• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.413-420
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• 2015

Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing ${\alpha}2$ adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce $Ca^{2+}$ release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger $Ca^{2+}$ peak or increase in the presence or absence of external $Ca^{2+}$. When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced $[Ca^{2+}]_i$ signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced $Ca^{2+}$ signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.5
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• pp.349-356
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• 2022

Background: Awake fiberoptic intubation (AFOI) is the procedure of choice for securing the airway in patients with a difficult airway when undergoing surgeries under general anesthesia. An ideal drug would not only provide conscious sedation but also maintain spontaneous ventilation, smooth intubation conditions, and stable hemodynamics. We compared the effects of dexmedetomidine alone and dexmedetomidine in combination with fentanyl at a dose lower than the standard dose for achieving conscious sedation during AFOI in difficult airway patients undergoing oral cancer and dental surgeries. Methods: We included 68 adult patients undergoing AFOI. The patients were randomized in two groups, wherein Group D received intravenous dexmedetomidine 1 ㎍/kg and Group DF received dexmedetomidine 0.5 ㎍/kg and fentanyl 1 ㎍/kg. The outcomes measured were airway obstruction score, intubation scores, fiberoptic intubation comfort score, sedation score, and hemodynamic variables. Results: Low-dose dexmedetomidine with fentanyl showed similar results as those with the standard dose of dexmedetomidine in terms of airway obstruction, vocal cord movement, degree of cough, degree of limb movements, and intubation comfort. However, the sedation achieved and incidence of hypotension and bradycardia were higher in Group D than in Group DF. Conclusions: A low dose of dexmedetomidine-fentanyl provides satisfactory intubation conditions as those with a standard dose of dexmedetomidine in AFOI, thereby avoiding bradycardia, hypotension, and sedation.

• The Korean Journal of Pain
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• v.27 no.4
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• pp.313-320
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• 2014

Dexmedetomidine, an imidazoline compound, is a highly selective ${\alpha}_2$-adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties. In order to minimize the patients' pain and anxiety during minimally invasive spine surgery (MISS) when compared to conventional surgery under general anesthesia, an adequate conscious sedation (CS) or monitored anesthetic care (MAC) should be provided. Commonly used intravenous sedatives and hypnotics, such as midazolam and propofol, are not suitable for operations in a prone position due to undesired respiratory depression. Dexmedetomidine converges on an endogenous non-rapid eye movement (NREM) sleep-promoting pathway to exert its sedative effects. The great merit of dexmedetomidine for CS or MAC is the ability of the operator to recognize nerve damage during percutaneous endoscopic lumbar discectomy, a representative MISS. However, there are 2 shortcomings for dexmedetomidine in MISS: hypotension/bradycardia and delayed emergence. Its hypotension/bradycardiac effects can be prevented by ketamine intraoperatively. Using atipamezole (an ${\alpha}_2$-adrenoceptor antagonist) might allow doctors to control the rate of recovery from procedural sedation in the future. MAC, with other analgesics such as ketorolac and opioids, creates ideal conditions for MISS. In conclusion, dexmedetomidine provides a favorable surgical condition in patients receiving MISS in a prone position due to its unique properties of conscious sedation followed by unconscious hypnosis with analgesia. However, no respiratory depression occurs based on the dexmedetomidine-related endogenous sleep pathways involves the inhibition of the locus coeruleus in the pons, which facilitates VLPO firing in the anterior hypothalamus.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.417-422
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• 2013

The aim of this study was to evaluate the synergistic potentiation effect of ineffective doses of dexmedetomidine on antinociception induced by morphine and fentanyl in acute pain model in rats. Seventy albino Wistar rats were separated into 7 groups. Data for the control and sham groups were recorded. The ineffective dose of dexmedetomidine was investigated and found to be 3 ${\mu}g/kg$. Each group was administered the following medications: 3 mg/kg morphine (intraperitoneal) to Group 3, 5 ${\mu}g/kg$ fentanyl (intraperitoneal) to Group 4, dexmedetomidine 3 ${\mu}g/kg$ (subcutaneously) to Group 5, dexmedetomidine 3 ${\mu}g/kg$ (subcutaneous)+3 mg/kg morphine (intraperitoneal) to Group 6 and finally 3 ${\mu}g/kg$ dexmedetomidine (subcutaneous)+5 ${\mu}g/kg$ fentanyl (intraperitoneal) to Group 7. Just before the application and 15, 30, 60, 90 and 120 min after the administration of medication, two measurements of tail flick (TF) and hot plate (HP) tests were performed. The averages of the measurements were recorded. TF and HP latencies were the main outcomes. The analgesic effect of the combinations with dexmedetomidine+morphine (Group 6) and dexmedetomidine+fentanyl (Group 7), compared to the analgesic effect of morphine alone and fentanyl alone was significantly higher at 15, 30, 60 and 90 minutes after administration. In this study, dexmedetomidine in ineffective doses, when combined with morphine and fentanyl, potentiates the effects of both morphine and fentanyl.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.239-252
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• 2024

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ㎍/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ㎍/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

• Journal of Korean Dental Science
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• v.10 no.2
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• pp.82-86
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• 2017

Oral and maxillofacial surgery (OMFS) trauma cases are commonly treated under general anesthesia. The purpose of this case report is to introduce an alternative method of anesthesia in patients who refuse general anesthesia. A combination of dexmedetomidine and ketamine for sedation anesthesia in 3 frequent fracture types in the field of OMFS-Le Fort I fracture, mandibular fracture, and alveolar bone fracture-was used. Dexmedetomidine as the single agent has not shown stable success rates for invasive procedures. To overcome some of the pitfalls with dexmedetomidine, combination sedation using ketamine was performed. Visual analogue scale scores were recorded postoperatively. Dexmedetomidine combined with ketamine administration provided safe and effective sedation and anxiolysis for surgical reduction and internal fixation of OMFS fractures. It showed advantages of decreased admission time, reduced expenses, minimal pain, and reduced anesthetic burden for the patient thus ultimately increasing overall satisfaction.

• Journal of The Korean Dental Society of Anesthesiology
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• v.13 no.4
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• pp.161-166
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• 2013

Dexmedetomidine is a potent alpha-2-adrenergic agonist, more selective than clonidine, with widespread actions on the mammalian brain. A large body of recent work supports its analgesia and sympatholytic properties. Dexmedetomidine is a useful medication with many clinical applications. The medication has shown efficacy in decreasing the need for opioids, benzodiazepines, propofol, and other sedative medications. Dexmedetomidine has been used effectively for sedation during invasive procedures and in the ICU. Short-term sedation has been shown to be safe in studies, although hypotension and bradycardia are the most significant side effects. Dexmedetomidine is emerging as an effective therapeutic agent in the management of a wide range of clinical conditions with an efficacious, safe profile.

• The Korean Journal of Pain
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• v.30 no.2
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• pp.134-141
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• 2017

Background: Postoperative pain is a common, distressing symptom following arthroscopic knee surgery. The aim of this study was to compare the potential analgesic effect of dexmedetomidine after intrathecal versus intra-articular administration following arthroscopic knee surgery. Methods: Ninety patients undergoing unilateral elective arthroscopic knee surgery were randomly assigned into three groups in a double-blind placebo controlled study. The intrathecal dexmedetomidine group (IT) received an intrathecal block with intrathecal dexmedetomidine, the intra-articular group (IA) received an intrathecal block and intra-articular dexmedetomidine, and the control group received an intrathecal block and intra-articular saline. The primary outcome of our study was postoperative pain as assessed by the visual analogue scale of pain (VAS). Secondary outcomes included the effect of dexmedetomidine on total postoperative analgesic use and time to the first analgesic request, hemodynamics, sedation, postoperative nausea and vomiting, patient satisfaction, and postoperative C-reactive protein (CRP) levels. Results: Dexmedetomidine administration decreased pain scores for 4 h in both the intrathecal and intra-articular groups, compared to only 2 h in the control patient group. Furthermore, there was a significant reduction in pain scores for 6 h in the intra-articular group. The time to the first postoperative analgesia request was longer in the intra-articular group compared to the intrathecal and control groups. The total meperidine requirement was significantly lower in the intra-articular and intrathecal groups than in the control group. Conclusions: Both intrathecal and intra-articular dexmedetomidine enhanced postoperative analgesia after arthroscopic knee surgery. Less total meperidine was required with intra-articular administration to extend postoperative analgesia to 6 h with hemodynamic stability.

• Journal of Audiology & Otology
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• v.23 no.2
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• pp.89-95
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• 2019

Background and Objectives: Knowing the ototoxic potential of the agents used in medical treatments is important for the protection of hearing. Although we have knowledge regarding some effects of dexmedetomidine, which is an anesthetic-sparing drug, its influence over the hearing system has never been studied and is obscure yet. The aim of this study is to determine the effects of intravenous dexmedetomidine application during sevoflurane anesthesia on otoacoustic emissions (OAEs). Subjects and Methods: This prospective randomized study was performed on 60 patients (34 male, 26 female, mean age: 30.6±9.2 years) who were scheduled for an elective surgery under general anesthesia and the patients were enrolled and randomly divided into 2 groups. They received dexmedetomidine (Group D) or Saline (Group S) infusion during a standardized Sevoflurane anesthesia. Transient and distortion product OAEs were measured preoperatively and postoperatively (24th hour). OAE results were compared within and between groups. Results: In group D postoperative OAEs were lower than preoperative OAEs and postoperative levels of group S, especially at low frequencies (p<0.05). Conclusions: Dexmedetomidine infusion affects the micromechanical function of cochlea especially in the low-frequency region. Dexmedetomidine should be carefully used during general anesthesia to avoid its probable harmful effects on cochlear micromechanics.

• Korean Journal of Audiology
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• v.23 no.2
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• pp.89-95
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• 2019

Background and Objectives: Knowing the ototoxic potential of the agents used in medical treatments is important for the protection of hearing. Although we have knowledge regarding some effects of dexmedetomidine, which is an anesthetic-sparing drug, its influence over the hearing system has never been studied and is obscure yet. The aim of this study is to determine the effects of intravenous dexmedetomidine application during sevoflurane anesthesia on otoacoustic emissions (OAEs). Subjects and Methods: This prospective randomized study was performed on 60 patients (34 male, 26 female, mean age: 30.6±9.2 years) who were scheduled for an elective surgery under general anesthesia and the patients were enrolled and randomly divided into 2 groups. They received dexmedetomidine (Group D) or Saline (Group S) infusion during a standardized Sevoflurane anesthesia. Transient and distortion product OAEs were measured preoperatively and postoperatively (24th hour). OAE results were compared within and between groups. Results: In group D postoperative OAEs were lower than preoperative OAEs and postoperative levels of group S, especially at low frequencies (p<0.05). Conclusions: Dexmedetomidine infusion affects the micromechanical function of cochlea especially in the low-frequency region. Dexmedetomidine should be carefully used during general anesthesia to avoid its probable harmful effects on cochlear micromechanics.