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Korean Journal of Anesthesiology Aug 2019Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist, with sedative, analgesic, anxiolytic, sympatholytic, and opioid-sparing properties.... (Review)
Review
Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist, with sedative, analgesic, anxiolytic, sympatholytic, and opioid-sparing properties. Dexmedetomidine induces a unique sedative response, which shows an easy transition from sleep to wakefulness, thus allowing a patient to be cooperative and communicative when stimulated. Dexmedetomidine may produce less delirium than other sedatives or even prevent delirium. The analgesic effect of dexmedetomidine is not strong; however, it can be administered as a useful analgesic adjuvant. As an anesthetic adjuvant, dexmedetomidine decreases the need for opioids, inhalational anesthetics, and intravenous anesthetics. The sympatholytic effect of dexmedetomidine may provide stable hemodynamics during the perioperative period. Dexmedetomidine-induced cooperative sedation with minimal respiratory depression provides safe and acceptable conditions during neurosurgical procedures in awake patients and awake fiberoptic intubation. Despite the lack of pediatric labelling, dexmedetomidine has been widely studied for pediatric use in various applications. Most adverse events associated with dexmedetomidine occur during or shortly after a loading infusion. There are some case reports of dexmedetomidine-related cardiac arrest following severe bradycardia. Some extended applications of dexmedetomidine discussed in this review are promising, but still limited, and further research is required. The pharmacological properties and possible adverse effects of dexmedetomidine should be well understood by the anesthesiologist prior to use. Moreover, it is necessary to select patients carefully and to determine the appropriate dosage of dexmedetomidine to ensure patient safety.
Topics: Adrenergic alpha-2 Receptor Agonists; Delirium; Dexmedetomidine; Dose-Response Relationship, Drug; Humans; Hypnotics and Sedatives; Patient Selection
PubMed: 31220910
DOI: 10.4097/kja.19259 -
JAMA Apr 2017Dexmedetomidine provides sedation for patients undergoing ventilation; however, its effects on mortality and ventilator-free days have not been well studied among... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Dexmedetomidine provides sedation for patients undergoing ventilation; however, its effects on mortality and ventilator-free days have not been well studied among patients with sepsis.
OBJECTIVES
To examine whether a sedation strategy with dexmedetomidine can improve clinical outcomes in patients with sepsis undergoing ventilation.
DESIGN, SETTING, AND PARTICIPANTS
Open-label, multicenter randomized clinical trial conducted at 8 intensive care units in Japan from February 2013 until January 2016 among 201 consecutive adult patients with sepsis requiring mechanical ventilation for at least 24 hours.
INTERVENTIONS
Patients were randomized to receive either sedation with dexmedetomidine (n = 100) or sedation without dexmedetomidine (control group; n = 101). Other agents used in both groups were fentanyl, propofol, and midazolam.
MAIN OUTCOMES AND MEASURES
The co-primary outcomes were mortality and ventilator-free days (over a 28-day duration). Sequential Organ Failure Assessment score (days 1, 2, 4, 6, 8), sedation control, occurrence of delirium and coma, intensive care unit stay duration, renal function, inflammation, and nutrition state were assessed as secondary outcomes.
RESULTS
Of the 203 screened patients, 201 were randomized. The mean age was 69 years (SD, 14 years); 63% were male. Mortality at 28 days was not significantly different in the dexmedetomidine group vs the control group (19 patients [22.8%] vs 28 patients [30.8%]; hazard ratio, 0.69; 95% CI, 0.38-1.22; P = .20). Ventilator-free days over 28 days were not significantly different between groups (dexmedetomidine group: median, 20 [interquartile range, 5-24] days; control group: median, 18 [interquartile range, 0.5-23] days; P = .20). The dexmedetomidine group had a significantly higher rate of well-controlled sedation during mechanical ventilation (range, 17%-58% vs 20%-39%; P = .01); other outcomes were not significantly different between groups. Adverse events occurred in 8 (8%) and 3 (3%) patients in the dexmedetomidine and control groups, respectively.
CONCLUSIONS AND RELEVANCE
Among patients requiring mechanical ventilation, the use of dexmedetomidine compared with no dexmedetomidine did not result in statistically significant improvement in mortality or ventilator-free days. However, the study may have been underpowered for mortality, and additional research may be needed to evaluate this further.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT01760967.
Topics: Aged; Aged, 80 and over; Dexmedetomidine; Female; Humans; Hypnotics and Sedatives; Intensive Care Units; Male; Middle Aged; Respiration, Artificial; Sepsis; Survival Analysis; Treatment Outcome; Ventilator Weaning
PubMed: 28322414
DOI: 10.1001/jama.2017.2088 -
Revista Brasileira de Anestesiologia 2012To update and review the application of dexmedetomidine in anesthesia and intensive care. This study is a comprehensive review of clinical uses, pharmacology,... (Review)
Review
BACKGROUND AND OBJECTIVES
To update and review the application of dexmedetomidine in anesthesia and intensive care. This study is a comprehensive review of clinical uses, pharmacology, pharmacokinetics, mechanism of action and adverse effects of dexmedetomidine.
CONTENT
The effective use of sedative-hypnotic agents and analgesics is an integral part of comfort and safety of patients. Dexmedetomidine is a potent and highly selective α-2 adrenoceptor agonist with sympatholytic, sedative, amnestic, and analgesic properties, which has been described as a useful and safe adjunct in many clinical applications. It provides a unique "conscious sedation", analgesia, without respiratory depression. The current reviewed uses include sedation at Intensive Care Unit-ICU (both adult and pediatric), emergency department, regional and general anesthesia, neurosurgery, sedation for pediatric procedures, awake fiber-optic intubation, cardiac surgery and bariatric surgery.
CONCLUSIONS
Dexmedetomidine offers a unique ability of providing both sedation and analgesia without respiratory depression. It is a new agent with a wide safety margin, excellent sedative capacity and moderate analgesic properties. Although its wide use is currently in patients of surgical and non-surgical intensive care units, dexmedetomidine seems to have promising future applications in neuroprotection, cardioprotection and renoprotection. More detailed studies are required to define its role as sedative in critical, neurosurgical and pediatric patients, as anesthesia adjunct and sedative during procedures.
Topics: Anesthesia; Critical Care; Dexmedetomidine; Humans; Hypnotics and Sedatives
PubMed: 22248773
DOI: 10.1016/S0034-7094(12)70110-1 -
Minerva Anestesiologica Dec 2019Intranasal dexmedetomidine, although still off-label, recently boasted an increasing consensus for different uses, namely, in diagnostic non-painful procedures, in... (Review)
Review
Intranasal dexmedetomidine, although still off-label, recently boasted an increasing consensus for different uses, namely, in diagnostic non-painful procedures, in painful procedures and in surgical premedication. However, at present, there is no consensus regarding indications, dosage and timing for administration. This article aims to provide a comprehensive literature analysis and summarize the more recent evidence of research on pediatric intranasal dexmedetomidine, in the effort to better delineate usefulness and limits for each specific indication. In summary, available pediatric evidence confirms efficacy and safety of dexmedetomidine for intranasal administration. Pharmacological profile for the various pediatric ages and procedures still needs quality studies and pharmacokinetic in-depth analysis.
Topics: Administration, Intranasal; Analgesics, Non-Narcotic; Child; Dexmedetomidine; Humans; Treatment Outcome
PubMed: 31630510
DOI: 10.23736/S0375-9393.19.13820-5 -
Dexmedetomidine versus Midazolam in Procedural Sedation. A Systematic Review of Efficacy and Safety.PloS One 2017To systematically review the literature comparing the efficacy and safety of dexmedetomidine and midazolam when used for procedural sedation. (Review)
Review
OBJECTIVES
To systematically review the literature comparing the efficacy and safety of dexmedetomidine and midazolam when used for procedural sedation.
MATERIALS AND METHODS
We searched MEDLINE, EMBASE and COCHRANE for clinical trials comparing dexmedetomidine and midazolam for procedural sedation up to June 20, 2016. Inclusion criteria: clinical trial, human subjects, adult subjects (≥18 years), article written in English, German, French or Dutch, use of study medication for conscious sedation and at least one group receiving dexmedetomidine and one group receiving midazolam. Exclusion criteria: patients in intensive care, pediatric subjects and per protocol use of additional sedative medication other than rescue medication. Outcome measures for efficacy comparison were patient and clinician satisfaction scores and pain scores; outcome measures for safety comparison were hypotension, hypoxia, and circulatory and respiratory complications.
RESULTS
We identified 89 papers, of which 12 satisfied the inclusion and exclusion criteria; 883 patients were included in these studies. Dexmedetomidine was associated with higher patient and operator satisfaction than midazolam. Patients receiving dexmedetomidine experienced less pain and had lower analgesic requirements. Respiratory and hemodynamic safety were similar.
CONCLUSIONS
Dexmedetomidine is a promising alternative to midazolam for use in procedural sedation. Dexmedetomidine provides more comfort during the procedure for the patient and clinician. If carefully titrated, the safety profiles are similar.
Topics: Dexmedetomidine; Hemodynamics; Humans; Hypnotics and Sedatives; Midazolam; Respiration
PubMed: 28107373
DOI: 10.1371/journal.pone.0169525 -
Brain, Behavior, and Immunity Jan 2021Sepsis-associated encephalopathy (SAE) is a significant clinical issue that is associated with increased mortality and cost of health care. Dexmedetomidine, an α2...
Sepsis-associated encephalopathy (SAE) is a significant clinical issue that is associated with increased mortality and cost of health care. Dexmedetomidine, an α2 adrenoceptor agonist that is used to provide sedation, has been shown to induce neuroprotection under various conditions. This study was designed to determine whether dexmedetomidine protects against SAE and whether α2 adrenoceptor plays a role in this protection. Six- to eight-week old CD-1 male mice were subjected to cecal ligation and puncture (CLP). They were treated with intraperitoneal injection of dexmedetomidine in the presence or absence of α2 adrenoceptor antagonists, atipamezole or yohimbine, or an α2A adrenoceptor antagonist, BRL-44408. Hippocampus and blood were harvested for measuring cytokines. Mice were subjected to Barnes maze and fear conditioning 14 days after CLP to evaluate their learning and memory. CLP significantly increased the proinflammatory cytokines including tumor necrosis factor α, interleukin (IL)-6 and IL-1β in the blood and hippocampus. CLP also increased the permeability of blood-brain barrier (BBB) and impaired learning and memory. These CLP detrimental effects were attenuated by dexmedetomidine. Intracerebroventricular application of atipamezole, yohimbine or BRL-44408 blocked the protection of dexmedetomidine on the brain but not on the systemic inflammation. Astrocytes but not microglia expressed α2A adrenoceptors. Microglial depletion did not abolish the protective effects of dexmedetomidine. These results suggest that dexmedetomidine reduces systemic inflammation, neuroinflammation, injury of BBB and cognitive dysfunction in septic mice. The protective effects of dexmedetomidine on the brain may be mediated by α2A adrenoceptors in the astrocytes.
Topics: Animals; Brain Diseases; Dexmedetomidine; Inflammation; Male; Mice; Receptors, Adrenergic; Sepsis
PubMed: 33039659
DOI: 10.1016/j.bbi.2020.10.008 -
Current Pain and Headache Reports Apr 2020Effective acute pain management has evolved considerably in recent years and is a primary area of focus in attempts to defend against the opioid epidemic. Persistent... (Review)
Review
PURPOSE OF REVIEW
Effective acute pain management has evolved considerably in recent years and is a primary area of focus in attempts to defend against the opioid epidemic. Persistent postsurgical pain (PPP) has an incidence of up to 30-50% and has negative outcome of quality of life and negative burden on individuals, family, and society. The 2016 American Society of Anesthesiologists (ASA) guidelines states that enhanced recovery after surgery (ERAS) forms an integral part of Perioperative Surgical Home (PSH) and is now recommended to use a multimodal opioid-sparing approach for management of postoperative pain. As such, dexmedetomidine is now being used as part of ERAS protocols along with regional nerve blocks and other medications, to create a satisfactory postoperative outcome with reduced opioid consumption in the Post anesthesia care unit (PACU).
RECENT FINDINGS
Dexmedetomidine, a selective alpha agonist, possesses analgesic effects and has a different mechanism of action when compared with opioids. When dexmedetomidine is initiated at the end of a procedure, it has a better hemodynamic stability and pain response than ropivacaine. Dexmedetomidine can be used as an adjuvant in epidurals with local anesthetic sparing effects. Its use during nerve blocks results in reduced postoperative pain. Also, local infiltration of IV dexmedetomidine is associated with earlier discharge from PACU. Perioperative use of dexmedetomidine has significantly improved postoperative outcomes when used as part of ERAS protocols. An in-depth review of the use of dexmedetomidine in ERAS protocols is presented for clinical anesthesiologists.
Topics: Analgesics, Non-Narcotic; Dexmedetomidine; Enhanced Recovery After Surgery; Humans; Pain Management; Pain, Postoperative
PubMed: 32240402
DOI: 10.1007/s11916-020-00853-z -
British Journal of Anaesthesia Mar 2021Postoperative delirium (POD) is a frequent complication in older patients. Dexmedetomidine might be effective in decreasing the incidence of POD. We hypothesised that... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Postoperative delirium (POD) is a frequent complication in older patients. Dexmedetomidine might be effective in decreasing the incidence of POD. We hypothesised that adding low-dose rate dexmedetomidine infusion to a propofol sedation regimen would have fewer side-effects and would counteract the possible delirium producing properties of propofol, resulting in a lower risk of POD than propofol with placebo.
METHODS
In this double-blind placebo-controlled trial, patients ≥60 yr old undergoing on-pump cardiac surgery were randomised 1:1 to the following postoperative sedative regimens: a propofol infusion and dexmedetomidine (0.4 μg kg h) or a propofol infusion and saline 0.9% (placebo group). The study drug was started at chest closure and continued for 10 h. The primary endpoint was in-hospital POD, assessed using the Confusion Assessment Method and chart review method.
RESULTS
POD over the course of hospital stay occurred in 31/177 (18%) and 33/172 (19%) patients in the dexmedetomidine and placebo arm, respectively (P=0.687; odds ratio=0.89; 95% confidence interval, 0.52-1.54). The incidence of POD in the intensive care alone, or on the ward alone, was also not significantly different between the groups. Subjects in the dexmedetomidine group spent less median time in a delirious state (P=0.026). Median administered postoperative norepinephrine was significantly higher in the dexmedetomidine group (P<0.001). One patient in the dexmedetomidine group and 10 patients in the placebo group died in the hospital.
CONCLUSIONS
Adding low-dose rate dexmedetomidine to a sedative regimen based on propofol did not result in a different risk of in-hospital delirium in older patients undergoing cardiac surgery. With a suggestion of both harm and benefit in secondary outcomes, supplementing postoperative propofol with dexmedetomidine cannot be recommended based on this study.
CLINICAL TRIAL REGISTRATION
NCT03388541.
Topics: Aged; Cardiac Surgical Procedures; Delirium; Dexmedetomidine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Hypnotics and Sedatives; Infusions, Intravenous; Male; Postoperative Complications; Propofol; Treatment Outcome
PubMed: 33358336
DOI: 10.1016/j.bja.2020.10.041 -
Anaesthesia Mar 2023The effects of dexmedetomidine in adults undergoing cardiac surgery are inconsistent. We conducted a systematic review and meta-analysis to analyse the effects of... (Meta-Analysis)
Meta-Analysis Review
The effects of dexmedetomidine in adults undergoing cardiac surgery are inconsistent. We conducted a systematic review and meta-analysis to analyse the effects of peri-operative dexmedetomidine in adults undergoing cardiac surgery. We searched MEDLINE via Pubmed, EMBASE, Scopus and Cochrane for relevant randomised controlled trials between 1 January 1990 and 1 March 2022. We used the Joanna Briggs Institute methodology checklist to assess study quality and the GRADE approach to certainty of evidence. We assessed the sensitivity of results to false data. We used random-effects meta-analyses to analyse the primary outcomes: durations of intensive care and tracheal intubation. We included 48 trials of 6273 participants. Dexmedetomidine reduced the mean (95%CI) duration of intensive care by 5.0 (2.2-7.7) h, p = 0.001, and tracheal intubation by 1.6 (0.6-2.7) h, p = 0.003. The relative risk (95%CI) for postoperative delirium was 0.58 (0.43-0.78), p = 0.001; 0.76 (0.61-0.95) for atrial fibrillation, p = 0.015; and 0.49 (0.25-0.97) for short-term mortality, p = 0.041. Bradycardia and hypotension were not significantly affected. Trial sequential analysis was consistent with the primary meta-analysis. Adjustments for possible false data reduced the mean (95%CI) reduction in duration of intensive care and tracheal intubation by dexmedetomidine to 3.6 (1.8-5.4) h and 0.8 (0.2-1.4) h, respectively. Binary adjustment for methodological quality at a Joanna Briggs Institute score threshold of 10 did not alter the results significantly. In summary, peri-operative dexmedetomidine reduced the durations of intensive care and tracheal intubation and the incidence of short-term mortality after adult cardiac surgery. The reductions in intensive care stay and tracheal intubation may or may not be considered clinically useful, particularly after adjustment for possible false data.
Topics: Adult; Humans; Dexmedetomidine; Cardiac Surgical Procedures; Emergence Delirium; Critical Care; Bradycardia
PubMed: 36535747
DOI: 10.1111/anae.15947 -
Science (New York, N.Y.) Sep 2022Because nonopioid analgesics are much sought after, we computationally docked more than 301 million virtual molecules against a validated pain target, the α-adrenergic...
Because nonopioid analgesics are much sought after, we computationally docked more than 301 million virtual molecules against a validated pain target, the α-adrenergic receptor (αAR), seeking new αAR agonists chemotypes that lack the sedation conferred by known αAR drugs, such as dexmedetomidine. We identified 17 ligands with potencies as low as 12 nanomolar, many with partial agonism and preferential G and G signaling. Experimental structures of αAR complexed with two of these agonists confirmed the docking predictions and templated further optimization. Several compounds, including the initial docking hit '9087 [mean effective concentration (EC) of 52 nanomolar] and two analogs, '7075 and PS75 (EC 4.1 and 4.8 nanomolar), exerted on-target analgesic activity in multiple in vivo pain models without sedation. These newly discovered agonists are interesting as therapeutic leads that lack the liabilities of opioids and the sedation of dexmedetomidine.
Topics: Adrenergic alpha-2 Receptor Agonists; Analgesics, Non-Narcotic; Animals; Dexmedetomidine; Drug Design; Drug Discovery; Humans; Ligands; Mice; Molecular Docking Simulation; Pain; Pain Management; Structure-Activity Relationship
PubMed: 36173843
DOI: 10.1126/science.abn7065