Effects of different doses of dexmedetomidine combined with sufentanil in intravenous controlled analgesia after Salter osteotomy in children.

Background: This study aimed to investigate the effect of different doses of dexmedetomidine combined with sufentanil on postoperative analgesia in developmental hip dislocation in children after Salter osteotomy. Methods: The clinical data of 98 children with developmental hip dislocation, who underwent Salter osteotomy in our center between January 2020 and February 2023, were selected. The children were randomly divided into four groups based on the application of patient-controlled intravenous analgesia (sufentanil + granisetron ± dexmedetomidine). All children received 1 µg/kg/day of sufentanil and 3 mg of granisetron. Group A did not receive dexmedetomidine, and Groups B, C, and D received 0.5, 0.75, and 1.0 µg/kg/day of dexmedetomidine, respectively. The pain indicators and immune factor levels of children in each group were compared. Results: The heart rate (HR) and respiratory rate (RR) 2 h after operation in Groups C and D were significantly lower than those in Groups A and B (P < 0.05). The pain scores decreased over time after treatment in all groups. When compared at the same time point, children in Group D had the lowest pain scores, which were significantly lower than the other three groups (P < 0.05). The total consumption of sufentanil in Groups C and D was significantly lower than that in Group A (P < 0.05). On the first day after surgery, the children in Group D had lower levels of serum adrenocorticotropic hormone, interleukin-6, and corticosterone than those in Group A (P < 0.05). Conclusion: Administration of 1.0 µg/kg/day of dexmedetomidine combined with sufentanil in intravenous controlled analgesia after Salter osteotomy for developmental hip dislocation in children has a better analgesic effect, less consumption of sufentanil, and low incidence of opioid adverse reactions.

Effects of perioperative dexmedetomidine on delayed graft function following renal transplant: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1,358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

Successful Second Awake Craniotomy Reoperation With Dexmedetomidine After an Initial Abandonment Case Due to Restlessness.

Awake craniotomy (AC) is sometimes aborted due to poor arousal and restlessness. Dexmedetomidine (DEX), an α2-adrenoreceptor agonist, has sedative, analgesic, and anesthetic-sparing effects, with a low risk of respiratory depression, making it effective for intraoperative pain and agitation during the awake phase. We report a case in which AC was successfully performed in combination with low-dose continuous administration of DEX during reoperation in a patient who experienced poor arousal and restlessness during their first surgery, leading to the abandonment of AC. The patient is a 48-year-old male who is scheduled for AC reoperation. Two years ago, the first AC was scheduled and performed under anesthesia with propofol and remifentanil. However, AC was abandoned due to poor intraoperative arousal and restlessness. At reoperation, general anesthesia was induced with propofol and continuous administration of remifentanil (0.1 µg/kg/min); following anesthesia induction (continuous infusion of propofol, remifentanil, and a bolus infusion of fentanyl), DEX was also administered (0.2 µg/kg/hour). We performed a scalp nerve block. Before the awake phase, the propofol dose was decreased as was DEX to 0.1 µg/kg/hour, and propofol and remifentanil were discontinued. The patient gradually awoke without any agitation and restlessness 24 min after stopping propofol and remifentanil and could perform language tasks without any complications. In this case, AC was successfully performed in combination with continuous low-dose administration of DEX at the time of reoperation in a patient who experienced poor arousal and restlessness during their first operation and had to discontinue AC.

Combination of dexamethasone and dexmedetomidine as adjuvants of transversus abdominis plane block for postoperative analgesia in gastric cancer patients: A double-blinded randomized controlled trial.

STUDY OBJECTIVE: We conducted this double-blinded randomized controlled trial to examine whether the combination of dexamethasone and dexmedetomidine as adjuvants of transversus abdominis plane (TAP) block could improve analgesia efficacy and duration for gastric cancer patients. DESIGN: Randomized controlled trial. SETTING: The preoperative area, operating room, postanesthesia recovery room and bed ward. PATIENTS: A total of 312 adult patients (104 per group) with gastric cancer were included. INTERVENTIONS: Patients received bilateral subcostal TAP block with three different anesthetics (60 ml 0.25% ropivacaine added with 10 mg dexamethasone and 1 µg·kg-1 dexmedetomidine [A] or 10 mg dexamethasone [B] or 1 µg·kg-1 dexmedetomidine [C]). MEASUREMENTS: The primary outcome was the incidence of moderate-to-severe pain 24 h on movement. Secondary outcomes included incidence of moderate-to-severe pain, pain score, opioids use, recovery quality and adverse events. MAIN RESULTS: The incidence of moderate-to-severe pain on movement 24 h postoperatively of group A was significantly lower than group B (45.19% vs 63.46%; RR 0.71; 95% CI, 0.55 to 0.92) and group C (45.19% vs 73.08%, RR 0.62; 95% CI, 0.49 to 0.79). The median moving pain scores decreased significantly at 24 h (3.00 [3.00,5.00] vs 4.00 [3.00,6.00] vs 4.00 [3.00,5.00]; P < 0.001). There were significant differences in the opioids consumption within the first 24 h (27.5 [17.0,37.2] vs 30.0 [20.0,42.0] vs 32.0 [25.0,44.0] mg; P = 0.01) and the duration to first rescue analgesia (65.5 ± 26.7 vs 45.9 ± 34.5 vs 49.2 ± 27.2 h; P = 0.04). CONCLUSIONS: The combination with dexamethasone and dexmedetomidine as adjuvants for TAP block reduced the incidence of moderate-to-severe pain and pain score both on movement and at rest at 24 h with prolonged duration to first rescue analgesia after gastric cancer surgery. TRIAL REGISTRATION NUMBER: ChiCTR2000037981.

Alleviation effects of dexmedetomidine on myocardial ischemia/reperfusion injury through fatty acid metabolism pathway via Elovl6.

Dexmedetomidine (Dex) is widely used in the sedation in intensive care units and as an anesthetic adjunct. Considering the anti-inflammatory and antioxidant properties of Dex, we applied in vivo rat model as well as in vitro cardiomyocyte models (embryonic rat cardiomyocytes H9c2 cells and neonatal rat cardiomyocytes, NRCMs) to evaluate the effects of Dex against myocardial ischemia reperfusion (I/R) injury. Transcriptomic sequencing for gene expression in heart tissues from control rats and Dex-treated rats identified that genes related to fatty acid metabolism were significantly regulated by Dex. Among these genes, the elongation of long-chain fatty acids (ELOVL) family member 6 (Elovl6) was most increased upon Dex-treatment. By comparing the effects of Dex on both wild type and Elovl6-knockdown H9c2 cells and NRCMs under oxygen-glucose deprivation/reoxygenation (OGD/R) challenge, we found that Elovl6 knockdown attenuated the protection efficiency of Dex, which was supported by the cytotoxicity endpoints (cell viability and lactate dehydrogenase release) and apoptosis as well as key gene expressions. These results indicate that Dex exhibited the protective function against myocardial I/R injury via fatty acid metabolism pathways and Elovl6 plays a key role in the process, which was further confirmed using palmitate exposure in both cells, as well as in an in vivo rat model. Overall, this study systematically evaluates the protective effects of Dex on the myocardial I/R injury and provides better understanding on the fatty acid metabolism underlying the beneficial effects of Dex.

Zona incerta mediates early life isoflurane-induced fear memory deficits.

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.

[Dexmedetomidine inhibits ferroptosis of human renal tubular epithelial cells by activating the Nrf2/HO-1/GPX4 pathway].

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. CONCLUSION: 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.

Awake reduction of hangman's fracture: An era of dexmedetomidine.

Hangman's fracture is a kind of unstable cervical spine injury which should be treated promptly to avoid life threatening consequences. Advanced neurological monitoring is essential during surgical intrervention. Resource limited setting, where advanced monitors like SSEP and MEP are not available makes it challenging to assess proper reduction of cervical spine without neurological compromise. Dexmedetomidine proved to be very useful drug to assess the neurological status intra operatively by awake sedation.

Dexmedetomidine Inhibits Hippocampal Neuronal Damage Caused by Persistent Isoflurane-Induced Hypotension in Rat Model of Chronic Cerebral Hypoperfusion.

Purpose The purpose of this study was to investigate the effect of dexmedetomidine (DEX) on hypotension-induced neuronal damage in a chronic cerebral hypoperfusion (CCH) model of rats, an established model of cerebral white matter lesions (WML) in humans, which is prevalent in the elderly and closely related to cognitive decline. Methods The CCH model rats were randomly assigned to one of four groups: normotension + no DEX (NN) group (n = 6), normotension + DEX (ND) group (n = 6), hypotension + no DEX (HN) group (n = 6), or hypotension + DEX (HD) group (n = 6). Under isoflurane anesthesia, mean arterial blood pressure was maintained at or above 80 mmHg (normotension) or below 60 mmHg (hypotension) for a duration of two hours. The DEX groups received 50 µg of DEX intraperitoneally. Two weeks later, the Y-maze test and, after preparing brain slices, immunohistochemical staining were performed using antibodies against neuronal nuclei (NeuN), microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP), and Ionized calcium-binding adapter molecule 1 (Iba1). Results Behavioral observations showed no significant differences among the groups. Significant reductions of both NeuN-positive cells and the MAP2-positive area were found in the hippocampal CA1 in the HN group compared with NN and ND groups, but not in the HD group. GFAP and Iba-1-positive areas were significantly increased in the HN group, but not in the HD group. Conclusion DEX significantly ameliorated hypotension-induced neuronal damage and both astroglial and microglial activation in the CA1 region of CCH rats.

TREK-1 channel as a therapeutic target for dexmedetomidine-mediated neuroprotection in cerebral ischemia.

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.

Effect of esketamine combined with dexmedetomidine on delirium in sedation for mechanically ventilated ICU patients: protocol for a nested substudy within a randomized controlled trial.

BACKGROUND: Use of sedatives and analgesics is associated with the occurrence of delirium in critically ill patients receiving mechanical ventilation. Dexmedetomidine reduces the occurrence of delirium but may cause hypotension, bradycardia, and insufficient sedation. This substudy aims to determine whether the combination of esketamine with dexmedetomidine can reduce the side effects and risk of delirium than dexmedetomidine alone in mechanically ventilated patients. METHODS: This single-center, randomized, active-controlled, superiority trial will be conducted at The First Affiliated Hospital of Nanjing Medical University. A total of 134 mechanically ventilated patients will be recruited and randomized to receive either dexmedetomidine alone or esketamine combined with dexmedetomidine, until extubation or for a maximum of 14 days. The primary outcome is the occurrence of delirium, while the second outcomes include the number of delirium-free days; subtype, severity, and duration of delirium; time to first onset of delirium; total dose of vasopressors and antipsychotics; duration of mechanical ventilation; ICU and hospital length of stay (LOS); accidental extubation, re-intubation, re-admission; and mortality in the ICU at 14 and 28 days. DISCUSSION: There is an urgent need for a new combination regimen of dexmedetomidine due to its evident side effects. The combination of esketamine and dexmedetomidine has been applied throughout the perioperative period. However, there is still a lack of evidence on the effects of this regimen on delirium in mechanically ventilated ICU patients. This substudy will evaluate the effects of the combination of esketamine and dexmedetomidine in reducing the risk of delirium for mechanically ventilated patients in ICU, thus providing evidence of this combination to improve the short-term prognosis. The study protocol has obtained approval from the Medical Ethics Committee (ID: 2022-SR-450). TRIAL REGISTRATION: ClinicalTrials.gov: NCT05466708, registered on 20 July 2022.

Comparison of intranasal dexmedetomidine and ketamine for paediatric premedication: A randomized study.

INTRODUCTION AND OBJECTIVES: 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.

The effect of post-anesthetic administration of dexmedetomidine versus remifentanil on postoperative agitation of strabismus surgery in children: a randomized double-blind clinical trial.

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.

Intraoperative application of low-dose dexmedetomidine or lidocaine for postoperative analgesia in pediatric patients following craniotomy: a randomized double-blind placebo-controlled trial.

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Clinical Trial Registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR1800019411].

[Effects of Dexmedetomidine on the Recovery Quality of Donors Undergoing Pure Laparoscopic Donor Hepatectomy]. / å³ç¾Žæ‰˜å’ªå®šå¯¹è ¹è ”é•œä¾›è‚èŽ·å–æœ¯ä¾›è€ è‹é†’æœŸæ¢å¤è´¨é‡çš„å½±å“.

Objective: To investigate the effects of intraoperative intravenous administration of dexmedetomidine (DEX) on the recovery quality of donors undergoing pure laparoscopic donor hepatectomy. Methods: A total of 56 liver donors who were going to undergo scheduled pure laparoscopic donor hepatectomy were enrolled and randomly assigned to two groups, a DEX group ( n=28) and a control group ( n=28). Donors in the DEX group received DEX infusion at a dose of 1 µg/kg over 15 minutes through a continuous pump, which was followed by DEX at 0.4 µg/(kg·h) until the disconnection of the portal branch. Donors in the control group were given an equal volume of 0.9% normal saline at the same infusion rate and over the same period of time as those of the dex infusion in the DEX group. The primary outcome was the incidence of emergence agitation (EA). The Aono's Four-point Scale (AFPS) score was used to assess EA. The secondary observation indicators included intraoperative anesthesia and surgery conditions, spontaneous respiration recovery time, recovery time, extubation time, scores for the Ramsay Sedation Scale, the incidence of chills, numeric rating scale (NRS) score for pain, and blood pressure and heart rate after extubation. Results: The incidence of EA was 10.7% and 39.3% in the DEX group and the control group, respectively, and the incidence of EA was significantly lower in the DEX group than that in the control group ( P=0.014). The APFS scores after extubation in the DEX group were lower than those in the control group (1 [1, 1] vs. 2 [1, 3], P=0.005). Compared to the control group, the dosages of intraoperative propofol and remifentanil were significantly reduced in the DEX group ( P<0.05). During the recovery period, the number of donors requiring additional boluses of analgesia, the blood pressure, and the heart rate were all lower in the DEX group than those in the control group ( P<0.05). No significant differences between the two groups were observed in the spontaneous respiration recovery time, recovery time, extubation time, the incidence of chills, NRS score, scores for the Ramsay Sedation Scale, and the length-of-stay in postanesthesia care unit (PACU) ( P>0.05). Conclusion: DEX can reduce the incidence of EA after pure laparoscopic donor hepatectomy and improve the quality of recovery without prolonging postoperative recovery time or extubation time.

Perioperative dexmedetomidine for pain management in craniotomy: a systematic review and meta-analysis.

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.

Analgesic Effect and Sleep Quality of Low-Dose Dexmedetomidine in Cardiac Surgical Patients After Ultrafast-Track Extubation: A Randomized Clinical Trial.

OBJECTIVE: To compare the analgesic and sleep quality effects of dexmedetomidine infusion versus placebo in patients undergoing cardiac surgery with ultra-fast track extubation. DESIGN: The randomized, double-blind clinical trial study. SETTING: At a single academic center hospital. PARTICIPANTS: We included patients aged 25 to 65 scheduled for elective cardiac surgery under general anesthesia with cardiopulmonary bypass from October 2021 to December 2022. INTERVENTION: 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. MEASUREMENTS AND MAIN 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.

Dexmedetomidine mitigates lipopolysaccharide-induced acute lung injury by modulating heat shock protein A12B to inhibit the toll-like receptor 4/nuclear factor-kappa B signaling pathway.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): Life-threatening medical conditions characterized by high morbidity and mortality rates, where the inflammatory process plays a crucial role in lung tissue damage, especially in models induced by lipopolysaccharide (LPS). Heat shock protein A12B (HSPA12B) has strong anti-infammatory properties However, it is unknown whether increased HSPA12B is protective against LPS-induced ALI. And Dexmedetomidine (DEX) is a potent α2-adrenergic receptor (α2-AR) agonist that has been shown to protect against sepsis-induced lung injury, however, the underlying mechanisms of this protection are not fully understood. This study utilized bioinformatics analysis and an LPS-induced ALI model to explore how DEX alleviates lung injury by modulating HSPA12B and inhibiting the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway. Results indicate that HSPA12B overexpression and DEX pre-treatment markedly mitigated LPS-induced lung injury, which was evaluated by the deterioration of histopathology, histologic scores, the W/D weight ratio, and total protein expression, tumor necrosis factor-alpha (TNF-α), and interleukin-1ß (IL-1ß) in the BALF, and the levels of NO, MDA,SOD and MPO in the lung. Moreover, HSPA12B overexpression and DEX pre-treatment significantly reduces lung injury and inflammation levels by upregulating HSPA12B and inhibiting the activation of the TLR4/NF-κB signaling pathway. On the contrary, when the expression of HSPA12B is inhibited, the protective effect of DEX pre-treatment on lung tissue is significantly weakened.In summary, our research demonstrated that the increased expression of AAV-mediated HSPA12B in the lungs of mice inhibits acute inflammation and suppresses the activation of TLR4/NF-κB pathway in a murine model of LPS-induced ALI. DEX could enhance HSPA12B and inhibit the initiation and development of inflammation through down-regulating TLR4/NF-κB pathway.These findings highlight the potential of DEX as a therapeutic agent for treating ALI and ARDS, offering new strategies for clinical intervention.

Dexmedetomidine enhances Mitophagy via PINK1 to alleviate hippocampal neuronal Pyroptosis and improve postoperative cognitive dysfunction in elderly rat.

Postoperative cognitive dysfunction (POCD) is a common complication in elderly surgical patients, significantly affecting their quality of life. Dexmedetomidine (Dex), an anesthetic, has shown promise in alleviating POCD, but its underlying mechanism remains unclear. This study aims to explore how Dex improves POCD in aged rats by targeting the PINK1-mediated mitochondrial autophagy pathway, reducing caspase-1/11-GSDMD-induced hippocampal neuronal pyroptosis. Transcriptome sequencing identified 300 differentially expressed genes enriched in the mitochondrial autophagy pathway in Dex-treated POCD rat hippocampal tissue, with Pink1 as a key candidate. In a POCD rat model, Dex treatment upregulated hippocampal PINK1 expression. In vitro experiments using H19-7 rat hippocampal neurons revealed that Dex enhanced mitochondrial autophagy and suppressed neuronal pyroptosis by upregulating PINK1. Further mechanistic validation demonstrated that Dex activated PINK1-mediated mitochondrial autophagy, inhibiting caspase-1/11-GSDMD-induced neuronal pyroptosis. In vivo experiments confirmed Dex's ability to reduce caspase-1/11-GSDMD-dependent hippocampal neuronal pyroptosis and improve postoperative cognitive function in aged rats. Dexmedetomidine improves postoperative cognitive dysfunction in elderly rats by enhancing mitochondrial autophagy via PINK1 upregulation, mitigating caspase-1/11-GSDMD-induced neuronal pyroptosis.

Dexmedetomidine-mediated improvement of perioperative neurocognitive disorders by miR-184-3p-mediated NLRP3.

BACKGROUND: Perioperative neurocognitive disorders (PND) is a neurological complication in the perioperative period, which may lead to severe poor prognosis. Dexmedetomidine (Dex) is a commonly used sedative in the perioperative period. However, the effect of intraoperative anesthetic Dex on PND remains complicated and confusing. METHODS: PND model was established using aged male mice, treated with Dex, and subjected to behavioral tests. The effect of Dex on pyroptosis was assessed by western blot, enzyme-linked immunosorbent assay and immunofluorescence. In addition, the miRNA expression profile of PND mice was identified by small RNA sequencing and performed PCR to detect miRNAs. Finally, the effect of miRNA on mice neuron pyroptosis was verified in vitro. RESULTS: We found postoperative cognitive was declined in PND mice compared with control group, while preoperative injection of Dex improved short-term working memory and anxious exploration behavior, alleviated the cognitive impairment. Intriguingly, Dex ameliorated hippocampal inflammation and neuron pyroptosis in PND mice as evidenced by the reduced GSDMD, NLRP3, IL-1ß and IL-18. The miRNA expression profile of PND mice hippocampus was disordered, including 5 miRNAs up-regulated and 17 miRNAs down-regulated, compared to the sham group. Dysregulated miRNAs were mainly enriched in biological functions related to neuronal development and signaling pathways related to pyroptosis. MiR-184-3p was the key miRNA, overexpression of miR-184-3p blocked the inhibitory effect of Dex on neuron pyroptosis, which was manifested as increased expression of GSDMD and NLRP3, increased inflammatory factors IL-1ß and IL-18. CONCLUSIONS: This study revealed that miR-184-3p may mediate NLRP3 to prevent the alleviating effect of Dex on PND, which provides a new potential way to improve the therapeutic intervention of PND.