The effect of methylphenidate on anaesthesia recovery: An experimental study in pigs.

INTRODUCTION: Due to the lack of specific antagonists for general anaesthetics, the pharmacological stimulation of the arousal pathways might contribute to reduce recovery time. We aimed at assessing the effect of methylphenidate on physiological parameters, nociceptive withdrawal reflex thresholds, electroencephalographic variables and time of reappearance of reflexes in pigs undergoing propofol anaesthesia. MATERIALS AND METHODS: Two experiments have been performed. Five (experiment 1) and sixteen (experiment 2) healthy juvenile pigs were anaesthetised with propofol. In experiment 1, saline, methylphenidate 10 mg/kg or methylphenidate 20 mg/kg was administered intravenously at the end of propofol administration, using a cross-over design. In experiment 2, saline (n = 8) or methylphenidate 20 mg/kg (n = 8) was administered immediately after extubation. In both experiments, physiological parameters, nociceptive withdrawal reflex thresholds, electroencephalographic variables and time of reappearance of reflexes were assessed. Comparison among groups was performed using either the two-way repeated measures ANOVA followed by Bonferroni-Test or the t-test in case of parametric data, and either the Kruskal-Wallis test or the Mann-Whitney Rank Sum test in case of non-parametric data. A p value < 0.05 was considered statistically significant. RESULTS: No clinically relevant changes were observed in both experiments for physiological parameters, nociceptive withdrawal reflex thresholds and electroencephalographic variables. CONCLUSIONS: Methylphenidate does not shorten or modify anaesthesia recovery in pigs, when the sole propofol is administered.

Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4.

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.

Local orchestration of distributed functional patterns supporting loss and restoration of consciousness in the primate brain.

A central challenge of neuroscience is to elucidate how brain function supports consciousness. Here, we combine the specificity of focal deep brain stimulation with fMRI coverage of the entire cortex, in awake and anaesthetised non-human primates. During propofol, sevoflurane, or ketamine anaesthesia, and subsequent restoration of responsiveness by electrical stimulation of the central thalamus, we investigate how loss of consciousness impacts distributed patterns of structure-function organisation across scales. We report that distributed brain activity under anaesthesia is increasingly constrained by brain structure across scales, coinciding with anaesthetic-induced collapse of multiple dimensions of hierarchical cortical organisation. These distributed signatures are observed across different anaesthetics, and they are reversed by electrical stimulation of the central thalamus, coinciding with recovery of behavioural markers of arousal. No such effects were observed upon stimulating the ventral lateral thalamus, demonstrating specificity. Overall, we identify consistent distributed signatures of consciousness that are orchestrated by specific thalamic nuclei.

Dexmedetomidine Alleviates Propofol Infusion Syndrome-Induced Myocardial Injury through Inhibiting Ferroptosis Associated with Accumulation of Reactive Oxygen Species.

OBJECTIVE: To observe the effect of dexmedetomidine (Dex) on propofol infusion syndrome (PRIS)-induced myocardial injury and explore the roles of ferroptosis and accumulation of reactive oxygen species (ROS). METHODS: Eighteen male Sprague-Dawley rats were evenly divided into the control group, model group and test group (n=6/group) based on a computer-generated random number table. The PRIS-induced myocardial injury model was prepared in the model group and test group through a 12 h-caudal vein infusion of 1% propofol medium and long chain fat emulsion injection at a rate of 20 mg·Kg-1·h-1 for the first 6 h and 40 mg·Kg-1·h--1 for the last 6 h, and meanwhile the test group was treated by Dex. The control group received the same amount of normal saline through the caudal vein. The following indicators were compared between the three groups including myocardial pathological results, enzymatic changes of myocardial injury, ferroptosis of myocardial cells and accumulation of ROS. RESULTS: Dex alleviated the myocardial pathological injury caused by propofol infusion. Propofol infusion caused time-dependent enzymatic changes of myocardial injury and Dex alleviated these enzymatic changes. Dex alleviated the ferroptosis of myocardial cells and accumulation of ROS caused by propofol infusion. CONCLUSIONS: Dex could alleviate PRIS-induced myocardial injury by inhibiting ferroptosis associated with accumulation of ROS. Combined sedation using propofol and Dex might be a potential strategy for the prevention and treatment of PRIS-induced cardiotoxicity.

Predicting the optimal concentration of remifentanil for skull pin fixation with hemodynamic and analgesia nociception index monitoring.

Inadequate antinociception during skull pin fixation may cause hemodynamic instability in intracranial surgery. The optimal concentration of remifentanil to provide adequate antinociception and stable hemodynamics during skull pin fixation under analgesia nociception index monitoring is unknown. This study is to assess the 90% effective concentration of remifentanil for skull pin fixation under hemodynamic and analgesia nociception index monitoring. Twenty-six patients were enrolled for intracranial surgery, anesthesia was induced and maintained under total intravenous anesthesia using target-controlled infusion for remifentanil and propofol under analgesia nociception index and bispectral index monitoring. Skull pin fixation was performed at different effect-site concentrations of remifentanil required for Dixon's up-and-down method with a step size of 0.5 ng/ml under bispectral index 40-60. Inadequate antinociception is defined when either ANI < 30 or > 20% in hemodynamic changes from baseline (e.g. heart rate > 100 beats/min, or blood pressure > 180/100 mmHg) and the effect-site concentration of remifentanil is considered as failure. It is considered success as ANI > 30 and < 20% hemodynamic changes from baseline simultaneously. Seven pairs of failure/success were used for probit analysis. The 90% effective concentration of remifentanil for skull pin fixation with adequate antinociception and hemodynamic stability was 4.7 ng/ml.

Application of remimazolam-0.6% sevoflurane anesthesia for flash visual evoked potential monitoring during pituitary adenoma resection: a non-inferiority randomized controlled trial.

BACKGROUND: Flash visual evoked potential (FVEP) is a critical method for monitoring intraoperative visual function during neurosurgery. A new benzodiazepine drug called remimazolam has recently been used for general anesthesia. However, the impact of remimazolam on FVEP remains unclear. Therefore, we aimed to investigate how remimazolam, in comparison to propofol, when combined with 0.6% sevoflurane anesthesia, affects the FVEP waveform during pituitary adenoma resection. METHODS: Overall, 36 patients undergoing pituitary adenoma resection under general anesthesia were randomly assigned to either the remimazolam group (Group R) or the propofol group (Group P) in a prospective, randomized, controlled, non-inferiority trial. For anesthesia induction, a bolus of 0.2 mg/kg remimazolam or 2 mg/kg propofol was intravenously infused for approximately one minute. The anesthesia was maintained by continuous infusion of either remimazolam (0.7-1.0 mg/kg/h) or propofol (4-6 mg/kg/h), in combination with 0.6% sevoflurane, aimed at sustaining the bispectral index (BIS) within the range of 40-60. The primary outcome was the N75-P100 amplitude of FVEP recorded at approximately 20 min after intubation (T0). 10% of the amplitude at T0 in group P was defined as the non-inferiority margin (δ). Confidence interval testing was used to evaluate the non-inferiority hypothesis. The secondary outcomes covered the P100 latency of FVEP, electroretinogram (ERG) b wave amplitude, demographic characteristics, hemodynamics, and occurrence of adverse events. RESULTS: The BIS index during anesthesia was comparable between the groups at the same measured time points (P > 0.05). The N75-P100 amplitude at T0 in group R was 7.64 ± 1.36 µV, while it was 6.96 ± 0.95 µV in group P (P = 0.09), with a mean difference of 0.68 µV (95% CI, -0.11 µV to 1.48 µV). The δ was set at 0.7 and the lower limit of the 95% CI exceeded the -δ. Both remimazolam and propofol had little effect on ERG b-wave amplitudes. At the designated time points, FVEP amplitude and P100 latency displayed no appreciable variation between the two groups (P > 0.05). Furthermore, there were no significant differences in the incidence of adverse events related to anesthesia, needle electrodes, or surgery between the two groups (P > 0.05). CONCLUSION: Our findings suggest that remimazolam-0.6% sevoflurane is non-inferior to propofol-0.6% sevoflurane for general anesthesia, based on the FVEP N75-P100 amplitude. The electrophysiological data obtained in both groups indicate that reproducible and stable FVEP and ERG waveforms can be acquired at set time points. Therefore, for reliable FVEP monitoring, remimazolam-0.6% sevoflurane appears to be a safe and effective protocol in general anesthesia. TRIALS REGISTRATION: This study was registered on chictr.org.cn (ChiCTR2200056803, 17/02/2022).

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.

Mass intraoperative endothelial glycocalyx shedding affects postoperative systemic inflammation response.

BACGROUND: Off-pump coronary artery bypass graft (OPCABG) has a high incidence of postoperative systemic inflammation response syndrome (SIRS), and perioperative endothelial glycocalyx layer (EGL) disruption can be one of the predisposing factors. We hypothesized that EGL shedding happened earlier in OPCABG which can influence on postoperative SIRS, and sevoflurane might preserve EGL better than propofol. METHODS: We randomly allocated 50 patients undergoing OPCABG to receive either sevoflurane-sufentanil or propofol-sufentanil anesthesia. Plasma syndecan-1, heparan sulfate (HS), atrial natriuretic peptide (ANP), IL-6, and cardiac troponin I (cTnI) were measured. Blood samples were collected at 6 timepoints: induction (T1), before grafting (T2), after grafting(T3), surgery done (T4), postoperative day1 (POD1,T5) and POD2 (T6). SIRS criteria and sequential organ failure assessment (SOFA) score were examined. RESULTS: There were neither differences of syndecan-1, HS, IL-6 nor of SIRS criteria or SOFA score between the sevoflurane and propofol groups. All patients were pooled as a single group for further statistical analyses, plasma syndecan-1 (P < 0.001) and IL-6 (P < 0.001) increased significantly as a function of time; syndecan-1 increasing correlated significantly with the duration of coronary graft anastomosis (r = 0.329, P = 0.026). Syndecan-1(T3) correlated significantly with ANP(T3) (r = 0.0.354, P = 0.016) and IL-6 (T5) (r = 0.570, P < 0.001). The maximum value of IL-6 correlated significantly with SIRS (r = 0.378, P = 0.010), the maximum value of SOFA score (r = 0.399, P = 0.006) and ICU days (r = 0.306, P = 0.039). The maximum value of SOFA score correlated significantly with the occurrence of SIRS (r = 0.568, P < 0.001) and ICU days (r = 0.338, P = 0.022). CONCLUSIONS: OPCABG intraoperative early EGL shedding caused of grafts anastomosis greatly affected postoperative SIRS and SOFA score, sevoflurane did not clinically preserve EGL better. TRIAL REGISTRATION: ChiCTR-IOR-17012535. Registered on 01/09/2017.

Haemodynamic effects of remifentanil during induction of general anaesthesia with propofol. A randomised trial.

BACKGROUND: Remifentanil may have a dose-dependent haemodynamic effect during the induction of general anaesthesia combined with propofol. Our objective was to investigate whether systolic arterial blood pressure (SAP) was reduced to a greater extent when the remifentanil dose was increased. METHODS: This randomised, double-blind, dose-controlled study was conducted at the Day Surgery Unit of Haugesund Hospital, Norway. Ninety-nine healthy women scheduled for gynaecological surgery were randomly allocated in a 1:1:1 ratio to receive remifentanil induction with a low, medium or high dose corresponding to maximum effect-site concentrations (Ce) of 2, 4 and 8 ng/mL. The induction dose of propofol was 1.8 mg/kg, with a Ce of 2.9 µg/mL. Anaesthesia was induced using target-controlled infusion. After 150 s of sedation, a bolus of remifentanil and propofol was administered. Baseline was defined as 55-5 s before the bolus dose, and the total observation time was 450 s. We used beat-to-beat haemodynamic monitoring with LiDCOplus. The primary outcome variable was the maximum decrease in SAP within 5 min after bolus administration of remifentanil and propofol. Absolute and relative changes from baseline to minimal values and the area under the curve (AUC) were used as effect measures. Comparisons of groups were performed using analysis of variance (ANOVA). RESULTS: Median remifentanil doses were 0.75, 1.5 and 3.0 µg/kg in the low-, medium- and high-dose groups, respectively. The absolute changes (mean ± standard deviation) in SAP in the low-, medium- and high-dose groups of remifentanil were -39 ± 9.6 versus -43 ± 9.1, and -41 ± 10 mmHg, respectively. No difference (95% confidence interval) in the absolute change in SAP was observed between the groups (ANOVA, p = .29); medium versus low dose 3.7 (-2.0, 9.4) mmHg, and high versus medium dose -2.2 (-8.0; 3.5) mmHg. The relative changes from baseline to minimum SAP values were -30% versus -32% versus -32% (p = .52). The between-group differences in the AUC were not statistically significant. Relative changes in heart rate (-20% vs. -21% vs. -21%), stroke volume (-19% vs. -16% vs. -16%), cardiac output (-32% vs. -32% vs. -32%), systemic vascular resistance (-24% vs. -27% vs. -28%), and AUC were not statistically significant. CONCLUSION: This trial demonstrated major haemodynamic changes during the induction of anaesthesia with remifentanil and propofol. However, we did not observe any statistically significant differences between low, medium or high doses of remifentanil when using continuous invasive high-accuracy beat-to-beat monitoring.

Interleaved Propofol-Ketamine Maintains DBS Physiology and Hemodynamic Stability: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy. OBJECTIVES: The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery. METHODS: Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events. RESULTS: Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively. CONCLUSIONS: Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The effect of esketamine combined with propofol-induced general anesthesia on cerebral blood flow velocity: a randomized clinical trial.

BACKGROUND: Esketamine is increasingly used in clinical anesthesia. The effect of esketamine on the blood flow velocity of the middle cerebral artery has a clinical guiding effect. To investigate the effect of esketamine combined with propofol-induced general anesthesia for endotracheal intubation on the blood flow velocity of middle cerebral artery and hemodynamics during the induction period. METHODS: The randomized clinical trial included 80 patients aged 20-65 years who would undergo non-intracranial elective surgery under general anesthesia in our hospital from May 2022 to May 2023. The participants were divided into two groups based on anesthesia drugs: sufentanil 0.5µg/kg (group C) or 1.5mg/kg esketamine (group E). The primary outcome was variation value in average cerebral blood velocity. The secondary outcomes included cerebral blood flow velocities (CBFV), blood pressure (BP) and heart rate (HR) at four different time points: before induction of general anesthesia (T0), 1 min after the induction drug injected (T1), before endotracheal intubation (T2), and 1min after endotracheal intubation (T3). The occurrence of hypotension, hypertension, tearing and choking during induction was also documented. RESULTS: The variation of average CBFV from time T0 to T2(ΔVm1) and the variation from time T3 to T0 (ΔVm2) were not obviously different. The median consumption of intraoperative sufentanil in group C was obviously lower than that in group E. At T1, the mean HR of group E was significantly higher than that of group C. At T2 and T3, the BP and HR of group E were obviously higher than that of group C. At T2, the CBFV in the group E were obviously higher than those in the group C. The incidence of hypotension was significantly reduced in the group E compared with the group C. There were no differences in the other outcomes. CONCLUSIONS: The induction of esketamine combined with propofol does not increase the blood flow velocity of middle cerebral artery. Esketamine is advantageous in maintaining hemodynamic stability during induction. Furthermore, the administration of esketamine did not result in an increased incidence of adverse effects. TRIAL REGISTRATION: 15/06/2023 clinicaltrials.gov ChiCTR2300072518 https://www.chictr.org.cn/bin/project/edit?pid=176675 .

Consistency analysis of consciousness index and bispectral index in monitoring the depth of sevoflurane anesthesia in laparoscopic surgery.

Background: The Index of Consciousness (IoC) is a new monitoring index of anesthesia depth reflecting the state of consciousness of the brain independently developed by China. The research on monitoring the depth of anesthesia mainly focuses on propofol, and bispectral index (BIS) is a sensitive and accurate objective index to evaluate the state of consciousness at home and abroad. This study mainly analyzed the effect of IoC on monitoring the depth of sevoflurane anesthesia and the consistency and accuracy with BIS when monitoring sevoflurane maintenance anesthesia. Objective: To investigate the monitoring value of the Index of Consciousness (IoC) for the depth of sevoflurane anesthesia in laparoscopic surgery. Methods: The study population consisted of 108 patients who experienced elective whole-body anesthesia procedures within the timeframe of April 2020 to June 2023 at our hospital. Throughout the anesthesia process, which encompassed induction and maintenance using inhaled sevoflurane, all patients were diligently monitored for both the Bispectral Index (BIS) and the Index of Consciousness (IoC). We conducted an analysis to assess the correlation between IoC and BIS throughout the anesthesia induction process and from the maintenance phase to the regaining of consciousness. To evaluate the predictive accuracy of IoC and BIS for the onset of unconsciousness during induction and the return of consciousness during emergence, we employed receiver operating characteristic (ROC) curve analysis. Results: The mean difference between BIS and IoC, spanning from the pre-anesthesia induction phase to the completion of propofol induction, was 1.3 (95% Limits of Agreement [-53.4 to 56.0]). Similarly, during the interval from the initiation of sevoflurane inhalation to the point of consciousness restoration, the average difference between BIS and IoC was 0.3 (95% LOA [-10.8 to 11.4]). No statistically significant disparities were observed in the data acquired from the two measurement methodologies during both the anesthesia induction process and the journey from maintenance to the regaining of consciousness (P > 0.05). The outcomes of the ROC curve analysis disclosed that the areas under the curve (AUC) for prognosticating the occurrence of loss of consciousness were 0.967 (95% CI [0.935-0.999]) for BIS and 0.959 (95% CI [0.924-0.993]) for IoC, with optimal threshold values set at 81 (sensitivity: 88.10%, specificity: 92.16%) and 77 (sensitivity: 79.55%, specificity: 95.45%) correspondingly. For the prediction of recovery of consciousness, the AUCs were 0.995 (95% CI [0.987-1.000]) for BIS and 0.963 (95% CI [0.916-1.000]) for IoC, each associated with optimal cutoff values of 76 (sensitivity: 92.86%, specificity: 100.00%) and 72 (sensitivity: 86.36%, specificity: 100.00%) respectively. Conclusion: The monitoring of sevoflurane anesthesia maintenance using IoC demonstrates a level of comparability to BIS, and its alignment with BIS during the maintenance phase of sevoflurane anesthesia is robust. IoC displays promising potential for effectively monitoring the depth of anesthesia.

A neurophysiological basis for aperiodic EEG and the background spectral trend.

Electroencephalograms (EEGs) display a mixture of rhythmic and broadband fluctuations, the latter manifesting as an apparent 1/f spectral trend. While network oscillations are known to generate rhythmic EEG, the neural basis of broadband EEG remains unexplained. Here, we use biophysical modelling to show that aperiodic neural activity can generate detectable scalp potentials and shape broadband EEG features, but that these aperiodic signals do not significantly perturb brain rhythm quantification. Further model analysis demonstrated that rhythmic EEG signals are profoundly corrupted by shifts in synapse properties. To examine this scenario, we recorded EEGs of human subjects being administered propofol, a general anesthetic and GABA receptor agonist. Drug administration caused broadband EEG changes that quantitatively matched propofol's known effects on GABA receptors. We used our model to correct for these confounding broadband changes, which revealed that delta power, uniquely, increased within seconds of individuals losing consciousness. Altogether, this work details how EEG signals are shaped by neurophysiological factors other than brain rhythms and elucidates how these signals can undermine traditional EEG interpretation.

Sedation with propofol and isoflurane differs in terms of microcirculatory parameters: A randomized animal study using dorsal skinfold chamber mouse model.

OBJECTIVE: This study aimed to explore the effects of sedative doses of propofol and isoflurane on microcirculation in septic mice compared to controls. Isoflurane, known for its potential as a sedation drug in bedside applications, lacks clarity regarding its impact on the microcirculation system. The hypothesis was that propofol would exert a more pronounced influence on the microvascular flow index, particularly amplified in septic conditions. MATERIAL AND METHODS: Randomized study was conducted from December 2020 to October 2021 involved 60 BALB/c mice, with 52 mice analyzed. Dorsal skinfold chambers were implanted, followed by intraperitoneal injections of either sterile 0.9 % saline or lipopolysaccharide for the control and sepsis groups, respectively. Both groups received propofol or isoflurane treatment for 120 min. Microcirculatory parameters were obtained via incident dark-field microscopy videos, along with the mean blood pressure and heart rate at three time points: before sedation (T0), 30 min after sedation (T30), and 120 min after sedation (T120). Endothelial glycocalyx thickness and syndecan-1 concentration were also analyzed. RESULTS: In healthy controls, both anesthetics reduced blood pressure. However, propofol maintained microvascular flow, differing significantly from isoflurane at T120 (propofol, 2.8 ± 0.3 vs. isoflurane, 1.6 ± 0.9; P < 0.001). In the sepsis group, a similar pattern occurred at T120 without statistical significance (propofol, 1.8 ± 1.1 vs. isoflurane, 1.2 ± 0.7; P = 0.023). Syndecan-1 levels did not differ between agents, but glycocalyx thickness index was significantly lower in the isoflurane-sepsis group than propofol (P = 0.001). CONCLUSIONS: Propofol potentially offers protective action against microvascular flow deterioration compared to isoflurane, observed in control mice. Furthermore, a lower degree of sepsis-induced glycocalyx degradation was evident with propofol compared to isoflurane.

Effects of propofol versus sevoflurane on surgical field visibility during arthroscopic rotator cuff repair: a randomized trial.

BACKGROUND: During arthroscopic rotator cuff repair (ARCR), clear surgical field visibility (SFV) is the basis of successful surgery, but the choice of anesthesia maintenance drugs may have different effects on SFV. In this study, we aimed to compare the effects of propofol- and sevoflurane-based general anesthesia on SFV in patients undergoing ARCR. METHODS: Patients (n = 130) undergoing elective ARCR in the lateral decubitus position were randomized into either the propofol group or sevoflurane group (65 per group). The duration of surgery and increased pressure irrigation (IPI), Boezaart score, rocuronium consumption and usage of remifentanil were recorded. The time of both spontaneous respiration recovery and extubation and the incidences of postoperative nausea and vomiting and agitation were also recorded. RESULTS: The Boezaart score, duration of IPI and ratio of the duration of IPI to the duration of surgery (IPI/S ratio) were similar between the groups (P > 0.05). Rocuronium consumption, number of patients requiring remifentanil infusion and total remifentanil consumption were significantly lower in the sevoflurane group (P < 0.05). The spontaneous respiration recovery time was significantly longer in the propofol group (P < 0.05), but there were no differences in the extubation time between the groups(P > 0.05). CONCLUSIONS: Compared with propofol, sevoflurane provides equally clear SFV while improving the convenience of anesthesia maintenance in ARCR patients with interscalene plexus (ISB) combined with general anesthesia. TRIAL REGISTRATION: This single-center, prospective, RCT was retrospective registered at Chinese Clinical Trial Registry with the registration number ChiCTR2300072110 (02/06/2023).

The effects of anesthetic drug choice on heart rate variability and echocardiography parameters in cats.

Heart rate variability (HRV) is one of the assessments of cardiovascular risk during general anesthesia. This study aimed to assess the effects of an anesthetic drug on HRV in cats and to provide information for clinical applications. Twenty-four healthy client-owned cats of various breeds, 12 females and 12 males scheduled for elective surgery, were enrolled in this study. The cats were premedicated and induced with 4 protocols: protocol 1, diazepam (0.3 mg/kg) and propofol (2-4 mg/kg) IV; protocol 2, diazepam (0.3 mg/kg) and alfaxalone (1-3 mg/kg) IV; protocol 3, diazepam (0.3 mg/kg) and ketamine (3-5 mg/kg) IV; and protocol 4, xylazine (1 mg/kg) and tiletamine/zolazepam (Zoletil) (5 mg/kg) IM. The heart rate and HRV of the 24 cats were collected before and at least 1 h after administering the anesthetic drugs. Echocardiography was performed to evaluate heart function. Oscillometric blood pressure monitoring was used to obtain the mean blood pressure. After anesthetic drug administration, higher heart rates were found in cats premedicated and induced with alfaxalone (p = 0.045) than in the other protocols. The lowest heart rate (HR) values were found in cats in protocol 4 using xylazine and Zoletil. The HRV low frequency (LF) and high frequency (HF) power ratios increased in all protocols except for cats premedicated and intubated with propofol. The standard deviation of the regular sinus beats (SDNN) was higher in cats premedicated and induced with ketamine than in other anesthetic protocols (p = 0.015). An increase in sympathetic activity and reduced HRV is associated with high blood pressure and left atrial dimension. The percentage of fractional shortening (FS) decreased in cats premedicated with ketamine. The results showed that the anesthesia method using diazepam and propofol caused the least disturbance of HRV compared with other anesthesia methods that were used in this study.

Curcumin inhibits propofol-induced autophagy of MN9D cells via Akt/mTOR/p70S6K signaling pathway.

The rapid rise in propofol dependency and abuse has highlighted limited resources for addressing substance abuse-related cognitive impairment, prompting the development of novel therapies. Dysregulated autophagy flow accelerates neuronal cell death, and interventions countering this dysregulation offer an appealing strategy for neuronal protection. Curcumin, a potent natural polyphenol derived from turmeric rhizomes, is renowned for its robust antineurotoxic properties and enhanced cognitive function. Utilizing CCK-8 and Ki67 fluorescent staining, our study revealed that curcumin treatment increased cell viability and proliferative potential in MN9D cells exposed to propofol-induced neurotoxicity. Furthermore, enzyme-linked immunosorbent assay and western blot analysis demonstrated the partial restoration of dopamine synthesis, secretion levels, and TH expression in damaged MN9D cells treated with curcumin. Scanning electrode microscope images displayed reduced autolysosomes and phagosomes in curcumin-treated cells compared to the propofol group. Immunoblotting revealed that curcumin mitigated the degradation of LC3I to LC3II and p62 induced by propofol stimulation, with green fluorescence expression of LC3 postcurcumin treatment resembling that following autophagy inhibitor HCQ treatment, indicating that modulating autophagy flow can alleviate propofol's toxic effects. Moreover, curcumin treatment upregulated the Akt/mTOR/p70S6K signaling pathway, suggesting that curcumin potentially curtails autophagy dysregulation in nerve cells by activating Akt/mTOR/p70S6K. In conclusion, our findings suggest that curcumin can ameliorate propofol abuse-induced neurotoxicity, partially through autophagy regulation and Akt/mTOR/p70S6K signaling activation.

Anaesthesia-induced Changes in Genomic Expression Leading to Neurodegeneration.

General anaesthetics (GA) have been in continuous clinical use for more than 170 years, with millions of young and elderly populations exposed to GA to relieve perioperative discomfort and carry out invasive examinations. Preclinical studies have shown that neonatal rodents with acute and chronic exposure to GA suffer from memory and learning deficits, likely due to an imbalance between excitatory and inhibitory neurotransmitters, which has been linked to neurodevelopmental disorders. However, the mechanisms behind anaesthesia-induced alterations in late postnatal mice have yet to be established. In this narrative review, we present the current state of knowledge on early life anaesthesia exposure-mediated alterations of genetic expression, focusing on insights gathered on propofol, ketamine, and isoflurane, as well as the relationship between network effects and subsequent biochemical changes that lead to long-term neurocognitive abnormalities. Our review provides strong evidence and a clear picture of anaesthetic agents' pathological events and associated transcriptional changes, which will provide new insights for researchers to elucidate the core ideas and gain an in-depth understanding of molecular and genetic mechanisms. These findings are also helpful in generating more evidence for understanding the exacerbated neuropathology, impaired cognition, and LTP due to acute and chronic exposure to anaesthetics, which will be beneficial for the prevention and treatment of many diseases, such as Alzheimer's disease. Given the many procedures in medical practice that require continuous or multiple exposures to anaesthetics, our review will provide great insight into the possible adverse impact of these substances on the human brain and cognition.