Dex Group Research Articles

Impact of adding dexmedetomidine to various lidocaine concentrations in the interscalene brachial plexus block for upper limb surgery

Background. The interscalene brachial plexus block is widely used in orthopedic surgery for procedures on the proximal upper limb. However, the main concern remains the systemic toxicity of local anesthetics due to the use of their high concentrations. The purpose of the study was to investigate the effect of adding dexmedetomidine to lidocaine solutions of different concentrations in the interscalene brachial plexus block by examining the onset time and duration of motor block and analgesia. Materials and methods. The study included 75 patients who underwent elective upper limb surgery under interscalene brachial plexus block. They were divided into three groups (n = 25 each): control group I (L1%), group II (Dex L1%), and group III (Dex L0.5%). In group I, the brachial plexus block was performed using a 1% lidocaine solution with the addition of 50 mcg of epinephrine (1 : 400,000). In group II, 50 mcg of dexmedetomidine was added to the same solution, while group III (Dex L0.5%) used a 0.5% lidocaine solution combined with 50 mcg of dexmedetomidine. The duration of analgesia, motor function of the upper limb, hemodynamic changes, and side effects were assessed. Results. Preoperatively, the time of complete motor block onset (Me [25 %; 75 %]) in groups L1% and Dex L1% was 12.5 [10.0; 15.0] minutes, which was slightly shorter than in group Dex L0.5% (15.0 [15.0; 20.0] minutes; p = 0.06). The duration of complete motor block was longest in the Dex L1% group (330 [270; 440] minutes) compared to the Dex L0.5% group (305 [235; 348] minutes; p = 0.25) and the L1% group (185 [180; 255] minutes; p < 0.002). The duration of analgesia in the Dex L1% group (460 [330; 480] minutes) was significantly longer than in the Dex L0.5% group (305 [248; 425] minutes; p = 0.35) and the L1% group (270 [210; 333] minutes; p = 0.018), with no statistically significant difference between Dex L0.5% and L1% groups (p = 0.29). The heart rate was significantly reduced at the start and the end of surgery compared to baseline in the Dex L1% and Dex L0.5% groups. Systolic blood pressure was significantly reduced in all groups at all stages compared to baseline. Conclusions. The addition of dexmedetomidine prolongs both motor block and analgesia after interscalene brachial plexus block and allows the lidocaine concentration to be reduced to 0.5 % without compromising efficacy.

Effect of different doses of dexmedetomidine on atrial fibrillation in adults after cardiac surgery.

In this study, we compared the effects of various doses of dexmedetomidine on the incidence of atrial fibrillation following cardiac surgery in adults. 224 adult patients who underwent elective cardiac surgery were randomly assigned to two groups. The DEX0.5 group received a continuous infusion of dexmedetomidine at a rate of 0.5 μg·kg⁻1·h⁻1, while the DEX1 group received it at a rate of 1 μg·kg⁻1·h⁻1 during the induction of anesthesia, which was maintained for 24 hours. The primary outcome was the incidence of atrial fibrillation, while the secondary outcomes included other tachyarrhythmias, bradycardia, hypotension, duration of mechanical ventilation, time spent in the cardiac care unit, and length of hospitalization. A total of 101 patients were included in the DEX0.5 group, while 104 patients were included in the DEX1 group. The incidence of atrial fibrillation was significantly lower in the DEX1 group compared to the DEX0.5 group (10.6% vs. 21.8%, P = 0.029). Additionally, the duration of mechanical ventilation was shorter in the DEX1 group than in the DEX0.5 group (8.9 vs. 15.2 hours, P = 0.018). Logistic regression analyses were conducted to investigate the factors influencing atrial fibrillation. The results indicated that the dose of dexmedetomidine was the only independent predictor (odds ratio = 0.394, 95% confidence interval 0.172 to 0.903, P = 0.028). Compared to a continuous infusion of 0.5 μg·kg⁻1·h⁻1, this study suggested that administering dexmedetomidine at a dose of 1 μg·kg⁻1·h⁻1 for 24 hours is effective in reducing the incidence of atrial fibrillation following cardiac surgery.

Efficacy of Dexamethasone as an Adjuvant for Scalp Nerve Blocks to Prolong Analgesia: A Prospective, Double-Blind, Randomized Controlled Study.

Scalp nerve blocks (SNB) may significantly reduce post-craniotomy pain (PCP) but only for a short period of time. Dexamethasone, as an adjuvant to local anesthetics, was reported to prolong the analgesia duration of never block; however, the addition of dexamethasone to SNB is rare. We therefore tested the hypothesis that dexamethasone as an adjuvant to bupivacaine in SNB is positive after craniotomy. Patients elective for craniotomy were randomly assigned to receive SNB with bupivacaine alone compared with dexamethasone and bupivacaine. The primary outcome was the duration of analgesia. The secondary outcomes include the cumulative amount of sufentanil consumption, the numeric rating scale (NRS), patient satisfaction score (PSS), the complications during the postoperative period, and SNB's relevant adverse events. There were 156 subjects included and 78 patients in each group (control and DEX group). The analgesia duration was significantly prolonged in the DEX group compared with the control group (660min (390,1005) vs 420min (314,504)) (p<0.001). The postoperative sufentanil consumption was lower in the DEX group compared with the control group at 12h (P<0.001), 24h (P=0.014), and 48h (P=0.049). The NRS scores were significantly lower in the DEX group compared with the control group at 8h (P<0.001) and 12h (P=0.007) after craniotomy. From 4h to 16h postoperative, the PSS in the control group was lower than the DEX group (P < 0.05). Perineural dexamethasone as an adjuvant to bupivacaine without background glucocorticoid has the potential to improve the postoperative analgesic effect and patients' satisfaction without serious complications after craniotomy.

Effects of the combination of Epimedium brevicornum Maxim, Ligustrum lucidum Ait and Dexamethasone on asthmatic rats by endogenous glucocorticoid pathway.

The theory of traditional Chinese medicine (TCM) believes that kidney deficiency is the fundamental cause of chronic refractory asthma, accompanied by pathological changes such as airway remodeling and a reduction of endogenous glucocorticoid (GC) synthesis. The combination of Epimedium brevicornum Maxim (EB) and Ligustrum lucidum Ait (LL) is frequently used in TCM for kidney tonifying and the alleviation of asthma symptoms. This approach is based on Pei-Ben formula, a renowned treatment for asthma developed by the distinguished Shanghai Practitioner, Professor Huiguang Xu, over 30 years of clinical experience. Long-term use of exogenous GC in the treatment of asthma lead to the inhibition of endogenous GC synthesis and further hypothalamic-pituitary-adrenal (HPA) axis function. Our previous experiments confirmed that the combination of Epimedium brevicornum Maxim and Ligustrum lucidum Ait (EL) with dexamethasone (Dex) enhances kidney Yin and Yang, boosts endogenous GC levels, and improves airway remodeling and HPA axis function in asthmatic rats. However, the underlying mechanism remains unclear. This study aimed to investigate the regulatory effect of EL with Dex on endogenous GC pathway in asthmatic rats. We employed an ovalbumin (OVA)-induced asthma rat model and an OVA-induced asthma rat model with Metyrapone (Met, an inhibitor of endogenous GC synthesis) intervention to evaluate the effects of Dex, EL and their combination (EL+Dex) on asthma treatment. The assessment included the lung histopathology, GC receptors (GR) countent and GC-GR binding in bronchoalveolar lavage fluid (BALF), corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone (CORT), cortisol (COR), interleukin 6 (IL-6), and immunoglobulin E (IgE) in serum, GC metabolites in urine, and hydroxysteroid dehydrogenase (HSD) 11B1, HSD11B2, cytochrome P450 family 11 subfamily B member 1 (CYP11B1) and steroidogenic factor 1 (SF1) in lung, liver, and adrenal gland. In the OVA-induced asthma model, we found that endogenous GC synthesis was suppressed in both the asthma group and the Dex group. The combination of EL and Dex could enhance HPA axis function, increase protein expression of key endogenous GC synthesis factors (HSD11B1, HSD11B2 in lung; CYP11B1, SF1 in adrenal; HSD11B2, CYP11B1 in liver), and improve the level of endogenous GC synthesis. In the OVA-induced asthma model with Met intervention, we observed a highly significant endogenous suppression in both the asthma+Met group and the Dex group. Additionally, the use of EL, either alone or in combination with Dex, demonstrated a significant effect in improving HPA axis function and enhancing the protein expression of key endogenous GC synthesis factors (HSD11B1, HSD11B2 in lung; HSD11B1, HSD11B2, CYP11B1, SF1 in adrenal; HSD11B1 in liver). In both asthma models, the combination of EL and Dex could relieve the pathological changes of airway inflammation and airway remodeling, and enhance GC-GR binding capacity. This study reveals that the combined use of EL and Dex could improve airway inflammation and airway remodeling in asthma through enhancing HPA axis function, endogenous GC synthesis, and GC-GR binding, offering a promising therapeutic strategy for asthma management.

Dexmedetomidine therapy promotes cardiac dysfunction and increases mortality in sepsis: A translational study.

Previous studies demonstrated that dexmedetomidine (Dex) posttreatment aggravated myocardial dysfunction and reduced survival in septic mice. Yet, whether Dex elicits similar effects in septic patients as defined by Sepsis-3 remains unknown. This study sought to assess the effects of Dex-based sedation on mortality and cardiac dysfunction in septic patients defined by Sepsis-3 and to further reveal the mechanisms in septic rats. In the retrospective cohort study, patients were categorised into sepsis with Dex, other sedatives (propofol or midazolam) or without sedatives, mortality at 28days were compared, and patients with measurements of cardiovascular biomarkers and echocardiography were used to examine the effect of Dex on cardiac dysfunction. Septic rats and Langendorff-perfused isolated rat hearts were used, cardiac function, mortality and pro-inflammatory mediators were analyzed. The all-cause mortality of septic patients receiving Dex reached to 35.2% on Day 28, significantly higher than that of patients with other sedatives (16.1%), while no difference with group of no sedatives (27.3%). Patients in Dex group showed lower left ventricular EF and lateral mitral annular early diastolic peak velocities, but higher interventricular septum diastolic dimension compared to those with other sedatives. The plasma levels of H-FABP, NT-proBNP and HMGB1 in Dex and other sedative groups showed no difference, while both were significantly lower than the group of no sedative. Notably, Dex posttreatment deteriorated cardiac dysfunction, increasing mortality in septic rats with enhanced systemic and myocardial proinflammatory mediators, including TNF-α, IL-1β, IL-6 and VCAM-1. Mechanistical study by Langendorff-perfusion revealed that Dex directly acted on the heart, aggravating LPS-induced myocardial inflammation and dysfunction. These results suggest that Dex increases mortality and deteriorates myocardial dysfunction compared with other sedatives in septic patients defined by Sepsis 3.0, maybe partly through promoting proinflammatory response via directly acting on the heart.

Does Intralesional Steroid Injection Effectively Mitigate Vocal Fold Scarring in A Rabbit Model?

To assess the efficacy of intralesional steroid treatment in preventing vocal fold scarring following vocal fold surgery using a rabbit model. The research involved 42 male New Zealand white rabbits. Fourteen rabbits underwent vocal fold scar surgery using a 532nm laser and served as controls (control group). The remaining rabbits were divided into two groups of 14: one group received vocal fold scar surgery followed by dexamethasone injection (Dexa group) and the other received the same surgery followed by triamcinolone injection (Triam group). Four weeks after surgery, histological examinations and high-speed video analyses of vocal fold vibration were conducted. The maximum amplitude of vibration was the primary measure for assessing vocal fold function. In addition, real-time polymerase chain reaction (PCR) studies were undertaken to analyze scar regeneration and remodeling. The maximum amplitude differences were notably higher in the Dexa and Triam groups than in controls. Histologically, the collagen density (CD) ratios in both the Dexa and Triam groups were significantly reduced compared with controls. Real-time PCR analysis indicated marked elevations of Has-2 and Mmp-9 in the Dexa and Triam groups relative to controls. Intralesional steroid injections after vocal fold surgery are effective for reducing vocal fold scarring in a rabbit model. NA Laryngoscope, 135:176-182, 2025.

Function of NLRP3 inflammasome activation in multiple myeloma

ABSTRACT Objective: The drug resistance of multiple myeloma (MM) cells is one of the main causes of relapse, refractory and progression of MM. Methods: First, Western blot analysis was used to detect the expression levels of NLRP3, ASC, pro-IL-1β and cleaved IL-1β, and RT-qPCR was used to detect the mRNA expression levels of them. The expression levels of IL-1β and IL-18 in the supernatant were detected by ELISA, and the expression levels of these factors in the activated group and the control group were compared to verify the activation of BMMCs and KM3. Result: 1. The protein expression of NLRP3 and cleavd-IL-1β in the BMMCs cells was significantly higher than that of the control group (P < 0.05). The mRNA expression levels of caspase-1 and IL-1β were higher than those of the control group (P = 0.03, P = 0.02). 2. The protein expression levels of NLRP3 and cleaved-IL-1β in the KM3 cells were significantly higher than those of the control group (P < 0.05). The expressions of caspase-1 mRNA(P = 0.016) and IL-1β mRNA(P = 0.037) were significantly increased compared with the control group. 3. The early apoptosis results of BMMCs showed that the apoptosis rate of the LPS+ATP+Dex group was lower than that of the Dex group (P = 0.017). The early apoptosis rate of the LPS+ATP+Dex+Vel group was decreased compared with the Dex+Vel group (P = 0.045). 4. The early apoptosis rate of KM3 in the LPS+ATP+Dex group was lower than that in the Dex group (P = 0.03). Conclusion: 1. LPS+ATP can activate NLRP3 inflammasome in multiple myeloma cells. 2. Activation of NLRP3 inflammasome inhibits the early apoptosis of myeloma cells induced by dexamethasone and bortezomib.

The effect of dexmedetomidine on acute kidney injury after elective major abdominal surgery : a retrospective single-center propensity score matched study

BackgroundMajor abdominal surgery is a kind of high-risk surgery type for postoperative acute kidney injury (AKI) among non-cardiac surgeries. Despite dexmedetomidine exerts significant renal protective effects in cardiac surgeries and animal studies, whether it is associated with a lower incidence of AKI in major abdominal surgeries remains unclear.MethodsFrom January 2019 to July 2021, patients undergoing elective major abdominal surgery in West China Hospital were enrolled. Participants were divided into two groups based on exposure to continuous intravenous dexmedetomidine: the Dex group (exposed) and the Control group (not exposed). The primary outcome was the incidence of AKI in the postoperative 7 days. Secondary outcomes included intraopertive average urine output, renal function on the first day after surgery, incidence of postoperative dialysis, postoperative intensive care unit (ICU) admission, in-hospital mortality, length of hospital stay, incidence of intraoperative hypotension and bradycardia, and intraoperative use of inotropes and vasopressors. Propensity score matching (PSM), based on participants’ baseline and intraoperative characteristics, was performed to minimize potential bias. Furthermore, a subgroup analysis was conducted based on the infusion rate and the use of a loading dose to explore the effects of different methods of dexmedetomidine administration on AKI. The subgroups included: loading dose, non-loading dose, low-infusion rate (infusion rate ≤ 0.4 µg/kg/h), and high-infusion rate (infusion rate > 0.4 µg/kg/h).ResultsAfter PSM with a ratio of 1:1, a total of 8836 patients were successfully matched. Dexmedetomidine administration had no association with the incidence of postoperative AKI, serum creatinine (Scr) level on the first postoperative day, incidence of postoperative dialysis, postoperative ICU admission, in-hospital mortality, length of hospital stay, intraoperative hypotension, or the use of inotropes and vasopressors, but had association with increased intraoperative average urine output (122.95 (76.80, 189.27) vs. 104.65 (67.04, 161.07) ml/h, P < 0.001), higher value of estimated glomerular filtration rate (eGFR) (97.33 ± 15.95 vs. 96.13 ± 16.35 ml/min/1.73m2, P < 0.001) on the first day after surgery and a higher incidence of intraoperative bradycardia (37.0% vs. 30.6%; P < 0.001). In the loading dose subgroup, dexmedetomidine use was significantly associated with a reduced incidence of postoperative AKI (odds ratio (OR): 0.44, 95% confidence interval (CI): 0.23–0.76, P = 0.006).The association between dexmedetomidine and postoperative AKI was absent in subgroups of high or low infusion rate and no loading dose use.ConclusionIn this single-center retrospective propensity-matched study, we did not detect a significant overall difference in post-operative AKI rates between patients treated with or without dexmedetomidine during major abdominal surgery. However, though additional prospective data are needed, our study found that administering dexmedetomidine with a loading dose may be associated with lower rates of AKI, potentially indicating a renoprotective effect of loading-dose dexmedetomidine in this setting.

Potential Effect of Defatted Mealworm Hydrolysate on Muscle Protein Synthesis in C2C12 Cells and Rats

(1) Background: the objective of this study was to examine the impact of defatted mealworm hydrolysate (DMH), formulated through protein hydrolysis, on muscle protein synthesis in C2C12 cells and rats; (2) Methods: C2C12 cells were treated with dexamethasone and DMH, and cell viability was quantified using the MTT assay. Twenty-four Sprague–Dawley rats were divided into three groups (control, DEX, and DEX + DMH) and treated for 8 weeks. The DEX and DEX + DMH groups were administered intraperitoneal injections of DEX at a concentration of 2.25 mg/kg over a 3-d period. The control and DEX groups were fed a control diet, whereas the DMH group had part of the protein composition of the control diet replaced with 3.5% of DMH. The impact of DMH on muscle protein synthesis was evaluated through the measurement of grip strength, gastrocnemius and tibialis anterior muscle weights, and the investigation of muscle protein synthesis and degradation factor mRNA expression utilising the real-time PCR method; (3) Results: in vitro experiments demonstrated that treatment with DMH at concentrations greater than 5 mg/mL markedly alleviated DEX-induced injury in C2C12 cells. In vivo experiments demonstrated that the mRNA expression levels of myogenin and myoblast determination proteins, which promote muscle protein synthesis, were significantly increased. Furthermore, rats fed DMH exhibited significantly enhanced grip strength and tibialis anterior weight; (4) Conclusions: these findings indicate that DMH may serve as a functional material capable of promoting muscle protein synthesis and that the utilization of proteolytic enzymes is advantageous for the effective utilization of mealworms.

Human Umbilical Cord Mesenchymal Stem Cells Prevent Steroid-Induced Avascular Necrosis of the Femoral Head by Modulating Cellular Autophagy.

Glucocorticoids (GCs) are critical regulatory molecules in the body, commonly utilized in clinical practice for their potent anti-inflammatory and immunosuppressive properties. However, prolonged, high-dose GC therapy is frequently associated with femoral head necrosis, a condition known as glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Emerging evidence suggests that enhanced autophagy may mitigate apoptosis, thereby protecting osteoblasts from GC-induced damage and delaying the progression of ONFH. This study aims to evaluate whether human umbilical cord mesenchymal stem cells (hUCMSCs) can alleviate GC-induced osteoblast injury through autophagy modulation. In vitro, osteoblasts were exposed to GCs for 48 h, followed by co-culture with hUCMSCs for an additional 12 h before further analysis. The osteoblasts were categorized into four experimental groups: (A) control group, (B) Dex group, (C) Dex + hUCMSC group, and (D) Dex + hUCMSC + 3-MA group. In vivo, rabbits were assigned to one of four groups: Con, MPS, core decompression (CD), and CD + hUCMSC (n = 12 per group), and subsequently subjected to CT imaging and HE staining. In vitro results demonstrate that hUCMSC treatment mitigated GC-induced osteoblast apoptosis and preserved osteogenic activity through autophagy modulation. In vivo, infusion of hUCMSCs enhanced trabecular thickness in the femoral head and improved the femoral head microenvironment. These findings suggest that hUCMSCs protect osteoblasts from GC-induced damage by regulating autophagy, offering new insights into the potential therapeutic use of hUCMSCs for treating ONFH via autophagy enhancement.

Entacapone alleviates muscle atrophy by modulating oxidative stress, proteolysis, and lipid aggregation in multiple mice models

BackgroundSkeletal muscle atrophy significantly affects quality of life and has socio-economic and health implications. This study evaluates the effects of entacapone (ENT) on skeletal muscle atrophy linked with oxidative stress and proteolysis.MethodsC2C12 cells were treated with dexamethasone (Dex) to simulate muscle atrophy. Four murine models were employed: diaphragm atrophy from mechanical ventilation, Dex-induced atrophy, lipopolysaccharide (LPS)-induced atrophy, and hyperlipidemia-induced atrophy. Each model utilized entacapone (10 mg/kg), with sample sizes: Control (9), MV (11), MV + ENT (5) for diaphragm atrophy; Control (4), Dex (4), Dex + ENT (5) for Dex model; Control (4), LPS (4), LPS + ENT (5) for LPS model; and similar for hyperlipidemia. Measurements included muscle strength, myofiber cross-sectional area (CSA), proteolysis, oxidative stress markers [uperoxide dismutase 1 (SOD1), uperoxide dismutase 2 (SOD2), 4-hydroxynonenal (4-HNE)], and lipid levels.ResultsOur findings confirm Dex-induced muscle atrophy, evidenced by increased expression of muscle atrophy-associated proteins, including Atrogin-1 and Murf-1, along with decreased diameter of C2C12 myotubes. Atrogin-1 levels rose by 660.6% (p &amp;lt; 0.05) in the Dex group compared to control, while entacapone reduced Atrogin-1 by 84.4% (p &amp;lt; 0.05). Similarly, Murf-1 levels increased by 365% (p &amp;lt; 0.05) in the Dex group and were decreased by 89.5% (p &amp;lt; 0.05) with entacapone. Dexamethasone exposure induces oxidative stress, evidenced by the upregulation of oxidative stress-related proteins Sod1, Sod2, and 4-HNE. Entacapone significantly reduced the levels of these oxidative stress markers, enhancing GSH-PX content by 385.6% (p &amp;lt; 0.05) compared to the Dex-treated group. Additionally, ENT effectively reduced the Dex-induced increase in MDA content by 63.98% (p &amp;lt; 0.05). Furthermore, entacapone effectively prevents the decline in diaphragm muscle strength and myofiber CSA in mice. It also mitigates diaphragm oxidative stress and protein hydrolysis. Additionally, entacapone exhibits the ability to attenuate lipid accumulation in the gastrocnemius muscle of hyperlipidemic mice and alleviate the reduction in muscle fiber CSA.ConclusionOur findings suggest that entacapone is a promising therapeutic candidate for muscle atrophy, functioning through the reduction of oxidative stress, proteolysis, and lipid aggregation. Future research should explore the underlying mechanisms and potential clinical applications of entacapone in muscle-wasting conditions.

Comparison of intranasal versus intravenous dexmedetomidine in postoperative pain control in traumatic mandibular fractures surgery: a randomized clinical trial

Objective: Effective pain management in mandibular fractures is crucial due to the complications associated with opioids, such as respiratory depression and re-intubation. Non-opioid methods are therefore important. This study aims to compare the effectiveness, safety, and efficiency of intranasal (IN) versus intravenous (IV) dexmedetomidine (Dex) for reducing acute pain following mandibular surgery. Methods: This study was a randomized, double-blind clinical trial. All patients underwent general anesthesia, laryngoscopy, and intubation in a standardized manner. For the IN administration group, Dex was prescribed at a dose of 0.2 µ/kg (in the form of drops) half an hour before the start of anesthesia. For the IV administration group, Dex was administered at a dose of 0.5 µ/kg intravenously over ten minutes, half an hour before anesthesia. During the first 24 hours after surgery, pain intensity and the total amount of opioid medication (measured in mg of pethidine) were recorded for each patient. Results: There was no significant difference in pain intensity between the two groups in the post-anesthesia care unit (P=0.898), one hour (P=0.052) and 24 hours post-surgery (P=0.898). However, pain intensity was significantly lower in the IN Dex group at the second (P=0.044), fourth (P=0.041), sixth (P=0.048), and twelfth (P=0.025) hours. Total pethidine injected in the IN Dex group was significantly lower than in the IV Dex group (P=0.041). Conclusion: This study underscores the efficacy of IN Dex as a viable alternative for postoperative pain management in traumatic mandibular fracture surgeries

Effects of esketamine combined with dexmedetomidine on postoperative delirium and quality of recovery in elderly patients undergoing thoracoscopic radical lung cancer surgery: a randomized controlled trial.

This study aimed to investigate the effects of esketamine (Esk) combined with dexmedetomidine (Dex) on postoperative delirium (POD) and quality of recovery (QoR) in elderly patients undergoing thoracoscopic radical lung cancer surgery. In this prospective, randomized, and controlled study, 172 elderly patients undergoing thoracoscopic radical lung cancer surgery were divided into two groups: the Esk+Dex group (n=86) and the Dex group a (n=86). The primary outcome was the incidence of POD within 7days after surgery and the overall Quality of Recovery-15 (QoR-15) scores within 3days after surgery. Secondary outcomes included postoperative adverse reactions, extubation time, PACU stay, and hospitalization time. Serum levels of IL-6, IL-10, S100β protein, NSE, CD3+, CD4+, and CD8+ were detected from T0 to T5. Compared with the Dex group, the incidence of POD in the Esk+Dex group was significantly lower at 7days after surgery (14.6% vs 30.9%; P=0.013). The QoR-15 score was significantly increased 3days after surgery (P<0.01). Levels of IL-6 and CD8+ were significantly decreased, and IL-10 levels were significantly increased at T1-T2 (P<0.05). At T1-T4, NSE levels were significantly decreased, while CD3+ and CD4+/CD8+ values were significantly increased (P<0.01). At T1-T5, serum S100β protein concentration decreased significantly, and CD4+ value increased significantly (P<0.01). The incidence of nausea/vomiting and hyperalgesia decreased significantly 48hours after surgery (P<0.01). The duration of extubation, PACU stay, and postoperative hospitalization were significantly shortened. Esketamine combined with dexmedetomidine can significantly reduce the POD incidence and improve the QoR in patients undergoing thoracoscopic radical lung cancer surgery, which may be related to the improvement of cellular immune function.

Dexmedetomidine Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting MDH2 Lactylation via Regulating Metabolic Reprogramming.

Myocardial ischemia-reperfusion injury (MIRI) significantly worsens the outcomes of patients with cardiovascular diseases. Dexmedetomidine (Dex) is recognized for its cardioprotective properties, but the related mechanisms, especially regarding metabolic reprogramming, have not been fully clarified. A total of 60 patients with heart valve disease are randomly assigned to Dex or control group. Blood samples are collected to analyze cardiac injury biomarkers and metabolomics. In vivo and vitro rat models of MIRI are utilized to assess the effects of Dex on cardiac function, lactate production, and mitochondrial function. It is found that postoperative CK-MB and cTNT levels are significantly lower in the Dex group. Metabolomics reveals that Dex regulates metabolic reprogramming and reduces lactate level. In Dex-treated rats, the myocardial infarction area is reduced, and myocardial contractility is improved. Dex inhibits glycolysis, reduces lactate, and improves mitochondrial function following MIRI. Lactylation proteomics identifies that Dex reduces the lactylation of Malate Dehydrogenase 2（MDH2), thus alleviating myocardial injury. Further studies reveal that MDH2 lactylation induces ferroptosis, leading to MIRI by impairing mitochondrial function. Mechanistic analyses reveal that Dex upregulates Nuclear Receptor Subfamily 3 Group C Member 1（NR3C1)phosphorylation, downregulates Pyruvate Dehydrogenase Kinase 4 (PDK4), and reduces lactate production and MDH2 lactylation. These findings provide new therapeutic targets and mechanisms for the treatment for MIRI.

Comparison of intravenous nalbuphine and dexmedetomidine in combination with lidocaine aerosol inhalation in awake direct laryngoscopy: a randomized, double-blind, placebo-controlled trial

BackgroundThe airway should be thoroughly and accurately evaluated before anesthesia induction and endotracheal intubation. Awake direct laryngoscopy (ADL) can provide rapid, accurate, and intuitive airway assessment, especially for suspected difficult airways, and sometimes eliminates the need for fiberoptic intubation in some suspicious difficult airway cases. However, an optimal regimen has not been determined.MethodsIn this double-blind, controlled study, prior to ADL, 60 patients scheduled for general anesthesia were randomly allocated to receive 0.75 μg/kg of dexmedetomidine (Dex group, n = 20), 0.15 mg/kg of nalbuphine (Nal group, n = 20), or a placebo (control group, n = 20) intravenously over 10 min. At the same time, all study subjects received nebulized lidocaine for 15 min. The primary outcome was patient tolerance as assessed by a 5-point ADL comfort score, while secondary outcomes included satisfaction, coughing, pain, nausea and vital signs.ResultsPatients undergoing ADL in the Nal group had higher tolerance scores than those in the control and Dex groups [4 (3,4) vs. 3 (2,2.75), P < 0.017, and 4 (3,4) vs. 2 (2,2,75), P < 0.001, respectively] and higher satisfaction [7 (6,8) vs. 4 (3,5.75), P < 0.017, and 7 (6,8) vs. 5.5 (5,6), P < 0.001, respectively]. Additionally, the Nal group had significantly fewer adverse events, such as pain and nausea than the control and Dex groups. The sedation score and peripheral oxygen and saturation were significantly higher in the Nal group than in the Dex group, with no difference between the Nal and control groups (P < 0.001, P = 0.159, respectively).ConclusionsIntravenous nalbuphine in combination with lidocaine aerosol inhalation significantly improved patient tolerance and satisfaction while reducing nausea, coughing, pain, sedation, and SpO2 levels during ADL.

Dexmedetomidine decreases cerebral hyperperfusion incidence following carotid stenting: A double-blind, randomized controlled trial.

Cerebral hyperperfusion syndrome (CHS) is a severe complication after carotid artery stenting (CAS). Dexmedetomidine (Dex) is an α2 adrenoceptor agonist with sedative, analgesic, and neuroprotective properties. This randomized, double-blind, placebo-controlled trial (ChiCTR1900024416) aims to investigate whether prophylactic low-dose Dex decreases CH-induced brain injury following CAS. After obtaining written informed consent, patients aged 18-80 who underwent CAS were enrolled between July 2019 and October 2022. Patients were randomly assigned to receive either intravenous Dex (0.1μg/kg/h, until post-operative day 3) (n= 80) or placebo (normal saline) (n= 80). The primary endpoint was the incidence of CH and CHS assessed up to the third post-operative day. The secondary endpoints included National Institute of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) scores within 30days of operation, extubation time, discharge from the hospital within 7days post-operation, length of hospital stay post-operation, and all-cause 30-day mortality. Blood samples were collected before and after surgery for lipidomics, brain-derived neurotrophic factor (BDNF), and neurofilament light chain (Nfl) measurements. Acceptability, safety, and efficacy were evaluated by Cox model and logistic model. CH occurred in 30 (37.5%) of 80 patients who received a placebo compared to 9 (11.2%) of 80 patients given Dex (prevalence: odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.088-0.467; p<0.001; incidence: hazard ratio [HR]: 0.27, 95% CI: 0.14-0.50; p<0.001). CHS was significantly higher in the placebo group (13.75%) than in the Dex group (2.5%) (prevalence: [OR]: 0.161, 95% CI: 0.024-0.626; p= 0.020; incidence: [HR]: 0.17, 95% CI: 0.06-0.52; p= 0.009). Dex significantly upregulated BDNF, decreased Nfl, and uniquely increased lysophosphatidylethanolamine. A low prophylactic dose of Dex significantly reduced the incidence of CH and CHS up to 72h after CAS. This work was funded byNational Natural Science Foundation of China(no.82271288) andtheHenan Provincial Science and Technology Research Project(nos.242300421192andJQRC2023004).

Dexamethasone acetate loaded poly(ε-caprolactone) nanofibers for rat corneal chemical burn treatment

Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1β, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1β and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1β and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

Effects of Dexmedetomidine in Improving Oxygenation and Reducing Pulmonary Shunt in High-Risk Pediatric Patients Undergoing One-Lung Ventilation for Thoracic Surgery: A Double-Blind Randomized Controlled Trial.

Background and objectives Pediatric thoracic surgery has unique considerations due to the immaturity of the respiratory system anatomically and physiologically, which presents technical and pharmacological considerations, including the very common technique of one-lung ventilation (OLV), which causes serious complications in children. Therefore, we investigated the effects of dexmedetomidine on oxygenation and pulmonary shunt fraction (Qs/Qt) in high-risk pediatric patients undergoing OLV for thoracic surgery. This randomized controlled trial aimed to investigate dexmedetomidine's effect on the partial pressure of arterial oxygen (PaO2) and pulmonary shunt fraction (Qs/Qt). Methods A total of 63 children underwent thoracic surgery with OLV and were divided into two groups. The dexmedetomidine group (group Dex, n = 32) received dexmedetomidine (0.4 μg/kg/hour), and the placebo group (group placebo, n = 31) received normal saline. Two arterial and central venous blood samples were taken for arterial and venous blood gas analysis at four time points: T1 (10 minutes after mechanical ventilation of total lung ventilation), T2 (10 minutes after OLV), T3 (60 minutes after OLV), and T4 (20 minutes after the end of OLV). At these intervals, the following parameters were measured: PaO2, Qs/Qt, mean arterial pressure (MAP), heart rate (HR), and peak inspiratory pressure (PIP). Results The two groups had no significant differences in FEV1/FVC and baseline pulmonary shunt fraction (Qs/Qt). Dexmedetomidine significantly improved PaO2 compared with placebo during OLV (T2 and T3). There was a significant decrease in Qs/Qt compared with placebo during OLV (T2, T3, and T4). There was a decrease in PIP compared with placebo during OLV (T2 and T3). No statistically significant differences in MAP or HR were observed between the groups. Conclusion Infusion of dexmedetomidine during OLV in high-risk pediatric thoracic surgery reduces shunt and pulmonary shunt fraction Qs/Qt, improves PaO2 and body oxygenation, reduces PIP and pressure load, and maintains hemodynamic stability (MAP, HR).

Haemodynamic effect of dexmedetomidine during paediatric kidney transplantation.

Dexmedetomidine is increasingly used for its ability to stabilise haemodynamic status during general anaesthesia. However, there is currently no data on paediatric kidney transplant recipients (pKTR). This study investigates the haemodynamic impact of dexmedetomidine administered perioperatively in pKTR. From 2019 to 2023, a retrospective study was conducted at Nantes University Hospital involving all pKTR under 18 years of age. The study compared intraoperative haemodynamic parameters between patients administered dexmedetomidine during kidney transplantation (DEX group) and those who did not receive it (no-DEX group). Mean arterial pressure (MAP) and heart rate (HR) were monitored throughout the duration of anaesthesia and compared. Graft function was assessed based on creatinine levels and glomerular filtration rate (GFR) at specific intervals. The perioperative use of fluids and vasoactive drugs, as well as their administration within 24 h post-surgery, were analysed. Thirty-eight patients were enrolled, 10 in the DEX group and 28 in the no-DEX group. Intraoperative HR was similar between the groups; however, MAP was higher in the DEX group (mean difference 9, standard deviation (SD, 1-11) mmHg, p = 0.039). No differences were found regarding the use of fluid and vasoactive drug therapy between groups. GFR at 1 month post-transplantation was significantly elevated in the DEX group (p = 0.009). pKTR receiving intraoperative dexmedetomidine exhibited higher perioperative MAP compared to those not administered dexmedetomidine. Additionally, the DEX group demonstrated superior graft function at 1 month. The direct impact of dexmedetomidine on immediate postoperative graft function in pTKR warrants further investigation in a prospective multicentre randomised study.

Exercise-activated hepatic autophagy combined with silymarin is associated with suppression of apoptosis in rats subjected to dexamethasone induced- fatty liver damage.

There is a need for effective treatments for non-alcoholic fatty liver disease (NAFLD) that are economically inexpensive, and have few side effects. The present study aimed to investigate exercise training and silymarin on hepatocyte death factors in rats with liver damage. Forty-nine male Wistar rats were assigned to seven groups: sedentary control, fatty liver control (DEX), fatty liver + high-intensity interval training (HIIT), fatty liver + HIIT + silymarin (HIIT + SILY), fatty liver + continuous training (CT), fatty liver + CT + silymarin (CT + SILY), and fatty liver + silymarin (SILY). A subcutaneous injection of dexamethasone for 7 days was used to induce fatty liver in rats. Masson's trichrome and hematoxylin-eosin staining were done to evaluate hepatic injury. The hepatocyte apoptosis was determined by TUNEL assay. Real-Time PCR was conducted to evaluate the gene expressions of caspase-9, adenosine monophosphate-activated protein kinase (AMPKα1), mitofusin 2 (Mfn2), and damage-regulated autophagy modulator (DRAM). Liver tissue changes and serum levels of liver enzymes were also evaluated. Liver apoptosis was decreased in the CT, HIIT, HIIT + SILY and CT + SILY groups compared to the DEX group. Both continuous and high-intensity training models produced beneficial alterations in liver morphology and hepatic injuries that were significant in exercise training + silymarin group. This impact was accompanied by increased AMPKα1 and DRAM gene expression and decreased caspase-9 and Mfn2 gene expression. Liver enzyme levels were high in the DEX group and treatment with silymarin significantly reduced it. Silymarin supplementation combined with interval or continuous training substantially improves DEX-induced hepatic steatosis and hepatocyte injury mostly through suppressing liver apoptosis and upregulating autophagy, which may provide a novel perspective for NAFLD treatment.