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.

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.

Transcutaneous electric acupoint stimulation reduced consumption of profopol in patients undergoing laparoscopic surgery: A randomized clinical trial.

BACKGROUND: Propofol is a common regimen for general anesthesia maintenance. But propofol can dose-dependently generate cardiopulmonary depression. Thus, any strategy to reduce propofol dosage during laparoscopic surgery may have underlying beneficial effect for patient prognosis. Previous studies indicated both analgesic and sedative effect of acupoint stimulation. However, its main sedative effect on patients under general anesthesia remains unclear. OBJECTIVE: The aim of this study was to investigate the sedative effect of transcutaneous electrical acupoint stimulation (TEAS) on patients scheduled for laparoscopic surgery under general anesthesia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: In this randomized clinical trial, patients scheduled for laparoscopic surgery under general anesthesia in Xijing hospital were randomly assigned to 3 groups, receiving electrical stimulation at the Shenmen (HT7)/Ximen (PC4) (TEAS group), stimulation at the shoulder (non-acupoint group) or no stimulation (control group), respectively. MAIN OUTCOME MEASURES: One hundred sixty-two patients completed the study. The primary outcome was the consumption of propofol, and secondary outcomes included features of recovery after surgery, major complications after surgery and by 1 year after surgery. RESULTS: In patients undergoing laparoscopic surgery, the doses of propofol decreased significantly in the TEAS group compared (0.10 ±â€…0.02 mg·kg-1·min-1) with the other 2 groups (both 0.12 ±â€…0.02 mg·kg-1·min-1, P < .001). The mean differences (95% confidence interval) for non-acupoint versus TEAS and control versus TEAS were 0.021 (0.012, 0.030) and 0.024 (0.013, 0.034), respectively. Time to awake and to extubation were not significantly different among the groups. The incidences of major complications after surgery and by 1 year after surgery were not significantly different among the groups. CONCLUSION: TEAS could induce additional sedative effect in patients during laparoscopic surgery and reduce propofol consumption.

Effects of Esketamine Combined with Propofol for Hysteroscopy Anesthesia on Patient Hemodynamics and Adverse Reactions.

Objective: To investigate the effect of esketamine combined with propofol on patient hemodynamics and its safety in hysteroscopy anesthesia. Methods: A total of 186 hysteroscopic patients admitted to our hospital from January 2021 to January 2022 were selected, and the patients were divided into group K and Group P according to a completely random number table, with 93 cases each. In short, all patients are uniformly numbered and adequately intermixed, according to the prescribed sampling starting point and order, the sample unit numbers were successively drawn from the random number table, until the extraction to the required sample size. Group K was given esketamine combined with propofol intravenously, and group P was given sufentanil combined with propofol intravenously. The changes in respiratory circulation [heart rate (HR), mean arterial pressure (MAP) and oxygen saturation (SpO2)] at the time of entering the operating room (T0), at the beginning of surgery (T1), 10 minutes after surgery(T2), and 10 minutes after the end of surgery (T3) were compared between the two groups, as well as the total time of surgery, the time to wake up after surgery, the amount of propofol used intraoperatively and the proportion of additional propofol were compared. The numerical rating scale (NRS) was used to assess the pain level of patients in both groups at different times after awakening and the occurrence of intraoperative and postoperative adverse reactions such as body movement, respiratory depression, bradycardia, injection site pain, nausea and vomiting, and dizziness were counted in both groups. Results: There were no significant changes in MAP, HR, and SpO2 in Group K at all moments compared with T0 (P > .05), MAP, HR and SpO2 in Group P at T1 and T2 were lower than those at T0 (P < .05). MAP, HR, and SpO2 were significantly lower in Group P at T1 and T2 moments compared with Group K, suggesting that circulatory depression was more pronounced in Group P at T1 and T2 moments (P < .05) and was not conducive to postoperative recovery. Compared with group P, the postoperative recovery time of group K was significantly shorter, and the dosage of propofol and the proportion of additional propofol were significantly lower (P < .05) which was beneficial to the health of patients. The pain level was significantly lower in Group K at 5, 15, and 30 minutes after awakening than in Group P (P < .05). The incidence of adverse reactions such as intraoperative motion, respiratory depression, bradycardia, injection site pain, and dizziness was significantly lower in group K than in group P (P < .05), and there was no significant difference in the incidence of nausea and vomiting between the two groups (P > .05), and prove that esketamine combined with propofol used for anesthesia which have high safety as well as more effective. Conclusion: The use of esketamine compounded with propofol in hysteroscopy anesthesia has less effect on the patient's circulatory and respiratory systems. This protocol can improve the postoperative analgesic effect of anesthesia in patients, reduce the amount of propofol during surgery, have fewer adverse effects and mild symptoms, is safe and effective, and can be used in clinical practice.

Effects of sedatives on radiologic enema reduction in children with ileocolic intussusception: A systematic review and meta-analysis.

BACKGROUND: In children with ileocolic intussusception, sedatives such as midazolam, ketamine and propofol may facilitate radiologic enema reduction, but studies on their separate and joint effects remain controversial. OBJECTIVES: We aimed to systematically analyze studies for the effects of sedatives on the radiologic reduction of ileocolic intussusception in children. METHODS: We searched PubMed, EMBASE, CINAHL, Scopus and Web of Science from database inception through March 2023 for articles that enrolled children with ileocolic intussusception who underwent non-operative pneumatic or hydrostatic enema reduction under ultrasound or fluoroscopic guidance with or without the use of sedatives. The primary and secondary outcomes were success rate in radiologic reduction of ileocolic intussusception and risk of perforation, respectively. Effect estimates from the individual studies were extracted and combined using the Hartung-Knapp-Sidik-Jonkman log-odds random-effects model. Heterogeneity between studies was checked using Cochran's Q test and the I2 statistic. RESULTS: A total of 17 studies with 2094 participants were included in the final review, of which 15 were included in the meta-analysis. Nine studies reported on the success rate of radiologic reduction performed under sedation in all participants, while six studies compared the success rate in two patient groups undergoing the procedure with or without sedation. The pooled success rate of non-operative reduction under sedation was 87 % (95 % CI: 80-95 %), P = 0.000 with considerable heterogeneity (I2 = 85 %). A higher success rate of 94 % (95 % CI: 88-99 %) and homogeneity (I2 = 12 %) were found in studies with pneumatic enema reduction. Among comparative studies, the odds of success of non-operative reduction were increased when the procedure was performed under sedation, with a pooled odds ratio of 2.41 (95 % CI: 1.27-4.57), P = 0.010 and moderate heterogeneity (I2 = 60 %). In a sensitivity analysis, homogeneity was found between analyzed studies when two outliers were excluded (I2 = 0.73 %). The risk of perforation was not significantly different (OR 1.52, 95 % CI: 0.09-23.34), P = 0.764 indicating small study effects. No publication, bias was detected on visual inspection of the funnel plots or the Begg's and Egger's bias tests. Most studies were categorized as having a low risk of bias using Joanna Briggs Institute checklists. CONCLUSIONS: In selected patient groups, sedation can increase the success rate of radiologic enema reduction in children with ileocolic intussusception without evidence of increased risk of perforation. Systematic review protocol registration: PROSPERO CRD42023404887.

Investigating Deep Sedation With Intravenous Ketamine in Spontaneous Respiration During Pulsed-Field Ablation.

OBJECTIVES: The authors report their experience of a protocol for deep sedation with ketamine in spontaneous respiration during the pulsed-field ablation (PFA) of atrial fibrillation (AF). DESIGN: Observational, prospective, nonrandomized fashion. SETTING: Single-center hospitalized patients. PARTICIPANTS: All consecutive patients undergoing PFA of AF. INTERVENTIONS: Patients undergoing deep sedation with intravenous ketamine. MEASUREMENTS AND MAIN RESULTS: The authors' sedation protocol involves the intravenous administration of fentanyl (1.5 µg/kg) and midazolam (2 mg) at low doses before local anesthesia with lidocaine. A ketamine adjunct (1 mg/kg) in 5-minute boluses was injected about 5 minutes before the first PFA delivery. The authors enrolled 117 patients (age = 59 ± 10 y, 74.4% males, body mass index = 27.6 ± 5 kg/m2, fluoroscopy time = 24 ± 14 minutes, skin-to-skin time = 80 ± 40 minutes and PFA LA dwell time = 24 ± 7 minutes). By the end of the procedure, pulmonary vein isolation had been achieved in all patients using PFA alone. The mean time under sedation was 54.9 ± 6 minutes, with 92 patients (79%) being sedated for <1 hour. A satisfactory Ramsay Sedation Scale level before ketamine administration was achieved in all patients, except one (80.3% of the patients with rank 3; 18.4% with rank 2). In all procedures, the satisfaction level was found acceptable by both the patient and the primary operator (satisfactory in 98.2% of cases). All patients achieved a Numeric Rating Scale for Pain ≤3 (none or mild). No major procedure or anesthesia-related complications were reported. CONCLUSION: The authors' standardized sedation protocol with the administration of drugs with rapid onset and pharmacologic offset at low doses was safe and effective, with an optimal degree of patient and operator satisfaction.

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.

Anesthetic Effect of Dezocine Combined with Propofol in Laparoscopic Surgery and Its Influence on T Cells and Inflammatory Factors in Patients.

Objective: To investigate the anesthetic effects of combining dezocine with propofol during laparoscopic surgeries, particularly its impact on T cells and inflammation. Methods: A prospective study was conducted on 80 patients undergoing laparoscopy at the Third Hospital of Qiqihar Medical University from January 1, 2021, to August 1, 2022. Patients were randomly divided into two groups of 40 each using the random number table method. The combined group received 0.1mg/kg dezocine and 2.5 mg/kg propofol, while the control group received only 2.5 mg/kg propofol. Postoperative levels of NK cells, T cells, TNF-α, and IL-1ß were analyzed. Results: Postoperative recovery times, including spontaneous breathing, eye-opening, verbal response, extubation, and orientation, were notably shorter in the combined group compared to the control. While both groups showed an increase in TNF-α and IL-1ß levels post-surgery, the combined group had significantly lower levels at specific timepoints (T1, T2). This group also showed elevated levels of NK cells, CD4+, and CD4+/CD8+. Additionally, the combined group reported significantly less pain and had fewer patients with a low body condition score after extubation. No significant difference was observed in postoperative adverse reactions between the groups. Conclusions: Combining dezocine with propofol offers superior anesthesia for laparoscopic procedures. This combination not only enhances recovery speed and reduces postoperative pain but also maintains high safety standards.

The non-specific matrix thalamus facilitates the cortical information processing modes relevant for conscious awareness.

The neurobiological mechanisms of arousal and anesthesia remain poorly understood. Recent evidence highlights the key role of interactions between the cerebral cortex and the diffusely projecting matrix thalamic nuclei. Here, we interrogate these processes in a whole-brain corticothalamic neural mass model endowed with targeted and diffusely projecting thalamocortical nuclei inferred from empirical data. This model captures key features seen in propofol anesthesia, including diminished network integration, lowered state diversity, impaired susceptibility to perturbation, and decreased corticocortical coherence. Collectively, these signatures reflect a suppression of information transfer across the cerebral cortex. We recover these signatures of conscious arousal by selectively stimulating the matrix thalamus, recapitulating empirical results in macaque, as well as wake-like information processing states that reflect the thalamic modulation of large-scale cortical attractor dynamics. Our results highlight the role of matrix thalamocortical projections in shaping many features of complex cortical dynamics to facilitate the unique communication states supporting conscious awareness.

Effects of intravenous administration of magnesium sulfate in propofol-based sedation for ERCP in elderly patients: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Propofol-based sedations are widely used in elderly patients for endoscopic retrograde cholangiopancreatography (ERCP) procedure, but respiratory depression and cardiovascular adverse events commonly occur. Magnesium administered intravenously can alleviate pain and decrease propofol requirements during surgery. We hypothesized that intravenous magnesium was used as adjuvant to propofol might be beneficial in elderly patients undergoing ERCP procedures. METHODS: Eighty patients aged from 65 to 79 years who were scheduled for ERCP were enrolled. All patients were intravenously administered 0.1 µg/kg sufentanil as premedication. The patients were randomized to receive either intravenous magnesium sulfate 40 mg/kg (group M, n = 40) or the same volume of normal saline (group N, n = 40) over 15 min before the start of sedation. Intraoperative sedation was provided by propofol. Total propofol requirement during ERCP was the primary outcome. RESULTS: The total propofol consumption were reduced by 21.4% in the group M compared with the group N (151.2 ± 53.3 mg vs. 192.3 ± 72.1 mg, P = 0.001). The incidences of respiratory depression episodes and involuntary movement were less in the group M than those in the group N (0/40 vs. 6/40, P = 0.011; 4/40 vs. 11/40, P = 0.045; respectively). In the group M, the patients experienced less pain than those in the group N at 30 min after the procedure (1 [0-1] vs. 2 [1-2], P < 0.001). Correspondingly, the patients' satisfaction was clearly higher in the group M (P = 0.005). There was a tendency towards lower intraoperative heart rate and mean arterial pressure in group M. CONCLUSIONS: A single bolus of 40 mg/kg of intravenous magnesium can significantly reduce propofol consumption during ERCP, with higher sedation success and lower adverse events. TRIAL REGISTRATION: ID UMIN000044737. Registered 02/07/2021.

Rapid thalamocortical network switching mediated by cortical synchronization underlies propofol-induced EEG signatures: a biophysical model.

Propofol-mediated unconsciousness elicits strong alpha/low-beta and slow oscillations in the electroencephalogram (EEG) of patients. As anesthetic dose increases, the EEG signal changes in ways that give clues to the level of unconsciousness; the network mechanisms of these changes are only partially understood. Here, we construct a biophysical thalamocortical network involving brain stem influences that reproduces transitions in dynamics seen in the EEG involving the evolution of the power and frequency of alpha/low-beta and slow rhythm, as well as their interactions. Our model suggests that propofol engages thalamic spindle and cortical sleep mechanisms to elicit persistent alpha/low-beta and slow rhythms, respectively. The thalamocortical network fluctuates between two mutually exclusive states on the timescale of seconds. One state is characterized by continuous alpha/low-beta-frequency spiking in thalamus (C-state), whereas in the other, thalamic alpha spiking is interrupted by periods of co-occurring thalamic and cortical silence (I-state). In the I-state, alpha colocalizes to the peak of the slow oscillation; in the C-state, there is a variable relationship between an alpha/beta rhythm and the slow oscillation. The C-state predominates near loss of consciousness; with increasing dose, the proportion of time spent in the I-state increases, recapitulating EEG phenomenology. Cortical synchrony drives the switch to the I-state by changing the nature of the thalamocortical feedback. Brain stem influence on the strength of thalamocortical feedback mediates the amount of cortical synchrony. Our model implicates loss of low-beta, cortical synchrony, and coordinated thalamocortical silent periods as contributing to the unconscious state.NEW & NOTEWORTHY GABAergic anesthetics induce alpha/low-beta and slow oscillations in the EEG, which interact in dose-dependent ways. We constructed a thalamocortical model to investigate how these interdependent oscillations change with propofol dose. We find two dynamic states of thalamocortical coordination, which change on the timescale of seconds and dose-dependently mirror known changes in EEG. Thalamocortical feedback determines the oscillatory coupling and power seen in each state, and this is primarily driven by cortical synchrony and brain stem neuromodulation.

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).

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.

[Effect of transcutaneous acupoint electrical stimulation at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy].

OBJECTIVE: To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy. METHODS: A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (PETCO2) and minimum value of oxygen saturation (SpO2) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T0), at the start of surgery (T1), thoracic exploration (T2) and lobectomy (T3), as well as 30 min (T4) and 60 min (T5) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups. RESULTS: The maximum value of PETCO2, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO2 in the observation group was higher than that of the control group (P < 0.01). At T1-T5, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01). CONCLUSION: For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.

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.

Electroconvulsive Therapy Anesthetic Choice and Clinical Outcomes.

OBJECTIVE: Etomidate and methohexital are the 2 commonly used anesthetics for electroconvulsive therapy (ECT) in the United States. The objective of this study was to examine how anesthetic choice between etomidate and methohexital is associated with real-world clinical outcomes. METHODS: This naturalistic retrospective cohort study examined longitudinal electronic health records for 495 adult patients who received 2 or more ECT treatments from 2010 to 2019 in Kaiser Permanente North California, a large integrated health care system. Study outcomes included 12-month posttreatment depression remission as measured by the 9-item Patient Health Questionnaire, psychiatric and all-cause emergency department visits, and psychiatric and all-cause hospitalizations. RESULTS: Anesthetic choice was not significantly related to depression severity, emergency department visits, or psychiatric hospitalizations at 12 months after completing ECT. In exploratory analyses, we found that etomidate compared with methohexital was associated with higher rates of patient discomfort adverse effects-postictal agitation, phlebitis, and myoclonus (2.4% vs 0.4%; P < 0.001). CONCLUSIONS: We present the first large comparison of etomidate and methohexital as anesthetics for ECT and their associations with real-world outcomes. Our study showed no significant difference on depression remission, emergency department visits, or hospitalizations 12-months posttreatment. Thus, clinicians should focus on other patient or treatment characteristics when deciding on anesthetics for ECT. Further investigation is needed to confirm our exploratory findings that etomidate use was correlated with a higher rate of patient discomfort adverse effects relative to methohexital.

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.

In Vivo Photoadduction of Anesthetic Ligands in Mouse Brain Markedly Extends Sedation and Hypnosis.

Photoaffinity ligands are best known as tools used to identify the specific binding sites of drugs to their molecular targets. However, photoaffinity ligands have the potential to further define critical neuroanatomic targets of drug action. In the brains of WT male mice, we demonstrate the feasibility of using photoaffinity ligands in vivo to prolong anesthesia via targeted yet spatially restricted photoadduction of azi-m-propofol (aziPm), a photoreactive analog of the general anesthetic propofol. Systemic administration of aziPm with bilateral near-ultraviolet photoadduction in the rostral pons, at the border of the parabrachial nucleus and locus coeruleus, produced a 20-fold increase in the duration of sedative and hypnotic effects compared with control mice without UV illumination. Photoadduction that missed the parabrachial-coerulean complex also failed to extend the sedative or hypnotic actions of aziPm and was indistinguishable from nonadducted controls. Paralleling the prolonged behavioral and EEG consequences of on target in vivo photoadduction, we conducted electrophysiologic recordings in rostral pontine brain slices. Using neurons within the locus coeruleus to further highlight the cellular consequences of irreversible aziPm binding, we demonstrate transient slowing of spontaneous action potentials with a brief bath application of aziPm that becomes irreversible on photoadduction. Together, these findings suggest that photochemistry-based strategies are a viable new approach for probing CNS physiology and pathophysiology.SIGNIFICANCE STATEMENT Photoaffinity ligands are drugs capable of light-induced irreversible binding, which have unexploited potential to identify the neuroanatomic sites of drug action. We systemically administer a centrally acting anesthetic photoaffinity ligand in mice, conduct localized photoillumination within the brain to covalently adduct the drug at its in vivo sites of action, and successfully enrich irreversible drug binding within a restricted 250 µm radius. When photoadduction encompassed the pontine parabrachial-coerulean complex, anesthetic sedation and hypnosis was prolonged 20-fold, thus illustrating the power of in vivo photochemistry to help unravel neuronal mechanisms of drug action.

Use of Remimazolam Combined With Alfentanil for Plastic Surgery Anesthesia Cases: A Clinical Trial.

OBJECTIVE: This study aims to observe the safety and effectiveness of remimazolam benzenesulfonate combined with alfentanil for painless and comfort anesthesia in plastic surgery. METHODS: Two hundred patients with American Society of Anesthesiologists (ASA) I-II for elective facial autologous lipofilling + autologous liposuction (thigh or abdomen) plastic surgery in our hospital were selected. One hundred patients received comfort anesthesia (observation group) on odd-numbered day of surgery, and other 100 patients received painless anesthesia (control group) on even-numbered day. Patients in both groups were given slow injection of remimazolam benzenesulfonate 0.1 mg/kg and alfentanil 5 µg/kg to induce sleep before local anesthesia. Depending on body action reaction to surgical stimulation, patients in the observation group were received with remimazolam 0.05 mg/kg and alfentanil 2.5 µg/kg for maintenance until the end of surgery after local anesthesia, and patients in the control group received with remimazolam 0.25 to 0.5 mg/kg/h and alfentanil 25 to 50 µg/kg/h in continuous pumps. Time to fall asleep, sedation score, time to end of medication, time to open eyes, recovery score, and the presence of body movement, glossoptosis, arousal or jaw support during hypoxia, hypotension, bradycardia, operation time, total amount of remimazolam and alfentanil used, and the presence of postoperative complications such as pruritus, dizziness, nausea, and vomiting were recorded in both 2 groups. RESULTS: There were no significant differences in the preoperative vital sign parameters as mean arterial pressure, heart rate, and oxygen saturation between 2 groups ( P > 0.05). Intraoperative mean arterial pressure and heart rate were significantly lower in both groups compared with preoperative ( P < 0.05), but there was no statistically significant between the 2 groups ( P > 0.05). There was no significant decrease in oxygen saturation in both groups under the condition of intraoperative oxygen inhalation ( P > 0.05). There was no significant difference between the 2 groups in the incidence of adverse reactions, such as intraoperative body movement induced by skin cutting, glossoptosis requiring jaw thrust, postoperative pruritus, dizziness, nausea, and vomiting ( P > 0.05). There was no statistically significant difference in time to fall asleep, sedation score during local anesthesia, time to open eyes after stopping anesthetics, and recovery score between the 2 groups ( P > 0.05). Meanwhile, the total amount of remimazolam and alfentanil use was significantly reduced in patients in the observation group compared with the control group ( P < 0.05). CONCLUSIONS: Remimazolam benzenesulfonate combined with alfentanil can be used as a comfort anesthesia and painless anesthesia protocol in plastic surgery, which has the advantages of rapid onset of action, safety and comfort for patients, rapid recovery, and good cooperation. Furthermore, the protocol of remimazolam benzenesulfonate combined with alfentanil used in the observation group can significantly reduce the total amount of remimazolam and alfentanil used.

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.