Trait Anxiety Inventory (S-STAI) was administered 30 to 60 min pre-operatively to assess the patient's current anxiety status and select appropriate patients. Patients in the experimental group received pre-surgical relaxation therapy. Decrease in oxygen saturation during the procedure was recorded for each patient group, and the relevant data were compared between the two groups. Results: The basic S-STAI scores of the experimental and control groups were 56.88 ± 2.91 and 57.27 ± 3.56, respectively (p = 0.331). The difference was not statistically significant. The incidence of hypoxia in the experimental group during painless artificial abortion [routine blood oxygen saturation (SpO2) <95%, duration >15 s] decreased from 30 to 12.3%. Conclusion: Relaxation therapy may effectively reduce the incidence of hypoxia during painless artificial abortion by using less dose of propofol. It may help patients relieve their anxiety and improve perioperative safety. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2000032109).

Effect of Sedation Anesthesia With Intravenous Propofol on Transrectal Ultrasound-Guided Prostate Biopsy Outcomes.

BACKGROUND: Sedation anesthesia during transrectal ultrasound (TRUS)-guided prostate biopsy is known to decrease patient pain and anxiety, but little is known whether it affects the procedure's prostate cancer detection and complication rates. This study aimed to determine the effect of sedation anesthesia with intravenous (IV) propofol on TRUS-guided prostate biopsy outcomes. METHODS: A retrospective analysis of 2,119 patients who underwent TRUS-guided prostate biopsy between November 2009 and February 2019 was undertaken. The patients were divided into two groups: patients who underwent sedation anesthesia with IV propofol and patients who underwent local anesthesia with intrarectal lidocaine gel instillation. Cancer detection and complication rates were compared between the two groups. Univariate and multivariate binary logistic regression and multinomial logistic regression analyses were conducted to investigate the effects of sedation anesthesia with IV propofol on prostate cancer detection and complication rates. RESULTS: The cancer detection rate of patients in the sedation group was 34.0%, whereas it was 29.2% in the local group (P = 0.024). Multivariate logistic regression analysis regarding factors associated with cancer detection rate after TRUS-guided prostate biopsy in patients with prostate specific antigen (PSA) < 10 showed that IV propofol usage, age, PSA density and core length were significant factors. Multivariate logistic regression analysis regarding factors associated with complications (voiding dysfunction, bleeding and infection) showed that IV propofol usage, age and prostate size were significant factors for voiding dysfunction. CONCLUSION: Sedation anesthesia with IV propofol during TRUS-guided prostate biopsy was associated with a higher cancer detection rate than local anesthesia with intrarectal lidocaine gel instillation. Cancer detection rate could be an important factor to consider when selecting for the optimal anesthesia for TRUS-guided prostate biopsy.

Propofol Inhibits Proliferation and Augments the Anti-Tumor Effect of Doxorubicin and Paclitaxel Partly Through Promoting Ferroptosis in Triple-Negative Breast Cancer Cells.

Background: Triple-negative breast cancer (TNBC) is relatively common in women and is associated with a poor prognosis after surgery and adjuvant chemotherapy. Currently, the mechanism underlying the relationship between propofol and breast cancer is controversial and limited to cell apoptosis. Moreover, there are only a few studies on the effect of propofol on the chemotherapeutic sensitivity of TNBC cells. Therefore, this study explored whether propofol and its commonly used clinical formulations affect the proliferation and chemotherapeutic effects on TNBC cells by regulating cell ferroptosis. Methods: We selected MDA-MB-231 cells, and the effects of propofol, propofol injectable emulsion (PIE), or fospropofol disodium, alone or combined with doxorubicin or paclitaxel on cell viability, apoptosis, intracellular reactive oxygen species (ROS) accumulation, ferroptosis-related morphological changes, intracellular Fe2+ levels, and the expression and localization of ferroptosis-related proteins were investigated. Results: We found that propofol significantly inhibited MDA-MB-231 cell proliferation, and all three propofol formulations augmented the anti-tumor effects of doxorubicin and paclitaxel. The results from the ROS assay, transmission electron microscopy, intracellular Fe2+ assay, western blotting, and multiplex immunohistochemistry revealed that propofol not only induced apoptosis but also triggered ferroptosis-related changes, including morphological changes of mitochondria, increased intracellular ROS levels, and intracellular iron accumulation in MDA-MB-231 cells. The ferroptosis-related p53-SLC7A11-GPX4 pathway was also altered under different treatment propofol, doxorubicin, or paclitaxel regimens. Conclusion: Propofol showed anti-proliferation effects on TNBC cells and could be a potential adjuvant to enhance the chemotherapeutic sensitivity of TNBC cells partly by promoting cell ferroptosis.

Clinical Study on the Combination of Transcutaneous Electrical Acupoint Stimulation and Lidocaine for Preventing Propofol Injection Pain.

Purpose: Propofol is a widely used intravenous anesthetic in clinical practice. Lidocaine pretreatment is currently the most commonly used method to reduce the pain of propofol injection. However, propofol injection pain has not been eliminated and its incidence remains high. Transcutaneous electrical acupoint stimulation is a green therapy that combines transcutaneous electrical nerve stimulation therapy with the traditional acupuncture therapy of our motherland. This study investigated the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) combined with lidocaine in preventing propofol injection pain and determined whether it can reduce postoperative complications and promote rapid postoperative recovery of patients. Patients and Methods: A total of 220 women scheduled to undergo hysteroscopic surgery were enrolled in the study. The included patients were randomly divided into four groups of 55 patients each: normal saline group (group K), lidocaine group (group L), TEAS group (group T), and lidocaine + TEAS group (group L + T). Patients in group K received 2 mL saline (0.9% NaCl) pre-injection before anesthesia induction. Group L received 40 mg lidocaine pre-injection (2 mL of 2% lidocaine) before anesthesia induction. Group T received 30 min of transcutaneous electrical stimulation at bilateral election Hegu, Neiguan, and 2 mL saline pre-injections before anesthesia induction. Group L + T received TEAS and lidocaine pre-injection. Results: The VAS scores and the four-point verbal rating scale of propofol injection were significantly different among the four groups. The prevalence of nausea, vomiting, abdominal pain, and abdominal distension after surgery among the four groups were statistically different. The bleeding days after surgery were significantly different among the four groups. Conclusion: TEAS combined with lidocaine pre-injection reduced the incidence of propofol injection pain and significantly reduced patients' pain levels compared with single lidocaine pre-injection. TEAS can also reduce the incidence of postoperative nausea and vomiting, abdominal pain, and abdominal distension, shorten postoperative bleeding days, and accelerate the postoperative recovery of patients.

Transcutaneous electrical nerve stimulation for pain during propofol injection: a randomized clinical trial.

Background: Propofol is a short-acting intravenous sedative widely used for procedural sedation and general anesthesia. However, pain during propofol injection is a distressing adverse effect. This study was designed to investigate whether transcutaneous electrical nerve stimulation (TENS) could reduce pain during propofol injection compared to sham TENS. Methods: In a randomized controlled trial, 80 patients were allocated to two groups: the active TENS group received electrical stimulation via two electrodes on the venous cannulation site, whereas the sham TENS group received no stimulus. After 20 min following TENS, propofol 0.5 mg/kg pain was injected intravenously and pain was evaluated using a four-point score (0 = none, 1 = mild, 2 = moderate, 3 = severe). Adverse effects associated with TENS were also recorded. Results: The overall incidence of pain during propofol injection was 47.5% in the TENS group and 87.5% in the sham group (P < 0.001). The incidence of moderate pain was significantly lower in the TENS group (7.5%) than in the sham TENS group (42.5%) (P < 0.001). There were no complications associated with TENS. Conclusion: Pre-treatment with TENS significantly reduced the incidence and intensity of pain during propofol injection.

Improved Individualized Patient-Oriented Depth-of-Hypnosis Measurement Based on Bispectral Index.

Total intravenous anesthesia is an anesthesiologic technique where all substances are injected intravenously. The main task of the anesthesiologist is to assess the depth of anesthesia, or, more specifically, the depth of hypnosis (DoH), and accordingly adjust the dose of intravenous anesthetic agents. However, it is not possible to directly measure the anesthetic agent concentrations or the DoH, so the anesthesiologist must rely on various vital signs and EEG-based measurements, such as the bispectral (BIS) index. The ability to better measure DoH is directly applicable in clinical practice-it improves the anesthesiologist's assessment of the patient state regarding anesthetic agent concentrations and, consequently, the effects, as well as provides the basis for closed-loop control algorithms. This article introduces a novel structure for modeling DoH, which employs a residual dynamic model. The improved model can take into account the patient's individual sensitivity to the anesthetic agent, which is not the case when using the available population-data-based models. The improved model was tested using real clinical data. The results show that the predictions of the BIS-index trajectory were improved considerably. The proposed model thus seems to provide a good basis for a more patient-oriented individualized assessment of DoH, which should lead to better administration methods that will relieve the anesthesiologist's workload and will benefit the patient by providing improved safety, individualized treatment, and, thus, alleviation of possible adverse effects during and after surgery.

[Effect of electroacupuncture at Baihui (GV 20) and Sishencong (EX-HN 1) on presurgical anxiety in patients with gynecological laparoscopic surgery].

OBJECTIVE: To observe the anti-anxiety effect of electroacupuncture at Baihui (GV 20) and Sishencong (EX-HN 1) in patients with gynecological laparoscopic surgery, and to explore its effect on the anesthetic dosage during anesthesia induction. METHODS: A total of 270 patients with gynecological laparoscopic surgery were randomized into an electroacupuncture group, a medication group and a control group, 90 cases in each group. At 24 h and 2 h before anesthesia induction, electroacupuncture was applied at Baihui (GV 20) and Sishencong (EX-HN 1) in the electroacupuncture group, with continuous wave, 100 Hz in frequency. At 30 min before anesthesia induction, midazolam of 0.02 mg/kg was given by intravenous drip in the medication group, while 0.9% sodium chloride solution was given by intravenous drip in the control group. At 10 min before anesthesia induction and 6 h after surgery, the scores of 6 item short form of state-trait anxiety inventory (STAI-S6) and visual analogue scale-anxiety (VAS-A) were observed; at 10 min before anesthesia induction (T1) and observer's assessment of alertness/sedation scale (OAA/S) grade 4 (T2), mean artery pressure (MAP), heart rate (HR) and value of bispectral index (BIS) were recorded; the dosage of propofol at T2 was recorded and the surgery related adverse reactions were compared among the 3 groups. RESULTS: At 10 min before anesthesia induction and 6 h after surgery, the STAI-S6 and VAS-A scores in the electroacupuncture group and the medication group were lower than those in the control group (P<0.05). Values of BIS at T1 and dosage of propofol at T2 in the electroacupuncture group and the medication group were lower than those in the control group (P<0.05). There were no statistical differences in MAP, HR and surgery related adverse reactions among the 3 groups (P>0.05). CONCLUSION: Electroacupuncture at Baihui (GV 20) and Sishencong (EX-HN 1) can effectively relieve the presurgical anxiety in patients with gynecological laparoscopic surgery, and reduce the dosage of propofol, its effect is similar to traditional anti-anxiety drug.

Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals.

We hypothesized whether propofol or active propofol component (2,6-diisopropylphenol [DIPPH] and lipid excipient [LIP-EXC]) separately may alter inflammatory mediators expressed by macrophages and neutrophils in lean and obese rats. Male Wistar rats (n = 10) were randomly assigned to receive a standard (lean) or obesity-inducing diet (obese) for 12 weeks. Animals were euthanized, and alveolar macrophages and neutrophils from lean and obese animals were exposed to propofol (50 µM), active propofol component (50 µM, 2,6-DIPPH), and lipid excipient (soybean oil, purified egg phospholipid, and glycerol) for 1 h. The primary outcome was IL-6 expression after propofol and its components exposure by alveolar macrophages extracted from bronchoalveolar lavage fluid. The secondary outcomes were the production of mediators released by macrophages from adipose tissue, and neutrophils from lung and adipose tissues, and neutrophil migration. IL-6 increased after the exposure to both propofol (median [interquartile range] 4.14[1.95-5.20]; p = .04) and its active component (2,6-DIPPH) (4.09[1.67-5.91]; p = .04) in alveolar macrophages from obese animals. However, only 2,6-DIPPH increased IL-10 expression (7.59[6.28-12.95]; p = .001) in adipose tissue-derived macrophages. Additionally, 2,6-DIPPH increased C-X-C chemokine receptor 2 and 4 (CXCR2 and CXCR4, respectively) in lung (10.08[8.23-29.01]; p = .02; 1.55[1.49-3.43]; p = .02) and adipose tissues (8.78[4.15-11.57]; p = .03; 2.86[2.17-3.71]; p = .01), as well as improved lung-derived neutrophil migration (28.00[-3.42 to 45.07]; p = .001). In obesity, the active component of propofol affected both the M1 and M2 markers as well as neutrophils in both alveolar and adipose tissue cells, suggesting that lipid excipient may hinder the effects of active propofol.

Cortical Responses to Vowel Sequences in Awake and Anesthetized States: A Human Intracranial Electrophysiology Study.

Elucidating neural signatures of sensory processing across consciousness states is a major focus in neuroscience. Noninvasive human studies using the general anesthetic propofol reveal differential effects on auditory cortical activity, with a greater impact on nonprimary and auditory-related areas than primary auditory cortex. This study used intracranial electroencephalography to examine cortical responses to vowel sequences during induction of general anesthesia with propofol. Subjects were adult neurosurgical patients with intracranial electrodes placed to identify epileptic foci. Data were collected before electrode removal surgery. Stimuli were vowel sequences presented in a target detection task during awake, sedated, and unresponsive states. Averaged evoked potentials (AEPs) and high gamma (70-150 Hz) power were measured in auditory, auditory-related, and prefrontal cortex. In the awake state, AEPs were found throughout studied brain areas; high gamma activity was limited to canonical auditory cortex. Sedation led to a decrease in AEP magnitude. Upon LOC, there was a decrease in the superior temporal gyrus and adjacent auditory-related cortex and a further decrease in AEP magnitude in core auditory cortex, changes in the temporal structure and increased trial-to-trial variability of responses. The findings identify putative biomarkers of LOC and serve as a foundation for future investigations of altered sensory processing.