Perioperative management of bariatric surgery patients presents multiple challenges for anesthesiologists, particularly optimizing airway and respiratory outcomes. This study investigated the feasibility of esketamine-led opioid-free anesthesia (OFA) for bariatric surgery and assessed postoperative pulmonary complications (PPCs). Patients scheduled for laparoscopic bariatric surgery under combined intravenous–inhalation anesthesia were randomized to receive either esketamine-led OFA (S-Ket group) or opioid-balanced anesthesia with sufentanil and remifentanil (SR-Fen group). The primary outcome was post-surgical PPC incidence, and secondary outcomes were total morphine milligram equivalents (MME) and visual analogue scale (VAS) pain scores at multiple postoperative times. Of the 263 patients screened, 100 were enrolled. Incidence of PPCs was significantly lower in the S-Ket group than the SR-Fen group (26.0

Abstract Metabolic syndrome (MetS)-associated cognitive impairment is a growing global health crisis. The hippocampus is particularly vulnerable to metabolic stress, yet the precise molecular mechanisms linking systemic metabolic dysfunction to cognitive decline remain unclear. High-mobility group box 1 (HMGB1), a damage-associated molecule, is elevated in MetS. However, its specific role in simultaneously regulating hippocampal neuronal ferroptosis and microglial activation is poorly defined. Here we show that HMGB1 exacerbates MetS-associated cognitive impairment by promoting both neuronal ferroptosis and microglial inflammation. Using a high-fat high-glucose diet mouse model and primary co-cultures, we found that HMGB1 neutralization alleviated cognitive deficits, reduced neuronal ferroptosis, and suppressed microglial activation. Mechanistically, extracellular HMGB1 acts through neuronal toll-like receptor 4 (TLR4) to trigger the ubiquitination and degradation of nuclear factor erythroid 2-related factor 2 (NRF2). This HMGB1-induced loss of NRF2 impairs autophagic flux, thereby aggravating ferroptosis and neuroinflammation. Furthermore, in vitro conditioned medium experiments revealed a reciprocal pathological aggravation, where ferroptotic neurons and activated microglia both secrete HMGB1 to exacerbate each other's pathological state. These findings position HMGB1 as a pivotal mediator linking metabolic stress specifically to neuronal ferroptosis and neuroimmune activation. Targeting the HMGB1-NRF2-autophagic flux axis therefore offers a promising therapeutic strategy for mitigating cognitive impairment in patients with MetS.

Postoperative Cognitive Dysfunction (POCD) is a neurocognitive complication after anaesthesia and surgery, with oxidative stress as a key pathological driver. Nuclear factor erythroid-related factor 2 (Nrf2) and Thioredoxin-Interacting Protein (TXNIP) are critical regulators of oxidative stress and inflammation, and TXNIP directly facilitates NLRP3 inflammasome activation. Using an 18-month-old mouse model of POCD established by tibial fracture surgery, we investigated the changes in the expression of TXNIP and the regulatory mechanism of the Nrf2/TXNIP/NLRP3 signaling pathway. Cognitive function was assessed by the Morris water maze test, and hippocampal samples were analyzed for protein levels(Nrf2, TXNIP, and NLRP3 inflammasome-related protein), pro-inflammatory factors (IL-1β and IL-18), Reactive Oxygen Species (ROS), and neuronal apoptosis. Anesthesia/surgery significantly upregulated TXNIP expression. Inhibiting TXNIP with verapamil attenuated oxidative stress, neuronal injury, and NLRP3 inflammasome activation, thereby ameliorating cognitive impairment. Similarly, sulforaphane (SFN)-mediated upregulation of Nrf2 suppressed TXNIP expression, decreased NLRP3 inflammasome-related proteins and pro-inflammatory factors, and alleviated cognitive deficits. These findings demonstrate thatthe Nrf2/TXNIP/NLRP3 axis mediates hippocampal oxidative stress and pyroptosis in POCD pathogenesis, highlighting this pathway as a potential therapeutic target.

BACKGROUND:Older surgical patients are at risk because of age-related physiologic decline and comorbidities. Some guidelines recommend Bispectral Index (BIS; Medtronic, USA) monitoring to optimize anesthetic depth, but robust evidence supporting improved outcomes is lacking. METHODS:A randomized, multicenter, double-blind trial was conducted across 21 tertiary-care hospitals in China (March 17, 2015, to February 5, 2022). Patients aged 65 yr or older scheduled for elective noncardiac surgery (American Society of Anesthesiologists [ASA] Physical Status I to IV) were randomized 1:1 to BIS-guided or routine anesthetic management. In patients assigned to BIS guidance, hypnotic depth was adjusted to maintain BIS between 40 and 60. Hypnotic depth in patients assigned to routine care per clinical judgment with masked BIS monitors. The primary outcome was 1-yr all-cause mortality. Secondary outcomes included moderate-to-severe complications within 30 days, functional independence, quality of life, the duration of postoperative critical care, the duration of postoperative hospitalization, unplanned intensive care unit admission, and hospital cost. RESULTS:Among 6,982 patients (mean ± SD age, 71 ± 5 yr), BIS values averaged 47 (BIS-guided) versus 46 (routine). One-year mortality was similar in BIS-guided patients (10.2% [356 of 3,485]) and routinely managed patients (10.0% [351 of 3,497]; hazard ratio, 1.02; 95% CI, 0.88 to 1.17; P = 0.812). The incidence of complications within 30 days after surgery were also comparable in each group: 10.4% versus 10.6% (relative risk, 0.99; 95% CI, 0.85 to 1.16; P = 0.938). No significant differences were observed in functional independence or quality of life. CONCLUSIONS:Hypnotic depth, as assessed by BIS, was similar in patients with or without BIS-guided anesthetic titration. Anesthesiologists thus apparently titrate hypnotic depth appropriately even without BIS guidance. Unsurprisingly, outcomes including postoperative 1-yr mortality and 30-day complications were similar in each group.

The lumbar sympathetic nerve block stands as a pivotal approach in managing complex regional pain syndrome (CRPS) in the lower limbs. Retroperitoneal hemorrhage is an extremely rare and severe complication of lumbar sympathetic nerve block. Here, we report for the first time a case of retroperitoneal hemorrhage that initially presented with symptoms of femoral nerve compression. An 81-year-old elderly female was diagnosed with CRPS. After undergoing an ultrasound-guided lumbar sympathetic nerve block at our hospital, discomfort in her right lower back was experienced, followed by stabbing pain, numbness in the anterior thigh, and significant lower limb movement impairment. We considered that the femoral nerve might be compressed by a hematoma or abscess. An emergency percutaneous drainage was performed, resulting in partial symptom relief. However, two days later, signs of hemorrhagic shock were observed in the patient. An emergency lumbar arterial embolization was performed, effectively stabilizing her vital signs. One week later, lower limb pain and numbness disappeared, and right lower limb motor function fully recovered. When retroperitoneal hemorrhage is suspected, prompt computed tomography (CT) or bedside ultrasound should be conducted. Once imaging supports the diagnosis, immediate digital subtraction angiography (DSA) could be utilized to identify the bleeding source and conduct embolization.

BACKGROUND:A post-marketing, parallel-controlled clinical trial (REST trial) was conducted to evaluate the safety and efficacy of cipepofol versus propofol for the induction of anesthesia/sedation in Chinese elderly patients undergoing gastroscopy. METHODS:All enrolled patients aged ≥65 years were assigned randomly in a 1:1 ratio to be administered intravenous cipepofol-0.3 mg/kg or propofol-1.5 mg/kg. The primary endpoint was incidence of respiratory-related adverse events (AEs) including respiratory depression (respiratory rate < 8 breaths/min lasting for >30 s), apnea (loss of thoracic movement for >15 s) and hypoxemia (SpO2 < 93 % lasting for >15 s). Secondary endpoints included: success rates of the gastroscopy procedure and gastroscope insertion; gastroscopy-related duration (successful anesthesia/sedation induction duration; time to full alertness; time to leaving the post-anesthesia care unit; gastroscope insertion duration); satisfaction rate for the anesthesia/sedation process and anesthetics. RESULTS:Among 890 randomized patients, 871 were finally included in the full analysis set (FAS), with 431 receiving cipepofol and 440 receiving propofol. Patients treated with cipepofol had a significantly lower incidence of respiratory-related AEs compared to propofol treatment (FAS: 22.3 % vs. 33.9 %, per-protocol set: 20.6 % vs. 34.5 %, all P < 0.001), regardless of sex. Multivariable analysis revealed that the risk of patients experiencing respiratory-related AEs was 1.82 times higher in the propofol group compared to cipepofol group (P < 0.001). The success rates of the gastroscopy procedure and gastroscope insertion were both 100 % in the two groups. Gastroscopy procedure-related durations were shorter in propofol group compared to cipepofol group (all P < 0.05). Patients treated with cipepofol exhibited a significantly lower rate of treatment-emergent AEs (TEAEs) (55.0 % vs. 67.7 %, P < 0.001), TEAEs of special interest (53.4 % vs. 65.2 %, P < 0.001) and injection pain (2.6 % vs. 28.4 %, P < 0.001). CONCLUSIONS:Cipepofol-0.3 mg/kg is a safe and effective intravenous anesthetic for Chinese elderly patients undergoing gastroscopy, especially complimented by lower incidences of respiratory-related AEs and injection pain. CLINICAL TRIALS REGISTRATION:Chinese Clinical Trial Registry, ChiCTR2100052299, registered on October 24, 2021.

Stress impacts pain sensation and its development, but the underlying neural mechanisms are largely unclear. Using restraint stress models and complete Freund’s adjuvant-induced pain model in male mice, we demonstrated that acute restraint stress (ARS) induces analgesia in both naïve and pain states. In contrast, chronic restraint stress (CRS) enhances pain hypersensitivity in naïve states, prolongs pain duration, and promotes anxiodepressive symptoms in pain states. Notably, ARS and CRS distinctly activate neuronal ensembles in the paraventricular nucleus of the hypothalamus (PVN). Using the targeted recombination in active populations strategy and chemogenetics, we found that these neuronal ensembles mediate the effects of acute and chronic stress on pain sensation and development. Furthermore, through a two-vector strategy and chemogenetic approach, these neuronal ensembles appear to exert their effects via PVN-locus coeruleus and PVN-lateral septum projections, respectively. Overall, our findings offer novel insights into pain sensation and pain chronification, and may provide effective therapeutic strategies for clinical pain and emotional comorbidities.

The intertransverse process block (ITPB) is a general term for a class of novel thoracic paraspinal nerve block techniques proposed in recent years, which can be divided into the mid-point transverse process to pleura block, multiple-injection costotransverse block, costotransverse foramen block and the subtransverse process interligamentary plane block. The four types of ITPB all target the retro-superior costotransverse ligament space, but slightly differ in terms of needle entry approach and needle tip target. ITPB is easy to locate, quick to perform, and provides reliable analgesic effects. Furthermore, this technique can effectively reduce the risk of pneumothorax, hematoma and intraspinal injection. Thus, it has been gradually used for anesthesia and analgesia in breast, cardiothoracic, abdominal and spinal surgeries, as well as for pain relief in trauma patients. However, due to the limited evidence base, its safety and efficacy remain inadequately understood, and few clinicians are proficient in performing ITPB. Further large-scale randomized controlled trials are required to validate its feasibility and superiority. This narrative review will summarize the anatomical basis, mechanism, operation methods, clinical application and shortcomings of ITPB to provide new ideas for multimodal analgesia.

Empathy plays a crucial role in social communication and the perception of affective states and behavioral processes. In this study, we observed that empathic interaction with a mouse experiencing pain resulted in decreased mechanical pain thresholds and anxiety-like behaviors in its bystander, though the underlying mechanisms remain unknown. We demonstrated that CD38 expression in the paraventricular nucleus (PVN) was upregulated during empathic pain, and the pain and emotions of CD38 knockout (CD38KO) mice as bystanders were not affected. Furthermore, fiber photometry recordings indicated that calcium activities of PVN neurons were increased during empathic pain. Interestingly, direct chemogenetic inhibition of PVN neurons attenuated the hyperalgesia and anxiety-like behaviors associated with empathic pain. In contrast, activating PVN neurons through chemogenetics in CD38KO mice induced hyperalgesia and anxiety-like effects in empathic pain. Oxytocin levels in PVN were upregulated during empathic pain, while CD38KO mice inhibit the upregulation in OXT levels, confirming that CD38 is involved in releasing brain OXT and that the CD38-OXT system in the PVN plays a role in empathic pain. Collectively, CD38-mediated oxytocin signaling in PVN is closely linked to empathic pain through its effect on the activation of PVN neurons, and it could be viable targets for novel empathic behavior interventions.

BACKGROUND & AIMS:Etomidate, a prevalent intravenous anesthetic agent, has been implicated in the attenuation of tumorigenesis. Our recent investigations elucidated its capacity to impede the malignant progression of hepatocellular carcinoma (HCC). This study aims to elucidate how etomidate modulates the immunosuppressive tumor microenvironment in HCC. METHODS:To investigate the multifaceted effects and underlying molecular mechanisms of etomidate, we employed an integrative approach encompassing in vitro and in vivo systems, including patient-derived HCC organoids, 3-dimensional co-culture platforms, patient-derived xenografts, and orthotopic HCC models. A suite of advanced methodologies such as single-cell cytometry by time-of-flight (CyTOF), multiplex immunohistochemistry, and flow cytometric analyses were applied. RESULTS:Our data reveal that etomidate suppresses programmed death-ligand 1 (PD-L1) expression in HCC cells, thereby potentiating antitumor immunity. Mechanistically, etomidate inhibits the Janus kinase 2/signal transducer and activator of transcription 3 axis in tumor cells, leading to reduced PD-L1 transcription and increased infiltration and activation of cytotoxic CD8+ T lymphocytes. CONCLUSIONS:These findings support the hypothesis that etomidate enhances antitumor immunity and boosts the therapeutic efficacy of immune checkpoint blockade, thereby laying a theoretical foundation for precision immunotherapy in HCC.

Background Opioid-induced hyperalgesia (OIH) is a serious complication during the pain treatment. Ketamine has been commonly reported to treat OIH, but the mechanisms remain unclear. Gut microbiota is recently recognized as one of the important mechanisms underlying the occurrence and treatment of OIH. However, whether ketamine enantiomers could alleviate OIH through gut microbiota that still needs to be clarified. Methods The OIH model was established by morphine injection for 3 consecutive days, followed by hierarchical clustering analysis of behavioral results into susceptible or resilient group. Broad-spectrum antibiotic cocktail (ABx) was used to eradicated the gut microbiota of mice. Subsequently, fecal microbiota transplantation (FMT) was performed. S- or R-ketamine was administered as pretreatment 30 min before morphine injection. Fecal samples were collected for 16S rRNA gene sequencing after completion of all behavioral tests. Results Approximately 60% of the mice developed OIH after morphine exposure with abnormal locomotion and anxiety-like behaviors. Pseudo germ-free mice treated with ABx did not develop hyperalgesia, whereas pseudo germ-free mice that received fecal microbiota transplantation from OIH mice developed hyperalgesia. Interestingly, S-ketamine but not R-ketamine rescued mice from OIH. The principal co-ordinates analysis (PCoA) suggested that the distribution of gut microbiota differed among the groups. Importantly, levels of Enterobacteriaceae were increased in OIH susceptible group, while decreased after S-ketamine treatment. Conclusion S-ketamine but not R-ketamine was able to alleviate morphine-induced OIH, and this mechanism is probably related to decreasing the levels of gut Enterobacteriaceae.

Empathy, which is typically regarded as a positive attribute, is now being critically evaluated for its potential negative implications for mental health. A growing body of research indicates that excessive empathy, particularly a high level of affective empathy, can lead to overwhelming emotional states, thereby increasing susceptibility to psychological distress and psychiatric disorders. In this review, we aim to explore the negative effects of empathy on mental health. We review both human and animal studies concerning the relationship between empathy and psychological disorders, revealing that while empathy enhances social interactions and emotional understanding, it may also heighten empathic distress and potentially contribute to the development of pain, internalizing disorders, depression, anxiety, emotional overinvolvement, burnout, vicarious trauma, and posttraumatic stress disorder. This review contributes to the broader discourse on empathy by delineating its dual impacts, integrating insights from neurobiology, psychology, and behavioral studies. This review may enhance our understanding of empathy's complex role in mental health, offering a nuanced perspective that acknowledges both its beneficial and detrimental impacts.

Ketamine compound was firstly synthesized for more than 60 years. It is widely used in clinical anesthesia due to its potent analgesic effect and lower deleterious impacts on circulatory and respiratory functions. Very recently, its rapid and long-lasting antidepressant effect attracted increasing attentions in the topic field. We therefore reviewed the pharmacological properties of ketamine, its clinical application as a narcotic analgesic, and antidepressant effect of its metabolites.

Placebo analgesia is observed in both humans and animals. Given the complexity of placebo analgesia involving a variety of neurobiological, psychological, and psychosocial processes, further investigation into its underlying mechanisms is essential. Gut microbiota has been implicated in the responsivity of placebo analgesia, but its precise role remains unknown and warrants further investigations. Here, we conducted a conditioning training model with chronic inflammatory pain induced by complete Freund’s adjuvant (CFA) in mice, associating parecoxib with different cues. Hierarchical clustering analysis of placebo analgesia behaviors was employed to classify mice into responders and non-responders phenotypes. Approximately 40% of CFA mice undergoing conditioning training exhibited placebo analgesia. Notably, placebo analgesia responders displayed reduced anxiety-like behaviors. 16S rRNA results revealed a distinct composition of gut microbiota composition among the control, placebo analgesia non-responders and responders groups. Notably, levels of Escherichia Shigella and Klebsiella in the gut were increased considerably in the placebo analgesia responders as compared to both control and non-responders groups. In conclusion, placebo analgesia responders demonstrated marked analgesia, reduced anxiety-like behaviors, and increased levels of Escherichia-Shigella and Klebsiella, implying a potential linkage between gut microbiota and placebo analgesia.

Malignant tumors constitute a major threaten to human health and are among the most serious public health challenges both in China and globally. Many patients with malignancy require neoadjuvant chemotherapy prior to surgery. Neoadjuvant chemotherapy, which involves administering systemic chemotherapy before local treatment (such as surgery or radiotherapy) for malignant tumors, offers several benefits. These include tumor shrinkage, the reduction of the pathological stage of primary lesions and metastatic lymph nodes, and the early elimination of possible smile metastases. This pre-operative therapy is advantageous as it paves the way for more successful surgical treatment. Nonetheless, research indicates that neoadjuvant chemotherapy may lead to cardiotoxicity, resulting in myocardial ischemia, arrhythmia, arterial hypertension, and even heart failure. Therefore, the use of precision anesthesia, combined with cardioprotective strategies during surgery, is essential. By employing these measures, the surgical procedure can be performed more effectively, ultimately contributing to improved long-term survival outcomes for patients. The focus of this review is to discuss the typical treatment protocols for neoadjuvant chemotherapy, the underlying mechanisms of cardiotoxicity, and the importance of monitoring, assessing, and safeguarding perioperative cardiac function in surgical patients who have undergone neoadjuvant chemotherapy. By examining these aspects, this review aims to offer insights that can guide anesthesia management during the perioperative period for cancer surgery patients.

Objective To review and analyze the airway and anesthesia management methods for patients who underwent endoscopic closure of tracheoesophageal fistula (TEF) and to summarize the experience of intraoperative airway management.Method We searched the anesthesia information system of the First Affiliated Hospital of Nanjing Medical University for anesthesia cases of TEF from July 2020 to July 2023 and obtained a total of 34 anesthesia records for endoscopic TEF occlusion. The intraoperative airway management methods and vital signs were recorded, and the patients' disease course and follow-up records were analyzed and summarized.Results The airway management strategies used for TEF occlusion patients included nasal catheter oxygen (NCO, n = 5), high-flow nasal cannula oxygen therapy (HFNC, n = 4) and tracheal intubation (TI, n = 25). The patients who underwent tracheal intubation with an inner diameter of 5.5 mm had stable hemodynamics and oxygenation status during surgery, while intravenous anesthesia without intubation could not effectively inhibit the stress response caused by occluder implantation, which could easily cause hemodynamic fluctuations, hypoxemia, and carbon dioxide accumulation. Compared with those in the TI group, the NCO group and the HFNC group had significantly longer surgical times, and the satisfaction score of the endoscopists was significantly lower. In addition, two patients in the NCO group experienced postoperative hypoxemia.Conclusion During the anesthesia process for TEF occlusions, a tracheal catheter with an inner diameter of 5.5 mm can provide a safe and effective airway management method.

Cancer, potentially the second leading cause of mortality globally, poses a significant health challenge. The conventional treatment for solid tumors typically involves surgical intervention, followed by chemotherapy, radiotherapy, and targeted therapies. However, cancer recurrence and metastasis remain major issues. Anesthesia is essential for ensuring patient comfort and safety during surgery. Despite its crucial role in surgery, the precise effect of anesthesia on cancer patients' outcomes has not been clearly understood. This comprehensive review aims to elucidate perioperative anesthesia strategies for cancer patients and their potential effects on prognosis. Given the complexity of cancer treatments, understanding the relationship between anesthesia and cancer outcomes is crucial. By examining potential implications of anesthesia strategies for cancer prognosis, this review may help better understand treatment efficacy and risk factors for cancer recurrence and metastasis. Ultimately, a detailed analysis of anesthesia practices in cancer surgery may provide insights to refine existing anesthesia protocols and reduce risk factors for poor patient outcomes.

Remimazolam is a novel ultrashort-acting sedative-hypnotics of benzodiazepines,which metabolized by tissue non-specific cholinesterase.It has the character that hardly influence on hemodynamics and respiratory function.With rapid metabolism,it has a strong controllability and doesn't accumulation after long-time infusion.Moreover,it provides a rapid recovery after anesthesia that can be antagonized by flumazenil specifically.Nowadays,remimazolam is used in procedure sedation in numerous situations of anesthesia.This article focuses on elderly,hepatic and renal impairment,pediatrics,obesity,and obstetrics patients,aims at providing references in clinical applications.

Empathy is the capacity to understand and share the experiences of others. This ability fosters connections between individuals, enriching the fabric of our shared world. One notable example is empathy for the pain of others. Such experiences facilitate the identification of potential dangers, both for oneself and for others. Neuroimaging studies have helped to pinpoint brain regions that modulate empathic pain. Recently, there has also been a surge in studies exploring the neural mechanisms of empathic pain in rodent models. Neuropsychiatric disorders such as autism, psychosis, and schizophrenia often exhibit empathy deficits. Targeting the modulation of empathic pain holds potential for alleviating core symptoms in these patients. Interestingly, empathy research may also benefit pain management, leading to new approaches for understanding the negative emotions associated with pain. This review summarizes recent advances in neuroimaging for the study of empathic pain, outlines the underlying neurocircuit mechanisms, describes therapeutic strategies, and explores promising avenues for future research. This article is part of the Special Issue on "Empathic Pain".