Effect of S-Ketamine on Postoperative Nausea and Vomiting in Patients Undergoing Video-Assisted Thoracic Surgery: A Randomized Controlled Trial.

Purpose: Postoperative nausea and vomiting (PONV) frequently occur in patients after surgery. In this study, the authors investigated whether perioperative S-ketamine infusion could decrease the incidence of PONV in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy. Patients and Methods: This prospective, randomized, double-blinded, controlled study was conducted a total of 420 patients from September 2021 to May 2023 at Xuzhou Central Hospital in China, who underwent elective VATS lobectomy under general anesthesia with tracheal intubation. The patients were randomly assigned to either the S-ketamine group or the control group. The S-ketamine group received a bolus injection of 0.5 mg/kg S-ketamine and an intraoperative continuous infusion of S-ketamine at a rate of 0.25 mg/kg/h. The control group received an equivalent volume of saline. All patients were equipped with patient-controlled intravenous analgesia (PCIA), with a continuous infusion rate of 0.03 mg/kg/h S-ketamine in the S-ketamine group or 0.03 µg/kg/h sufentanil in the control group. The primary outcome was the incidence of PONV. Secondary outcomes included perioperative opioid consumption, hemodynamics, postoperative pain, and adverse events. Results: The incidence of PONV in the S-ketamine group (9.7%) was significantly lower than in the control group (30.5%). Analysis of perioperative opioid usage revealed that remifentanil usage was 40.0% lower in the S-ketamine group compared to the control group (1414.8 µg vs 2358.2 µg), while sufentanil consumption was 75.2% lower (33.1 µg vs 133.6 µg). The S-ketamine group demonstrated better maintenance of hemodynamic stability. Additionally, the visual analogue scale (VAS) scores on postoperative day 1 (POD-1) and postoperative day 3 (POD-3) were significantly lower in the S-ketamine group. Finally, no statistically significant difference in other postoperative adverse reactions was observed between the two groups. Conclusion: The results of this trial indicate that perioperative S-ketamine infusion can effectively reduce the incidence of PONV in patients undergoing VATS lobectomy.

Infliximab alleviates memory impairment in rats with chronic pain by suppressing neuroinflammation and restoring hippocampal neurogenesis.

Patients with chronic pain commonly report impaired memory. Increasing evidence has demonstrated that inhibition of neurogenesis by neuroinflammation plays a crucial role in chronic pain-associated memory impairments. There is currently a lack of treatment strategies for this condition. An increasing number of clinical trials have reported the therapeutic potential of anti-inflammatory therapies targeting tumour necrosis factor-α (TNF-α) for inflammatory diseases. The present study investigated whether infliximab alleviates chronic pain-associated memory impairments in rats with chronic constriction injury (CCI). We demonstrated that infliximab alleviated spatial memory impairment and hyperalgesia induced by CCI. Furthermore, infliximab inhibited the activation of hippocampal astrocytes and microglia and decreased the release of proinflammatory cytokines in CCI rats. Furthermore, infliximab reversed the decrease in the numbers of newborn neurons and mature neurons in the dentate gyrus (DG) caused by chronic pain. Our data provide evidence that infliximab alleviates chronic pain-associated memory impairments, suppresses neuroinflammation and restores hippocampal neurogenesis in a CCI model. These facts indicate that infliximab may be a potential therapeutic agent for the treatment of chronic pain and associated memory impairments.

TAK1 Reduces Surgery-induced Overactivation of RIPK1 to Relieve Neuroinflammation and Cognitive Dysfunction in Aged Rats.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common clinical complication in elderly patients, but its underlying mechanism remains unclear. Receptor-interacting protein kinase 1 (RIPK1), a key molecule mediating necroptosis and regulated by transforming growth factor ß-activated kinase 1 (TAK1), was reported to be associated with cognitive impairment in several neurodegenerative diseases. This study was conducted to investigate the possible role of TAK1/RIPK1 signalling in POCD development following surgery in rats. METHODS: Young (2-month-old) and old (24-month-old) Sprague-Dawley rats were subjected to splenectomy under isoflurane anaesthesia. The young rats were treated with the TAK1 inhibitor takinib or the RIPK1 inhibitor necrostatin-1 (Nec-1) before surgery, and old rats received adeno-associated virus (AAV)-TAK1 before surgery. The open field test and contextual fear conditioning test were conducted on postoperative day 3. The changes in TNF-α, pro-IL-1ß, AP-1, NF-κB p65, pRIPK1, pTAK1 and TAK1 expression and astrocyte and microglia activation in the hippocampus were assessed. RESULTS: Old rats had low TAK1 expression and were more susceptible to surgery-induced POCD and neuroinflammation than young rats. TAK1 inhibition exacerbated surgery-induced pRIPK1 expression, neuroinflammation and cognitive dysfunction in young rats, and this effect was reversed by a RIPK1 inhibitor. Conversely, genetic TAK1 overexpression attenuated surgery-induced pRIPK1 expression, neuroinflammation and cognitive dysfunction in old rats. CONCLUSION: Ageing-related decreases in TAK1 expression may contribute to surgery-induced RIPK1 overactivation, resulting in neuroinflammation and cognitive impairment in old rats.

Lung ultrasound to evaluate pulmonary changes in patients with cardiogenic shock undergoing extracorporeal membrane oxygenation: a retrospective study.

PURPOSE: The aim of the study was to evaluate the value of lung ultrasound (LUS) in patients with cardiogenic shock treated by venoarterial extracorporeal membrane oxygenation (VA-ECMO). METHODS: A retrospective study was conducted in Xuzhou Central Hospital from September 2015 to April 2022. Patients with cardiogenic shock who received VA-ECMO treatment were enrolled in this study. The LUS score was obtained at the different time points of ECMO. RESULTS: Twenty-two patients were divided into a survival group (n = 16) and a nonsurvival group (n = 6). The intensive care unit (ICU) mortality was 27.3% (6/22). The LUS scores in the nonsurvival group were significantly higher than those in the survival group after 72 h (P < 0.05). There was a significant negative correlation between LUS scores and PaO2/FiO2 and LUS scores and pulmonary dynamic compliance(Cdyn) after 72 h of ECMO treatment (P < 0.001). ROC curve analysis showed that the area under the ROC curve (AUC) of T72-LUS was 0.964 (95% CI 0.887 ~ 1.000, P < 0.01). CONCLUSION: LUS is a promising tool for evaluating pulmonary changes in patients with cardiogenic shock undergoing VA-ECMO. TRIAL REGISTRATION: The study had been registered in the Chinese Clinical Trial Registry(NO.ChiCTR2200062130 and 24/07/2022).

Inflammation Disrupts the Brain Network of Executive Function after Cardiac Surgery.

OBJECTIVE: To investigate postoperative functional connectivity (FC) alterations across impaired cognitive domains and their causal relationships with systemic inflammation. BACKGROUND: Postoperative cognitive dysfunction commonly occurs after cardiac surgery, and both systemic and neuroinflammation may trigger its development. Whether FC alterations underlying deficits in specific cognitive domains after cardiac surgery are affected by inflammation remains unclear. METHODS: Seventeen patients, who underwent cardiac valve replacement, completed a neuropsychological test battery and brain MRI scan before surgery and on days 7 and 30 after surgery compared to age-matched healthy controls. Blood samples were taken for tumor necrosis factor-a and interleukin-6 measurements. Seed-to-voxel FC of the left dorsolateral prefrontal cortex (DLPFC) was examined. Bivariate correlation and linear regression models were used to determine the relationships among cognitive function, FC alterations, and cytokines. RESULTS: Executive function was significantly impaired after cardiac surgery. At day 7 follow-up, the surgical patients, compared to the controls, demonstrated significantly decreased DLPFC FC with the superior parietal lobe and attenuated negative connectivity in the default mode network, including the angular gyrus and posterior cingulate cortex. The left DLPFC enhanced the connectivity in the right DLPFC and posterior cingulate cortex, all of which were related to the increased tumor necrosis factor-a and decreased executive function up to day 7 after cardiac surgery. CONCLUSIONS: The decreased FC of executive control network and its anticorrelation with the default mode network may contribute to executive function deficits after cardiac surgery. Systemic inflammation may trigger these transient FC changes and executive function impairments.

Neuropathic pain-induced cognitive dysfunction and down-regulation of neuronal pentraxin 2 in the cortex and hippocampus.

Evidence from both basic and clinical science suggests that neuropathic pain can induce cognitive dysfunction. However, these results are mainly based on a series of behavioral tests, there is a lack of quantitative variables to indicate cognitive impairment. Neuronal activity-regulated pentraxin (NPTX2) is a ubiquitously expressed, secreted protein in the nervous system. NPTX2 has been implicated to be involved in a variety of neuropathic diseases including Parkinson's disease, ischemia, and Alzheimer's disease. In a mouse model of chronic pain, NPTX2 is involved in the regulation of inflammatory responses. Here, we employ a variety of behavioral approaches to demonstrate that mice with chronic neuropathic pain have cognitive impairment and exhibit an increased anxiety response. The expression of NPTX2, but not NPTX1, was down-regulated in the hippocampus and cortex after chronic neuropathic pain exposure. The modulation effect of NPTX2 on cognitive function was also verified by behavioral tests using Nptx2 knock-out mice. Above all, we conclude that downregulation of NPTX2 induced by neuropathic pain may serve as an indicator of a progressive cognitive dysfunction during the induction and maintenance of spared nerve injury.

Association of Preexisting Neurocognitive Impairments and Perioperative Neurocognitive Disorders for Hip Joint Replacement Surgery: A Prospective Cohort Study.

BACKGROUND The association of preexisting neurocognitive impairments with perioperative neurocognitive disorders is not well-established. The objective of this study was to record incidences of perioperative neurocognitive disorders, to record changes in perioperative neurocognition, and to analyze factors of perioperative neurocognitive changes after hip joint replacement surgeries. MATERIAL AND METHODS Patients scheduled for hip joint replacement surgery were included in the test group (n=499) and patients with osteoarthritis but who were not planned for any type of surgeries were included in the control group (n=499). The cognitive tests were evaluated at the time of enrollment and at 1 week, 3 months, 1 year, and 4 years after baseline. Neurocognitive disorders for the individual parameter was defined as more than 2 SD of mean below norms for that parameter. Neurocognitive disorders were defined as a significant worst condition in at least 2 parameters out of all parameters. RESULTS Compared to baseline, after 3 months the numbers of patients with perioperative neurocognitive disorders were increased (55 vs. 81, p=0.021). After 4 years, there was a significant decline in numbers of patients with perioperative neurocognitive disorders in the test group (55 vs. 3, p<0.0001). At the end of the 3-month follow-up period, elderly patients (p=0.002) and patients with preexisting neurocognitive impairments (p=0.005) had a higher incidence of perioperative neurocognitive disorders. CONCLUSIONS Age and preexisting neurocognitive impairments are markers predicting the risk of perioperative neurocognitive disorders.

FKBP51 is associated with early postoperative cognitive dysfunction in elderly patients undergoing hip fracture surgery.

Enhanced inflammation response was increasingly reported in association with postoperative cognitive dysfunction (POCD). Glucocorticoid receptor (GR) signal plays a key role in suppression of inflammation. This prospective cohort study aimed to evaluate GR signaling in elderly patients undergoing selective operation.One hundred twenty-six elderly patients were scheduled for hip fracture surgery with general anesthesia. Plasma cortisol levels and the expression levels of GR and FK506 binding protein 51 (FKBP51) in leukocytes were determined at 1 day preoperatively and 7 days. Postoperatively postoperative pain was assessed following surgery using visual analog pain scale (VAS). Neuropsychological tests were performed before surgery and 1 week postoperation. A decline of 1 or more standard deviations in 2 or more tests was considered to reflect POCD.POCD incidence in participants was 28.3% at 1 week after surgery. POCD patients presented significantly higher cortisol and FKBP51 levels compared with non-POCD patients (P < .05). Compared with non-POCD patients, VAS scores at 12 hours after surgery were higher in POCD patients (P < .05). No significant difference in expression levels of GR was found between groups POCD and non-POCD patients.High expression of FKBP51 in leukocytes and glucocorticoid resistance were associated with POCD in aged patients following hip fracture surgery.

Effect of Ulinastatin Combined With Dexmedetomidine on Postoperative Cognitive Dysfunction in Patients Who Underwent Cardiac Surgery.

Background: Recent studies have shown that early diagnosis and intervention promote the patient's good prognosis. For patients who underwent cardiac surgery and require extracorporeal circulation support, the incidence of postoperative cognitive dysfunction (POCD) is higher than in other types of surgery due to greater changes in brain perfusion compared with normal physiological conditions. Recent studies have confirmed that the use of ulinastatin or dexmedetomidine in the perioperative period effectively reduces the incidence of POCD. In this study, ulinastatin was combined with dexmedetomidine to assess whether the combination of the two drugs could reduce the incidence of POCD. Methods: One hundred and eighty patients with heart valve replacement surgery undergoing cardiopulmonary bypass from August 2017 to December 2018 were enrolled, with age 60-80 years, American Society of Anesthesiologists (ASA) grades I-III, education level above elementary school, and either gender. According to the random number table method, patients were grouped into ulinastatin + dexmedetomidine (U+D) group, ulinastatin (U) group, dexmedetomidine (D) group, and normal saline (N) control group. Group U was pumped 20,000 UI/kg immediately after induction and the first day after surgery, group D continued to pump 0.4 µg/kg/h from induction to 2 h before extubation, group U+D dexmedetomidine 0.4 µg/kg/h + ulinastatin 20,000 UI/kg, and group N equal volume of physiological saline. The patients were enrolled with Mini-Mental State Examination (MMSE) before surgery. The cognitive function was assessed by Montreal Cognitive Assessment (MoCA) on the first day before surgery and on the seventh day after surgery. Inflammatory factors, such as S100ß protein, interleukin (IL)-6, matrix metalloproteinase (MMP)-9, and tumor necrosis factor (TNF)-α, were detected in peripheral blood before anesthesia (T0), immediately after surgery (T1), and immediately after extubation (T2). Results: One hundred and fifty-four patients enrolled in this study. Compared with group N, the incidence of POCD in group U+D was the lowest (P < 0.05), followed by group U and group D. Group U+D had the lowest concentration of inflammatory factors at the T1 and T2 time points, followed by group U and group D. Conclusions: Both ulinastatin and dexmedetomidine can reduce the perioperative inflammatory response and the incidence of POCD in patients with heart valve surgery, and their combination can better reduce the incidence of POCD.

Protective Effect of Celecoxib on Early Postoperative Cognitive Dysfunction in Geriatric Patients.

Objective: Inflammation plays a key role in the etiology and pathology of postoperative cognitive dysfunction (POCD). Cyclooxygenase (COX)-2 inhibitor celecoxib is used for the treatment of acute pain due to its potent anti-inflammatory and analgesic effects. Herein, we evaluated the effects of celecoxib on POCD in geriatric patients. Methods: A total of 178 geriatric patients undergoing total knee arthroplasty were randomly divided into two groups and treated with celecoxib (group C) or placebo (group P). The levels of perioperative plasma COX-2, IL-1ß, IL-6, TNF-α, neuron-specific enolase, and S100ß were detected in all patients. The pain intensity was measured by numerical rating scale (NRS). A battery of 9 neuropsychological tests was performed pre-operatively and 1 week, and 3 months postoperatively. Patients, whose postoperative performance declined by ≧1 standard deviation as compared to each preoperative test score on ≧2 tests, were classified as POCD. Results: A significant decrease in POCD incidence was found in group C as compared to group P on postoperative day 7 (12.3% vs. 34.1%; p < 0.05). POCD incidence did not differ between the two groups at the 3-month follow-up (8.8 vs. 9.7%). NRS scores at days 3 and 4 post-surgery were significantly lower in group C (p < 0.05). Patients in group C showed lower level of plasma COX-2, IL-1ß, IL-6, TNF-α, and S100ß as compared to group P postoperatively (p < 0.05). Conclusion: These results demonstrated that celecoxib can decrease early POCD incidence after total knee arthroplasty in geriatric patients, which might be mediated by suppressing inflammation and acute postoperative pain caused by surgical trauma. Registration: Chinese Clinical Trial Register, ChiCTR-IOR-16008168.

Reprint of: Efficacy and safety of different doses of dezocine for preemptive analgesia in gynecological laparoscopic surgeries: A prospective, double blind and randomized controlled clinical trial.

BACKGROUND: The incidence of reproductive system tumors in Chinese females is increasing year by year, with the trend of younger onset ages. Laparoscopic surgery has been recognized by the majority of medical staff and patients, but the postoperative pain still exists. Therefore, it has become the focus of attention of medical workers to take effective analgesia measures to alleviate postoperative pain as well as to improve the degree of comfort and satisfaction for the patients. OBJECTIVES: The research objective was to study the effect of different doses of dezocine preemptive analgesia on the safety and the pain post laparoscopic surgeries, in order to explore the best dose of dezocine for postoperative analgesia in gynecological laparoscopic surgeries. METHODS: Gynecological laparoscopic surgery patients conformed to the criteria (n = 390) were randomly divided into three groups (group A, B and C) by the methods of randomized, double-blind studies. 0.1 mg/kg, 0.15 mg/kg or 0.2 mg/kg dezocine was intravenously injected 15 min before surgeries for preemptive analgesia. VAS score, Ramsay score and MMSE score were used to evaluate the efficacy and safety of dezocine in preemptive analgesia and sedation, and the use of adjuvant analgesic drugs and the incidence of adverse reactions were also observed. RESULTS: The VAS scores of the 0.15 mg/kg and 0.2 mg/kg dezocine groups were significantly lower than that of the 0.1 mg/kg group at 2h, 4h, 6h, 8h, 12h and 24h post-surgery, and the difference was statistically significant (p < 0.05). There was no statistically significant difference between the 0.15 mg/kg and 0.2 mg/kg groups (p > 0.05) except for the 12h time point. The MMSE scores 12h post-surgery of the three groups were compared with those 12h prior-to-surgery, and the differences were not statistically significant (p > 0.05) and no increase in the incidence of cognitive impairment was observed. The use rate of analgesic drugs in the 0.1 mg/kg group was significantly higher than those in the 0.15 mg/kg and 0.2 mg/kg groups, and the difference was statistically significant (p < 0.05). There were no significant differences in the incidence of adverse events between the three groups (P > 0.05). CONCLUSIONS: The analgesia and sedation effects of dezocine were enhanced with the increase of usage dose, which suggested that the effects of dezocine were dose-dependent. Intravenous injection of 0.15 mg/kg dezocine 15 min before gynecological laparoscopic surgery showed better analgesic and sedative effects as well as less adverse reactions, and should be the appropriate dose to be used in the preemptive analgesia in gynecological laparoscopic surgeries.

Efficacy and safety of different doses of dezocine for preemptive analgesia in gynecological laparoscopic surgeries: A prospective, double blind and randomized controlled clinical trial.

BACKGROUND: The incidence of reproductive system tumors in Chinese females is increasing year by year, with the trend of younger onset ages. Laparoscopic surgery has been recognized by the majority of medical staff and patients, but the postoperative pain still exists. Therefore, it has become the focus of attention of medical workers to take effective analgesia measures to alleviate postoperative pain as well as to improve the degree of comfort and satisfaction for the patients. OBJECTIVES: The research objective was to study the effect of different doses of dezocine preemptive analgesia on the safety and the pain post laparoscopic surgeries, in order to explore the best dose of dezocine for postoperative analgesia in gynecological laparoscopic surgeries. METHODS: Gynecological laparoscopic surgery patients conformed to the criteria (n = 390) were randomly divided into three groups (group A, B and C) by the methods of randomized, double-blind studies. 0.1 mg/kg, 0.15 mg/kg or 0.2 mg/kg dezocine was intravenously injected 15 min before surgeries for preemptive analgesia. VAS score, Ramsay score and MMSE score were used to evaluate the efficacy and safety of dezocine in preemptive analgesia and sedation, and the use of adjuvant analgesic drugs and the incidence of adverse reactions were also observed. RESULTS: The VAS scores of the 0.15 mg/kg and 0.2 mg/kg dezocine groups were significantly lower than that of the 0.1 mg/kg group at 2h, 4h, 6h, 8h, 12h and 24h post-surgery, and the difference was statistically significant (p < 0.05). There was no statistically significant difference between the 0.15 mg/kg and 0.2 mg/kg groups (p > 0.05) except for the 12h time point. The MMSE scores 12h post-surgery of the three groups were compared with those 12h prior-to-surgery, and the differences were not statistically significant (p > 0.05) and no increase in the incidence of cognitive impairment was observed. The use rate of analgesic drugs in the 0.1 mg/kg group was significantly higher than those in the 0.15 mg/kg and 0.2 mg/kg groups, and the difference was statistically significant (p < 0.05). There were no significant differences in the incidence of adverse events between the three groups (P > 0.05). CONCLUSIONS: The analgesia and sedation effects of dezocine were enhanced with the increase of usage dose, which suggested that the effects of dezocine were dose-dependent. Intravenous injection of 0.15 mg/kg dezocine 15 min before gynecological laparoscopic surgery showed better analgesic and sedative effects as well as less adverse reactions, and should be the appropriate dose to be used in the preemptive analgesia in gynecological laparoscopic surgeries.