Evaluating the effects of S-ketamine on postoperative delirium in elderly patients following total hip or knee arthroplasty under intraspinal anesthesia: a single-center randomized, double-blind, placebo-controlled, pragmatic study protocol.

Introduction: Postoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and mortality. A small number of trials have explored the role of S-ketamine in the treatment of POD due to its neuroprotective effects. Surprisingly, these trials have failed to yield supportive results. However, heterogeneity in delirium assessment methodologies, sample sizes, and outcome settings as well as deficiencies in S-ketamine use methods make the evidence provided by these studies less persuasive. Given the severe impact of POD on the health of elderly patients and the potential for S-ketamine to prevent it, we believe that designing a large sample size, and rigorous randomized controlled trial for further evaluation is necessary. Methods: This is a single-center, randomized, double-blind, placebo-controlled, pragmatic study. Subjects undergoing total hip or knee arthroplasty will be randomized in a 1:1 ratio to intervention (n = 186) and placebo (n = 186) groups. This trial aims to explore the potential role of S-ketamine in the prevention of POD. Its primary outcome is the incidence of POD within 3 postoperative days. Secondary outcomes include the number of POD episodes, the onset and duration of POD, the severity and subtype of POD, pain scores and opioid consumption, sleep quality, clinical outcomes, and safety outcomes. Discussion: To our knowledge, this is the first pragmatic study that proposes to use S-ketamine to prevent POD. We reviewed a large body of literature to identify potential preoperative confounding variables that may bias associations between the intervention and primary outcome. We will use advanced statistical methods to correct potential confounding variables, improving the test's power and external validity of test results. Of note, the patient population included in this trial will undergo intraspinal anesthesia. Although large, multicenter, randomized controlled studies have found no considerable difference in the effects of regional and general anesthesia on POD, patients receiving intraspinal anesthesia have less exposure to at-risk drugs, such as sevoflurane, propofol, and benzodiazepines, than patients receiving general anesthesia. At-risk drugs have been shown to negatively interfere with the neuroprotective effects of S-ketamine, which may be the reason for the failure of a large number of previous studies. There is currently a lack of randomized controlled studies evaluating S-ketamine for POD prevention, and our trial helps to fill a gap in this area.Trial registration: http://www.chictr.org.cn, identifier ChiCTR2300075796.

Effects of permissive hypercapnia on intraoperative cerebral oxygenation and early postoperative cognitive function in older patients with non-acute fragile brain function undergoing laparoscopic colorectal surgery: protocol study.

BACKGROUND: Perioperative brain protection in older patients has been the focus of research recently; meanwhile, exploring the relationship between regional cerebral oxygen saturation (rSO2) and brain function in the perioperative period has been an emerging and challenging area-the difficulties related to the real-time monitoring of rSO2 and the choice of feasible interventions. As an advanced instrument for intraoperative rSO2 monitoring, the clinical application of near-infrared spectrum (NIRS) cerebral oxygen monitoring has gradually increased in popularity and is being recognized for its beneficial clinical outcomes in patients undergoing cardiac and noncardiac surgery. In addition, although sufficient evidence to support this hypothesis is still lacking, the effect of permissive hypercapnia (PHC) on rSO2 has expanded from basic research to clinical exploration. Therefore, monitoring intraoperative rSO2 in older patients with NIRS technology and exploring possible interventions that may change rSO2 and even improve postoperative cognitive performance is significant and clinically valuable. METHODS: This study is a single-center randomized controlled trial (RCT). 76 older patients are enrolled as subjects. Patients who meet the screening criteria will be randomly assigned 1:1 to the control and intervention groups. PHC-based mechanical ventilation will be regarded as an intervention. The primary outcome is the absolute change in the percent change in rSO2 from baseline to the completion of surgery in the intervention and control groups. Secondary outcomes mainly include observations of intraoperative cerebral oxygenation and metabolism, markers of brain injury, and assessments of patients' cognitive function using scale through postoperative follow-up. DISCUSSION: The findings of this RCT will reveal the effect of PHC on intraoperative rSO2 in older patients with nonacute fragile brain function (NFBF) and the approximate trends over time, and differences in postoperative cognitive function outcomes. We anticipate that the trial results will inform clinical policy decision-makers in clinical practice, enhance the management of intraoperative cerebral oxygen monitoring in older patients with comorbid NFBF, and provide guidance for clinical brain protection and improved postoperative cognitive function outcomes. TRIAL REGISTRATION: ChiCTR, ChiCTR2200062093, Registered 9/15/2022.

Tetramethylpyrazine ameliorates endotoxin-induced acute lung injury by relieving Golgi stress via the Nrf2/HO-1 signaling pathway.

PURPOSE: Endotoxin-induced acute lung injury (ALI) is a severe disease caused by an imbalanced host response to infection. It is necessary to explore novel mechanisms for the treatment of endotoxin-induced ALI. In endotoxin-induced ALI, tetramethylpyrazine (TMP) provides protection through anti-inflammatory, anti-apoptosis, and anti-pyroptosis effects. However, the mechanism of action of TMP in endotoxin-induced ALI remains unclear. Here, we aimed to determine whether TMP can protect the lungs by inhibiting Golgi stress via the Nrf2/HO-1 pathway. METHODS AND RESULTS: Using lipopolysaccharide (LPS)-stimulated C57BL/6J mice and MLE12 alveolar epithelial cells, we observed that TMP pretreatment attenuated endotoxin-induced ALI. LPS + TMP group showed lesser lung pathological damage and a lower rate of apoptotic lung cells than LPS group. Moreover, LPS + TMP group also showed decreased levels of inflammatory factors and oxidative stress damage than LPS group (P < 0.05). Additionally, LPS + TMP group presented reduced Golgi stress by increasing the Golgi matrix protein 130 (GM130), Golgi apparatus Ca2+/Mn2+ ATPases (ATP2C1), and Golgin97 expression while decreasing the Golgi phosphoprotein 3 (GOLPH3) expression than LPS group (P < 0.05). Furthermore, TMP pretreatment promoted Nrf2 and HO-1 expression (P < 0.05). Nrf2-knockout mice or Nrf2 siRNA-transfected MLE12 cells were pretreated with TMP to explore how the Nrf2/HO-1 pathway affected TMP-mediated Golgi stress in endotoxin-induced ALI models. We observed that Nrf2 gene silencing partially reversed the alleviating effect of Golgi stress and the pulmonary protective effect of TMP. CONCLUSION: Our findings showed that TMP therapy reduced endotoxin-induced ALI by suppressing Golgi stress via the Nrf2/HO-1 signaling pathway in vivo and in vitro.

Effects of esketamine on postoperative rebound pain in patients undergoing unilateral total knee arthroplasty: a single-center, randomized, double-blind, placebo-controlled trial protocol.

Introduction: Rebound pain, transient and acute postoperative pain after the disappearance of regional block anesthesia, has been a concern in recent years. Insufficient preemptive analgesia and hyperalgesia induced by regional block are the main mechanisms. At present, the evidence for the treatment of rebound pain is limited. The esketamine, as an antagonist of the N-methyl-D-aspartate receptor, has been proven to prevent hyperalgesia. Therefore, this trial aims to evaluate the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. Methods/design: This study is a single-center, prospective, double-blind, randomized, placebo-controlled trial. Participants who plan to undergo total knee arthroplasty will be randomly assigned to the esketamine group (N = 178) and placebo group (N = 178) in a ratio of 1:1. This trial aims to evaluate the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. The primary outcome of this trial is the incidence of rebound pain within 12 h after the operation in the esketamine group and the placebo group. The secondary outcome will be to compare (1) the incidence of rebound pain 24 h after the operation; (2) the time to enter the pain cycle for the first time within 24 h after the procedure; (3) the first time of rebound pain occurred within 24 h after surgery; (4) the modified rebound pain score; (5) NRS score under rest and exercise at different time points; (6) the cumulative opioid consumption at different time points; (7) patient's prognosis and knee joint function evaluation; (8) blood glucose and cortisol concentration; (9) patient's satisfaction score; (10) adverse reactions and adverse events. Discussion: The effect of ketamine on preventing postoperative rebound pain is contradictory and uncertain. The affinity of esketamine to the N-methyl-D-aspartate receptor is about four times higher than levo-ketamine, the analgesic effect is 3 times higher than levo-ketamine, and there are fewer adverse mental reactions. To our knowledge, there is no randomized controlled trial to verify the impact of esketamine on postoperative rebound pain in patients undergoing total knee arthroplasty. Therefore, this trial is expected to fill an important gap in relevant fields and provide novel evidence for individualized pain management. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2300069044.

Ultrasound-guided posterior quadratus lumborum block can reduce postoperative opioid consumption and promote rapid recovery in patients undergoing sutureless laparoscopic partial nephrectomy: A triple-blind, randomized, controlled study.

Purpose: We hypothesized that posterior quadratus lumborum block would reduce postoperative opioid consumption and improve the quality of recovery in patients undergoing sutureless laparoscopic partial nephrectomy. Materials and methods: The study included 60 patients, ages 18-65 with American Society of Anesthesiologists scores of I-II scheduled for elective sutureless laparoscopic partial nephrectomy. Before general anesthesia, 60 participating patients were randomly allocated to receive a 30-ml injection posterior to the quadratus lumborum muscle with either 0.375% ropivacaine (n = 30) or normal saline (n = 30). The primary outcomes included cumulative opioid consumption within 12 h postoperatively and quality of postoperative recovery at 48 h. Secondary outcomes included the Numerical Rating Scale (NRS), opioid consumption by period, first time to press the analgesic pump, number of patients needing rescue analgesia, blood glucose and cortisol concentrations, early postoperative recovery indicators, and adverse events. Results: There were 48 patients included in the final analysis. The intervention group had lower cumulative consumption of sufentanil within 12 h postoperatively and higher quality of postoperative recovery scores at 48 h postoperatively compared with the control group (p < 0.001). The NRS at resting and movement of the intervention group was lower at 0 h, 6 h, and 12 h after surgery than in the control group (p < 0.05). At prespecified intervals (0 to 2 h, 2 to 6 h, 6 to 12 h, 12 to 24 h, and 24 to 48 h) after surgery, the intervention group had lower consumption of sufentanil compared with the control group (p < 0.05). The intervention group took longer to press the analgesic pump for the first time within 48 h after surgery compared with the control group (p < 0.001). The postoperative blood glucose and cortisol concentrations in the intervention group were lower than in the control group (p < 0.05). The times to first excretion, ambulation, and discharge were shorter in the intervention group compared with the control group (p < 0.05). There was no significant difference in adverse events between the two groups. Conclusions: Our trial demonstrated that patients who received posterior quadratus lumborum block had significantly lower opioid consumption within 12 h postoperatively and had a better quality of recovery at 48 h postoperatively. Therefore, we recommend posterior quadratus lumborum block as an option for postoperative analgesia in patients undergoing sutureless laparoscopic partial nephrectomy. Trial Registration: http://www.chictr.org.cn, identifier ChiCTR2100053439.

Carbon Dioxide Embolism During Transanal Total Mesorectal Excision: Case Report and Literature Review.

The actual incidence of carbon dioxide embolism during transanal total mesorectal excision (taTME) is unknown, but the reported incidence in the existing literature is reassuring. However, the incidence of CO2 embolism, which can be life-threatening, is severely underestimated. By reviewing the available data on carbon dioxide embolism during taTME and synthesizing other reports on CO2 embolism in laparoscopic procedures, we provide the first comprehensive account of the etiology, pathophysiology, and recommend tools to monitor carbon dioxide embolism during taTME. Additionally, we provide guidance and recommendations on preventive and therapeutic measures to minimize the adverse consequences of this potentially severe complication, knowledge about which we hope will improve patients' safety.

Neuroinflammation as the Underlying Mechanism of Postoperative Cognitive Dysfunction and Therapeutic Strategies.

Postoperative cognitive dysfunction (POCD) is a common neurological complication following surgery and general anesthesia, especially in elderly patients. Severe cases delay patient discharge, affect the patient's quality of life after surgery, and are heavy burdens to society. In addition, as the population ages, surgery is increasingly used for older patients and those with higher prevalences of complications. This trend presents a huge challenge to the current healthcare system. Although studies on POCD are ongoing, the underlying pathogenesis is still unclear due to conflicting results and lack of evidence. According to existing studies, the occurrence and development of POCD are related to multiple factors. Among them, the pathogenesis of neuroinflammation in POCD has become a focus of research in recent years, and many clinical and preclinical studies have confirmed the correlation between neuroinflammation and POCD. In this article, we reviewed how central nervous system inflammation occurred, and how it could lead to POCD with changes in peripheral circulation and the pathological pathways between peripheral circulation and the central nervous system (CNS). Furthermore, we proposed some potential therapeutic targets, diagnosis and treatment strategies at the cellular and molecular levels, and clinical applications. The goal of this article was to provide a better perspective for understanding the occurrence of POCD, its development, and preventive strategies to help manage these vulnerable geriatric patients.

The fabrication, nano/micro-structure, heat- and wear-resistance of the superhydrophobic PPS/PTFE composite coatings.

A simple engineering method was used to fabricate stability and wear-resistance of superhydrophobic PPS-based PPS/PTFE surfaces through nano/micro-structure design and modification of the lowest surface energy groups (-CF2-), which was inspired by the biomimic lotus leaves. The hydrophobic properties and wear-resistance of the coatings were measured by a contact angle meter and evaluated on a pin-on-disk friction and wear tester, respectively. Moreover, the surfaces of the PPS/PTFE composite coatings were investigated by means of scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), and thermogravimetry (TG) analysis. Results showed that the highest contact angle of the PPS/PTFE surface, with papillae-like randomly distributed double-scale structure, could reach up to 162°. When 1 wt.% PDMS was added, the highest contact angle could hold is 172°. The coatings also retained superhydrophobicity, even under high temperature environment. The investigation also indicated that the coatings were not only superhydrophobic but also oleophobic behavior at room temperature, such as the crude oil, glycerol, and oil-water mixture. The PPS/45%PTFE coatings had more stable friction coefficient and excellent wear-resistance (331,407 cycles) compared with those with less than 45% of PTFE.