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British Journal of Anaesthesia May 2018Intranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomisation (MAD...
BACKGROUND
Intranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomisation (MAD Nasal).
METHODS
This prospective, three-period, crossover, double-blind study compared the pharmacokinetic (PK) and pharmacodynamic (PD) profile of i.v. administration with these two different modes of administration. In each session each subject received 1 μg kg dexmedetomidine, either i.v., intranasal with the atomiser or intranasal by drops. Dexmedetomidine plasma concentration and Ramsay sedation score were used for PK/PD modelling by NONMEM.
RESULTS
The i.v. route had a significantly faster onset (15 min, 95% CI 15-20 min) compared to intranasal routes by atomiser (47.5 min, 95% CI 25-135 min), and by drops (60 min, 95%CI 30-75 min), (P<0.001). There was no significant difference in sedation duration across the three treatment groups (P=0.88) nor in the median onset time between the two modes of intranasal administration (P=0.94). A 2-compartment disposition model, with transit intranasal absorption and clearance driven by cardiac output using the well-stirred liver model, was the final PK model. Intranasal bioavailability was estimated to be 40.6% (95% CI 34.7-54.4%) and 40.7% (95% CI 36.5-53.2%) for atomisation and drops respectively. Sedation score was modelled via a sigmoidal E model driven by an effect compartment. The effect compartment had an equilibration half time 3.3 (95% CI 1.8-4.7) min, and the EC50 was estimated to be 903 (95% CI 450-2344) pg ml.
CONCLUSIONS
There is no difference in bioavailability with atomisation or nasal drops. A similar degree of sedation can be achieved by either method.
CLINICAL TRIAL REGISTRATION
HKUCTR-1617.
Topics: Administration, Intranasal; Administration, Intravenous; Adult; Cross-Over Studies; Dexmedetomidine; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Male; Prospective Studies
PubMed: 29661413
DOI: 10.1016/j.bja.2017.11.100 -
JAMA Network Open Jun 2022Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown.
OBJECTIVE
To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant.
DESIGN, SETTING, AND PARTICIPANTS
This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population.
INTERVENTIONS
Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 μg/kg/h intraoperatively and 0.1 μg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine.
MAIN OUTCOMES AND MEASURES
The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30.
RESULTS
Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants.
TRIAL REGISTRATION
Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.
Topics: Adult; Death; Delayed Graft Function; Dexmedetomidine; Humans; Kidney Transplantation; Male; Renal Dialysis; Saline Solution
PubMed: 35657627
DOI: 10.1001/jamanetworkopen.2022.15217 -
Oncoimmunology 2024Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist that is widely used in intensive and anesthetic care for its sedative and anxiolytic properties. DEX... (Review)
Review
Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist that is widely used in intensive and anesthetic care for its sedative and anxiolytic properties. DEX has the capacity to alleviate inflammatory pain while limiting immunosuppressive glucocorticoid stress during major surgery, thus harboring therapeutic benefits for oncological procedures. Recently, the molecular mechanisms of DEX-mediated anticancer effects have been partially deciphered. Together with additional preclinical data, these mechanistic insights support the hypothesis that DEX-induced therapeutic benefits are mediated the stimulation of adaptive anti-tumor immune responses. Similarly, published clinical trials including ancillary studies described an immunostimulatory role of DEX during the perioperative period of cancer surgery. The impact of DEX on long-term patient survival remains elusive. Nevertheless, DEX-mediated immunostimulation offers an interesting therapeutic option for onco-anesthesia. Our present review comprehensively summarizes data from preclinical and clinical studies as well as from ongoing trials with a distinct focus on the role of DEX in overcoming (tumor microenvironment (TME)-imposed) cancer therapy resistance. The objective of this update is to guide clinicians in their choice toward immunostimulatory onco-anesthetic agents that have the capacity to improve disease outcome.
Topics: Humans; Dexmedetomidine; Hypnotics and Sedatives; Neoplasms; Clinical Trials as Topic
PubMed: 38481729
DOI: 10.1080/2162402X.2024.2327143 -
Indian Journal of Cancer 2020Dexmedetomidine is a centrally acting α2 adrenoreceptor agonist used in perioperative medicine due to its sedative, analgesic and sympatholytic properties. Recently... (Review)
Review
Dexmedetomidine is a centrally acting α2 adrenoreceptor agonist used in perioperative medicine due to its sedative, analgesic and sympatholytic properties. Recently animal data has pointed towards potential role of dexmedetomidine in promoting cancer recurrence and metastasis when used perioperatively especially after breast surgeries. This is because of presence of α2 adrenoreceptors in breast cancer tissue. We reviewed existing literature in which dexmedetomidine was used in cancer surgeries and investigated its role in recurrence and metastasis.
Topics: Dexmedetomidine; Humans; Hypnotics and Sedatives; Neoplasms
PubMed: 32769293
DOI: 10.4103/ijc.IJC_376_19 -
American Journal of Veterinary Research Oct 2019To determine pharmacokinetic and pharmacodynamic properties of the injectable formulation of dexmedetomidine administered via the oral transmucosal (OTM) route to...
OBJECTIVE
To determine pharmacokinetic and pharmacodynamic properties of the injectable formulation of dexmedetomidine administered via the oral transmucosal (OTM) route to healthy dogs.
ANIMALS
6 healthy dogs.
PROCEDURES
Injectable dexmedetomidine was administered IV (5 μg/kg) or via the OTM route (20 μg/kg) in a blinded, single-observer, randomized crossover study. Dogs received dexmedetomidine and a sham treatment at each administration. Serial blood samples were collected from a catheter in a saphenous vein. Heart rate, respiratory rate, and subjective sedation score were assessed for 24 hours after administration. Plasma samples were analyzed for dexmedetomidine concentrations by use of ultraperformance liquid chromatography-tandem mass spectrometry.
RESULTS
For the OTM route, the mean ± SD maximum plasma concentration was 3.8 ± 1.3 ng/mL, which was detected 73 ± 33 minutes after administration. The mean maximum concentration for the IV dose, when extrapolated to the time of administration, was 18.6 ± 3.3 ng/mL. The mean terminal-phase half-life was 152 ± 146 minutes and 36 ± 6 minutes for OTM and IV administration, respectively. After IV administration, total clearance was 8.0 ± 1.6 mL/min/kg and volume of distribution at steady state was 371 ± 72 mL/kg. Bioavailability for OTM administration of dexmedetomidine was 11.2 ± 4.5%. Peak sedation scores did not differ significantly between routes of administration. Decreases in heart rate, respiratory rate, and peak sedation score were evident sooner after IV administration.
CONCLUSIONS AND CLINICAL RELEVANCE
OTM administration of the injectable formulation of dexmedetomidine resulted in a similar degree of sedation and prolonged duration of action, compared with results for IV administration, despite relatively low bioavailability.
Topics: Administration, Intravenous; Administration, Mucosal; Administration, Oral; Animals; Biological Availability; Chromatography, Liquid; Cross-Over Studies; Dexmedetomidine; Dogs; Female; Half-Life; Heart Rate; Hypnotics and Sedatives; Infusions, Intravenous; Male; Respiratory Rate
PubMed: 31556717
DOI: 10.2460/ajvr.80.10.969 -
Contrast Media & Molecular Imaging 2022The aim of this study is to investigate the effect of dexmedetomidine on cognitive dysfunction and inflammatory cytokines in the hippocampus after surgery in aged rats.
OBJECTIVE
The aim of this study is to investigate the effect of dexmedetomidine on cognitive dysfunction and inflammatory cytokines in the hippocampus after surgery in aged rats.
METHODS
A total of 30 healthy male Sprague Dawley rats were divided into control group, sham group, and dexmedetomidine group. A splenectomy rat model was established and dexmedetomidine was intraperitoneally injected before operation. The cognitive function of rats was examined by Morris Water-Maze Test, open field experiment, and passive avoidance memory test. And the expression levels of IL-6, IL-1, and TNF- in the hippocampus were examined by ELISA.
RESULTS
The escape latency for 5 continuous days in dexmedetomidine group was significantly decreased comparing with control group (all < 0.05). The number of times of swimming and the percentage of swimming time in dexmedetomidine group were significantly more than those in control group (all < 0.05). What is more, rats in dexmedetomidine group had the decreased time of stay in the central square and the increased number of standing times in comparison with the control group, and the statistical differences were found (all < 0.05). Compared with the control group, dexmedetomidine intraperitoneally injected before surgery could significantly inhibit the expression levels of IL-6, IL-1, and TNF- in the hippocampus, and there were statistical differences (all < 0.05).
CONCLUSION
Dexmedetomidine could significantly relieve the postoperative cognitive dysfunction in aged rats. The mechanism may be associated with the decreased inflammatory cytokines in the hippocampus.
Topics: Animals; Cytokines; Dexmedetomidine; Inflammation; Interleukin-6; Male; Postoperative Cognitive Complications; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha
PubMed: 35866065
DOI: 10.1155/2022/8830706 -
PloS One 2018This study aimed to evaluate the efficacy and safety of dexmedetomidine versus any other treatment without dexmedetomidine in patients who have undergone cardiac... (Meta-Analysis)
Meta-Analysis
This study aimed to evaluate the efficacy and safety of dexmedetomidine versus any other treatment without dexmedetomidine in patients who have undergone cardiac surgery. Electronic databases including PubMed, Embase, and Cochrane Library were systematically searched without limitations of language and publication time. Randomized controlled trials (RCTs) aiming to evaluate the efficacy and safety of dexmedetomidine versus any other treatment without dexmedetomidine in patients that have undergone cardiac surgery were selected. Endpoints such as hemodynamic indexes and adverse events in eligible studies were extracted by two researchers, independently. The data was analyzed using RevMan 5.3 and Stata 11.0 software. A total of 18 RCTs met the inclusion criteria, involving 1730 patients. Compared to control (any treatment without dexmedetomidine), dexmedetomidine showed a pooled mean difference (MD) of -14.46 [95% confidence interval(CI): -24.69, -4.23; p<0.01] for systolic arterial pressure, a standardized mean difference (SMD) of -1.74 for mean arterial blood pressure (95% CI: -2.80, -0.68; P < 0.01), -2.12 (95%CI: -3.23, -1.00; p<0.01) for heart rate, and combined odds ratio (OR) of 0.22 (95%CI: 0.11, 0.44; p<0.01) for tachycardia, 3.44 (95%CI: 1.95, 5.96; p<0.01) for bradycardia, 0.74 (95%CI: 0.49, 1.12; p>0.05) for atrial fibrillation, and 0.99 (95%CI: 0.51, 1.90; p>0.05) for hypotension. In addition, dexmedetomidine could reduce time of surgery and stay in intensive care units, improve delirium with good safety. Our study shows clinical application of dexmedetomidine in cardiac surgery patients can reduce risks of abnormal hemodynamics with good safety.
Topics: Analgesics, Non-Narcotic; Cardiac Surgical Procedures; Dexmedetomidine; Hemodynamics; Humans; Intensive Care Units; Operative Time; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 30231052
DOI: 10.1371/journal.pone.0202620 -
American Journal of Veterinary Research Dec 2022The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following...
OBJECTIVE
The goal of this study was to determine plasma, urine, and synovial fluid concentrations and describe the effects on biomarkers of cartilage toxicity following intra-articular dexmedetomidine administration to horses.
ANIMALS
12 research horses.
PROCEDURES
Horses received a single intra-articular administration of 1 μg/kg or 5 μg/kg dexmedetomidine or saline. Plasma, urine, and synovial fluid were collected prior to and up to 48 hours postadministration, and concentrations were determined. The effects on CS846 and C2C were determined in synovial fluid at 0, 12, and 24 hours postadministration using immunoassays.
RESULTS
Plasma concentrations of dexmedetomidine fell below the limit of quantification (LOQ) (0.005 ng/mL) by 2.5 and 8 hours postadministration of 1 and 5 μg/kg, respectively. Synovial fluid concentrations were above the LOQ (0.1 ng/mL) of the assay at 24 hours in both dose groups. Drug was not detected in urine samples at any time postdrug administration. CS846 concentrations were significantly decreased relative to baseline at 12 hours postadministration in the saline group and significantly increased in the 5-μg/kg-dose group at 24 hours. Concentrations of C2C were significantly decreased at 12 and 24 hours postadministration in the saline treatment group. There were no significant differences in CS846 or C2C concentrations between dose groups at any time.
CLINICAL RELEVANCE
Systemic concentrations of dexmedetomidine remained low, compared to synovial fluid concentrations. CS846, a marker of articular cartilage synthesis, increased in a dose-dependent fashion. Based on these findings, further dose titration and investigation of analgesic and adverse effects are warranted.
Topics: Horses; Animals; Dexmedetomidine; Injections, Intra-Articular; Synovial Fluid; Cartilage, Articular; Biomarkers; Horse Diseases
PubMed: 36476411
DOI: 10.2460/ajvr.22.08.0146 -
Psychiatry Research May 2023Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders that affects children and even continues into adulthood....
Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders that affects children and even continues into adulthood. Dexmedetomidine (DEX), a short-term sedative, can selectively activate the α2-adrenoceptor. Treatment with α2-adrenergic agonists in patients with ADHD is becoming increasingly common. However, the therapeutic potential of DEX for the treatment of ADHD is unknown. Here, we evaluated the effect of DEX on ADHD-like behavior in spontaneously hypertensive rats (SHRs), a widely used animal model of ADHD. DEX treatment ameliorated hyperactivity and spatial working memory deficits and normalized θ electroencephalogram (EEG) rhythms in SHRs. We also found that DEX treatment altered the gut microbiota composition and promoted the enrichment of beneficial gut bacterial genera associated with anti-inflammatory effects in SHRs. The gut pathological scores and permeability and the level of inflammation observed in the gut and brain were remarkably improved after DEX administration. Moreover, transplantation of fecal microbiota from DEX-treated SHRs produced effects that mimicked the therapeutic effects of DEX administration. Therefore, DEX is a promising treatment for ADHD that functions by reshaping the composition of the gut microbiota and reducing inflammation in the gut and brain.
Topics: Rats; Animals; Dexmedetomidine; Attention Deficit Disorder with Hyperactivity; Gastrointestinal Microbiome; Encephalitis; Rats, Inbred SHR; Inflammation
PubMed: 36958092
DOI: 10.1016/j.psychres.2023.115172 -
Medicine Apr 2021Awake fiberoptic endoscope intubation (AFOI) is the primary strategy for managing anticipated difficult airways. Adequate sedation, most commonly being achieved with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Awake fiberoptic endoscope intubation (AFOI) is the primary strategy for managing anticipated difficult airways. Adequate sedation, most commonly being achieved with remifentanil and dexmedetomidine, is integral to this procedure. This meta-analysis aimed to compare the safety and efficacy of these 2 sedatives.
METHODS
We conducted electronic searches in Embase, Web of Science, PubMed, Google Scholar, Medline, Springer, and Web of Science with no language restrictions. Studies comparing safety and efficacy between the sole use of remifentanil and dexmedetomidine among patients who underwent AFOI were included. Eight randomized controlled trials, comprising 412 patients, met the inclusion criteria. The primary outcomes were first attempt intubation success rate and incidence of hypoxia. The secondary outcomes were the Ramsay Sedation Scale score at intubation, memory recall of endoscopy, and unstable hemodynamic parameters during intubation.
RESULTS
Dexmedetomidine significantly reduced the incidence of hypoxemia during AFOI (risk ratio: 2.47; 95% confidence [CI]: 1.32-4.64]) compared with remifentanil; however, the first intubation success rates were equivalent (risk ratio: 1.12; 95% CI: 0.87-1.46]. No significant differences between the 2 sedatives were found for the Ramsay Sedation Scale score at intubation (mean difference: -0.14; 95% CI: -0.66-0.38) or unstable hemodynamic parameters during intubation (risk ratio: 0.83; 95% CI: 0.59-1.17). Dexmedetomidine reduced memory recall of endoscopy (risk ratio: 1.39; 95% CI: 1.13-1.72).
CONCLUSIONS
While both remifentanil and dexmedetomidine are effective for AFOI and well-tolerated, dexmedetomidine may be more effective in reducing the incidence of hypoxemia and memory recall of endoscopy.
PROSPERP REGISTRATION NUMBER
CRD42020169612.
Topics: Conscious Sedation; Dexmedetomidine; Endoscopy; Fiber Optic Technology; Hemodynamics; Humans; Hypnotics and Sedatives; Hypoxia; Intubation, Intratracheal; Randomized Controlled Trials as Topic; Remifentanil
PubMed: 33832107
DOI: 10.1097/MD.0000000000025324