Impact of various anesthetic regimens on motor-evoked potentials in infants undergoing spinal surgery: A case series.

Motor-evoked potential (MEP) monitoring is commonly used in children. MEP monitoring in infants is difficult due to smaller signals requiring higher stimulation voltages. There is limited information on the effect of different anesthetics on MEP monitoring in this age group. This case series describes the effect of different anesthetic regimens on MEP monitoring in infants. Patients <1 year of age who underwent spinal surgery with MEP monitoring between February 2022 and July 2023 at a single tertiary care children hospital were reviewed. The motor-evoked potential amplitudes were classified into 4 levels based on the voltage in the upper and lower limbs (none, responded, acceptable, sufficient). "Acceptable" or "sufficient" levels were defined as successful monitoring. A total of 19 infants were identified, involving 3 anesthesia regimens: 4/19 (21.1%) cases were anesthetized with propofol/remifentanil total intravenous anesthesia (TIVA), 3/19 (15.8%) with propofol/remifentanil/low-dose sevoflurane and another 12/19 (63.2%) cases who initially received propofol/remifentanil/sevoflurane and were converted to propofol/remifentanil anesthesia intraoperatively. The 4 cases with propofol/remifentanil showed 20/32 (62.5%) successful monitoring points. In contrast, 6/24 (25%) successful points were achieved with propofol/remifentanil intravenous anesthesia/0.5 age-adjusted minimum alveolar concentration sevoflurane. In 12 cases converted from propofol/remifentanil/low-dose inhalational anesthetics to TIVA alone, successful MEP monitoring points increased from 46/96 (47.9%) to 81/96 (84.4%). Adding low-dose inhalation anesthetic to propofol-based TIVA suppresses MEP amplitudes in infants. The optimal anesthetic regimen for infants requires further investigation.

Etomidate enhances cerebellar CF-PC synaptic plasticity through CB1 receptor/PKA cascade in vitro in mice.

Etomidate (ET) is a widely used intravenous imidazole general anesthetic, which depresses the cerebellar neuronal activity by modulating various receptors activity and synaptic transmission. In this study, we investigated the effects of ET on the cerebellar climbing fiber-Purkinje cells (CF-PC) plasticity in vitro in mice using whole-cell recording technique and pharmacological methods. Our results demonstrated that CF tetanic stimulation produced a mGluR1-dependent long-term depression (LTD) of CF-PC excitatory postsynaptic currents (EPSCs), which was enhanced by bath application of ET (10 µM). Blockade of mGluR1 receptor with JNJ16259685, ET triggered the tetanic stimulation to induce a CF-PC LTD accompanied with an increase in paired-pulse ratio (PPR). The ET-triggered CF-PC LTD was abolished by extracellular administration of an N-methyl-(D)-aspartate (NMDA) receptor antagonist, D-APV, as well as by intracellular blockade of NMDA receptors activity with MK801. Furthermore, blocking cannabinoids 1 (CB1) receptor with AM251 or chelating intracellular Ca2+ with BAPTA, ET failed to trigger the CF-PC LTD. Moreover, the ET-triggered CF-PC LTD was abolished by inhibition of protein kinase A (PKA), but not by inhibition of protein kinase C inhibiter. The present results suggest that ET acts on postsynaptic NMDA receptor resulting in an enhancement of the cerebellar CF-PC LTD through CB1 receptor/PKA cascade in vitro in mice. These results provide new evidence and possible mechanism for ET anesthesia to affect motor learning and motor coordination by regulating cerebellar CF-PC LTD.

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.

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.

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).

Implementation of a Bayesian based advisory tool for target-controlled infusion of propofol using qCON as control variable.

This single blinded randomized controlled trial aims to assess whether the application of a Bayesian-adjusted CePROP (effect-site of propofol) advisory tool leads towards a more stringent control of the cerebral drug effect during anaesthesia, using qCON as control variable. 100 patients scheduled for elective surgery were included and randomized into a control or intervention group (1:1 ratio). In the intervention group the advisory screen was made available to the clinician, whereas it was blinded in the control group. The settings of the target-controlled infusion pumps could be adjusted at any time by the clinician. Cerebral drug effect was quantified using processed EEG (CONOX monitor, Fresenius Kabi, Bad Homburg, Germany). The time of qCON between the desired range (35-55) during anaesthesia maintenance was defined as our primary end point. Induction parameters and recovery times were considered secondary end points and coefficient of variance of qCON and CePROP was calculated in order to survey the extent of control towards the mean of the population. The desired range of qCON between 35 and 55 was maintained in 84% vs. 90% (p = 0.15) of the case time in the control versus intervention group, respectively. Secondary endpoints showed similar results in both groups. The coefficient of variation for CePROP was higher in the intervention group. The application of the Bayesian-based CePROP advisory system in this trial did not result in a different time of qCON between 35 and 55 (84 [21] vs. 90 [18] percent of the case time). Significant differences between groups were hard to establish, most likely due to a very high performance level in the control group. More extensive control efforts were found in the intervention group. We believe that this advisory tool could be a useful educational tool for novices to titrate propofol effect-site concentrations.

Electroencephalographic density spectral array monitoring during propofol/sevoflurane coadministration in children, an exploratory observational study.

INTRODUCTION: Propofol and sevoflurane have a long history in pediatric anesthesia. Combining both drugs at low dose levels offers new opportunities. However, monitoring the hypnotic effects of this drug combination in children is challenging, because the currently available processed EEG-based systems are insufficiently validated in young children and the co-administration of anesthetics. This study investigated electroencephalographic density spectral array monitoring during propofol/sevoflurane coadministration with fixed sevoflurane- and variable propofol dosages. PATIENTS AND METHODS: We analyzed the density spectral array pattern recorded during propofol/sevoflurane anesthesia in pediatric patients from birth to 11 years of age. Data from 78 patients were suitable for analysis. The primary outcome parameter of this study was the correlation between variable propofol dosages and the expression of the four electroencephalogram frequency bands ß, α, θ, and δ. The main secondary outcome parameters were the intra-operative total EEG power and the prevalence of burst suppression. RESULTS: In patients above the age of 1 year, a dose-dependent correlation between the propofol dosage and the relative percentage of ß (-12.2%, p < 0.001) and δ (5.1%, p < 0.001) was found. There was an age-dependent trend toward increasing mean EEG power, with the most significant increase in the first year of life. In 14.1% of our patients, at least one episode of burst suppression occurred. CONCLUSION: DSA-guided augmentation of propofol anesthesia with sevoflurane provides sufficient depth of anesthesia at doses usually considered sub-anesthetic in children, leading to less anesthetic drug exposure for the individual child.

Association between telomere length in the DNA of peripheral blood leukocytes and the propofol dose in anesthesia induction: an observational study

Abstract Introduction: Propofol is a widely used anesthetic and its dose is closely related to aging. Telomere length (TL) is a unique heritable trait, and emerging as a biomarker of aging, health and disease. Telomerase RNA component (TERC) plays an important role in maintaining TL. We proposed a hypothesis that propofol dose in general anesthesia can be predicted by measuring TL before operation, which greatly reduced the risk of anesthesia, especially the elderly. Methods: The association between the propofol dose in anesthesia induction and: TL in the DNA of peripheral blood leukocytes; body weight; sex; difference of the Bispectral Index (BIS) before and after anesthesia induction in patients was evaluated by multivariable linear regression analyses. The mutation at the 5'end or 3'end of TERC was detected. We recruited 100 patients of elective surgery. Results: We found that propofol dose in anesthesia induction was clearly correlated significantly with TL (r = 0.78, p < 0.001), body weight (r = 0.84, p = 0.004), sex (r = 0.83, p= 0.84, p = 0.004), sex (r = 0.83, p = 0.004), and difference of BIS before and after anesthesia induction (r = 0.85, p = 0.029). By comparing the absolute values of standardized regression coefficients (0.58, 0.21, 0.19, and 0.12) of the four variables, it can be seen that TL contributes the most to the propofol dose in anesthesia induction. However, the mutation at the 5' end or 3' end of TERC was not found. Conclusions: These findings provide preliminary evidence that the propofol dose in anesthesia induction was clearly correlated with genetically determined TL. TL may be a promising predictor of the propofol dose, which is beneficial to improve the safety of anesthesia and reduce perioperative complications.

Type of anesthesia for cancer resection surgery: No differential impact on cancer recurrence in mouse models of breast cancer.

BACKGROUND: Surgery is essential for curative treatment of solid tumors. Evidence from recent retrospective clinical analyses suggests that use of propofol-based total intravenous anesthesia during cancer resection surgery is associated with improved overall survival compared to inhaled volatile anesthesia. Evaluating these findings in prospective clinical studies is required to inform definitive clinical guidelines but will take many years and requires biomarkers to monitor treatment effect. Therefore, we examined the effect of different anesthetic agents on cancer recurrence in mouse models of breast cancer with the overarching goal of evaluating plausible mechanisms that could be used as biomarkers of treatment response. METHODS: To test the hypothesis that volatile anesthesia accelerates breast cancer recurrence after surgical resection of the primary tumor, we used three mouse models of breast cancer. We compared volatile sevoflurane anesthesia with intravenous propofol anesthesia and used serial non-invasive bioluminescent imaging to track primary tumor recurrence and metastatic recurrence. To determine short-term perioperative effects, we evaluated the effect of anesthesia on vascular integrity and immune cell changes after surgery in animal models. RESULTS: Survival analyses found that the kinetics of cancer recurrence and impact on survival were similar regardless of the anesthetic agent used during cancer surgery. Vascular permeability, immune cell infiltration and cytokine profiles showed no statistical difference after resection with inhaled sevoflurane or intravenous propofol anesthesia. CONCLUSIONS: These preclinical studies found no evidence that choice of anesthetic agent used during cancer resection surgery affected either short-term perioperative events or long-term cancer outcomes in mouse models of breast cancer. These findings raise the possibility that mouse models do not recapitulate perioperative events in cancer patients. Nonetheless, the findings suggest that future evaluation of effects of anesthesia on cancer outcomes should focus on cancer types other than breast cancer.

Prediction of blood pressure changes during surgical incision using the minimum evoked current of vascular stiffness value under sevoflurane anesthesia.

Necessary and sufficient opioids should be administered for safe and stable anesthesia. However, opioid sensitivity varies among individuals. We previously reported that sympathetic responses to nociceptive stimuli under propofol anesthesia could be predicted by measuring the minimum evoked current of the vascular stiffness value (MECK). However, this result has only been proven under propofol anesthesia. We propose that MECK could be used under anesthesia with a volatile anesthetic. Thirty patients undergoing laparotomy with sevoflurane anesthesia received 0.7 minimum alveolar concentration (MAC) sevoflurane and intravenous remifentanil at a constant concentration of 2 ng/mL, followed by tetanic stimulation, to measure MECK. After tetanic stimulation, the same anesthetic conditions were maintained, and the rate of change in systolic blood pressure (ROCBP) during the skin incision was measured. The correlation coefficient between the MECK and ROCBP during skin incision under sevoflurane anesthesia was R = - 0.735 (P < 0.01), similar to that in a previous study with propofol (R = - 0.723). Thus, a high correlation was observed. The slope of the linear regression equation was - 0.27, similar to that obtained in the study on propofol (- 0.28). These results suggest that, as with propofol anesthesia, MECK can be used as a predictive index for ROCBP under 0.7 MAC sevoflurane anesthesia.Clinical trial registration: Registry, University hospital Medical Information Network; registration number, UMIN000047425; principal investigator's name, Noboru Saeki; date of registration, April 8, 2022.

EEG spectral slope: A reliable indicator for continuous evaluation of consciousness levels during propofol anesthesia.

The level of consciousness undergoes continuous alterations during anesthesia. Prior to the onset of propofol-induced complete unconsciousness, degraded levels of behavioral responsiveness can be observed. However, a reliable index to monitor altered consciousness levels during anesthesia has not been sufficiently investigated. In this study, we obtained 60-channel EEG data from 24 healthy participants during an ultra-slow propofol infusion protocol starting with an initial concentration of 1 µg/ml and a stepwise increase of 0.2 µg/ml in concentration. Consecutive auditory stimuli were delivered every 5 to 6 s, and the response time to the stimuli was used to assess the responsiveness levels. We calculated the spectral slope in a time-resolved manner by extracting 5-second EEG segments at each auditory stimulus and estimated their correlation with the corresponding response time. Our results demonstrated that during slow propofol infusion, the response time to external stimuli increased, while the EEG spectral slope, fitted at 15-45 Hz, became steeper, and a significant negative correlation was observed between them. Moreover, the spectral slope further steepened at deeper anesthetic levels and became flatter during anesthesia recovery. We verified these findings using an external dataset. Additionally, we found that the spectral slope of frontal electrodes over the prefrontal lobe had the best performance in predicting the response time. Overall, this study used a time-resolved analysis to suggest that the EEG spectral slope could reliably track continuously altered consciousness levels during propofol anesthesia. Furthermore, the frontal spectral slope may be a promising index for clinical monitoring of anesthesia depth.

General intravenous anesthetics - pharmacodynamics, pharmacokinetics and chiral properties.

In continuation of our published review on general inhalational anesthetics, the current article presents a survey of intravenous agents for general anaesthesia. From chemical point of view these compounds belong to structurally diverse categories, such as barbiturates - thiopental (Sodium pentothal®, Trapanal®, Pentothal®), methohexital (Brevital®), and hexobarbital (Evipan®, Hexenal®, Citopan®, Tobinal®); non-barbiturate derivatives - ketamine (Ketalar® Ketaset®), esketamine (Ketanest®), and etomidate (Amidate®, Hypnomidate®), phenolic derivatives - propofol (Diprivan®); steroid derivatives - mixture of alfadolone and alfaxalone (Althesin® in human and Saffan® in veterinary anesthesia); and derivatives of phenylacetic acid - propanidid (Epontol®, Sombrevin®). Most of these compounds are chiral, with the exception of propofol and propanidid. Apart from etomidate and esketamine, they are used in the form of their racemates. Besides their characteristics and mechanism of action, attention is centred also on their chiral properties.

Etomidate Depresses Spontaneous Complex Spikes Activity of Cerebellar Purkinje Cells via Cannabinoid 1 Receptor in vivo in Mice.

INTRODUCTION: Complex spikes (CSs) activity of cerebellar Purkinje cells plays critical roles in motor coordination and motor learning by transferring information to cerebellar cortex, which is an accessible and useful model for neurophysiological investigation. Etomidate is an ultrashort-acting nonbarbiturate intravenous anesthetic, which inhibits the spontaneous activity of cerebellar Purkinje cells through activation of GABAA and glycine receptors in vivo in mice. However, the effect of etomidate on the spontaneous CSs activity of cerebellar Purkinje cells in living mouse is not clear. METHODS: We here investigated the effects of etomidate on spontaneous CSs activity of cerebellar Purkinje cell in urethane-anesthetized mice by electrophysiology recording technique and pharmacological methods. RESULTS: Our results showed that cerebellar surface perfusion of etomidate significantly depressed the activity of spontaneous CSs, which exhibited decreases in the number of spikelets and the area under curve (AUC) of the CSs. The etomidate-produced inhibition of CSs activity was persisted in the presence of GABAA and glycine receptors antagonists. However, application of cannabinoid 1 (CB1) receptor antagonist, AM-251, completely blocked the etomidate-induced inhibition of CSs. Furthermore, application of the CB1 receptor agonist, WIN55212-2, induced a decrease of CSs. Moreover, in the presence of a specific protein kinase A (PKA) inhibitor, KT5720, etomidate failed to produce decreases in the spikelets number and the AUC of the spontaneous CSs. CONCLUSION: These results indicate that cerebellar surface application of etomidate facilitates CB1 receptor activity resulting in a depression of spontaneous CSs activity of Purkinje cells via PKA signaling pathway in mouse cerebellar cortex. Our present results suggest that the etomidate administration may impair the function of cerebellar cortical neuronal circuitry by inhibition of the climbing fiber - Purkinje cells synaptic transmission through activation of CB1 receptors in vivo in mice.

Effects of anesthetics on nociceptive sensory evoked potentials by intraepidermal noxious electrical stimulation of A-δ fibers.

PURPOSE: Generation of nociceptive sensory evoked potentials (NEPs) by selective stimulation of nociceptive intraepidermal nerve fibers is a simple technique which could be used as intraoperative nociception monitor. We evaluated the effects of remifentanil, propofol and sevoflurane on NEPs by this technique. METHODS: Patients undergoing general anesthesia were assigned to groups in two studies. A-δ fiber selective NEPs were recorded. Study 1: NEPs were recorded at control, under anesthetics administration: remifentanil at an effect-site concentration (Ce) of 1.0 ng/mL (n = 10), propofol at Ce of 0.5 µg/mL (n = 10), or sevoflurane at 0.2 minimum alveolar concentration (MAC) (n = 10), and recovery from the anesthetics. Study 2: NEPs were recorded at control and under administration of higher dose anesthetics: propofol at Ce of 0.5 and 1.0 µg/mL (n = 10) or sevoflurane at 0.2 and 0.5 MAC (n = 10). A P-value < 0.016 was considered statistically significant in multiple analyses. RESULTS: Study 1: Remifentanil at Ce of 1.0 ng/mL significantly suppressed the amplitude of NEPs (mean amplitude (standard deviation) of control vs. remifentanil administration: 16.8 µV (3.8) vs. 10.1 µV (2.5), P < 0.001). Propofol and sevoflurane did not suppress the amplitude significantly. Study 2: Propofol at Ce of 0.5 and 1.0 µg/mL and sevoflurane at 0.2 and 0.5 MAC did not suppress the amplitude significantly. CONCLUSION: The amplitude of A-δ fiber selective NEPs was suppressed by remifentanil but not propofol or sevoflurane. NEPs with intraepidermal electrical stimulation can assess the analgesic effect of anesthetics. CLINICAL TRIAL NUMBER: UMIN000038214 REGISTRY URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043328.

Effects of propofol and sevoflurane on social and anxiety-related behaviours in sleep-deprived rats.

BACKGROUND: Sleep disorders can profoundly affect neurological function. We investigated changes in social and anxiety-related brain functional connectivity induced by sleep deprivation, and the potential therapeutic effects of the general anaesthetics propofol and sevoflurane in rats. METHODS: Twelve-week-old male Sprague-Dawley rats were subjected to sleep deprivation for 20 h per day (from 14:00 to 10:00 the next day) for 4 consecutive weeks. They were free from sleep deprivation for the remaining 4 h during which they received propofol (40 mg kg-1 i.p.) or sevoflurane (2% for 2 h) per day or no treatment. These cohorts were instrumented for EEG/EMG recordings on days 2, 14, and 28. Different cohorts were used for open field and three-chambered social behavioural tests, functional MRI, nuclear magnetic resonance spectroscopy, and positron emission tomography imaging 48 h after 4 weeks of sleep deprivation. RESULTS: Propofol protected against sleep deprivation-induced anxiety behaviours with more time (44.7 [8.9] s vs 24.2 [4.1] s for the sleep-deprivation controls; P<0.001) spent in the central area of the open field test and improved social preference index by 30% (all P<0.01). Compared with the sleep-deprived rats, propofol treatment enhanced overall functional connectivity by 74% (P<0.05) and overall glucose metabolism by 30% (P<0.01), and improved glutamate kinetics by 20% (P<0.05). In contrast, these effects were not found after sevoflurane treatment. CONCLUSIONS: Unlike sevoflurane, propofol reduced sleep deprivation-induced social and anxiety-related behaviours. Propofol might be superior to sevoflurane for patients with sleep disorders who receive anaesthesia, which should be studied in clinical studies.

Dexmedetomidine alleviates propofol-induced neural injury in developing rats.

Propofol, a commonly used intravenous anesthetic, has been associated with neurodegeneration in the developing brain upon repeated exposure. Dexmedetomidine is an α2 adrenoceptor agonist that was previously reported to possess neuroprotective properties. Here, we confirmed the impacts of dexmedetomidine on propofol-induced neuroapoptosis and subsequent spatial learning and memory deficits in neonatal rats. We found that dexmedetomidine effectively mitigated propofol-induced spatial learning and memory impairments and improved aversive memory in developing rats. Dexmedetomidine reduced propofol-induced cell apoptosis in the hippocampus and modulated the mRNA expression of Bcl-2 and Bax. Additionally, dexmedetomidine attenuated the propofol-induced increase of inflammatory factors IL-6 and TNF-α. The reduced phosphorylation levels of Akt and CREB levels by propofol were re-activated by dexmedetomidine. In conclusion, our findings demonstrated that dexmedetomidine effectively mitigated propofol-induced cognitive and memory impairments in developing rats by modulating apoptosis and reducing inflammation via activating the Akt/CREB/BDNF signaling pathway. These findings suggest potential strategies to protect the developing brain from the adverse effects of anesthetics and improve patient care in pediatric anesthesia practice.

The effect of age on the induction dose of propofol for general anesthesia in dogs.

OBJECTIVE: In people, the dose of propofol (DOP) required for procedural sedation and anesthesia decreases significantly with age. The objective of this study was to determine if the DOP required to perform endotracheal intubation decreases with age in dogs. STUDY DESIGN: Retrospective case series. ANIMALS: 1397 dogs. METHODS: Data from dogs anesthetized at referral center (2017-2020) were analyzed with three multivariate linear regression models with backward elimination using a combination of either absolute age, physiologic age, or life expectancy (ratio between age at the time of anesthetic event and expected age of death for each breed obtained from previous literature) as well as other factors as independent variables, and DOP as the dependent variable. The DOP for each quartile of life expectancy (<25%, 25-50%, 50-75%, 75-100%, >100%) was compared using one-way ANOVA. Significance was set at alpha = 0.025. RESULTS: Mean age was 7.2 ± 4.1 years, life expectancy 59.8 ± 33%, weight 19 ± 14 kg, and DOP 3.76 ± 1.8 mg kg-1. Among age models, only life expectancy was a predictor of DOP (-0.37 mg kg-1; P = 0.013) but of minimal clinical importance. The DOP by life age expectancy quartile was 3.9 ± 2.3, 3.8 ± 1.8, 3.6 ± 1.8, 3.7 ± 1.7, and 3.4 ± 1.6 mg kg-1, respectively (P = 0.20). Yorkshire Terrier, Chihuahua, Maltese, mixed breed dogs under 10 kg, and Shih Tzu required higher DOP. Status of neutered male, ASA E, and Boxer, Labrador and Golden Retriever breeds decreased DOP, along with certain premedication drugs. CONCLUSIONS AND CLINICAL RELEVANCE: In contrast to what is observed in people, an age cut-off predictive of DOP does not exist. Percentage of elapsed life expectancy along with other factors such as breed, premedication drug, emergency procedure, and reproductive status significantly alter DOP. In older dogs, the dose of propofol can be adjusted based on their elapsed life expectancy.

Efficacy of Isoflurane-Remifentanil versus Propofol-Remifentanil on Controlled Hypotension and Surgeon Satisfaction in Rhinoplasty: A Single-Blind Clinical Trial Study.

Background: Rhinoplasty is a complex but popular surgery in Iran. The main complications of the surgery are post-operative bleeding and nasal septal hematoma due to poor intra-operative controlled hypertension. This study aimed to compare the efficacy of isoflurane-remifentanil (I-R) versus propofol-remifentanil (P-R) to induce controlled hypotension and to assess surgeon satisfaction with each of these combinations during rhinoplasty. Methods: In 2020-2021, a single-blind clinical study was conducted on 98 patients aged 18-50 years undergoing rhinoplasty at Mother and Child Hospital (Shiraz, Iran). Patients were randomly divided into P-R (n=48) and I-R (n=50) groups. Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were assessed during surgery and in the recovery room. A questionnaire was used to evaluate the level of surgeon satisfaction. Data were analyzed using independent samples t test, Chi-square test, and repeated measures ANOVA with SPSS software. P<0.05 was considered statistically significant. Results: Five minutes after anesthesia induction, the P-R combination had a greater effect on reducing SBP (P=0.010), DBP (P=0.007), MAP (P=0.003), and HR (P=0.026) than I-R. However, from the 40th minute to the end of surgery and after 30 minutes of recovery, the I-R combination had a slightly better effect on blood pressure reduction than P-R. There was no difference in surgeon satisfaction with either of the two drug combinations. Conclusion: Both P-R and I-R combinations are recommended to induce hypotension during rhinoplasty. However, I-R is more effective than P-R in inducing the desired controlled hypotension.

Anesthetic Binding Induced Motion of GABAA Receptors Revealed by Coarse-Grained Molecular Dynamics Simulations.

General anesthetics are indispensable in modern medicine because they induce a reversible loss of consciousness and sensation in humans. On the other hand, their molecular mechanisms of action have not yet been elucidated. Several studies have identified the main targets of some general anesthetics. The structures of γ-aminobutyric acid A (GABAA) receptors with the intravenous anesthetics such as propofol and etomidate have recently been determined. Although these anesthetic binding structures provide essential insights into the mechanism of action of anesthetics, the detailed molecular mechanism of how the anesthetic binding affects the Cl- permeability of GABAA receptors remains to be elucidated. In this study, we performed coarse-grained molecular dynamics simulations for GABAA receptors and analyzed the resulting simulation trajectories to investigate the effects of anesthetic binding on the motion of GABAA receptors. The results showed large structural fluctuations in GABAA receptors, correlations of motion between the amino acid residues, large amplitude motion, and autocorrelated slow motion, which were obtained by advanced statistical analyses. In addition, a comparison of the resulting trajectories in the presence or absence of the anesthetic molecules revealed a characteristic pore motion related to the gate-opening motion of GABAA receptors.