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As the primary Ca2+ release channel in skeletal muscle sarcoplasmic reticulum (SR), mutations in type 1 ryanodine receptor (RyR1) or its binding partners underlie a constellation of muscle disorders, including malignant hyperthermia (MH). In patients with MH mutations, triggering agents including halogenated volatile anaesthetics bias RyR1 to an open state resulting in uncontrolled Ca2+ release, increased sarcomere tension, and heat production. Propofol does not trigger MH and is commonly used for patients at risk of MH. The atomic-level interactions of any anaesthetic with RyR1 are unknown. RyR1 opening was measured by [3H]ryanodine binding in heavy SR vesicles (wild type) and single-channel recordings of MH mutant R615C RyR1 in planar lipid bilayers, each exposed to propofol or the photoaffinity ligand analogue m -azipropofol (AziP m). Activator-mediated wild-type RyR1 opening as a function of propofol concentration was measured by Fura-2 Ca2+ imaging of human skeletal myotubes. AziP m binding sites, reflecting propofol binding, were identified on RyR1 using photoaffinity labelling. Propofol binding affinity to a photoadducted site was predicted using molecular dynamics (MD) simulation. Both propofol and AziP m decreased RyR1 opening in planar lipid bilayers (P <0.01) and heavy SR vesicles, and inhibited activator-induced Ca2+ release from human skeletal myotube SR. Several putative propofol binding sites on RyR1 were photoadducted by AziP m. MD simulation predicted propofol K D values of 55.8 μM and 1.4 μM in the V4828 pocket in open and closed RyR1, respectively. Propofol demonstrated direct binding and inhibition of RyR1 at clinically plausible concentrations, consistent with the hypothesis that propofol partially mitigates malignant hyperthermia by inhibition of induced Ca2+ flux through RyR1. [ABSTRACT FROM AUTHOR]

Patients with congenital heart disease are living longer due to improved medical and surgical care. Congenital heart disease encompasses a wide spectrum of defects with varying pathophysiology and unique anesthetic challenges. These patients often present for noncardiac surgery before or after surgical repair and are at increased risk for perioperative morbidity and mortality. Although there is no singular safe anesthetic technique, identifying potential error traps and tailoring perioperative management may help reduce morbidity and mortality. In this article, we discuss five error traps based on the collective experience of the authors. These error traps can occur when providing perioperative care to patients with congenital heart disease for noncardiac surgery and we present potential solutions to help avoid adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: Postoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery. Methods: One hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb. Discussion: The current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD. Trial registration: The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024. [ABSTRACT FROM AUTHOR]

Introduction: Propofol is an intravenous anesthetic administered as a bolus or continuous infusion during anesthetic induction and maintenance. Its pharmacokinetic characteristics include hepatic and extrahepatic metabolism with a rapid onset of action and short duration, which provides a smooth anesthetic induction without excitatory effects. Objective: To evaluate whether the isolated use of propofol in anesthetic induction in dogs changes the hemodynamic variables assessed via echocardiography. Study Design: Prospective clinical study. Animals: Twelve healthy dogs. Methods: The dogs were induced with propofol (dose/effect) at 3 mg/kg/minute, and echocardiographic evaluations were performed immediately before anesthetic induction (MB) and immediately after its interruption (MI), at the end of the supply of the anesthetic agent. Results: A significant reduction was observed between the values of the following hemodynamic variables: Ejection Fraction (EF%), which varied from 70% to 65% (p = 0.011) between moments, and the Doppler Ejection Index (DEI), which ranged from 27.1 mL/beat/m2 to 22.4 mL/beat/m2 (p = 0.044). The heart rate (HR) and the other studied hemodynamic variables showed no significant differences between the evaluated moments. Conclusion and Clinical Relevance: Propofol was a safe anesthetic‐inducing agent, maintaining stable hemodynamic indices during anesthetic induction at the used rate. [ABSTRACT FROM AUTHOR]

Introduction: Ciprofol is a new intravenous anesthetic with a similar chemical structure to propofol. We aimed to compare the incidence of adverse actions like injection pain and time indexes of ciprofol versus propofol on anesthesia in patients undergoing endoscopy. We also compared anesthetists' satisfaction during the procedure. Methods: Two independent researchers (Liu and Zeng) searched the Cochrane Library, Embase databases, and PubMed for controlled clinical trials. This meta-analysis of randomized controlled trials (RCTs) was performed with the Review Manager, Stata and the Cochrane Risk-of-Bias 2 tool to evaluate methodological quality. Relative risks with 95% confidence interval (CI) were calculated for outcomes. Results: Ten trials, including 1545 patients, were examined in the current meta-analysis. During anesthesia in patients undergoing endoscopy, the incidence of injection pain was significantly reduced in the research group. Compared with propofol, the pooled risk difference (RD) with the use of ciprofol for injection pain for all the procedures was − 0.34 (95% confidence interval [CI], -0.48 to 0.19), and RR for hypotension was 0.73(95% CI:0.58 to 0.92). GRADE showed this meta-analysis has moderate or low confidence. Trial sequential analysis for mortality indicated insufficient sample size for a definitive judgment for lower incidence of hypotension. Conclusion: In painless endoscopy, compared with propofol, ciprofol exhibited non-inferiority anesthesia/sedation in patients, and had a good safety profile with a lower incidence of pain on injection and may reduce the chance of hypotension. Trial sequential analysis suggested the need for more cases, and GRADE highlighted moderate certainty, emphasizing the necessity for further targeted RCTs. Systematic review registration: PROSPERO, CRD42023433627. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We aimed to investigate the surgical outcomes following inguinal and subinguinal urologic procedures under deep intravenous sedation (DIVS) with multimodal local anesthesia (LA). METHODS: We conducted a retrospective cohort study from September 2022 to December 2023 including adult patients deemed eligible for day surgery (American Society of Anesthesiologist score 1-3) undergoing radical orchiectomy (RO), microscopic varico- score 1-3) undergoing radical orchiectomy (RO), microscopic varico-celectomy (MV), or microscopic denervation of the spermatic cord (MDSC). All procedures were performed at a single urologic ambulatory surgical center and outpatient clinic, and by a single surgeon (PP). Procedures were performed through a subinguinal or inguinal approach with DIVS and adjunctive multimodal LA. We evaluated intraoperative complications and relevant surgical outcomes and parameters. RESULTS: A total of 103 patients were included in the analysis with a mean age ± standard deviation of 37.3±9.6. This included 25 patients who underwent RO, 54 patients who underwent MV, and 24 patients who underwent MDSC. All procedures were completed successfully without intraoperative complications. Oncologic outcomes were preserved, fertility outcomes improved, and pain scores reduced similarly to the expected rates in the literature. CONCLUSIONS: Our preliminary results demonstrate the safety, effectiveness, and feasibility of performing inguinal and subinguinal urologic procedures under DIVS with LA. These findings suggest that this technique preserves high-quality care while avoiding the unnecessary risks of general or spinal anesthesia, representing an opportunity to transfer these cases outside of hospitals' operating rooms into outpatient ambulatory centers. [ABSTRACT FROM AUTHOR]

Background: Most ovarian cancer cases are diagnosed at an advanced stage, leading to poor outcomes and a relatively low 5-year survival rate. While tumor resection in the early stages can be highly effective, recurrence following primary treatment remains a significant cause of mortality. Propofol is a commonly used intravenous anesthetic agent in cancer resection surgery. Previous research has shown that propofol anesthesia was associated with improved survival in patients undergoing elective surgery for epithelial ovarian cancer. However, the underlying antitumor mechanisms are not yet fully understood. Methods: This study aimed to uncover the antitumor properties of propofol alone and combined with cisplatin or doxorubicin, in human SKOV3 and OVCAR3 ovarian cancer cells. We applied flowcytometry analysis for mitochondrial membrane potential, apoptosis, and autophagy, colony formation, migration, and western blotting analysis. Results: Given that chemotherapy is a primary clinical approach for managing advanced and recurrent ovarian cancer, it is essential to address the limitations of current chemotherapy, particularly in the use of cisplatin and doxorubicin, which are often constrained by their side effects and the development of resistance. First of all, propofol acted synergistically with cisplatin and doxorubicin in SKOV3 cells. Moreover, our data further showed that propofol suppressed colony formation, disrupted mitochondrial membrane potential, and induced apoptosis and autophagy in SKOV3 and OVCAR3 cells. Finally, the effects of combined propofol with cisplatin or doxorubicin on mitochondrial membrane potential, apoptosis, autophagy, and epithelial-mesenchymal transition were different in SKOV3 and OVCAR3 cells, depending on the p53 status. Conclusion: In summary, repurposing propofol could provide novel insights into the existing chemotherapy strategies for ovarian cancer. It holds promise for overcoming resistance to cisplatin or doxorubicin and may potentially reduce the required chemotherapy dosages and associated side effects, thus improving treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: Open liver resection necessitates a substantial upper abdominal inverted-L incision, resulting in severe pain and compromising patient recovery. Despite the efficacy of epidural analgesia in providing adequate postoperative analgesia, the potential epidural-related adverse effects should be carefully considered. This study aims to compare the efficacy and safety of continuous epidural analgesia and intravenous analgesia in open liver resection. Methods: A retrospective study was conducted, collecting data from patients who underwent open liver resection between 2007 and 2017. Propensity score matching was implemented to mitigate confounding variables, with patients being matched in a 1:1 ratio based on propensity scores. The primary outcome was the comparison of postoperative morphine consumption at 24, 48, and 72 hours between the two groups. Secondary outcomes included pain scores, postoperative outcomes, and epidural-related adverse effects. Results: A total of 612 patients were included, and after matching, there were 204 patients in each group. Opioid consumption at 24, 48, and 72 hours postoperatively was statistically lower in the epidural analgesia group compared to the intravenous analgesia group (p < 0.001). However, there was no significant difference in pain scores (p = 0.422). Additionally, perioperative hypotension requiring treatment, as well as nausea and vomiting, were significantly higher in the epidural analgesia group compared to the intravenous analgesia group (p < 0.001). Conclusions: Epidural analgesia is superior to intravenous morphine in terms of reducing postoperative opioid consumption within the initial 72 h after open liver resection. Nevertheless, perioperative hypotension, which necessitates management, should be approached with consideration and vigilance. Trial registration: The study was registered in the Clinical Trials Registry at www.clinicaltrials.gov/, NCT number: NCT06301932. [ABSTRACT FROM AUTHOR]

To evaluate the propofol-sparing and hemodynamic effects of guaifenesin administered for co-induction of anesthesia in sheep. Prospective, blinded, two-way crossover experimental study. Thirteen healthy adult female sheep. Anesthesia was induced without premedication with intravenous (IV) guaifenesin 5% at 100 mg kg–1 (GGE) or an equivalent volume of physiologic saline (SAL), followed by IV propofol at a controlled rate (1 mg kg–1 min–1). Heart rate (HR), respiratory rate and oscillometric noninvasive arterial blood pressure (NIBP) were recorded at baseline after co-induction administration, following endotracheal intubation and every 2 minutes thereafter for 10 minutes. Propofol doses required to achieve intubation after each co-induction treatment were compared by independent Student's t -test. Values of p < 0.05 were considered statistically significant. The propofol dose required (mean ± standard deviation) to achieve intubation was significantly lower (p = 0.001) in the GGE treatment (3.40 ± 0.74 mg kg–1) than in the SAL treatment (5.94 ± 1.09 mg kg–1). HR was increased after anesthetic induction compared with baseline in both treatments. HR was generally lower in the GGE treatment than in the SAL treatment. NIBP did not vary between GGE and SAL treatments. Guaifenesin, when administered as a co-induction agent with propofol in sheep, reduces propofol dose requirements and maintains hemodynamic variables within a clinically acceptable range. [ABSTRACT FROM AUTHOR]

Abstract Background Postoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery. Methods One hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb. Discussion The current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD. Trial registration The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024.

Background Methods Results Conclusion Trials Registration Dexmedetomidine, an α2‐adrenergic agonist, reduces propofol and remifentanil requirements when used as an adjunct to total intravenous anesthesia in adults, but studies in a pediatric population are sparse. This study investigates the magnitude of dose‐sparing effects of a postinduction dexmedetomidine bolus on propofol and remifentanil requirements during pediatric surgery.In this randomized, double‐blind, controlled trial, children aged 2–10 years undergoing elective dental surgery were assigned to one of four groups: placebo, 0.25 mcg/kg dexmedetomidine, 0.5 mcg/kg dexmedetomidine, and 1 mcg/kg dexmedetomidine. Maintenance with fixed‐ratio propofol and remifentanil total intravenous anesthesia followed a bispectral index (BIS)‐guided algorithm designed to maintain a stable depth of anesthesia. The primary outcomes were time‐averaged maintenance infusion rates of propofol and remifentanil. Secondary outcomes in the postanesthetic care unit included sedation scores, pain scores, and time to discharge.Data from 67 patients were available for analysis. The median [interquartile range] propofol infusion rate was lower in the 1 mcg/kg dexmedetomidine group (180 [164–185] mcg/kg/min) versus placebo (200 [178–220] mcg/kg/min): percent change −10.0%; 95% CI −2.4 to −19.8; p = 0.013. The remifentanil infusion rate was also lower in the 1 mcg/kg dexmedetomidine group (0.089 [0.080, 0.095] mcg/kg/min) versus placebo (0.103 [0.095, 0.106] mcg/kg/min): percent change, −13.7%; 95% CI −5.47 to −21.0; p = .022. However, neither propofol nor remifentanil infusion rates were significantly different in the 0.25 or 0.5 mcg/kg dexmedetomidine groups. In the postanesthesia care unit, there were no differences in pain or sedation scores, and time to discharge was not significantly prolonged in any dexmedetomidine group.Dexmedetomidine 1 mcg/kg reduced the propofol and remifentanil requirements during maintenance of anesthesia in children when administered as a postinduction bolus.ClinicalTrials.gov: NCT03422978, date of registration 2018‐02‐06. [ABSTRACT FROM AUTHOR]

Background: Surgery for pediatric cleft lip and palate repair often utilizes high-dose opioids and inhaled anesthesia, thereby causing postoperative complications such as desaturation and/or severe agitation after anesthesia. These complications are detrimental to the child and medical personnel and cause tremendous psychologic stress to parents. Our aim is to decrease these complications through dexmedetomidine, an alpha-2 receptor agonist with anxiolytic, sympatholytic, and analgetic properties. Devoid of respiratory depressant effect, it allows patients to maintain effective ventilation and reduce agitation, postoperatively. Its unique anesthetic property may shed light on providing safe anesthesia and gentle emergence to this young, vulnerable population. Case presentation: A total of 21 patients of Sundanese ethnicity, aged 3 months to 8 years (9 males and 12 females), underwent cleft lip or cleft palate surgery using total intravenous dexmedetomidine. Anesthesia was induced using sevoflurane, fentanyl, and propofol, and airway was secured. Intravenous dexmedetomidine 1.5 μg/kg was administered within 10 minutes, and a maintenance dose of 1.5 μg/kg/hour was continued as the sole anesthetic maintenance agent thereafter. Hemodynamics and anesthetic depth using Patient State Index (SEDLine™ monitor, Masimo Corporation, Irvine, CA, USA) were monitored carefully throughout the surgical procedure. Dexmedetomidine did not cause any hemodynamic derangements or postoperative complications in any of our patients. We found agitation in 9.5% (2/21) of patients. Conclusion: Dexmedetomidine can be used as a total intravenous anesthetic agent to maintain anesthesia and provide gentle emergence to infants and young children undergoing cleft lip and palate repair. [ABSTRACT FROM AUTHOR]

Background: Surgical Patients and hospitals are now facing financial strain due to direct anesthetic demand as a result of the development of new anesthetic drugs, equipment, and techniques. Up to 15% of a hospital's pharmacy budget is currently allocated to anesthetic drug expenses. Drug wastage during anesthesia practice is a widespread hidden source of healthcare waste that leads to anesthetic drug shortages as well as poor operating room efficiency. On the other hand, despite the fact that it is preventable in the vast majority of cases, it is well described that drug wastage is routinely observed, including in developing countries where the consequences significantly affect both hospitals and patients. Methods: This review aims to review the prevalence of anesthetic drug waste across the world and systematically formulate and describe preventive strategies. Relevant publications were identified using systematic searches on databases including Google Scholar, Medline (PubMed), the Cochrane Library, and Embase. In addition, papers were detected and then selected through the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria guidelines and the inclusion and exclusion criteria. Using the predetermined terms and dates from the searching databases, a total of 504 articles were identified. Based on the screening criteria, 16 papers were considered eligible and included in the final review. In addition, the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis was used for evaluating the quality of selected articles. This study is registered on PROSPERO, number CRD42024497044. Results: Of the sixteen publications from eleven different nations that were considered suitable for inclusion, only two of them addressed the waste of inhalational anesthetics. In more than half of eligible articles, propofol was the frequently wasted drug that contributed to increased financial loss through drug waste. The first most significant factor contributing to the waste of intravenous and inhalational anesthetics was the disposal of multidrug vials following their use for a single patient and high fresh gas flow, respectively. Conclusion: Anesthetic medication waste is a common occurrence worldwide, despite the fact that it is expensive and has a significant negative impact on operating room efficiency. Because the majority of drug waste is avoidable, preventive measures may lower drug waste and improve patient and hospital efficiency. [ABSTRACT FROM AUTHOR]

Background: Postoperative nausea and vomiting (PONV) is a significant problem following paediatric surgery, and volatile anaesthetics are an important cause of this phenomenon. BIS-guided anaesthesia, by reducing the consumption of anaesthetics, leads to a decrease in PONV in adult patients. Study objective: Evaluate the role of BIS-guided anaesthesia in reducing the incidence of paediatric PONV. Design: Prospective, randomized, double-blind study. Setting: A single center study in university hospital in Czech republic, from June 2021 to November 2022. Patients: A total of 163 children, aged 3–8 years with ASA I-II who underwent endoscopic adenoidectomy under general anaesthesia were included. Interventions: In the intervention group, the depth of anaesthesia was maintained to values between 40 and 60 of BIS. Main outcome measure: The primary outcome was the incidence of postoperative nausea and vomiting during 24 h after surgery. Results: The use of BIS-guided anaesthesia led to a significant decrease in the incidence of nausea and vomiting compared to the control group [17% vs. 53%; RR (95%CI) 0.48 (0.27–0.86); p < 0.001and 16% vs. 34%; RR (95%CI) 0.33 (0.20–0.54); p = 0.01, respectively]. Conclusions: BIS-guided anaesthesia decreases the incidence of postoperative nausea and vomiting in children undergoing adenoidectomy. Trial registration: Clinicaltrials.gov identifier: NCT04466579. [ABSTRACT FROM AUTHOR]

Purpose: Awake extubation and deep extubation are commonly used anesthesia techniques. In this study, the safety of propofol-assisted deep extubation in the dental treatment of children was assessed. Materials and methods: Children with severe caries who received dental treatment under general anesthesia and deep extubation between January 2017 and June 2023 were included in this study. Data were collected on the following variables: details and time of anesthesia, perioperative vital signs, and incidence of postoperative complications. The incidence of laryngeal spasm (LS) was considered to be the primary observation indicator. Results: The perioperative data obtained from 195 children undergoing dental treatment was reviewed. The median age was 4.2 years (range: 2.3 to 9.6 years), and the average duration of anesthesia was 2.56 h (range 1 to 4.5 h). During intubation with a videoscope, purulent mucus was found in the pharyngeal cavity of seven children (3.6%); LS occurred in five of them (2.6%), and one child developed a fever (T = 37.8 °C) after discharge. Five children (2.6%) experienced emergence agitation (EA) in the recovery room. Also, 13 children (6.7%) experienced epistaxis; 10 had a mild experience and three had a moderate experience. No cases of airway obstruction (AO) and hypoxemia were recorded. The time to open eyes (TOE) was 16.3 ± 7.2 min. The incidence rate of complications was 23/195 (11.8%). Emergency tracheal reintubation was not required. Patients with mild upper respiratory tract infections showed a significantly higher incidence of complications (P < 0.001). Conclusions: Propofol-assisted deep extubation is a suitable technique that can be used for pediatric patients who exhibited non-cooperation in the outpatient setting. Epistaxis represents the most frequently encountered complication. Preoperative upper respiratory tract infection significantly increases the risk of complications. The occurrence of EA was notably lower than reported in other studies. [ABSTRACT FROM AUTHOR]

Objective: This review specifically investigates ketamine's role in SRSE management. Methods: PubMed, EMBASE, and Google Scholar databases were searched from inception to May 1st, 2023, for English-language literature. Inclusion criteria encompassed studies on SRSE in humans of all ages and genders treated with ketamine. Results: In this systematic review encompassing 19 studies with 336 participants, age ranged from 9 months to 86 years. Infections, anoxia, and metabolic issues emerged as the common causes of SRSE, while some cases had unknown origins, termed as NORSE (New Onset RSE) or FIRESs (Febrile Infection-Related Epilepsy Syndrome). Most studies categorized SRSE cases into convulsive (N = 105) and non-convulsive (N = 197). Ketamine was used after failed antiepileptics and anesthetics in 17 studies, while in others, it was a first or second line of treatment. Dosages varied from 0.5 mg/kg (bolus) and 0.2-15 mg/kg/hour (maintenance) in adults and 1-3 mg/kg (bolus) and 0.5-3 mg/kg/hour (maintenance) in pediatrics, lasting one to 30 days. Ketamine was concurrently used with other drugs in 40–100% of cases, most frequently propofol and midazolam. Seizure resolution rate varied from 53.3 to 91% and 40–100% in larger (N = 42–68) and smaller case series (N = 5–20) respectively. Seizure resolution occurred in every case of case report except in one in which the patient died. Burst suppression in EEG was reported in 12 patients from two case series and two case reports. Recurrence was reported in 11 patients from five studies. The reported all-cause mortality varied from 38.8 to 59.5% and 0-36.4% in larger and smaller case series., unrelated directly to ketamine dosage or duration. Significance: Ketamine demonstrates safety and effectiveness in SRSE, offering advantages over GABAergic drugs by acting on NMDA receptors, providing neuroprotection, and reducing vasopressor requirement. Key points: 1. Infection, anoxia and metabolic cause were the most commonly reported etiology 2. Ketamine showed better efficacy when administered earlier 3. Ketamine infusion significantly resulted in decreased vasopressor requirement [ABSTRACT FROM AUTHOR]

Background: Intra-operative anaesthesia management should be optimised to reduce the occurrence of postoperative nausea and vomiting in high-risk patients; however, a single intervention may not effectively reduce postoperative nausea and vomiting in such patients. This study assessed the effect of an optimised anaesthetic protocol versus a conventional one on postoperative nausea and vomiting in patients who underwent laparoscopic sleeve gastrectomy. Methods: A single-centre randomised trial was conducted at Peking University Shenzhen Hospital from June 2021 to December 2022. Among 168 patients who underwent laparoscopic sleeve gastrectomy, 116 qualified, and 103 completed the study with available data. Patients were categorized into the conventional group (received sevoflurane and standard fluids) and the optimised group (underwent propofol-based anaesthesia and was administered goal-directed fluids). The primary endpoints were postoperative nausea and vomiting incidence and severity within 24 h. Results: Postoperative nausea and vomiting assessment at 0–3 h post-surgery revealed no significant differences between groups. However, at 3–24 h, the optimised anaesthetic protocol group showed lower postoperative nausea and vomiting incidence and severity than those of the conventional group (P = 0.005). In the conventional group, 20 (37.04%) patients experienced moderate-to-severe postoperative nausea and vomiting, compared to six (12.25%) patients in the optimised group (odds ratio = 0.237; 95% CI = 0.086, 0.656; P = 0.006). No significant differences were noted in antiemetic treatment, moderate-to-severe pain incidence, anaesthesia recovery, post-anaesthetic care unit stay, or postoperative duration between the groups. While the total intra-operative infusion volumes were comparable, the optimised group had a significantly higher colloidal infusion volume (500 mL vs. 0 mL, P = 0.014) than that of the conventional group. Conclusions: The incidence and severity of postoperative nausea and vomiting 3–24 h postoperatively in patients who underwent laparoscopic sleeve gastrectomy were significantly lower with propofol-based total intravenous anaesthesia and goal-directed fluid therapy than with sevoflurane anaesthesia and traditional fluid management. Total intravenous anaesthesia is an effective multimodal antiemetic strategy for bariatric surgery. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC- 2,100,046,534, registration date: 21 May 2021). [ABSTRACT FROM AUTHOR]

Status epilepticus (SE) is a neurological emergency that requires timely pharmacological therapy to cease seizure activity. The treatment approach varies based on the time and the treatment stage of SE. Benzodiazepines are considered the first-line therapy during the emergent treatment phase of SE. Antiseizure medicines such as phenytoin, valproic acid, and levetiracetam are recommended during the urgent treatment phase. These drugs appear to have a similar safety and efficacy profile, and individualized therapy should be chosen based on patient characteristics. Midazolam, propofol, pentobarbital, and ketamine are continuous intravenous infusions of anesthetic medications utilized in the refractory SE (RSE) period. The most efficacious pharmacotherapeutic treatments for RSE and superrefractory status epilepticus are not clearly defined. [ABSTRACT FROM AUTHOR]

Background: Non-convulsive status epilepticus (NCSE) is defined as status epilepticus (SE) with no obvious motor phenomenon and is diagnosed based on electroencephalogram (EEG). Refractory SE (RSE) is the persistence of seizures despite treatment with an adequately dosed first-line and second-line agents. Although guidelines for convulsive RSE include third-line agents such as intravenous anesthetic drugs (midazolam, propofol, or barbiturates), the therapeutic approach to NCSE is not well outlined. Treatment with traditional anesthetics invariably includes endotracheal intubation, which is associated with significant adverse events. Comparatively, ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist is not associated with significant cardiorespiratory depression and may help in avoiding intubation. Objective: In this case series, we describe our experience with the early use of intravenous ketamine as the first anesthetic agent in patients with refractory NCSE to avoid endotracheal intubation. Methods: We present a case series of nine patients managed in the Neurointensive Care Unit at a university-affiliated tertiary care hospital. The study was approved by the hospital and university institutional review boards and the requirement for informed consent was waived for retrospective analysis of existing data, per institutional policy. All cases of SE were identified from a prospective database, and a subsequent retrospective chart review identified all patients with a diagnosis of refractory NCSE in whom ketamine was used as the first anesthetic agent. The primary endpoint was the avoidance of endotracheal intubation while on ketamine infusion. The secondary endpoint was defined as cessation of both clinical and electrographic seizures recorded on continuous EEG within 24 h of ketamine administration. Results: A total of nine patients experiencing refractory NCSE were included in this case series, with a median age of 61 (range 26–72) years and seven patients were male. The primary endpoint, avoiding intubation, was achieved in five out of nine (55%) cases. Six patients experienced resolution of refractory NCSE with ketamine administration as the sole anesthetic agent. Four patients required endotracheal intubation and three patients had a failure of seizure cessation with ketamine. Hypersalivation and pneumonia were the most common ketamine associated adverse events. In non-intubated patients, no deaths occurred. One patient was discharged home, four to subacute rehabilitation, one to a long term acute care hospital, and one patient to hospice. Conclusion: The use of ketamine as the primary anesthetic agent may be a reasonable option to avoid endotracheal intubation in a subset of patients with refractory NCSE. This study is limited by its small sample size, retrospective design, and reliance on information obtained from chart review. [ABSTRACT FROM AUTHOR]

Emergence delirium (ED) is a common mental complication during recovery from anesthesia. However, studies on the effects of esketamine, an intravenous anesthetic for pediatrics, on ED are still lacking. This study aimed to investigate the effects of a single-dose of esketamine during anesthesia induction on ED after minor surgery in preschool children. A total of 230 children (aged 2–7 years) completed the study. The exposed group (0.46 mg kg−1: average dose of esketamine) was associated with an increased incidence of ED and a higher maximum Pediatric Anesthesia Emergence Delirium score than the non-exposed group. The length of post-anesthesia care unit stay was longer in the exposed group than the non-exposed group. In contrast, extubation time, face, legs, activity, cry, and consolability (FLACC) scores, and the proportions of rescue analgesics were comparable between the two groups. Furthermore, five factors, including preoperative anxiety scores, sevoflurane and propofol compared with sevoflurane alone for anesthesia maintenance, dezocine for postoperative analgesia, FLACC scores, and esketamine exposure, were associated with ED. In conclusion, a near-anesthetic single-dose of esketamine for anesthesia induction may increase the incidence of ED in preschool children after minor surgery. The use of esketamine in preschool children for minor surgery should be noticed during clinical practice. [ABSTRACT FROM AUTHOR]

Esketamine is a widely used intravenous general anesthetic. However, its safety, particularly its effects on the heart, is not fully understood. In this study, we investigated the effects of esketamine exposure on zebrafish embryonic heart development. Zebrafish embryos were exposed to esketamine at concentrations of 1, 10, and 100 mg/L from 48 h post-fertilization (hpf) to 72 hpf. We found that after exposure, zebrafish embryos had an increased hatching rate, decreased heart rate, stroke volume, and cardiac output. When we exposed transgenic zebrafish of the Tg(cmlc2:EGFP) strain to esketamine, we observed ventricular dilation and thickening of atrial walls in developing embryos. Additionally, we further discovered the abnormal expression of genes associated with cardiac development, including nkx2.5, gata4, tbx5, and myh6, calcium signaling pathways, namely ryr2a, ryr2b, atp2a2a, atp2a2b, slc8a3, slc8a4a, and cacna1aa, as well as an increase in acetylcholine concentration. In conclusion, our findings suggest that esketamine may impair zebrafish larvae's cardiac development and function by affecting acetylcholine concentration, resulting in weakened cardiac neural regulation and subsequent effects on cardiac function. The insights garnered from this research advocate for a comprehensive safety assessment of esketamine in clinical applications. [ABSTRACT FROM AUTHOR]

Addictive properties of propofol have been demonstrated in both humans and animals. The nucleus accumbens (NAc) shell (NAsh) in the brain, along with the interactions between N‐methyl‐D‐aspartate receptor (NMDAR) and the dopamine D1 receptor (D1R), as well as their downstream ERK/CREB signalling pathway in the NAc, are integral in regulating reward‐seeking behaviour. Nevertheless, it remains unclear whether NMDARs and the NMDAR‐D1R/ERK/CREB signalling pathway in the NAsh are involved in mediating propofol addiction. To investigate it, we conducted experiments with adult male Sprague–Dawley rats to establish a model of propofol self‐administration behaviour. Subsequently, we microinjected D‐AP5 (a competitive antagonist of NMDARs, 1.0–4.0 μg/0.3 μL/site) or vehicle into bilateral NAsh in rats that had previously self‐administered propofol to examine the impact of NMDARs within the NAsh on propofol self‐administration behaviour. Additionally, we examined the protein expressions of NR2A and NR2B subunits, and the D1R/ERK/CREB signalling pathways within the NAc. The results revealed that propofol administration behaviour was enhanced by D‐AP5 pretreatment in NAsh, accompanied by elevated expressions of phosphorylation of NR2A (Tyr1246) and NR2B (Tyr1472) subunits. There were statistically significant increases in the expressions of D1Rs, as well as in the phosphorylated ERK1/2 (p‐ERK1/2) and CREB (p‐CREB). This evidence substantiates a pivotal role of NMDARs in the NAsh, with a particular emphasis on the NR2A and NR2B subunits, in mediating propofol self‐administration behaviour. Furthermore, it suggests that this central reward processing mechanism may operate through the NMDAR‐D1R/ERK/CREB signal transduction pathway. [ABSTRACT FROM AUTHOR]

To compare the perioperative analgesic effects of an opioid-free (OFA) and an opioid-sparing (OSA) anaesthetic protocol in dogs undergoing laparoscopic ovariectomy. Prospective, randomized, blinded, clinical trial. A group of 28 client-owned dogs. Dogs were allocated to one of two groups. The OFA group was administered intramuscular (IM) dexmedetomidine 5 μg kg–1 and ketamine 1 mg kg–1, followed by two intraoperative constant rate infusions (CRIs) of dexmedetomidine (3 μg kg–1 hour–1) and lidocaine (1 mg kg–1 loading dose, 2 mg kg–1 hour–1). The OSA group was administered IM dexmedetomidine 5 μg kg–1, ketamine 1 mg kg–1 and methadone 0.2 mg kg–1, followed by two intraoperative saline CRIs. In both groups, anaesthesia was induced with intravenous (IV) propofol 2 mg kg–1 and diazepam 0.2 mg kg–1 and maintained with isoflurane. Rescue dexmedetomidine (0.5 μg kg–1) was administered IV if there was a 20% increase in cardiovascular variables compared with pre-stimulation values. Ketorolac (0.5 mg kg–1) was administered IV when the surgery ended. Postoperative analgesia was evaluated using the Short Form-Glasgow Composite Measure Pain Scale and methadone (0.2 mg kg–1) was administered IM if the pain score was ≥ 6/24. Statistical analysis included mixed analysis of variance, Chi-square test and Mann–Whitney U test. There were no significant differences in the intraoperative monitored variables between groups. The OFA group showed a significantly lower intraoperative rescue analgesia requirement (p = 0.016) and lower postoperative pain scores at 3 (p =0.001) and 6 (p < 0.001) hours. No dogs were administered rescue methadone postoperatively. Although both groups achieved acceptable postoperative pain scores with no need for further intervention, the analgesic efficacy of the OFA protocol was significantly superior to that of the OSA protocol presented and was associated with a lower intraoperative rescue analgesia requirement and early postoperative pain scores. [ABSTRACT FROM AUTHOR]

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General anesthesia is widely applied in clinical practice. However, the precise mechanism of loss of consciousness induced by general anesthetics remains unknown. Here, we measured the dynamics of five neurotransmitters, including γ-aminobutyric acid, glutamate, norepinephrine, acetylcholine, and dopamine, in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective. Results revealed that the concentrations of γ-aminobutyric acid, glutamate, norepinephrine, and acetylcholine increased in the cortex during propofo-linduced loss of consciousness. Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia. Notably, the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness. Furthermore, the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups. These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the effects of intravenous anesthetic drugs on fertilization rate in subjects receiving oocyte retrieval by assisted reproduction technology (ART). Methods: A retrospective cohort study was designed. The clinical information of subjects who received oocyte retrieval procedure was collected. The subjects were divided into two groups based on the type of anesthesia used: the no-anesthesia group and the intravenous anesthesia group. Propensity score matching (PSM) was performed and multiple linear regression analyses were conducted. Fertilization rate was compared between the two groups before and after PSM. Results: A total of 765 subjects were divided into two groups: the no-anesthesia group (n = 482) and the intravenous anesthesia group (n = 283). According to propensity scores, 258 pairs of subjects were well matched, and the baseline data between the two groups were not significantly different (P > 0.05). Fertilization rate was 77% in the intravenous anesthesia group, and 76% in the no-anesthesia group, without significant between-group difference (P = 0.685). Before matching, Poisson regression analysis showed no effect of intravenous anesthetic drugs on fertilization rate (RR = 0.859, 95%CI: 0.59 to 1.25, P = 0.422). After matching, no difference was found either (RR = 0.935, 95%CI: 0.67 to 1.29, P = 0.618). Conclusion: Intravenous anesthetic drugs may exert no effects on fertilization rate in subjects receiving ART. [ABSTRACT FROM AUTHOR]

The adverse effects of general anesthesia on the long-term cognition of young children and senior adults have become of concern in recent years. Previously, mechanistic and pathogenic investigations focused on neurons, and little is known about the effect of commonly used intravenous anesthetics such as propofol and ketamine on astrocytes. Recently, astrocyte dysfunction has been implicated in a wide range of age-related brain diseases. In this study, we examined the survival and viability of both young and senescent astrocytes in culture after adding propofol and ketamine to the media at varying strengths. Oxidative stimulus was applied to commercially available fetal cell lines of human astrocytes in vitro to induce morphological changes in cellular senescence. Our results indicate that propofol reduces the survival of young astrocytes as compared to controls, as well as to ketamine. These effects were seen in comparisons of total cell count and at both high and low dose concentrations. High doses of propofol also significantly reduced cell viability compared to those exposed to baseline controls and ketamine. Senescent astrocytes, on the other hand, demonstrated cell count reductions as compared to baseline controls and ketamine when exposed to either DMSO or propofol. The data show differential susceptibility of young astrocytes to propofol than to ketamine. The observed cell count reduction may be related to the adverse effects of propofol on mitochondrial function and free radical production, as described in previous studies. We speculate that ketamine may have a more favorable safety profile in infants and young children. [ABSTRACT FROM AUTHOR]

In this paper, we present the development and the validation of a novel index of nociception/anti-nociception (N/AN) based on skin impedance measurement in time and frequency domain with our prototype AnspecPro device. The primary objective of the study was to compare the Anspec-PRO device with two other commercial devices (Medasense, Medstorm). This comparison was designed to be conducted under the same conditions for the three devices. This was carried out during total intravenous anesthesia (TIVA) by investigating its outcomes related to noxious stimulus. In a carefully designed clinical protocol during general anesthesia from induction until emergence, we extract data for estimating individualized causal dynamic models between drug infusion and their monitored effect variables. Specifically, these are Propofol hypnotic drug to Bispectral index of hypnosis level and Remifentanil opioid drug to each of the three aforementioned devices. When compared, statistical analysis of the regions before and during the standardized stimulus shows consistent difference between regions for all devices and for all indices. These results suggest that the proposed methodology for data extraction and processing for AnspecPro delivers the same information as the two commercial devices. [ABSTRACT FROM AUTHOR]

Remimazolam, a novel intravenous anesthetic, has been proven to be safe and efficacious in the gastroscopy setting among the elderly. However, reports comparing the effectiveness and safety of using equivalent doses of remimazolam with propofol have not been seen. The aim of this study was to compare the sedation efficacy and safety of the 95% effective doses (ED95) of remimazolam versus propofol combined with sufentanil in the gastroscopy setting among the elderly. In the first step of this two-step study, a modified up-and-down method was used to calculate the ED95 of remimazolam and propofol when combined with 0.1 µg/kg sufentanil in inhibiting body movement of elderly patients undergoing gastroscopy. In the second step, ED95 of both agents calculated in the first step were administered, endpoints of efficacy, safety, and incidence of adverse events were compared. A total of 46 individuals completed the first step. The ED95 of remimazolam was 0.163 mg/kg (95% CI 0.160–0.170 mg/kg), and that of propofol was 1.042 mg/kg (95% CI 1.007–1.112 mg/kg). In the second step, 240 patients completed the trial. The anesthetic effective rates of the remimazolam group and the propofol group were 78% and 83%, respectively, with no statistical difference (P = 0.312). Patients in the remimazolam group had more stable circulatory functions (P < 0.0001) and a lower incidence of pain on injection (3.3% vs. 19.5%, P < 0.0001). The incidence of hypotension was low in the remimazolam versus propofol group (15.6% vs. 39.0%, P < 0.0001). Overall adverse event was low in the remimazolam versus propofol group (21.3% vs. 62.7%, P < 0.0001).In this study, we found that when anesthesia was administered to elderly gastroscopy patients based on 95% effective doses of remimazolam and propofol, remimazolam was as effective as propofol, but was safer with a lower incidence of adverse events. Study registration: Chinese Clinical Trial Registry, ChiCTR2000034234. Registered 29/06/2020, https://www.chictr.org.cn. [ABSTRACT FROM AUTHOR]

Background: HSK3486 (ciprofol), a new candidate drug similar to propofol, exerts sedative and hypnotic effects through gamma-aminobutyric acid type A receptors; however, its potential role in colorectal cancer is currently unknown. Aims: This study aimed to evaluate the effects of HSK3486 on colorectal cancer cell proliferation. Methods: Imaging was performed to detect reactive oxygen species and mitochondrial membrane potential. Western blotting was used to determine the expression of target signals. The HSK3486 molecular mechanism was investigated through ATPase inhibitory factor 1 knockdown and xenograft model experiments to assess mitochondrial function in colorectal cancer cells. Results: Cell Counting Kit-8 and Annexin V/propidium iodide double staining assays showed that HSK3486 inhibited colorectal cancer cell proliferation in a concentration-dependent manner. In addition, HSK3486 treatment increased the expression of B-cell lymphoma-2-associated X, cleaved caspase 3, and cleaved poly (ADP-ribose) polymerase, whereas myeloid cell leukemia-1 and B-cell lymphoma 2 expression decreased. HSK3486 promoted mitochondrial dysfunction by inducing ATPase inhibitor factor 1 expression. Furthermore, HSK3486 promoted oxidative stress, as shown by the increase in reactive oxygen species and lactate dehydrogenase levels, along with a decrease in mitochondrial membrane potential and ATP levels. ATPase inhibitor factor 1 small interfering RNA pretreatment dramatically increased the mitochondrial membrane potential and tumor size in a xenograft model following exposure to HSK3486. Conclusion: Collectively, our findings revealed that HSK3486 induces oxidative stress, resulting in colorectal cancer cell apoptosis, making it a potential candidate therapeutic strategy for colorectal cancer. [ABSTRACT FROM AUTHOR]

The C(sp2)-aryl sulfonate functional group is found in bioactive molecules, but their synthesis can involve extreme temperatures (>190 °C or flash vacuum pyrolysis) and strongly acidic reaction conditions. Inspired by the 1917 Tyrer industrial process for a sulfa dye that involved an aniline N(sp2)-SO3 intermediate en route to a C(sp2)-SO3 rearranged product, we investigated tributylsulfoammonium betaine (TBSAB) as a milder N-sulfamation to C-sulfonate relay reagent. Initial investigations of a stepwise route involving TBSAB on selected anilines at room temperature enabled the isolation of N(sp2)-sulfamate. Subsequent thermal rearrangement demonstrated the intermediary of a sulfamate en route to the sulfonate; however, it was low-yielding. Investigation of the N-sulfamate to C--sulfonate mechanism through control experiments with variation at the heteroatom positions and kinetic isotope experiments (KIEH/D) confirmed the formation of a key N(sp2)-SO3 intermediate and further confirmed an intermolecular mechanism. Furthermore, compounds without an accessible nitrogen (or oxygen) lone pair did not undergo sulfamation- (or sulfation) -to-sulfonation under these conditions. A one-pot sulfamation and thermal sulfonation reaction was ultimately developed and explored on a range of aniline and heterocyclic scaffolds with high conversions, including N(sp2)-sulfamates (O(sp2)-sulfates) and C(sp2)-sulfonates, in up to 99 and 80% (and 88% for a phenolic example) isolated yield, respectively. Encouragingly, the ability to modulate the ortho-para selectivity of the products obtained was observed under thermal control. A sulfonated analog of the intravenous anesthetic propofol was isolated (88% yield), demonstrating a proof-of-concept modification of a licensed drug alongside a range of nitrogen- and sulfur-containing heterocyclic fragments used in drug discovery. [ABSTRACT FROM AUTHOR]

Processed electroencephalographic indices such as the Patient State Index (PSi) have been proposed as a method of monitoring the depth of general anaesthesia. However, in order to establish the validity of PSi, it is necessary to compare its accuracy to other techniques, such as the isolated forearm technique (IFT). 30 ASA (American Society of Anaesthesiologists classification) I–III patients were administered standard propofol-sevoflurane anaesthesia with PSi monitoring. Before each dose of muscle relaxant, the forearm contralateral to the intravenous cannula was isolated for 30 minutes. PSi, hand movements, and exhaled sevoflurane concentrations were recorded during the induction of anaesthesia, intubation, throughout the surgical procedure, prior to extubation, and patients' responses to commands were classified as positive or negative. The Brice questionnaire was used to assess intraoperative awareness after the patient regained consciousness. All patients completed the study without memory of the surgery or IFT commands, 53.3% of patients showed a response to IFT commands during intubation. PSi values ranged around 26 (23.5; 30) in IFT non-responders and 33.5 (26; 42) in responders (p = 0.15). The best cut-off value for PSi to predict IFT response was 55, with a sensitivity of 60% and specificity of 85.2%, which led to the conclusion that PSi is not a fully reliable tool for monitoring the depth of anaesthesia. [ABSTRACT FROM AUTHOR]

Background: Postoperative nausea and vomiting (PONV) following atrial fibrillation (AF) ablation can cause considerable distress. Aim: Continuous intravenous propofol sedation with adaptive servo-ventilation (ASV) with or without an analgesic, pentazocine, during AF ablation was studied in 272 consecutive patients with paroxysmal, persistent, and long-standing persistent AF. The study objectives were to determine the incidence of PONV after AF ablation and to assess the predictive value of factors for PONV using the area under the receiver operating characteristic curve (AUC). Results: The present sedation maneuver was successfully accomplished with a low incidence of hypotension and without discontinuation of ablation or switching to general anesthesia, while maintaining an acceptable procedural time (102 ± 32 min). The incidence of PONV was 5.5% (15/272). Nausea occurred in nine patients after an average of 4.6 ± 3.5 h (range: 2-12 h) postablation, and vomiting with nausea occurred in six patients after an average of 4.5 ± 3.1 h (range: 1-9 h) postablation. The postablation interval did not differ significantly between the occurrence of nausea and nausea accompanied by vomiting. AUCs based on various factors, including the Apfel score, ranged from 0.55 to 0.67, indicating low accuracy in predicting PONV occurrence. Conclusions: The incidence of PONV after propofol sedation with ASV was the lowest (5.5%) reported to date. Scoring systems, which included the Apfel score, were ineffective in predicting PONV. The low PONV incidence in addition to the efficacy of propofol sedation with ASV revealed the adequacy of this regimen for AF ablation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Patients diagnosed with stage III breast cancer often undergo surgery, radiation therapy, and chemotherapy as part of their treatment. The choice of anesthesia technique during surgery has been a subject of interest due to its potential association with immune changes and prognosis. In this study, we aimed to compare the mortality rates between stage III breast cancer patients undergoing surgery with propofol-based intravenous general anesthesia and those receiving inhaled anesthetics. Methods: Using data from Taiwan's National Health Insurance Research Database and Taiwan Cancer Registry, we identified a cohort of 10,896 stage III breast cancer patients. Among them, 1,506 received propofol-based intravenous anesthetic maintenance, while 9,390 received inhaled anesthetic maintenance. To ensure comparability between the two groups, we performed propensity-score matching. Results: Our findings revealed a significantly lower mortality rate in patients who received inhaled anesthetics compared to those who received propofol-based intravenous anesthesia. Sensitivity analysis further confirmed the robustness of our results. Conclusions: This study suggests that inhaled anesthesia technique is associated with a lower mortality rate in clinical stage III breast cancer. Further research is needed to validate and expand upon these results. [ABSTRACT FROM AUTHOR]

General anesthetics were first used over 170 years ago; however, the mechanisms of how general anesthetics induce loss of consciousness (LOC) remain unclear. Ciprofol, a novel intravenous anesthetic, has been developed by incorporating cyclopropyl into the chemical structure of propofol. This modification offers the benefits of rapid onset and minimal injection pain. Recent studies have revealed that the glutamatergic neurons of the lateral habenula (LHb) play a crucial role in modulating the LOC induced by propofol and sevoflurane. Nevertheless, the specific involvement of LHb in the anesthetic effects of ciprofol remains uncertain. Here, using targeted recombination in active populations (TRAP) combined with electroencephalogram/electromyography recordings and the righting reflex behavioral test, our study revealed that intravenous infusion of ciprofol for 1 h could lead to the induction of c-Fos expression in the LHb in mice. The combination of TRAP and gene ablation, aimed at selectively ablating ciprofol-activated neurons in the LHb, has been shown to facilitate the emergence of ciprofol anesthesia and decrease the proportion of delta waves during the emergence phase. Chemogenetic inhibition of these neurons produced a comparable effect, whereas chemogenetic activation resulted in the opposite outcome. Chemogenetic activation of ciprofol-activated neurons in the LHb delays the emergence of anesthesia and induces a deep hypnotic state during the emergence phase. Taken together, our findings suggest that LHb ciprofol-activated neurons modulate the state of consciousness and could potentially be targeted to manipulate consciousness during ciprofol anesthesia. [ABSTRACT FROM AUTHOR]

Background: Anesthetic agents, particularly intravenous anesthetics, may affect immune function and tumorigenic factors. We herein investigated whether the anti‐inflammatory effects of anesthetic agents are attributed to their antioxidant properties. The antioxidant and anti‐inflammatory effects of remimazolam, a new anesthetic, remain unclear. We hypothesized that remimazolam exerts anti‐inflammatory effects due to its antioxidant properties, which may affect the postoperative inflammatory response. This retrospective clinical study examined this hypothesis using laboratory and clinical approaches. Methods: The antioxidant effects of remimazolam and dexmedetomidine were assessed by electron spin resonance (ESR) spectroscopy, and postoperative inflammatory responses were compared in 143 patients who underwent transcatheter aortic valve replacement at Kindai University Hospital between April 2021 and December 2022. The primary endpoint was the presence or absence of the antioxidant effects of the anesthetics themselves using ESR. Results: Remimazolam at clinical concentrations exerted antioxidant effects, whereas dexmedetomidine did not. Increases in C‐reactive protein (CRP) levels on POD3 from preoperative values were significantly smaller in the remimazolam group than in the dexmedetomidine group (1.33 ± 1.29 vs. 2.17 ± 1.84, p =.014). Conclusions: Remimazolam exerted stronger anti‐inflammatory effects than dexmedetomidine, and these effects were enhanced by its antioxidant properties, which may have affected postoperative CRP production. [ABSTRACT FROM AUTHOR]

Objective: To describe seizure activity in juvenile dogs successfully weaned from long‐term mechanical ventilation. Case Series Summary: Three juvenile dogs (all approximately 3 months old) underwent long‐term mechanical ventilation with IV anesthesia for suspected noncardiogenic pulmonary edema. Within 24 hours of extubation and within 10 hours of discontinuing midazolam continuous infusions, all dogs experienced seizures, which is 1 sign of iatrogenic withdrawal syndrome. Each dog was treated with an anticonvulsant protocol, and none experienced seizures after being discharged. New or Unique Information Provided: Each dog received IV anesthesia, including fentanyl, dexmedetomidine, midazolam, and propofol, during mechanical ventilation and subsequently experienced seizures after successful weaning from mechanical ventilation. Juvenile dogs may be at risk for seizures after weaning from mechanical ventilation and IV anesthesia. Neurological monitoring and further research into an appropriate weaning protocol may prove beneficial in juvenile dogs requiring prolonged anesthesia. [ABSTRACT FROM AUTHOR]

Intestinal ischemia-reperfusion injury (IRI) is a potentially severe clinical syndrome after major surgical procedures. In addition to causing intestinal mucosa injury, intestinal IRI further damages distant organs, causing the severity of the condition in patients. So far, effective therapy for intestinal IRI is still absent, and the survival rate of the patients is low. Previous experimental studies have shown that some anesthetics can alleviate intestinal IRI and protect organs while exerting their pharmacological effects, indicating that reasonable perioperative anesthesia management may provide potential benefits for patients to avoid intestinal IRI. These meaningful findings drive scholars to investigate the mechanism of anesthetics in treating intestinal IRI in-depth to discuss the possible new clinical uses. In the present mini-review, we will introduce the protective effects of different anesthetics in intestinal IRI to help us enrich our knowledge in this area. [ABSTRACT FROM AUTHOR]

Processed electroencephalogram (pEEG) is a record of electrical activity of the brain. In certain circumstances, it can reflect pathophysiological alterations and hemodynamic compromise. A 79-year-old woman diagnosed with subarachnoid hemorrhage and postcardiac arrest status was transferred for emergency ventriculostomy. The frontal monitoring with pEEG (SedLine, Masimo) from baseline showed low frontal activity, left and right spectral edge frequency (SEF) without numerical value, low activity in bilateral density spectral array (DSA), and zero in the patient state index (PSI). After ventricular puncture and placement of the ventriculostomy system, the pEEG showed an increase in the frequency and amplitude of the four-channel waveform of the pEEG, DSA, and numerical value of SEF and PSI. The use of pEEG can determine the depth of anesthesia and perhaps detect various cerebral and systemic pathophysiological and hemodynamic alterations; however, single monitoring may not be as predictive, so the use of multimodal monitoring is recommended. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the effect of esketamine on the dose–effect relationship between remifentanil and the cardiovascular response to endotracheal intubation during target-controlled infusion (TCI) of propofol. Methods: Patients underwent elective gynecological laparoscopic surgery under general anesthesia with endotracheal intubation, aged 18–65 years, American Society of Anesthesiologists class I or II, 18 kg/m2 ≤ body mass index ≤ 30 kg/m2, were randomly divided into the control (group C) and esketamine groups (group E). Before anesthesia induction, group E received an intravenous injection of 0.3 mg/kg of esketamine, while group C received an equal dose of physiological saline. TCI of propofol to the effect-site concentration (EC) of 3.0 μg/mL, and then TCI of remifentanil to the effect room and intravenous injection of rocuronium 0.6 mg/kg after MOAA/S was 0. Endotracheal intubation was performed after 2 min. Dixon's modified sequential method was used, and the initial EC of remifentanil was 3.0 ng/mL. The EC of remifentanil was determined according to the intubation response of the previous patient, with an adjacent concentration gradient of 0.3 ng/mL. The EC50 and EC95 values and their 95% confidence intervals (CIs) were determined using probit regression analysis. Results: The EC50 for cardiovascular response inhibition to endotracheal intubation using remifentanil was 3.91 ng/mL (95% CI: 3.59–4.33 ng/mL) and EC95 was 4.66 ng/mL (95% CI: 4.27–6.23 ng/mL) with TCI of propofol 3.0 μg/mL. After intravenous administration of 0.3 mg/kg of esketamine, the EC50 of remifentanil was 3.56 ng/mL (95% CI: 3.22–3.99 ng/mL) and EC95 was 4.31 ng/mL (95% CI: 3.91–5.88 ng/mL). Conclusions: Combined with TCI of propofol 3.0 μg/mL for anesthesia induction, esketamine significantly reduced the EC50 and EC95 of remifentanil to inhibit the cardiovascular response to endotracheal intubation. Trial registration: The trial was registered in the Chinese Clinical Trials Registry (www.chictr.org.cn; registration number: ChiCTR2200064932; date of registration:24/10/2022). [ABSTRACT FROM AUTHOR]

Randomized controlled trials have shown a higher risk of postoperative hypoxemia and delayed extubation with opioid‐free anesthesia (OFA), compared with opioid anesthesia. The practice of OFA is not standardized. The objective of this study is to investigate the association between the dexmedetomidine administration protocol used and the occurrence of postoperative respiratory complications. This work is a retrospective, propensity score‐adjusted study (inverse probability of treatment weighting) conducted between January 2019 and September 2021 in a French tertiary care university hospital, including 180 adult patients undergoing major digestive surgery. Comparison of 2 anesthesia protocols: with a continuous intravenous maintenance dose of dexmedetomidine following a bolus (group B+M, n = 105) or with a bolus dose alone (group B, n = 75). The main outcome measure was a composite respiratory end point within 24 hours of surgery. There was no significant difference in the incidence of overall respiratory complications, as assessed by the primary end point. Nevertheless, there were more patients with postoperative hypercapnia in group B+M than in group B (16% vs 2.5%, P =.004). Patients in group B+M were extubated later than patients in group B (group B+M, median 40 minutes, IQR 20‐74 minutes; group B, median 20 minutes, IQR 10‐50 minutes; P =.004). Our study showed negative results for the primary end point. However, data on the increased risk of postoperative hypercapnia in patients receiving a maintenance dose of dexmedetomidine are new. Other prospective randomized studies with greater power are necessary to confirm these data and to make OFA safer, by reducing the prescribed doses of dexmedetomidine. [ABSTRACT FROM AUTHOR]

Rationale: A subanesthetic dose of ketamine, a non-competitive N-methyl-D-aspartate glutamate receptor (NMDAR) antagonist, elicits dissociation in individuals with posttraumatic stress disorder (PTSD), who also often suffer from chronic dissociative symptoms in daily life. These debilitating symptoms have not only been linked to worse PTSD trajectories, but also to increased resting-state functional connectivity (RSFC) between medial prefrontal cortex (mPFC) and amygdala, supporting the conceptualization of dissociation as emotion overmodulation. Yet, as studies were observational, causal evidence is lacking. Objectives: The present randomized controlled pilot study examines the effect of ketamine, a dissociative drug, on RSFC between mPFC subregions and amygdala in individuals with PTSD. Methods: Twenty-six individuals with PTSD received either ketamine (0.5mg/kg; n = 12) or the control drug midazolam (0.045mg/kg; n = 14) during functional magnetic resonance imaging (fMRI). RSFC between amygdala and mPFC subregions, i.e., ventromedial PFC (vmPFC), dorsomedial PFC (dmPFC) and anterior-medial PFC (amPFC), was assessed at baseline and during intravenous drug infusion. Results: Contrary to pre-registered predictions, ketamine did not promote a greater increase in RSFC between amygdala and mPFC subregions from baseline to infusion compared to midazolam. Instead, ketamine elicited a stronger transient decrease in vmPFC-amygdala RSFC compared to midazolam. Conclusions: A dissociative drug did not increase fronto-limbic RSFC in individuals with PTSD. These preliminary experimental findings contrast with prior correlative findings and call for further exploration and, potentially, a more differentiated view on the neurobiological underpinning of dissociative phenomena in PTSD. [ABSTRACT FROM AUTHOR]

Purpose: Various basic and clinical studies have investigated the association between the types of anesthetic agents and prognosis. However, the results have varied among studies and remain controversial. In the present study, we aimed to investigate whether the risk of all-cause mortality differs between inhaled or intravenous anesthetics in patients with gastric cancer undergoing gastrectomy. Methods: Using a Japanese nationwide insurance claims database, we analyzed patients who underwent gastrectomy under general anesthesia for gastric cancer between January 2005 and September 2019. Postoperative outcomes were compared between two groups: those who received inhaled anesthetics (Sevoflurane, Isoflurane, or Desflurane) and those who received intravenous anesthetics (propofol), using a multivariable Cox proportional hazards model. The primary outcome was overall survival. Results: Among 2671 eligible patients, 2105 were in the inhaled anesthetic group, and 566 were in the intravenous anesthetic group. The median (interquartile range) age was 58 (51–63) years, and 1979 (74.1%) were men. The median follow-up period was 795 days. We identified 56 (2.7%) and 16 (2.8%) deaths during the follow-up period in the inhaled and intravenous anesthetic use groups, respectively. There was no difference in postoperative overall survival between the two groups (hazard ratio, 0.97; 95% confidence interval, 0.56–1.70; P = 0.93). Conclusions: We found no significant difference in the postoperative risks of overall survival between inhaled and intravenous anesthesia in patients with gastric cancer undergoing gastrectomy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Quadratus lumborum block (QLB) has been found to be advantageous for laparoscopic colorectal surgery. This study hypothesized that preoperative anterior QLB at lateral supraarcuate ligament (QLB-LSAL) would decrease postoperative opioid usage and offer improved analgesia within the context of multimodal analgesia compared with lateral QLB (LQLB) for laparoscopic colorectal surgery. STUDY DESIGN: In this randomized controlled trial, 82 American Society of Anesthesiologists physical status I to III class colorectal cancer patients undergoing laparoscopic radical resection were enrolled and randomly assigned to receive either LQLB or QLB-LSAL (0.375% ropivacaine 0.3 mL/kg bilaterally for each group). The primary outcomes were the total intravenous morphine equivalent consumption at 24 hours postoperatively. RESULTS: Intravenous morphine equivalent consumption at 24 hours postoperatively was significantly reduced in the QLB-LSAL group compared with that in the LQLB group with per-protocol analysis (29.2 ± 5.8 vs 40.5 ± 9.6 mg, p < 0.001) and intention-to-treat analysis (29.6 ± 6.1 vs 40.8 ± 9.5 mg, p < 0.001). Time to first patient-controlled analgesia request was notably longer in the QLB-LSAL group than that in the LQLB group (10.4 ± 3.9 vs 3.7 ± 1.5 hours, p < 0.001). CONCLUSIONS: Preoperative bilateral ultrasound-guided QLB-LSAL reduces morphine usage and extends the duration until the first patient-controlled analgesia demand within the framework of multimodal analgesia when compared with LQLB after laparoscopic colorectal surgery. [ABSTRACT FROM AUTHOR]

Propofol is the most widely used intravenous general anesthetic; however, the neuronal circuits that mediate its anesthetic effects are still poorly understood. Glutamatergic neurons in the lateral hypothalamus have been reported to be involved in maintenance of arousal and consciousness. Using Vglut2- Cre transgenic mice, we recorded this group of cells specifically and found that propofol can directly inhibit the glutamatergic neurons, and enhance inhibitory synaptic inputs on these cells, thereby reducing neuronal excitability. Through chemogenetic interventions, we found that inhibition of these neurons increased the duration of propofol-induced anesthesia and reduced movement in the animals after the recovery of right reflex. In contrast, activating this group of cells reduced the duration of propofol anesthesia and increased the animals' locomotor activity after the recovery of right reflex. These results suggest that propofol-induced anesthesia involves the inhibition of glutamatergic neurons in the lateral hypothalamus. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]