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Die Anaesthesiologie Oct 2022Acutely occurring organ damage significantly contributes to morbidity and mortality in the perioperative context. (Review)
Review
BACKGROUND
Acutely occurring organ damage significantly contributes to morbidity and mortality in the perioperative context.
OBJECTIVE
This article highlights new clinical perspectives on how perioperative organ damage can be prevented and ameliorated by influencing the high mobility group box 1 protein (HMGB1) signaling.
MATERIAL AND METHODS
A MEDLINE search was performed in the fields of clinical and basic research. The presentation of basic mechanisms of perioperative organ damage and the discussion of the importance of HMGB1 in prevention and treatment by pharmaceutical and nonpharmaceutical interventions are the focus of the review.
RESULTS
The HMGB1 is a central element in the pathogenesis of septic and aseptic inflammation-induced organ damage. Remote ischemic preconditioning (RIPC) and dexmedetomidine are highly effective approaches to mitigate or prevent organ damage.
CONCLUSION
The RIPC and dexmedetomidine offer protective properties in ischemia-reperfusion injury as well as in inflammation-related organ damage, which are mediated by HMGB1, among others. This effectively protects the kidneys, heart, lungs, liver and brain. The application of these concepts should be considered in routine clinical practice.
Topics: Dexmedetomidine; HMGB1 Protein; Humans; Inflammation; Ischemic Preconditioning; Pharmaceutical Preparations
PubMed: 36064976
DOI: 10.1007/s00101-022-01197-6 -
Advances in Anesthesia Dec 2022Dexmedetomidine's unique sedative properties have led to its widespread use. Dexmedetomidine has a beneficial pharmacologic profile including analgesic sparing effects,... (Review)
Review
Dexmedetomidine's unique sedative properties have led to its widespread use. Dexmedetomidine has a beneficial pharmacologic profile including analgesic sparing effects, anxiolysis, sympatholysis, organ-protective effects against ischemic and hypoxic injury, and sedation which parallels natural sleep. An understanding of predictable side effects, effects of age-related physiologic changes, and pharmacokinetic and pharmacodynamic effects of dexmedetomidine is crucial to maximize its safe administration in adults and children. This review focuses on the growing body of literature examining advances in applications of dexmedetomidine in children and adults.
Topics: Child; Adult; Humans; Dexmedetomidine; Hypnotics and Sedatives; Anesthesia; Critical Care
PubMed: 36333042
DOI: 10.1016/j.aan.2022.06.003 -
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 -
British Journal of Anaesthesia Oct 2023Cortical excitability is higher in unconsciousness than in wakefulness, but it is unclear how this relates to anaesthesia. We investigated cortical excitability in...
BACKGROUND
Cortical excitability is higher in unconsciousness than in wakefulness, but it is unclear how this relates to anaesthesia. We investigated cortical excitability in response to dexmedetomidine, the effects of which are not fully known.
METHODS
We recorded transcranial magnetic stimulation (TMS) and EEG in frontal and parietal cortex of 20 healthy subjects undergoing dexmedetomidine sedation in four conditions (baseline, light sedation, deep sedation, recovery). We used the first component (0-30 ms) of the TMS-evoked potential (TEP) to measure cortical excitability (amplitude), slope, and positive and negative peak latencies (collectively, TEP indices). We used generalised linear mixed models to test the effect of condition, brain region, and responsiveness on TEP indices.
RESULTS
Compared with baseline, amplitude in the frontal cortex increased by 6.52 μV (P<0.001) in light sedation, 4.55 μV (P=0.003) in deep sedation, and 5.03 μV (P<0.001) in recovery. Amplitude did not change in the parietal cortex. Compared with baseline, slope increased in all conditions (P<0.02) in the frontal but not parietal cortex. The frontal cortex showed 5.73 μV higher amplitude (P<0.001), 0.63 μV ms higher slope (P<0.001), and 2.2 ms shorter negative peak latency (P=0.001) than parietal areas. Interactions between dexmedetomidine and region had effects over amplitude (P=0.004) and slope (P=0.009), with both being higher in light sedation, deep sedation, and recovery compared with baseline.
CONCLUSIONS
Transcranial magnetic stimulation-evoked potential amplitude changes non-linearly as a function of depth of sedation by dexmedetomidine, with a region-specific paradoxical increase. Future research should investigate other anaesthetics to elucidate the link between cortical excitability and depth of sedation.
Topics: Humans; Transcranial Magnetic Stimulation; Dexmedetomidine; Evoked Potentials; Anesthesia; Frontal Lobe
PubMed: 37596183
DOI: 10.1016/j.bja.2023.05.030 -
Anesthesiology Aug 2020
Topics: Analgesics, Non-Narcotic; Animals; Cognitive Dysfunction; Critical Care; Critical Illness; Dexmedetomidine; Disease Models, Animal; Humans; Mice; Rodentia
PubMed: 32665488
DOI: 10.1097/ALN.0000000000003391 -
Journal of Clinical Pharmacy and... Mar 2022Currently, dexmedetomidine is widely used in the treatment of sepsis patients requiring mechanical ventilation; however, its role remains controversial. The aim of this... (Meta-Analysis)
Meta-Analysis Review
WHAT IS KNOWN AND OBJECTIVE
Currently, dexmedetomidine is widely used in the treatment of sepsis patients requiring mechanical ventilation; however, its role remains controversial. The aim of this study was to assess the efficacy and safety of dexmedetomidine in sepsis patients requiring mechanical ventilation.
METHODS
The PubMed, Embase and Cochrane Library electronic databases were searched to identify relevant studies; Review Manager version 5.4 was used to perform the meta-analysis. Primary outcomes included the all-cause mortality rate at the longest follow-up available and the duration of mechanical ventilation. Secondary outcomes included length of intensive care unit (ICU) stay, length of hospital stay, and adverse events (bradycardia).
RESULTS
Five randomized controlled trials (RCTs), including 926 patients, were assessed. Overall, dexmedetomidine did not reduce all-cause mortality in mechanically ventilated patients with sepsis (relative risk [RR]: 0.9, 95% confidence interval [CI]: 0.77 to 1.05, p = 0.18, I = 37%). However, dexmedetomidine was associated with decreases in the length of hospital stay (mean difference [MD]: -2.99, 95% CI: -4.72 to -1.26, p = 0.0007, I = 0%), ICU length of stay (MD: -1.15, 95% CI: -2.06 to -0.24, p = 0.01, I = 32%) and duration of mechanical ventilation (MD: -0.72, 95% CI: -1.38 to -0.07, p = 0.03, I = 20%). However, dexmedetomidine increased the risk for bradycardia (22% versus 12.6%, respectively; RR: 1.73, 95% CI: 1.24 to 2.41, p = 0.001, I = 0%).
WHAT IS NEW AND CONCLUSION
Results suggested that dexmedetomidine did not reduce all-cause mortality in mechanically ventilated patients with sepsis. However, it was associated with decreases in length of hospital stay, ICU length of stay and duration of mechanical ventilation, although it increased the risk for bradycardia.
Topics: Dexmedetomidine; Humans; Intensive Care Units; Length of Stay; Respiration, Artificial; Sepsis
PubMed: 34664723
DOI: 10.1111/jcpt.13548 -
Journal of Anesthesia Dec 2023Dexmedetomidine (DEX), a highly selective alpha2-adrenoceptors agonist, is not only a sedative drug used during mechanical ventilation in the intensive care unit but... (Review)
Review
Dexmedetomidine (DEX), a highly selective alpha2-adrenoceptors agonist, is not only a sedative drug used during mechanical ventilation in the intensive care unit but also a cardio-protective drug against ischemia-reperfusion injury (IRI). Numerous preclinical in vivo and ex vivo studies, mostly evaluating the effect of DEX pretreatment in healthy rodents, have shown the efficacy of DEX in protecting the hearts from IRI. However, whether DEX can maintain its cardio-protective effect in hearts with comorbidities such as diabetes has not been fully elucidated. Multiple clinical trials have reported promising results, showing that pretreatment with DEX can attenuate cardiac damage in patients undergoing cardiac surgery. However, evidence of the post-treatment effects of DEX in clinical practice remains limited. In this narrative review, we summarize the previously reported evidence of DEX-induced cardio-protection against IRI and clarify the condition of the hearts and the timing of DEX administration that has not been tested. With further investigations evaluating these knowledge gaps, the use of DEX as a cardio-protective drug could be further facilitated in the management of patients undergoing cardiac surgery and might be considered in a broader area of clinical settings beyond cardiac surgery, including patients with acute myocardial infarction.
Topics: Humans; Dexmedetomidine; Pharmaceutical Preparations; Heart; Reperfusion Injury; Protective Agents
PubMed: 37750978
DOI: 10.1007/s00540-023-03261-w -
Neurochemical Research Feb 2022To evaluate the effects of dexmedetomidine (Dex) and oxycodone (Oxy) on neurocognitive and inflammatory response after tourniquet-induced ischemia-reperfusion (I/R)...
To evaluate the effects of dexmedetomidine (Dex) and oxycodone (Oxy) on neurocognitive and inflammatory response after tourniquet-induced ischemia-reperfusion (I/R) injury. C57/BL6 mice were used to construct the mouse model of tourniquet-induced I/R injury. Mice (n = 48) were randomly divided into sham, I/R, Dex or Oxy group. Morris water maze test was performed to assess the spatial learning and memory function. The expression of NF-κB, TLR4, NR2B, M1 (CD68 and TNF-α) and M2 (CD206 and IL-10) polarization markers in mice hippocampus were detected by western blot or immunofluorescent staining. Spontaneous excitatory post-synaptic currents (sEPSCs) were recorded by electrophysiology. Dex treatment alleviated I/R-induced declines in learning and memory (p < 0.05), while Oxy had no significant effect on it. Compared with I/R group, Dex and Oxy treatment down-regulated the expression of NF-κB, TLR4, TNF-α and CD68 (all p < 0.05), while no significantly different was found in CD206 and IL-10. In addition, Dex treatment down-regulated the expression of NR2B and reduced the frequency and amplitude of sEPSCs in I/R model mice (all p < 0.05), while Oxy had no significant effect on them. Tourniquet-induced I/R could impair the neurocognitive function of mice. Dex treatment could alleviate I/R-induced neurocognitive disorder by inhibiting abnormal synaptic transmission in hippocampal neurons. Both Dex and Oxy could alleviate the inflammatory response likely by inhibiting the polarization of microglia toward M1 phenotype via TLR4/NF-κB pathway. Future studies are needed to further examine the effects of Dex on neurocognitive disorder after tourniquet-induced I/R injury and investigate the exact mechanism.
Topics: Animals; Dexmedetomidine; Mice; NF-kappa B; Oxycodone; Reperfusion Injury; Tourniquets
PubMed: 34625874
DOI: 10.1007/s11064-021-03461-4 -
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 -
European Journal of Pharmacology Nov 2023Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received increasing attention due to increased morbidity and mortality. To date, there are no effective treatments. Dexmedetomidine (DEX), a highly selective α-adrenergic receptor agonist, has been demonstrated to be effective against intestinal IRI. In this systematic review and meta-analysis, we evaluated the efficacy and potential mechanisms of DEX as a treatment for intestinal IRI in animal models.
METHODS
Five databases (PubMed, Embase, Web of Science, Cochrane Library, and Scopus) were searched until March 15, 2023. Using the SYRCLE risk bias tool, we assessed methodological quality. Statistical analysis was conducted using STATA 12 and R 4.2.2. We analyzed the related outcomes (mucosa damage-related indicators; inflammation-relevant markers, oxidative stress markers) relied on the fixed or random-effects models.
RESULTS
There were 15 articles including 18 studies included, and 309 animals were involved in the studies. Compared to the model groups, DEX improved intestinal IRI. DEX decreased Chiu's score and serum diamine oxidase (DAO) level. DEX reduced the level of inflammation-relevant markers (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α). DEX also improved oxidative stress (decreased malondialdehyde (MDA), increased superoxide dismutase (SOD)).
CONCLUSIONS
DEX's effectiveness in ameliorating intestinal IRI has been demonstrated in animal models. Antioxidation, anti-inflammation, anti-apoptotic, anti-pyroptosis, anti-ferroptosis, enhancing mitophagy, reshaping the gut microbiota, and gut barrier protection are possible mechanisms. However, in light of the heterogeneity and methodological quality of these studies, further well-designed preclinical studies are warranted before clinical implication.
Topics: Rats; Animals; Dexmedetomidine; Rats, Sprague-Dawley; Adrenergic alpha-2 Receptor Agonists; Reperfusion Injury; Inflammation; Ischemia
PubMed: 37778612
DOI: 10.1016/j.ejphar.2023.176090