A study comparing brain wave patterns of fentanyl and ketamine in adult patients undergoing minimally invasive surgery.

This study aimed to investigate and compare the neurophysiological impacts of two widely used anesthetic agents, Fentanyl and Ketamine, on EEG power spectra during different stages of anesthesia in adult patients undergoing minimally invasive surgery. EEG data were collected from patients undergoing anesthesia with either Fentanyl or Ketamine. The data were analyzed for relative power spectrum and fast-to-slow wave power ratios, alongside Spectral Edge Frequency 95% (SEF95), at 3 key stages: pre-anesthesia, during stable anesthesia, and post-anesthesia. EEG Relative Power Spectrum: Initially, both groups exhibited similar EEG spectral profiles, establishing a uniform baseline (P > .05). Upon anesthesia induction, the Fentanyl group showed a substantial increase in delta band power (P < .05), suggesting deeper anesthesia, while the Ketamine group maintained higher alpha and beta band activity (P < .05), indicative of a lighter sedative effect. Fast and Slow Wave Power Ratios: The Fentanyl group exhibited a marked reduction in the fast-to-slow wave power ratio during anesthesia (P < .05), persisting post-anesthesia (P < .05) and indicating a lingering effect on brain activity. Conversely, the Ketamine group demonstrated a more stable ratio (P > .05), conducive to settings requiring rapid cognitive recovery. Spectral Edge Frequency 95% (SEF95): Analysis showed a significant decrease in SEF95 values for the Fentanyl group during anesthesia (P < .05), reflecting a shift towards lower frequency power. The Ketamine group experienced a less pronounced decrease (P > .05), maintaining a higher SEF95 value that suggested a lighter level of sedation. The study highlighted the distinct impacts of Fentanyl and Ketamine on EEG power spectra, with Fentanyl inducing deeper anesthesia as evidenced by shifts towards lower frequency activity and a significant decrease in SEF95 values. In contrast, Ketamine's preservation of higher frequency activity and more stable SEF95 values suggests a lighter, more dissociative anesthetic state. These findings emphasize the importance of EEG monitoring in anesthesia for tailoring anesthetic protocols to individual patient needs and optimizing postoperative outcomes.

A real-world pharmacovigilance study of esketamine nasal spray.

Mining and updating the post-marketing safety signals of esketamine nasal spray for better identification of adverse drug event (ADE) signals and medication monitoring during clinical use to ensure patient medication safety. Downloading data from the US Food and Drug Administration Adverse Event Reporting System from Q1 2019 to Q2 2023, the reporting odds ratio, proportional reporting ratio, Multi-item Gamma Poisson Shrinker, and Bayesian Confidence Propagation Neural Network methods of the disproportionality method were used to mine and analyze ADEs, and finally to screen for signals of ADEs with esketamine nasal spray as the primary suspected drug. The Preferred Terminology of the Medical Dictionary of Regulatory Activities (version 26.0) was used to standardize the description of ADEs and to attribute ADEs to the System Organ Classification. A total of 5132 ADEs reports of esketamine nasal spray as the primary suspected drug were obtained from the Food and Drug Administration Adverse Event Reporting System. The most frequently observed ADEs are dissociation, sedation, and hypertension, while some new rare signals have been detected, such as interstitial cystitis, substance abuse, and drug diversion. The present study identified significant new ADEs signals for esketamine nasal spray, which may provide a source for healthcare professionals to assess patients' symptoms and risk identification.

Diurnal variation of postoperative delirium in elderly patients undergoing esketamine anesthesia for elective noncardiac surgery: a randomized clinical trial.

BACKGROUND: Postoperative delirium (POD) is a serious and common complication. The aim of present study is to investigate the diurnal variation of POD and the effects of esketamine in elderly patients. METHODS: A randomized, double-blind, placebo-controlled clinical trial with factorial design was conducted. Patients (aged 65 to 85 years) with normal Mini-Mental State Examination (MMSE) score were stratified by age (≤70 vs. >70) and American Society of Anesthesiologists physical status classification (Ⅱ vs. Ⅲ), then randomly assigned to either morning (08:00-12:00) or afternoon (14:00-18:00) noncardiac operation under general anesthesia with or without esketamine administration (0.2 mg/kg). The primary outcome was the incidence of POD (3-Minute Diagnostic Interview for Confusion Assessment Method-defined Delirium, 3D-CAM) on postoperative days 1, 3, and 7. The secondary outcomes were the scores of MMSE and Hospital Anxiety and Depression Scale. The intention-to-treat analysis of the outcomes were performed by generalized estimating equation. RESULTS: Six patients who did not receive an intervention because of canceled operation were excluded after randomization. The datasets containing 426 cases were analyzed following the intention-to-treat principle after handling missing data via multiple imputation method. The incidence of POD declined from about 55% on postoperative day 1 to 31 and 18% on postoperative days 3 and 7, respectively. Afternoon operation [B=-0.583, OR (95% CI) 0.558 (0.319-0.976); P=0.041], but not esketamine, significantly decreased the incidence of POD. Both esketamine and operation time failed to significantly affect MMSE, HAD, and NRS score. There was no interaction among operation time, esketamine, and follow up time. CONCLUSION: Elderly patients undergoing elective noncardiac surgery in the afternoon displayed lower POD incidence than those operated in the morning. A single low-dose of esketamine before general anesthesia induction failed to significantly decrease the risk of POD but decrease the risk of intraoperative hypotension and emergence agitation.

Opioid-free anesthesia improves postoperative recovery quality of small and medium-sized surgery: a prospective, randomized controlled study.

BACKGROUND: Opioid anesthesia (OA) is currently the predominant anesthetic method. However, its associated side effects, such as nausea and vomiting, coupled with the principle of enhanced recovery after surgery (ERAS), have spurred the adoption of opioid-free anesthesia (OFA) in select surgical procedures. For small and medium-sized operations, ERAS is particularly important. The aim of this study was to investigate the effect of OFA, utilizing esketamine in combination with dexmedetomidine and sevoflurane, on postoperative recovery quality following small and medium-sized surgical interventions. METHODS: A total of 120 patients who underwent various small and medium-sized operations were randomly allocated to OFA and OA groups. The OA group received sufentanyl and sevoflurane, while the OFA group received esketamine, dexmedetomidine, and sevoflurane. The primary outcome measure was the postoperative quality of recovery-40 scores (QoR-40) 24 hours after surgery. Secondary outcomes included hemodynamic changes at different time intervals, the incidences of adverse events were recorded. RESULTS: Patients in the OFA group exhibited a higher QoR-40 score of 184.0 (182.0, 186.2) compared to 182.0 (180.0, 184.0) in the OA group (P<0.001). The disparities were particularly noble in terms of Physical comfort and Emotional status. Multivariable analysis identified postoperative nausea and vomiting (PONV) as a significant independent factor impacting QoR-40 (ß=-4.49 [-6.1, -2.87], P<0.001). Hemodynamic stability was more pronounced in the OFA than in the OA group. The incidence of PONV was substantially lower in the OFA group (one [1.6%] vs. 14 [25%], P<0.001), with a reduced need for vasoactive drugs (five [7.8%] vs. 15 [26.8%], P=0.005), and a lower incidence of respiratory depression (0 [0%] vs. six [10.7%], P=0.009). CONCLUSIONS: OFA improves the postoperative recovery quality in small and medium-sized surgical procedures, potentially attributed to decreased incidence of PONV. Additionally, OFA facilitates the maintenance of more stable hemodynamics throughout the operation.

Evaluation of the Effects of Repetitive Anaesthesia Administration on the Brain Tissues and Cognitive Functions of Rats with Experimental Alzheimer's Disease.

Introduction: We evaluated the effects of repeated ketamine, propofol, and ketamine + propofol administration on cognitive functions and brain tissue of elderly rat models with streptozotocin-induced Alzheimer's disease. Materials and Methods: Thirty elderly male Wistar Albino rats were divided into five groups: control (Group C), Alzheimer's (Group A), Alzheimer's + ketamine (Group AK), Alzheimer's + propofol (Group AP), and Alzheimer's + propofol + ketamine (Group APK). Alzheimer's disease was induced in Groups A, AK, AP, and APK via intracerebroventricular streptozotocin. Four weeks after surgery, ketamine, propofol, and ketamine + propofol were administered intraperitoneally for 3 days to Groups AK, AP, and APK, respectively. The radial arm maze test (RAMT) was performed in the initial, 1st, 2nd, 3rd, and 4th weeks after surgery and daily following anaesthesia. Blood and brain tissue samples were obtained. Results: The RAMT results of Groups A, AK, AP, and APK decreased compared to Group C 2 weeks after Alzheimer's disease onset. Compared to Group A, the RAMT results increased in Groups AK and APK after the first anaesthesia, and in Group AP after the second anaesthesia. Brain tissue paraoxonase-1 (PON-1) and catalase (CAT) activities were low, and the thiobarbituric acid reactive substance (TBARS) level was high in Group A compared to Group C. TBARS levels of Groups AP and APK were lower than Group A, while CAT activity was higher. PON-1 activity was higher in Groups AK, AP, and APK than in Group A. Histopathological changes decreased in Groups AP and AK. A decrease in p53 was found in Group C compared to Group A. Ketamine and propofol were found to be effective at Bcl-2 immunoexpression, but a decrease in Caspase-3 was observed in Group APK. GFAP immunoexpression increased in Group A compared to Group C and in Group AP compared to Group AK. Conclusions: Repetitive anaesthesia application was found to positively affect cognitive functions. This was supported by histopathological and biochemical markers.

Ketamine for catatonia: A novel treatment for an old clinical challenge? A systematic review of the evidence.

INTRODUCTION: Catatonia, documented since the 19th century, remains a significant challenge in terms of recognition and treatment. Over the last two decades, ketamine has brought new perspectives to psychiatry, sparking widespread interest. Concurrently, catatonia has attracted heightened scientific attention. Preliminary evidence suggests the therapeutic potential of ketamine for catatonia. METHODS: We systematically searched Medline/PubMed, Embase, PsycINFO, Lilacs, and Cochrane Library databases, as well as Google Scholar, for studies with ketamine or its enantiomers as intervention for catatonia, with no restrictions to underlying diagnosis, date, language, or study design. RESULTS: Twenty articles were included, encompassing a total of 25 catatonic patients receiving ketamine or esketamine. Predominantly female (61.9 %), with a mean age of 44.4 years, patients mostly exhibited manifestations compatible with the retarded subtype of catatonia. Mood disorders were the most prevalent underlying diagnoses. Ketamine was primarily administered intravenously over a 40-minute period and in multiple-dosing schemes. Mean response and remission rates of catatonic manifestations for the whole sample were 80 % and 44 %, respectively, with no reports of worsening catatonic features or psychotic symptoms. Only one patient discontinued treatment due to intolerable dissociative effects. CONCLUSION: Challenging the conventional contraindication of ketamine in psychotic disorders, current evidence highlights its potential efficacy, particularly in treating catatonia. Pending further research, we advocate reevaluating this contraindication, as it may offer a promising therapeutic option, especially for challenging cases. Preliminary evidence suggests potentially greater benefits for catatonic patients with underlying mood disorders compared to primary psychotic disorders.

Evaluation of SK-N-SH Cells as a Model for NMDA Receptor Induced Toxicity.

BACKGROUND/AIMS: Over the years, the number of patients with neurodegenerative diseases is constantly rising illustrating the need for new neuroprotective drugs. A promising treatment approach is the reduction of excitotoxicity induced by rising (S)-glutamate levels and subsequent NMDA receptor overactivation. To facilitate the search for new NMDA receptor inhibitors neuronal cell models are needed. In this study, we evaluated the suitability of human SK-N-SH cells to serve as a cell model for neurodegeneration induced by NMDA receptor overstimulation. METHODS: The cytoprotective effect of the unselective NMDA receptor blocker ketamine as well as the GluN2B-selective inhibitor WMS14-10 was evaluated utilizing different cell viability assays, such as endpoint (LDH, CCK-8, DAPI/FACS) and time dependent methods (bioimpedance). RESULTS: Non-differentiated as well as differentiated SK-N-SH cells express GluN1 and GluN2B subunits. Furthermore, 50 mM (S)-glutamate led to an instantaneous decrease in cell survival. Only application of unselective channel blocker ketamine could protect differentiated cells against this effect, while the selective inhibitor WMS14-10 did not significantly increase cell survival. CONCLUSION: SK-N-SH cells show an increased sensitivity to (S)-glutamate mediated cytotoxicity with higher differentiation level, that is only partially induced by NMDA receptor overstimulation. Furthermore, we showed that only unselective NMDA receptor inhibition can partially reverse (S)-glutamate-induced toxicity.

Opioid-free anesthesia with esketamine-dexmedetomidine versus opioid-based anesthesia with propofol-remifentanil in shoulder arthroscopy: a randomized controlled trial.

BACKGROUND: OFA (Opioid-free anesthesia) has the potential to reduce the occurrence of opioid-related adverse events and enhance postoperative recovery. Our research aimed to investigate whether OFA, combining esketamine and dexmedetomidine, could serve as an alternative protocol to traditional OBA (opioid-based anesthesia) in shoulder arthroscopy, particularly in terms of reducing PONV (postoperative nausea and vomiting). METHODS: A total of 60 patients treated with shoulder arthroscopy from September 2021 to September 2022 were recruited. Patients were randomly assigned to the OBA group (n = 30) and OFA group (n = 30), receiving propofol-remifentanil TIVA (total intravenous anesthesia) and esketamine-dexmedetomidine intravenous anesthesia, respectively. Both groups received ultrasound-guided ISBPB(interscalene brachial plexus block)for postoperative analgesia. RESULTS: The incidence of PONV on the first postoperative day in the ward (13.3% vs. 40%, P < 0.05) was significantly lower in the OFA group than in the OBA group. Moreover, the severity of PONV was less severe in the OFA group than in the OBA group in PACU (post-anesthesia care unit) (0 [0, 0] vs. 0 [0, 3], P<0.05 ) and in the ward 24 h postoperatively ( 0 [0, 0] vs. 0 [0, 2.25], P<0.05). Additionally, the OFA group experienced a significantly shorter length of stay in the PACU compared to the OBA group (39.4 ± 6.76 min vs. 48.7 ± 7.90 min, P < 0.001). CONCLUSIONS: Compared to the OBA with propofol-remifentanil, the OFA with esketamine- dexmedetomidine proved to be feasible for shoulder arthroscopy, resulting in a reduced incidence of PONV and a shorter duration of stay in the PACU. TRIAL REGISTRATION: The Chinese Clinical Trial Registry (No: ChiCTR2100047355), 12/06/2021.

Compounding Trade Association Issues Ketamine, Office Pay Best Practices APC Also Updated Position Statements on Constructive Transfer and Peptide Compounding.

The Alliance for Pharmacy Compounding recently released four resource documents aimed at shaping compounding best practices and regulatory compliance.

Ketamine for Pain in Hospice Patients - A Transdermal Gel Applied to the Painful Site.

The author has been using ketamine to treat hospice patients for several years, with varying degrees of success, and reports being most successful with the transdermal-gel form. He has also had success with ketamine administered as a nasal spray. In addition to providing general comments on the use of ketamine in this context, he presents four brief case reports demonstrating the use of ketamine and other medications in treating pain associated with various types of cancer.

Comparison Between Esketamine and Alfentanil for Hysteroscopy: A Prospective, Double-Blind, Randomized Controlled Trial.

Purpose: This study aimed to establish the 95% effective dose (ED95) of esketamine in combination with propofol for hysteroscopy and then to evaluate its efficacy and safety profile. Patients and Methods: This prospective, double-blind, randomized controlled trial consisted of two cohorts. In cohort 1, 45 women aged 18-65 years undergoing hysteroscopy were randomly assigned to either group E (esketamine + propofol) or group A (alfentanil + propofol). Dixon's up-and-down method was used to determine the ED95 of esketamine and alfentanil. In cohort 2, 86 patients were randomized to group E and group A, with the calculated ED95 dose of the study drugs used for induction. The success rate of anesthesia using the ED95% dose, along with parameters related to anesthesia induction, recovery, and adverse events were also recorded. Results: The ED95 of esketamine was 0.254 mg/kg (95% CI: 0.214-1.004), while that of alfentanil was 9.121 µg/kg (95% CI: 8.479-13.364). The anesthesia success rate was 93.0% in group E and 95.2% in group A (p = 0.664). After resuscitation, both groups achieved a 100% success rate. The induction time was significantly shorter in group E (60.0 [55.0-70.0] s) compared to group A (67.0 [61.0-79.3] s) (p = 0.006). Group E had lower rates of respiratory depression (p < 0.001), hypoxia (p = 0.006), minimum perioperative SpO2 (p = 0.010), and hypotension (p = 0.001). Esketamine had less effect on respiratory rate, heart rate, mean blood pressure, and end-tidal carbon dioxide compared to alfentanil (all p < 0.001). There were no significant differences in postoperative pain between the two groups. Conclusion: This study determined the ED 95 dose of esketamine for intravenous general anesthesia during hysteroscopy. Esketamine showed less respiratory and hemodynamic depression, as well as fewer adverse effects compared to alfentanil. Esketamine is an ideal anesthetic agent compared to alfentanil for hysteroscopic anesthesia. Trial Registration: www.chictr.org.cn, (ChiCTR2300077283); registered November 3, 2023.

Subanesthetic Dose of Esketamine Improves the Sedative and Analgesic Effects of Dexmedetomidine and Remifentanil in Liposuction Anesthesia: A Prospective, Double-Blinded, Randomized Controlled Trial.

Purpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15-0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction. Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62-0.79), anxiety level (OR, 0.77; 95% CI, 0.62-0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56-0.98) were identified as significant predictors associated with patient satisfaction. Conclusion: A subanesthetic dose of esketamine (0.15-0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Clinical Trial Registration: ChiCTR2400080363.

Comparing the Sedative Effects of Intranasal Dexmedetomidine, Midazolam, and Ketamine in Outpatient Pediatric Surgeries: A Randomized Clinical Trial.

Background: The management of preoperative anxiety in pediatric patients, as well as its implications, has remained challenging for anesthesiologists. In this study, we compared the safety and efficacy of intranasal dexmedetomidine, midazolam, and ketamine as surgical premedication in children. Methods: This double-blinded randomized clinical trial was conducted at two tertiary hospitals in January 2014, on 90 children aged between 2-7 years old. The participants' American Society of Anesthesiologists (ASA) physical status was I or II, and they were scheduled for elective unilateral inguinal herniorrhaphy. Using the block randomization method, the patients were randomly assigned to three groups, each receiving intranasal dexmedetomidine (2 µg/Kg), midazolam (0.2 mg/Kg), and ketamine (8 mg/Kg) 60 min before induction of anesthesia. Anxiety and sedation state were evaluated before drug administration, and then every 10 min for the next 50 min. Parental separation anxiety, mask acceptance, postoperative agitation, pain, nausea, and vomiting were also recorded and compared between these groups. All the statistical analyses were performed using SPSS software (version 21.0). P<0.05 was considered statistically significant. Results: Ketamine indicated the strongest sedative effect 10, 20, and 30 min after administration of premedication (P<0.001, P=0.03, P=0.01, respectively). However, dexmedetomidine was more effective than other drugs after 40 and 50 min (P<0.001). Other variables indicated no statistically significant difference. Conclusion: In case of emergencies, intranasal ketamine, with the shortest time of action, could be administered. Intranasal dexmedetomidine, which was revealed to be the most potent drug in this study, could be administrated 40-50 min before elective pediatric surgeries.Trial registration number: IRCT2013081614372N1.

Comparing sedative and non-sedative reduction techniques in paediatric intussusception: Insights from a 6-year study.

INTRODUCTION: Intussusception is a prevalent paediatric emergency condition. The standard of care involves the reduction using air or fluid enema is considered a safe procedure. Sedation-induced muscle relaxation thus optimising the treatment. We present a comprehensive 6- year study involving non sedative reduction (NSR) versus sedative reduction (SR) utilising ketamine and midazolam. MATERIALS AND METHODS: A retrospective cohort study was conducted between January 2017 and July 2023 in Yogyakarta, Indonesia. A total of 85 children diagnosed with intussusception underwent hydrostatic reduction, which employed water-soluble contrast administered into the rectum. Cases that were unsuccessful in reduction underwent immediate surgical intervention. RESULTS: Among the 85 children with intussusception underwent reduction, 22 children underwent the SR procedure and 63 underwent NSR procedure. We found a successful outcome in 17 cases (77%) of SR procedure with one recurrent and the other five (23%) got surgical reduction such as anastomosis resection (3 cases) due to Meckel- Diverticula. On the other hand, we found 24 successful cases (38.0%) in NSR procedure with one recurrent after case. 39 others who failed with NSR continued to surgical reduction. Manual reduction was done for 31 patients with one case mortality due to pulmonary bleeding. Anastomosis resection (4 cases) and, stoma (4 cases) were decided for others surgical reduction. The relative risk (RR) on this study was 2.02 (p value < 0.05, CI 95%). CONCLUSION: Implementation of the SR procedure may reduce surgery rates in paediatric intussusception, thereby enhancing patient management. Furthermore, the success rate of hydrostatic reduction higher in under sedation procedure. We contribute to evolve insight of non-operative approaches of paediatric intussusception management, particularly in the Yogyakarta.

Esketamine mitigates mechanical ventilation-induced lung injury in chronic obstructive pulmonary disease rats via inhibition of the MAPK/NF-κB signaling pathway and reduction of oxidative stress.

PURPOSE: To investigate esketamine's impact on inflammation and oxidative stress in ventilated chronic obstructive pulmonary disease (COPD) rats, examining its regulatory mechanisms. METHODS: Rats were divided into four groups: control group (Con), COPD model group (M), COPD model with saline treatment group (M+S), and COPD model with esketamine treatment group (M+K), with 12 rats in each group. After two months, all rats underwent anesthesia and mechanical ventilation. Group M+K received 5 mg/kg esketamine intravenously, while Group M+S received the same volume of saline. Lung tissues were collected for analysis two hours later, including airway peak pressure, wet-to-dry(W/D) ratio, lung permeability index(LPI), hematoxylin and eosin(H&E) staining, and transmission electron microscopy(TEM). Tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-8(IL-8), and interleukin-10(IL-10) levels were determined by enzyme-linked immunosorbent assay(ELISA); phosphorylated Nuclear Factor Kappa B(p-NF-κB), mitogen-activated protein kinase 14(p38), phosphorylated p38 (p-p38), c-Jun N-terminal kinase(JNK), and phosphorylated JNK (p-JNK) expressions by Western blotting and immunohistochemistry; and malondialdehyde(MDA), myeloperoxidase(MPO), and superoxide dismutase(SOD) levels were also measured by corresponding biochemical assays. RESULTS: Lung specimens from groups M, M+S, and M+K manifested hallmark histopathological features of COPD. Compared with group Con, group M displayed increased peak airway pressure, W/D ratio, and LPI. In group M+K, compared with group M, esketamine significantly reduced the W/D ratio, LPI, and concentrations of pro-inflammatory cytokines TNF-α, IL-6, and IL-8 while concurrently elevating IL-10 levels. Furthermore, the treatment attenuated the activation of the NF-κB and MAPK pathways, indicated by decreased levels of p-NF-κB, p-p38, and p-JNK.Additionally, compared to group M, group M+K showed decreased MDA and MPO levels and increased SOD levels in lung tissue. CONCLUSION: Esketamine attenuates mechanical ventilation-induced lung injury in COPD rat models by inhibiting the MAPK/NF-κB signaling pathway and reducing oxidative stress.

The effect and mechanism of low-dose esketamine in neuropathic pain-related depression-like behavior in rats.

BACKGROUND: Clinical evidence suggests that Esketamine (ESK) is an effective treatment for depression. However, the effects of Esketamine in treating depression-like behavior induced by neuropathic pain is unclear. The underlying molecular mechanisms require further investigation to provide new therapeutic targets for the treatment of clinical neuropathic pain-related depression. METHODS: A neuropathic pain-related depression model was established in rats with spared nerve injury (SNI). Male Sprague-Dawley rats were randomly divided into four groups: Sham Group, SNI group, SNI + Normal Saline (NS) Group and SNI + ESK5mg/kg Group. Mechanical pain thresholds were measured to assess pain sensitivity in SNI rats. On the 14th day after surgery a forced swim test and sucrose preference test were used to evaluate the depressive-like behavior of rats in each group. Further, a proteomic analysis was used to quantify differentially expressed proteins. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed to explore the main protein targets of SNI in the medial prefrontal cortex. The expression of proteins was detected by Western blotting. RESULTS: A neuropathic pain-related depression model was established. Compared with the Sham group, the mechanical pain threshold was decreased significantly (13.2 ± 1.0 vs. 0.7 ± 0.01 g n = 8), while immobility on the forced swim test was also decreased (93.1 ± 7.4 vs. 169.5 ± 9.6 s n = 8), and sucrose preference rate was significantly increased (98.8 ± 0.3 vs. 73.1 ± 1.4n = 7) in SNI group rats. Compared with the SNI + NS group, the mechanical pain threshold was not statistically significant, while immobility on the forced swim test was clearly decreased (161.1 ± 11.6 vs. 77.9 ± 5.0 s n = 8), and sucrose preference rate was significantly increased (53.1 ± 8.9 vs. 96.1 ± 1.4n = 7) in SNI + ESK5mg/kg group rats. To further investigate the underlying mechanism, we employed proteomics to identify proteins exhibiting more than a 1.2-fold difference (P < 0.05) in expression levels within each group for subsequent analysis. Relative to the Sham group, 88 downregulated and 104 up-regulated proteins were identified in the SNI group, while 120 and 84 proteins were up- and down-regulated in the Esketamine treatment group compared with the SNI + NS group. Compared with Sham group, the expressions of mGluR5 and Homer1a were up-regulated in the medial prefrontal cortex (mPFC) in SNI group (mGluR5:0.97 ± 0.05 vs 1.47 ± 0.15, Homer1a:1.03 ± 0.06 vs 1.46 ± 0.16n = 6), and down-regulated after intervention with Esketamine (mGluR5:1.54 ± 0.11 vs 1.06 ± 0.07, Homer1a:1.51 ± 0.13 vs 1.12 ± 0.34n = 6). CONCLUSIONS: Low-dose Esketamine appeared to relieve depression-like behavior induced by neuropathic pain. The Homer1a-mGluR5 signaling pathway might be the mechanism of antidepressant effect of Esketamine.

Effect of modified opioid sparing anaesthesia on postoperative quality of recovery in patients undergoing laparoscopic bariatric surgery: protocol for a monocentre, double-blind randomised controlled trial - the MOSA study.

INTRODUCTION: Obesity patients undergoing laparoscopic bariatric surgery (LBS) are frequently encountered perioperative adverse events related to opioids-based anaesthesia (OBA) or opioids-free anaesthesia (OFA). While modified opioid-sparing anaesthesia (MOSA) has been shown to lower the occurrence of adverse events related to OBA and OFA. This study is to assess the efficacy of MOSA in enhancing the recovery quality among individuals undergoing LBS. METHODS AND ANALYSIS: A single-centre, prospective, double-blind, randomised controlled trial is conducted at a tertiary hospital. A total of 74 eligible participants undergoing elective LBS will be recruited and randomly allocated. Patients in the MOSA group will receive a combination of low-dose opioids, minimal dexmedetomidine, esketamine and lidocaine, while in the OBA group will receive standard general anaesthesia with opioids. Patients in both groups will receive standard perioperative care. The primary outcome is the quality of recovery-15 score assessed at 24 hours after surgery. Secondary outcomes include pain levels, anxiety and depression assessments, gastrointestinal function recovery, perioperative complication rates, opioid consumption and length of hospital stay. ETHICS AND DISSEMINATION: Ethical approval has been provided by the Ethical Committee of Yan'an Hospital of Kunming City (approval No. 2023-240-01). Eligible patients will provide written informed consent to the investigator. The outcomes of this trial will be disseminated in a peer-reviewed scholarly journal. TRIAL REGISTRATION NUMBER: The study protocol is registered at https://www.chictr.org.cn/ on 19 December 2023. (identifier: ChiCTR2300078806). The trial was conducted using V.1.0.

Comparing different postoperative sedation strategies for patients in the intensive care unit after cardiac surgery: A systematic review of randomized controlled trials and network meta-analysis.

BACKGROUND: Various postoperative sedation protocols with different anaesthetics lead to profound effects on the outcomes for post-cardiac surgery patients. However, a comprehensive analysis of optimal postoperative sedation strategies for patients in the intensive care unit (ICU) after cardiac surgery is lacking. METHODS: We systematically searched for randomized controlled trials (RCTs) in databases including PubMed and Embase. The primary outcome measured the duration of mechanical ventilation (MV) in the ICU, and the secondary outcome encompassed the length of stay (LOS) in the ICU and hospital and the monitoring adverse events. RESULTS: The literature included 18 RCTs (1652 patients) with 13 sedation regimens. Dexmedetomidine plus ketamine and sevoflurane were associated with a significantly reduced duration of MV when compared with propofol. Our results also suggested that dexmedetomidine plus ketamine may associated with a shorter LOS in ICU, and sevoflurane associated with a shorter LOS in the hospital, respectively. CONCLUSIONS: The combination of dexmedetomidine and ketamine seems to be a better option for adult patients needing sedation after cardiac surgery, and the incidence of side effects is lower with dexmedetomidine. These findings have potential implications for medication management in the perioperative pharmacotherapy of cardiac surgery patients.