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Intensive Care Medicine Jul 2022The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in...
PURPOSE
The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU).
METHODS
We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web‑based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities.
RESULTS
The ICM‑RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia".
CONCLUSION
This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.
Topics: Adult; Anesthesia; Dexmedetomidine; Humans; Hypnotics and Sedatives; Intensive Care Units; Respiration, Artificial
PubMed: 35587274
DOI: 10.1007/s00134-022-06660-x -
Journal of Cardiothoracic and Vascular... May 2024The highly selective α2-adrenoceptor agonist dexmedetomidine is a commonly used sedative drug for patients undergoing anesthesia and intensive care treatment. Several... (Review)
Review
The highly selective α2-adrenoceptor agonist dexmedetomidine is a commonly used sedative drug for patients undergoing anesthesia and intensive care treatment. Several studies have indicated that dexmedetomidine may have a potential role in preventing and treating perioperative tachyarrhythmias. However, the specific effect and mechanism of action of dexmedetomidine in this context remain unclear. Dexmedetomidine is known to regulate the electrophysiologic function of the myocardium by inhibiting the function of the sinus node and atrioventricular node, as well as affecting myocardial repolarization. This paper aims to provide a theoretical basis for the prevention and treatment of perioperative arrhythmias by summarizing the effects of dexmedetomidine on myocardial electrophysiologic function and its impact on different types of arrhythmias.
Topics: Humans; Dexmedetomidine; Arrhythmias, Cardiac; Hypnotics and Sedatives; Anesthesia; Critical Care
PubMed: 38443205
DOI: 10.1053/j.jvca.2024.01.006 -
Revista Espanola de Anestesiologia Y... Oct 2022Dexmedetomidine (DEX) is an anaesthetic agent that mimics natural deep sleep and produces minimal cardiorespiratory depression. As such, it is a very valuable option in... (Review)
Review
Dexmedetomidine (DEX) is an anaesthetic agent that mimics natural deep sleep and produces minimal cardiorespiratory depression. As such, it is a very valuable option in the management of such a challenging population as paediatric patients. The main objective of this mini review was to evaluate the role of DEX as a perioperative analgesic in children receiving anaesthesia. We searched Google, Pubmed, Embase and the Cochrane Library for articles published between 2010 and 2021, and reviewed various of aspects of DEX, such as pharmacology, effectiveness, safety, and the most recent evidence on its clinical use as an analgesic in paediatric anaesthesia. We also include a cost estimate of perioperative analgesia with DEX.
Topics: Analgesia; Analgesics; Anesthesia; Child; Dexmedetomidine; Humans
PubMed: 36100555
DOI: 10.1016/j.redare.2022.08.003 -
Best Practice & Research. Clinical... Jul 2021Dexmedetomidine can be used for sedation and analgesia and has been approved for this use by the European Medicines Agency since 2017. It causes an arousable state of... (Review)
Review
Dexmedetomidine can be used for sedation and analgesia and has been approved for this use by the European Medicines Agency since 2017. It causes an arousable state of sedation, which is beneficial during neurosurgical procedures that require the patient to cooperate with neurological tests (i.e. tumor surgery or implantation of deep brain stimulators). During procedures where monitoring of somatosensory evoked potentials and/or motor evoked potentials is required, dexmedetomidine can be used as an adjunct to general anesthesia with GABAergic drugs to decrease the dose of the latter when these drugs impair the monitoring signals. The use of dexmedetomidine has also been associated with neuroprotective effects and a decreased incidence of delirium, but studies confirming these effects in the peri-operative (neuro-)surgical setting are lacking. Although dexmedetomidine does not cause respiratory depression, its hemodynamic effects are complex and careful patient selection, choice of dose, and monitoring must be performed.
Topics: Dexmedetomidine; Evoked Potentials, Motor; Evoked Potentials, Somatosensory; Humans; Hypnotics and Sedatives; Neurosurgical Procedures; Respiratory Insufficiency
PubMed: 34030806
DOI: 10.1016/j.bpa.2020.10.002 -
Trends in Pharmacological Sciences Dec 2022Cerebrospinal fluid (CSF) flows through the central nervous system (CNS) via the glymphatic pathway to clear the interstitium of metabolic waste. In preclinical studies,... (Review)
Review
Cerebrospinal fluid (CSF) flows through the central nervous system (CNS) via the glymphatic pathway to clear the interstitium of metabolic waste. In preclinical studies, glymphatic fluid flow rate increases with low central noradrenergic tone and slow-wave activity during natural sleep and general anesthesia. By contrast, sleep deprivation reduces glymphatic clearance and leads to intracerebral accumulation of metabolic waste, suggesting an underlying mechanism linking sleep disturbances with neurodegenerative diseases. The selective α-adrenergic agonist dexmedetomidine is a sedative drug that induces slow waves in the electroencephalogram, suppresses central noradrenergic tone, and preserves glymphatic outflow. As recently developed dexmedetomidine formulations enable self-administration, we suggest that dexmedetomidine could serve as a sedative-hypnotic drug to enhance clearance of harmful waste from the brain of those vulnerable to neurodegeneration.
Topics: Humans; Dexmedetomidine; Glymphatic System; Brain; Electroencephalography; Hypnotics and Sedatives
PubMed: 36280451
DOI: 10.1016/j.tips.2022.09.007 -
American Journal of Therapeutics
Topics: Dexmedetomidine; Humans; Hypernatremia; Polyuria
PubMed: 34010160
DOI: 10.1097/MJT.0000000000001383 -
Journal of Cardiovascular Pharmacology Feb 2023Dexmedetomidine, an alpha-2 adrenoreceptor agonist that is widely used as a sedative medication, is becoming more and more attractive in clinical application on cardiac... (Review)
Review
Dexmedetomidine, an alpha-2 adrenoreceptor agonist that is widely used as a sedative medication, is becoming more and more attractive in clinical application on cardiac surgery patients. In this review, we aim to summarize and discuss both retrospective studies and clinical trials regarding the effect of dexmedetomidine on patients who underwent cardiac surgery (including coronary artery bypass grafting, valve surgery, aortic surgery, percutaneous coronary intervention, and so on), which illustrates that the clinical effects of dexmedetomidine could effectively reduce mortality, major complications, and the intensive care unit and hospital length of stay without comprising safety. In addition, inconsistent results from both retrospective studies and clinical trials have also been demonstrated. Although the effectiveness and safety of dexmedetomidine on cardiac surgery patients is suggested, high-quality clinical trials are needed for further verification.
Topics: Humans; Dexmedetomidine; Retrospective Studies; Cardiac Surgical Procedures; Hypnotics and Sedatives; Coronary Artery Bypass
PubMed: 36607614
DOI: 10.1097/FJC.0000000000001384 -
Immunity, Inflammation and Disease Jun 2023The aim of this study was to investigate the effect of dexmedetomidine (Dex) on inflammation and organ injury in sepsis, as well as the potential relationship between...
PURPOSE
The aim of this study was to investigate the effect of dexmedetomidine (Dex) on inflammation and organ injury in sepsis, as well as the potential relationship between Dex and nuclear receptor 77 (Nur77).
METHODS
We investigated the effects of dexmedetomidine on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells and organ injury in the cecal ligation and puncture (CLP) mouse model. Additionally, we examined the relationship between dexmedetomidine and Nur77. The expression levels of Nur77 in RAW264.7 cells were analyzed under various types of stimulation using quantitative reverse transcription polymerase chain reaction and western blot analysis. Inflammatory cytokine levels in the cells were evaluated using enzyme-linked immunoassay. Organ injuries were assessed by examining tissue histology and pathology of the lung, liver, and kidney.
RESULTS
Dexmedetomidine increased the expression of Nur77 and IL-10, and downregulated inflammatory cytokines (IL-1β and TNF-α) in LPS-treated RAW264.7 cells. The effect of dexmedetomidine on inhibiting inflammation in LPS-treated RAW264.7 cells was promoted by overexpressing Nur77, while it was reversed by downregulating Nur77. Additionally, dexmedetomidine promoted the expression of Nur77 in the lung and CLP-induced pathological changes in the lung, liver, and kidney. Activation of Nur77 with the agonist Cytosporone B (CsnB) significantly suppressed the production of IL-1β and TNF-α in LPS-treated RAW264.7 cells. In contrast, knockdown of Nur77 augmented IL-1β and TNF-α production in LPS-treated RAW264.7 cells.
CONCLUSION
Dexmedetomidine can attenuate inflammation and organ injury, at least partially, via upregulating Nur77 in sepsis.
Topics: Animals; Mice; Cytokines; Dexmedetomidine; Inflammation; Lipopolysaccharides; Sepsis; Tumor Necrosis Factor-alpha; Nuclear Receptor Subfamily 4, Group A, Member 1
PubMed: 37382273
DOI: 10.1002/iid3.883 -
Journal of Perinatology : Official... Feb 2024Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences.... (Review)
Review
Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences. Dexmedetomidine, a highly selective alpha-2-adrenoreceptor agonist, has piqued interest as a viable alternative for neonates, owing to its potential analgesic and neuroprotective attributes. We conducted a systematic review to assess the efficacy and safety of dexmedetomidine utilization in neonates. We conducted a comprehensive search of Ovid, MEDLINE, EMBASE, PubMed, Cochrane, and CINAHL, spanning from January 2010 to September 2022. Our review encompassed six studies involving 252 neonates. Overall, dexmedetomidine may be effective in achieving sedation and analgesia. Furthermore, it may reduce the need for adjunctive sedation or analgesia, shorten the time to extubation, decrease the duration of mechanical ventilation, and accelerate the attainment of full enteral feeds. Notably, no significant adverse effects associated with dexmedetomidine were reported. Nevertheless, additional well-designed studies to establish both the efficacy and safety of dexmedetomidine in neonatal care are needed.
Topics: Infant, Newborn; Humans; Dexmedetomidine; Pain; Adrenergic alpha-2 Receptor Agonists; Pain Management; Analgesia
PubMed: 37845426
DOI: 10.1038/s41372-023-01802-5 -
Anaesthesia Dec 2023Cardiac surgery requiring cardiopulmonary bypass is associated with postoperative acute kidney injury and neurocognitive disorders, including delirium. Intra-operative...
Cardiac surgery requiring cardiopulmonary bypass is associated with postoperative acute kidney injury and neurocognitive disorders, including delirium. Intra-operative inflammation and/or impaired tissue perfusion/oxygenation are thought to be contributors to these outcomes. It has been hypothesised that these problems may be ameliorated by the highly selective α -agonist, dexmedetomidine. We tested the effects of dexmedetomidine on renal and cerebral microcirculatory tissue perfusion, oxygenation and histology in a clinically relevant ovine model. Sixteen sheep were studied while conscious, after induction of anaesthesia and during 2 h of cardiopulmonary bypass. Eight sheep were allocated randomly to receive an intravenous infusion of dexmedetomidine (0.4-0.8 μg.kg .h ) from induction of anaesthesia to the end of cardiopulmonary bypass, and eight to receive an equivalent volume of matched placebo (0.9% sodium chloride). Commencement of cardiopulmonary bypass decreased renal medullary tissue oxygenation in the placebo group (mean (95%CI) 5.96 (4.24-7.23) to 1.56 (0.84-2.09) kPa, p = 0.001), with similar hypoxic levels observed in the dexmedetomidine group (6.33 (5.33-7.07) to 1.51 (0.33-2.39) kPa, p = 0.002). While no differences in kidney function (i.e. reduced creatinine clearance) were evident, a greater incidence of histological renal tubular injury was observed in sheep receiving dexmedetomidine (7/8 sheep) compared with placebo (2/8 sheep), p = 0.041. Graded on a semi-quantitative scale (0-3), median (IQR [range]) severity of histological renal tubular injury was higher in the dexmedetomidine group compared with placebo (1.5 (1-2 [0-3]) vs. 0 (0-0.3 [0-1]) respectively, p = 0.013). There was no difference in cerebral tissue microglial activation (neuroinflammation) between the groups. Dexmedetomidine did not reduce renal medullary hypoxia or cerebral neuroinflammation in sheep undergoing cardiopulmonary bypass.
Topics: Animals; Brain; Cardiopulmonary Bypass; Dexmedetomidine; Kidney; Microcirculation; Neuroinflammatory Diseases; Sheep
PubMed: 37880924
DOI: 10.1111/anae.16152