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Drug Design, Development and Therapy 2023Myocardial ischemia-reperfusion (I/R) injury is a detrimental disease, resulting in high morbidity and mortality globally. In this study, we aimed to investigate the...
OBJECTIVE
Myocardial ischemia-reperfusion (I/R) injury is a detrimental disease, resulting in high morbidity and mortality globally. In this study, we aimed to investigate the role of Dex in mitigating cardiac I/R injury.
METHODS
H9c2 cells were treated with Dex (1 μM) for 24 h followed by oxygen-glucose deprivation/re-oxygenation (OGD/R). and mRNA of H9c2 cells and the LDH release were measured. Apoptosis of H9c2 cells was analyzed by flow cytometry. Mitochondrial membrane potential and superoxide production were detected by JC-1 staining and MitoSOX Red, respectively. Cell aerobic respiration was measured using Seahorse analysis. In vivo, mice were injected with Dex (25 μg/kg, i.p., once daily) for 5 days and then subjected to heart I/R. Heart function was analyzed by echocardiography. CK-MB and LDH were measured by Elisa. Infarct size was measured using TTC-Evans blue staining. Mitochondrial ultrastructure was observed using transmission electron microscopy. DHE staining, SOD activity, the content of MDA, and the content of GSH/GSSG of heart were measured to evaluate the oxidative stress. In addition, inflammatory cytokines were measured in vivo and in vitro. Furthermore, AMPK, SIRT3, and autophagy-related protein expression in the heart were detected by Western blot.
RESULTS
Dex reduced the H9c2 cells injury exposed to OGD/R, accompanied by improved mitochondrial function and membrane potential. In vivo, Dex improved heart function, myocardial injury, and the mitochondria ultrastructure following I/R injury. Meanwhile, Dex inhibited myocardial oxidative stress and inflammation in the myocardial I/R. Furthermore, Compound C (an AMPK inhibitor) could inhibit Dex-induced autophagy in the I/R heart and the 3-MA (an autophagy inhibitor) could partially interfere with the effects of Dex on the protection of I/R heart.
CONCLUSION
Dex suppressed oxidative stress and inflammation by promoting autophagy through activating the AMPK/SIRT3 pathway, thus protecting the heart against the I/R injury.
Topics: Animals; Mice; AMP-Activated Protein Kinases; Apoptosis; Autophagy; Dexmedetomidine; Inflammation; Ischemia; Myocardial Ischemia; Myocardial Reperfusion Injury; Reperfusion Injury; Signal Transduction; Sirtuin 3
PubMed: 37908314
DOI: 10.2147/DDDT.S428024 -
Clinical Interventions in Aging 2023We investigated the effects of intraoperative intravenous lidocaine or dexmedetomidine infusion on inflammatory factors and cognitive function in patients undergoing... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of the Effects of Dexmedetomidine and Lidocaine on Stress Response and Postoperative Delirium of Older Patients Undergoing Thoracoscopic Surgery: A Randomized Controlled Trial.
PURPOSE
We investigated the effects of intraoperative intravenous lidocaine or dexmedetomidine infusion on inflammatory factors and cognitive function in patients undergoing thoracoscopic surgery.
PATIENTS AND METHODS
Patients aged >65 years undergoing elective thoracoscopic lobectomy or segmentectomy were randomly grouped as dexmedetomidine group (group D), lidocaine group (group L), and control group (group C). The plasma cortisol, interleukin-6, and tumor necrosis factor-α concentrations were measured before anesthesia (T0) and immediately (T1), 24 h (T2), and 48 h postoperatively (T3). Postoperative delirium (POD) was assessed by 3D-CAM on days 2 and 7.
RESULTS
The cortisol concentrations decreased for all groups at T1 from T0 although they were significantly higher at T2. Group L had significantly lower interleukin-6 concentrations at T1 and T2 than the other groups (<0.05). The interleukin-6 concentrations were significantly higher at T1, T2, and T3 than at T0 for all the groups, significantly lower for groups D and L than for group C at T1 and T2 (<0.05), and significantly lower for group L than for group D at T2 (<0.05). The tumor necrosis factor-α concentrations were significantly higher at T1, T2, and T3 than at T0 for all the groups and significantly lower for groups D and L than for group C at T1 and T2 (<0.05), although they were not statistically significantly different for groups D and L. There were no statistically significant differences in the postoperative incidence of POD between the three groups on days 2 and day 7.
CONCLUSION
Intraoperative continuous intravenous lidocaine or dexmedetomidine infusion reduced surgical stress and inflammatory responses. The inhibitory effect of lidocaine on surgical stress remained significant for up to 24 h postoperatively without affecting patient awakening. However, the administration of either drug failed to prevent postoperative POD.
Topics: Humans; Dexmedetomidine; Emergence Delirium; Hydrocortisone; Interleukin-6; Lidocaine; Tumor Necrosis Factor-alpha; Thoracic Surgery
PubMed: 37554513
DOI: 10.2147/CIA.S419835 -
Biomedicine & Pharmacotherapy =... Dec 2023Hepatic ischemia-reperfusion injury (HIRI) adversely affects liver transplant and resection outcomes. Recently, ferroptosis has been associated with HIRI....
Hepatic ischemia-reperfusion injury (HIRI) adversely affects liver transplant and resection outcomes. Recently, ferroptosis has been associated with HIRI. Dexmedetomidine (Dex), a potent sedative with anti-inflammatory, antioxidant, and anti-apoptotic properties, protects organs from hypoxic or ischemia-reperfusion (I/R) injuries. However, the mechanisms underlying this protective effect against I/R-induced liver injury remain unclear. This study evaluated the effect of Dex on HIRI in mouse models and the oxygen-glucose deprivation/reperfusion (OGD/R) AML12 cell model. We examined ferroptosis-related markers, including Fe levels, reactive oxygen species (ROS) content, mitochondrial morphology, GPX4 protein expression, 4-hydroxynonenal (4-HNE), and Nrf2. The Nrf2 inhibitor ML385 was used in combination with Dex to treat HIRI mice and OGD/R-induced cellular models to explore the pathways by which Dex counteracts ferroptosis. Our results showed that Dex treatment significantly ameliorated OGD/R-induced ferroptosis in AML12 cells, including reduced Fe, ROS, malondialdehyde (MDA), and 4-HNE levels. Dex also ameliorated liver tissue damage and reduced serum AST, ALT, and inflammatory factor levels in HIRI mice. Additionally, Dex increased the levels of GSH, an antioxidative stress marker, and GPX4 expression in HIRI mice. Mechanistically, Nrf2 expression and nuclear translocation were significantly inhibited in both HIRI mice and OGD/R-treated AML12 cells. Dex treatment also restored the I/R-induced inhibition of Nrf2 expression and nuclear translocation. ML385 significantly inhibited Dex-promoted Nrf2 nuclear aggregation with Gpx4 protein expression, hindering the efficacy of Dex. In conclusion, Dex ameliorates ferroptosis in HIRI by positively regulating the Nrf2/GPx4 axis, potentially presenting a therapeutic avenue for addressing HIRI.
Topics: Animals; Mice; Antioxidants; Dexmedetomidine; NF-E2-Related Factor 2; Ferroptosis; Reactive Oxygen Species; Liver; Reperfusion Injury
PubMed: 38000361
DOI: 10.1016/j.biopha.2023.115915 -
Journal of Clinical Medicine Nov 2023We aimed to evaluate the intraoperative hemodynamics, opioid consumption, muscle relaxant use, postoperative analgesic effects, and possible adverse effects (such as...
We aimed to evaluate the intraoperative hemodynamics, opioid consumption, muscle relaxant use, postoperative analgesic effects, and possible adverse effects (such as nausea and vomiting) of dexmedetomidine and tramadol added as adjuvants to bupivacaine in the transversus abdominis plane block (TAP block) to provide postoperative analgesia. This was a prospective, randomized, controlled trial on patients who underwent laparoscopic cholecystectomy. After obtaining ethical approval at the Van Yuzuncu Yil University and written informed consent, this investigation was registered with ClinicalTrials.gov (NCT05905757). The study was conducted with 67 patients with ASA I-II physical status, aged 20-60 years, of either sex who were scheduled for an elective laparoscopic cholecystectomy under general anesthesia. Exclusion criteria were the patient's refusal, ASA III and above, a history of allergy to the study drugs, patients with severe systemic diseases, pregnancy, psychiatric illness, seizure disorder, and those who had taken any form of analgesics in the last 24 h. The patients were equally randomized into one of two groups: Group T (TAP Block group) and Group D (Dexmedetomidin group). Standard general anesthesia was administered. After intubation, Group T (Bupivacaine + adjuvant tramadol) = solutions containing 0.250% bupivacaine 15 mL + adjuvant 1.5 mg/kg (100 mg maximum) tramadol 25 mL and Group D (Bupivacaine + adjuvant dexmedetomidine) = solutions containing 0.250% bupivacaine 15 mL + 0.5 mcg/kg and (50 mcg maximum) dexmedetomidine 25 mL; in total, 40 mL and 20 mL was applied to groups T and D, respectively. A bilateral subcostal TAP block was performed by the same anesthesiologist. Intraoperative vital signs, an additional dose of opioid and muscle relaxant requirements, complications, postoperative side effects (nausea, vomiting), postoperative analgesic requirement, mobilization times, and the zero-hour mark (patients with modified Aldrete scores of 9 and above were recorded as 0 h), the third-hour, and sixth-hour visual analog scale (VAS) scores were recorded. The main outcome measurements were the effect on pain scores and analgesic consumption within the first 6 h postoperatively, postoperative nausea and vomiting (PONV), and time to ambulation. The secondary aim was to evaluate intraoperative effects (on hemodynamics and opioid and muscle relaxant consumption). It was observed that dexmedetomidine and tramadol did not have superiority over each other in terms of postoperative analgesia time, analgesic consumption, side effect profile, and mobilization times ( > 0.05). However, more stable hemodynamics were observed with dexmedetomidine as an adjuvant. We think that the use of adjuvant dexmedetomidine in the preoperative TAP block procedure will provide more stable intraoperative hemodynamic results compared with the use of tramadol. We believe that our study will be a guide for new studies conducted with different doses and larger numbers of participants.
PubMed: 38002616
DOI: 10.3390/jcm12227001 -
Pain Physician Oct 2023Opioid-based general anesthesia was previously used to alleviate perioperative pain; however, several complications associated with using anesthesia have raised several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Opioid-based general anesthesia was previously used to alleviate perioperative pain; however, several complications associated with using anesthesia have raised several concerns. Various studies have investigated the application prospect of using opioid-free general anesthesia, such as dexmedetomidine, as an opioid substitute.
OBJECTIVES
We performed a systematic review and meta-analysis to explore and highlight the safety and effectiveness of dexmedetomidine as an opioid substitute for opioid-free anesthesia.
STUDY DESIGN
A systematic review and meta-analysis.
SETTING
We screened for suitable clinical trials from electronic databases, including "PubMed," "Cochrane Library," "EMBASE," and "Web of Science." Eligible trials were included in this meta-analysis.
METHODS
The quality of the screened randomized controlled trials (RCTs) was determined using the risk of bias assessment criteria by the Cochrane Collaboration tool. We used the "Review Manager 5.3" and "Stata 10.0" software to perform the meta-analysis. We evaluated the quality of evidence using the "Grading of Recommendations Assessment, Development, and Evaluation" approach.
RESULTS
For the analysis, we included 32 RCTs encompassing 2,509 patients. In the opioid-free group, the 2-hour postoperative pain score of patients (mean difference = -0.53, 95% CI: -1.00, -0.07; P = 0.02, I2=78%) was significantly lower compared to those in the opioid-based group. In addition, several patients required rescue analgesia (risk ratio = 0.70, 95% CI: 0.58, 0.84, P < 0.05, I2 = 71%) and opioids postsurgery. However, the duration of extubation and postanesthesia care unit, as well as the incidences of bradycardia, were high in patients receiving dexmedetomidine as opioid-free general anesthesia.
LIMITATIONS
Subgroup analysis for different anesthesia-maintaining drugs had not been conducted. The heterogeneity did not reduce after subgroup analysis. Different doses of dexmedetomidine had not been evaluated.
CONCLUSIONS
These findings indicate that opioid-free general anesthesia based on dexmedetomidine could be effective; however, prolonged extubation time and cardiovascular complications are a few risks associated with dexmedetomidine.
Topics: Humans; Dexmedetomidine; Analgesics, Opioid; Pain, Postoperative; Anesthesia, General; Analgesia
PubMed: 37847917
DOI: No ID Found -
Drug Design, Development and Therapy 2023This study evaluated the effect of a combined infusion of dexmedetomidine and esketamine on the quality of recovery in patients undergoing modified radical mastectomy. (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Dexmedetomidine and Two Different Doses of Esketamine Combined Infusion on the Quality of Recovery in Patients Undergoing Modified Radical Mastectomy for Breast Cancer - A Randomised Controlled Study.
PURPOSE
This study evaluated the effect of a combined infusion of dexmedetomidine and esketamine on the quality of recovery in patients undergoing modified radical mastectomy.
METHODS
A total of 135 patients were randomly divided into three groups: dexmedetomidine group (group D) received dexmedetomidine (0.5 µg/kg loading, 0.4 µg/kg/h infusion), dexmedetomidine plus low-dose esketamine group (group DE) received dexmedetomidine (0.5 µg/kg loading, 0.4 µg/kg/h infusion) and esketamine (0.5 mg/kg loading, 2 µg/kg/min infusion), dexmedetomidine plus high-dose esketamine group (group DE) received dexmedetomidine (0.5 µg/kg loading, 0.4 µg/kg/h infusion) and esketamine (0.5 mg/kg loading, 4 µg/kg/min infusion). The primary outcome was the overall quality of recovery-15 (QoR-15) scores at 1 day after surgery. The secondary endpoints were total QoR-15 scores at 3 days after surgery, propofol and remifentanil requirement, awaking and extubation time, postoperative visual analogue scale (VAS) pain scores, rescue analgesic, nausea and vomiting, bradycardia, excessive sedation, nightmares, and agitation.
RESULTS
The overall QoR-15 scores were much higher in groups DE and DE than in groups D 1 and D 3 days after surgery ( < 0.05). VAS pain scores at 6, 12, 24 h postoperatively, propofol and remifentanil requirements were significantly lower in groups DE and DE than in group D ( < 0.05). Compared with group D, awaking time, extubation time, and post-anesthesia care unit (PACU) stay were significantly prolonged in groups DE and DE ( < 0.05) and were much longer in group DE than in group DE ( < 0.05). The proportion of postoperative rescue analgesics and bradycardia was higher and the incidence of excessive sedation was lower in group D than in groups DE and DE ( < 0.05).
CONCLUSION
Dexmedetomidine plus esketamine partly improved postoperative recovery quality and decreased the incidence of bradycardia but prolonged awaking time, extubation time, and PACU stay, especially dexmedetomidine plus 4 µg/kg/min esketamine.
Topics: Humans; Female; Breast Neoplasms; Mastectomy, Modified Radical; Dexmedetomidine; Bradycardia; Propofol; Remifentanil; Mastectomy; Pain
PubMed: 37664451
DOI: 10.2147/DDDT.S422896 -
Scandinavian Journal of Trauma,... Apr 2024
Topics: Child; Humans; Child, Preschool; Dexmedetomidine; Double-Blind Method; Ketamine; Pain; Analgesia
PubMed: 38594764
DOI: 10.1186/s13049-024-01200-6 -
BMC Anesthesiology Sep 2023To observe and evaluate the effectiveness and safety of Esketamine or Sufentanil combined with Dexmedetomidine for sedation and analgesia in lung tumor percutaneous... (Randomized Controlled Trial)
Randomized Controlled Trial
A comparative study of esketamine-dexmedetomidine and sufentanil-dexmedetomidine for sedation and analgesia in lung tumor percutaneous radiofrequency ablation (PRFA): a randomized double-blind clinical trial.
OBJECTIVE
To observe and evaluate the effectiveness and safety of Esketamine or Sufentanil combined with Dexmedetomidine for sedation and analgesia in lung tumor percutaneous radiofrequency ablation (PRFA) to provide a clinical basis for the optimization of sedation and analgesia in lung tumor PRFA protocols outside the operating room.
METHODS
In this trial, 44 patients aged 37 to 84 undergoing lung tumor PRFA were enrolled and assigned to Group E (n = 22, Esketamine 0.2 mg/kg) or Group S (n = 22,Sufentanil 0.1 μg/kg ). Dexmedetomidine was infused intravenously as a sedative in both groups. The modified observer's assessment of alertness and sedation scale (MOAAS), physical movement pain scale, intraoperative vital signs, anesthesia recovery time, radiologist and patient satisfaction rates, incidence of respiratory depression, and incidence of postoperative nausea and vomiting were recorded.
RESULTS
Although there was no significant difference in the physical movement pain scale, blood oxygen saturation or incidence of perioperative adverse events between the two groups during ablation, the MOAAS, mean arterial pressure (MAP) and heart rate (HR) were higher in Group E than in Group S. The anesthesia recovery time was shorter in Group E than in Group S, and radiologist satisfaction was better in Group E than in Group S, but there was no significant difference between the two groups in terms of patient satisfaction.
CONCLUSION
Esketamine or Sufentanil combined with Dexmedetomidine is safe for lung tumor PRFA. However, in elderly patients with multiple underlying diseases, low-dose Esketamine combined with Dexmedetomidine has fewer hemodynamic effects on patients, milder respiratory depression, shorter recovery time, and better radiologist satisfaction because of its better controllability of sedation depth.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (Registration number#ChiCTR ChiCTR21000500 21); Date of Registration: 16/08/2021.
Topics: Aged; Humans; Sufentanil; Dexmedetomidine; Analgesia; Anesthesia; Lung Neoplasms; Pain
PubMed: 37684574
DOI: 10.1186/s12871-023-02266-y -
Biomedicine & Pharmacotherapy =... Sep 2023The current study intended to delve into the mechanisms of dexmedetomidine (Dex) in regulating myocardial pyroptosis against myocardial ischemia/reperfusion injury...
The current study intended to delve into the mechanisms of dexmedetomidine (Dex) in regulating myocardial pyroptosis against myocardial ischemia/reperfusion injury (MIRI). The rat MIRI models were induced by ligation/release of the coronary artery in vivo and Langendorff perfusion ex vivo. Hemodynamic parameters, infarction sizes, and histopathological changes were assessed to understand the effects of Dex on MIRI. We explored the mechanisms through functional experiments on an H9c2 cell hypoxia/reoxygenation (H/R) model. Cell viability and apoptosis were evaluated using cell counting kit 8 (CCK-8) and AV/PI dual staining respectively. The expressions of miR-665 and MEF2D mRNA were detected by qRT-PCR. Western blot was employed to determine the expression levels of pyroptosis- and signaling pathway- related proteins. The interplays between miR-665 and MEF2D were validated by Dual-luciferase reporter assays. Our findings indicated that Dex preconditioning dramatically attenuated hemodynamic derangements, infarct size, and histopathological damage in rats undergoing MIRI. Dex markedly augmented cell viability, while suppressing cell apoptosis and expressions of NLRP3, cleaved-caspase-1, ASC, GSDMD, IL-1β, and IL-18 in H9c2 cells subjected to H/R injury. MiR-665 was significantly upregulated, MEF2D and Nrf2 downregulated following H/R, whereas Dex preconditioning reversed these changes. MEF2D was validated to be a target gene of miR-665. Overexpression of miR-665 decreased the expression of MEF2D and blunted the protective effects of Dex in H9c2 cells. Moreover, the functional rescue experiment further verified that Dex regulated MEF2D/Nrf2 pathway via miR-665. In conclusion, Dex mitigates MIRI through inhibiting pyroptosis via regulating miR-665/MEF2D/Nrf2 axis.
Topics: Rats; Animals; Myocardial Reperfusion Injury; Pyroptosis; Dexmedetomidine; NF-E2-Related Factor 2; Cell Line; MicroRNAs; Apoptosis; Myocytes, Cardiac; Reperfusion Injury; MEF2 Transcription Factors
PubMed: 37549462
DOI: 10.1016/j.biopha.2023.115255 -
European Journal of Anaesthesiology Oct 2023Pain after craniotomy can be intense and its management is often suboptimal.
BACKGROUND
Pain after craniotomy can be intense and its management is often suboptimal.
OBJECTIVES
We aimed to evaluate the available literature and develop recommendations for optimal pain management after craniotomy.
DESIGN
A systematic review using procedure-specific postoperative pain management (PROSPECT) methodology was undertaken.
DATA SOURCES
Randomised controlled trials and systematic reviews published in English from 1 January 2010 to 30 June 2021 assessing pain after craniotomy using analgesic, anaesthetic or surgical interventions were identified from MEDLINE, Embase and Cochrane Databases.
ELIGIBILITY CRITERIA
Each randomised controlled trial (RCT) and systematic review was critically evaluated and included only if met the PROSPECT requirements. Included studies were evaluated for clinically relevant differences in pain scores, use of nonopioid analgesics, such as paracetamol and NSAIDs, and current clinical relevance.
RESULTS
Out of 126 eligible studies identified, 53 RCTs and seven systematic review or meta-analyses met the inclusion criteria. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol, NSAIDs, intravenous dexmedetomidine infusion, regional analgesia techniques, including incision-site infiltration, scalp nerve block and acupuncture. Limited evidence was found for flupirtine, intra-operative magnesium sulphate infusion, intra-operative lidocaine infusion, infiltration adjuvants (hyaluronidase, dexamethasone and α-adrenergic agonist added to local anaesthetic solution). No evidence was found for metamizole, postoperative subcutaneous sumatriptan, pre-operative oral vitamin D, bilateral maxillary block or superficial cervical plexus block.
CONCLUSIONS
The analgesic regimen for craniotomy should include paracetamol, NSAIDs, intravenous dexmedetomidine infusion and a regional analgesic technique (either incision-site infiltration or scalp nerve block), with opioids as rescue analgesics. Further RCTs are required to confirm the influence of the recommended analgesic regimen on postoperative pain relief.
Topics: Humans; Pain Management; Dexmedetomidine; Acetaminophen; Analgesics; Pain, Postoperative; Craniotomy; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37417808
DOI: 10.1097/EJA.0000000000001877