BACKGROUND: Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is widely used for sedation and anesthesia in patients undergoing hepatectomy. However, the effect of DEX on autophagic flux and liver regeneration remains unclear.
OBJECTIVE: This study aimed to determine the role of DEX in hepatocyte autophagic flux and liver regeneration after PHx.
METHODS: In mice, DEX was intraperitoneally injected 5 min before and 6 h after PHx. In vitro, DEX was co-incubated with culture medium for 24 h. Autophagic flux was detected by LC3-II and SQSTM1 expression levels in primary mouse hepatocytes and the proportion of red puncta in AML-12 cells transfected with FUGW-PK-hLC3 plasmid. Liver regeneration was assessed by cyclinD1 expression, Edu incorporation, H&E staining, ki67 immunostaining and liver/body ratios. Bafilomycin A1, si-GSK3β and Flag-tagged GSK3β, α2-ADR antagonist, GSK3β inhibitor, AKT inhibitor were used to identify the role of GSK3β in DEX-mediated autophagic flux and hepatocyte proliferation.
RESULTS: Pre- and post-operative DEX treatment promoted liver regeneration after PHx, showing 12 h earlier than in DEX-untreated mice, accompanied by facilitated autophagic flux, which was completely abolished by bafilomycin A1 or α2-ADR antagonist. The suppression of GSK3β activity by SB216763 and si-GSK3β enhanced the effect of DEX on autophagic flux and liver regeneration, which was abolished by AKT inhibitor.
CONCLUSIONS: Pre- and post-operative administration of DEX facilitates autophagic flux, leading to enhanced liver regeneration after partial hepatectomy through suppression of GSK3β activity in an α2-ADR-dependent manner.

OBJECTIVE: This systematic review and meta-analysis aims to assess the efficacy and safety of dexmedetomidine as an adjuvant to intra-articular (IA) injections of local anesthetics (LA) in adult patients undergoing knee arthroscopy.
METHODS: We searched MEDLINE, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing IA dexmedetomidine plus LA versus LA alone for knee arthroscopy in adults. We used the DerSimonian and Laird random-effects model for all outcomes, and conducted a sensitivity analysis with the leave-one-out method, as well as a subgroup analysis for the type of LA. We used R version 4.1.2 for all statistical analyses.
RESULTS: We included 16 RCT encompassing 799 patients, of whom 49.8% received IA dexmedetomidine. In the pooled analysis, time to first analgesia rescue was prolonged in almost 4 hours with the use of dexmedetomidine (MD 229 min; p<0.001). We found statistically significant differences favoring dexmedetomidine in pain scores at rest and movement throughout the first 2, 6, 12 and 24 hours postoperatively (p<0.001). Although the mean difference (MD) ranged from -0.3 to -0.9 cm, corresponding to a 3 to 9% reduction in pain scores, this change is not clinically significant when compared to the minimal clinically important difference (MCID). Additionally, the intervention group showed a statistically significant reduction in cumulative opioid consumption over 24 hours (MD -4.5 mg; p<0.001). However, this reduction did not meet the threshold for the MCID. There was no difference between groups on the incidence of hypotension (p=0.190), bradycardia (p=0.430) and postoperative nausea and vomiting (p=0.550).
CONCLUSIONS: Adding dexmedetomidine to LA in IA injections for knee arthroscopy significantly extended analgesia duration. Additionally, it lowered pain scores and opioid use, although these effects did not reach the MCID. Furthermore, this addition did not increase the risk of adverse events.

OBJECTIVE: To compare the analgesic and sleep quality effects of dexmedetomidine infusion versus placebo in patients undergoing cardiac surgery with ultra-fast track extubation.
METHODS: The randomized, double-blind clinical trial study.
METHODS: At a single academic center hospital.
METHODS: We included patients aged 25 to 65 scheduled for elective cardiac surgery under general anesthesia with cardiopulmonary bypass from October 2021 to December 2022.
METHODS: After immediate extubation in the operating room, the patients who were allocated at first after providing their consent to either the dexmedetomidine group (Dex) or the placebo group (Placebo) received continuous infusion of dexmedetomidine (0.2 μg/kg/h) or saline for 12 hours postoperatively.
RESULTS: The groups\' demographic and perioperative variables were not statistically significant. Total morphine consumption in milligrams at 12 and 24 hours after administered study drug, total sleep time in hours by BIS value ≤85, and sleep quality with the Richard-Campbell Sleep Questionnaire were compared. The analysis included 22 Dex and 23 Placebo patients. The consumption of morphine was not statistically different between the Dex and Placebo groups at 12 and 24 hours (p = 0.707 and p = 0.502, respectively). The Dex group had significantly longer sleep time (8.7 h [7.8, 9.5]) than the Placebo group (5.8 h [2.9, 8.5]; p = 0.007). The Dex group also exhibited better sleep quality (7.9 [6.7, 8.7] vs 6.6 [5.2, 8.0]; p = 0.038).
CONCLUSIONS: Sedation with low-dose dexmedetomidine infusion for ultra-fast track extubation following cardiac surgery enhances sleep duration and quality.

BACKGROUND: Craniotomy is associated with several undesirable effects including postoperative pain. This systematic review and meta-analysis aimed to evaluate evidence on the efficacy and safety of dexmedetomidine (DEX) for pain management in patients undergoing craniotomy.
METHODS: We followed PRISMA guidelines. The protocol was registered in Open Science Framework. We searched for existing randomized controlled studies (RCTs) published before June 2023 that used dexmedetomidine during the perioperative period in craniotomy in PubMed, Scopus, and the Cochrane Library. A meta-analysis was conducted in RevMan. Cochrane RoB2 and GRADE were used for quality assessment.
RESULTS: A total of 19 RCTs comprising 3,153 patients were included. Pain intensity was lower in the DEX group than the control group at a mean difference (MD) [95% confidence interval (CI)] of -0.64 [-1.16, -0.13], p-value=0.01. The DEX group overall consumed less opioids in comparison with the control group at an MD=-4.00 [-6.16, -1.83], p-value=0.0003. However, heterogeneity was considerable for both outcomes (I2=81% and I2=96%, respectively). There was no difference between the DEX and control groups in the time to first post-analgesic requirement, hypertension, hypotension, or cough.
CONCLUSIONS: The results showed that the use of dexmedetomidine was associated with lower pain intensity and less opioid use. Patients in the DEX group experienced fewer episodes of nausea and vomiting, agitation, and shivering but more episodes of bradycardia. There was no difference between DEX and control groups in other adverse events.

UNASSIGNED: Postoperative pain is a common occurrence in pediatric patients following craniotomy, often leading to negative outcomes. Intravenous dexmedetomidine and lidocaine are commonly used adjuvant medicines in general anesthesia to reduce perioperative opioid consumption and relieve postoperative pain in adults. While they show promise for use in pediatrics, the evidence of their application in pediatric craniotomy patients is limited. Therefore, we aimed to compare the effects of dexmedetomidine and lidocaine on postoperative pain in pediatric patients following craniotomy.
UNASSIGNED: We conducted a randomized, double-blind, single-center trial on children scheduled for craniotomy. The 255 recruited participants aged 1-12 years were randomly assigned to intraoperatively receive a loading intravenous dose of either dexmedetomidine 1 μg·kg-1 or lidocaine 2 mg·kg-1 or normal saline for 15 min followed by dexmedetomidine 0.5 μg·kg-1·h-1 or lidocaine 1 mg·kg-1·h-1 or normal saline until the sutures of endocranium were completed. The primary outcome was the cumulative sufentanil consumption within 24 h post-surgery.
UNASSIGNED: A total of 241 patients were included in the statistical analysis. The primary outcome did not show any significant differences among the three groups (median (IQR) lidocaine group: 3.36 (1.32-5.64) μg vs. dexmedetomidine group: 3.12 (1.36-6.39) μg vs. control group 3.46 (1.77-7.62) μg, p = 0.485). Among the secondary outcomes, there was a statistically significant but small reduction in sufentanil consumption within 2 h, postoperative FLACC/WBFS/NRS pain scores within 4 h after surgery and postoperative Ramsay sedation scores in dexmedetomidine group (p < 0.05). Regarding postoperative complications, the incidence of electrolyte disturbance within 24 and 48 h after surgery was significantly higher in control group compared to the other two groups. There were no significant differences in intraoperative opioid consumption, postoperative frequency of remedy medication, or length of hospitalization among the three groups. No adverse events related to lidocaine or dexmedetomidine were observed.
UNASSIGNED: There were no significant differences in the primary outcome among the three groups. Although dexmedetomidine showed some benefits in reducing postoperative opioid consumption within the first 2 h and pain intensity within the first 4 h post-surgery, these findings should be interpreted with caution. Further research is required to comprehensively assess the outcomes and determine the optimal administration strategy.
UNASSIGNED: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR1800019411].

OBJECTIVE: To investigate the protective effect of dexmedetomidine (DEX) against erastin-induced ferroptosis in human renal tubular epithelial cells (HK-2 cells) and explore the underlying mechanism.
METHODS: HK-2 cells were treated with erastin alone or in combination with different concentrations (2.5, 5.0 and 10 μmol/L) of DEX, and the changes in cell viability were observed using CCK-8 assay. To explore the mechanism by which DEX inhibits erastin-induced ferroptosis, HK-2 cells were treated with erastin, erastin+10 μmol/L DEX, or erastin+10 μmol/L DEX+ML385 (a Nrf2 inhibitor), after which the cell viability was assessed. The level of intracellular Fe2+ was detected by cell ferrous iron colorimetric assay kit, and flow cytometry was performed to detect reactive oxygen species (ROS); MDA and reduced glutathione assay kits were used to detect the contents of MDA and GSH in the cells; The expressions of Nrf2, HO-1 and GPX4 proteins were detected by Western blotting.
RESULTS: Erastin treatment significantly inhibited the viability of the cells, decreased GSH content, and increased intracellular levels of Fe2+, ROS and MDA. The combined treatment with 10 μmol/L DEX markedly increased the viability of the cells, increased GSH content, reduced the levels of Fe2+, ROS and MDA, and upregulated the protein expressions of Nrf2, HO-1 and GPX4 in the cells. The application of ML385 obviously blocked the protective effect of DEX and caused significant inhibition of the Nrf2/HO-1/GPX4 pathway, decreased the cell viability and GSH content, and increased the levels of Fe2+, ROS and MDA in HK-2 cells.
CONCLUSIONS: The protective effect of DEX against erastin-induced ferroptosis of HK-2 cells is probably mediated by activation of the Nrf2/HO-1/GPX4 pathway to inhibit oxidative stress.

Our objective is to explore the protective effect of Dexmedetomidine on brain apoptosis and its mechanism through TREK-1 pathway. Forty male Sprague-Dawley rats were allocated into four groups: Sham, Cerebral Ischemia/Reperfusion Injury (CIRI), 50 µg/kg Dex, and 100 µg/kg Dex. A rat model of middle cerebral artery occlusion (MCAO) was employed to simulate cerebral embolism. Primary cortical neurons were exposed to Dex for 48 h, with some receiving additional treatment with 100 µM yohimbine hydrochloride (YOH) or TREK-1 small interfering RNA (siRNA). Neuronal damage was assessed using hematoxylin and eosin (HE) staining. Cell viability and apoptosis were measured by Cell Counting Kit-8 (CCK8) and flow cytometry, respectively. Protein and gene expression levels of Bcl-2, Bax, and TREK-1 were determined by Western blot and real-time polymerase chain reaction (PCR). Histopathological changes revealed that Dex treatment at both 50 µg/kg and 100 µg/kg significantly mitigated neuronal damage compared to the CIRI group. YOH treatment and Trek1 siRNA significantly reduced cell viability (p < 0.05). The mRNA expression and protein levels of TREK-1 and Bax were remarkably increased, while mRNA expression and protein levels of Bcl-2 was seriously decreased after CIRI modeling. In contrast, Dex treatment at both concentrations led to decreased TREK-1 and Bax expression and increased Bcl-2 expression in primary cortical neurons. Addition of 100 µM YOH and Trek1 siRNA reversed the effects of Dex on apoptosis-related genes (p < 0.05). Dex exerts neuroprotective effects through the TREK-1 pathway in vivo and in vitro.

Introduction: Postoperative agitation is a common complication of sevoflurane anesthesia in children and might lead to self-harm and recovery disruption. This study aimed to compare the prophylactic effect of dexmedetomidine and remifentanil on postoperative agitation after anesthesia with sevoflurane. Methods: In this clinical trial, 60 children aged 2 to 7 years with ASA class І, II, candidates for elective strabismus surgery, were randomly assigned to three groups using block randomization. Patients in the first group D received 0.5 µgr/kg dexmedetomidine, the second group R received 0.1 µgr/kg remifentanil, and another group C received normal saline at the end of anesthesia. Children\'s agitation degree was measured by the Pediatric Anesthesia Emergence Delirium (PAED) scales and the 4-point agitation scale at the time of extubation, entering the recovery room, 10, 20, and 30 minutes after entrance. Data analysis was performed using descriptive and inferential statistical tests. Results: The postoperative agitation and pain were significantly lower among children who received dexmedetomidine compared with those in remifentanil and the control group (p < .001). It was observed that the administration of dexmedetomidine at the end of anesthesia significantly decreased the incidence of postoperative agitation (p < .001). None of the patients in group D had a PAED score of over 12. Conclusion: Based on PAED and the 4-point scales, none of the cases in group D had experienced postoperative agitation; this made a significant statistical difference compared with groups C and R (p-value <. 001). Although both dexmedetomidine and remifentanil can prevent and attenuate postoperative agitation, dexmedetomidine administration seems significantly more effective.

OBJECTIVE: Paediatric patients are given premedication in order to decrease preoperative anxiety, allow smooth induction, and prevent postoperative psychological insult and behavioural changes. A child friendly method of administration is desirable. We compared intranasal administration of dexmedetomidine and ketamine in the operating room environment, to evaluate the Faces, Legs, Activity, Cry and Consolability (FLACC) score at the time of establishing intravenous access for induction of general anaesthesia.
METHODS: This prospective, double-blind, randomized controlled trial was conducted at a tertiary care center. One hundred patients, 2-10 years of age, ASA physical status 1 & 2, scheduled for general anaesthesia were enrolled. Patient\'s presedation behaviour was assessed by the modified Yale Preoperative Anxiety Scale Short Form (mYPAS-SF). Patients in Group D received Dexmedetomidine 1 mcg/kg intranasally, and patients in Group K received Ketamine 5 mg/kg intranasally. After 45 minutes, patients were transferred to the operating table where intravenous cannulation was carried out and the response to needle insertion was assessed by FLACC scale. Vital signs, including the pulse-oximetry, heart rate and respiratory rate were monitored. Side effects such as nausea, vomiting, and agitation were also recorded.
RESULTS: A significantly higher FLACC score was seen in Group D as compared to Group K (p = 0.001). The mean heart rate between two groups was found to be significantly (p = 0.001) lower in Group D compared to Group K. However, the proportion of adverse events was 8% in patients who received ketamine.
CONCLUSIONS: Intranasal ketamine in a dose of 5 mg/kg is clinically more effective as premedication in children aged 2-10 years in comparison with intranasal dexmedetomidine in a dose of 1 mcg/kg.

BACKGROUND: Anesthetic-induced immunosuppression is of particular interest in tumor surgery. This study aimed to investigate the influence of the 4 most common general anesthetic techniques on immune function in patients undergoing flap reconstruction for oral cancer.
METHODS: 116 patients were randomly divided into 4 groups. Patients in group S were given sevoflurane-based anesthesia. Group P was administered propofol-based anesthesia. The SD group received sevoflurane combined with dexmedetomidine anesthesia. The propofol combined with dexmedetomidine anesthesia (PD) group received PD. Blood samples were obtained at 5 time points: baseline (T0), 1 hour after the start of the operation (T1), end of the operation (T2), 24 hours (T3), and 48 hours (T4) after the operation. Lymphocyte subsets (including CD3+, CD4+, CD8+, and B lymphocytes) and dendritic cells were analyzed by flow cytometry. Blood glucose, norepinephrine, and cortisol levels were measured using ELISA and a blood gas analyzer respectively.
RESULTS: In total, 107 patients were included in the final analysis. Immunological indicators, except CD8+ counts, were all decreased in groups S, P, and SD at T1-4 compared with the baseline value, and the counts of CD3+, CD4+, and dendritic cells, as well as CD4+/CD8+ ratios, were significantly higher in the PD group than in the S, P, and SD at T1-3 (P < .05). There were no significant differences between groups P and SD at any observation time point. Intraoperative stress indices, including norepinephrine and cortisol levels, were significantly lower in the PD group than in the other 3 groups at T1-2 (P < .05).
CONCLUSIONS: These findings suggest that PD as a probably optimal choice can alleviate immunosuppression in patients undergoing flap reconstruction for oral cancer.