Dexmedetomidine, sold under the trade name Precedex among others, is a
drug used in humans for sedation.[3] Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses.[6][7] It is also used in humans to treat acute agitation associated with
schizophrenia or
bipolar I or II disorder.[4]
Compared with other sedatives, some studies suggest dexmedetomidine may be associated with less
delirium.[11] However, this finding is not consistent across multiple studies.[10] At the very least, when aggregating many study results together, use of dexmedetomidine appears to be associated with less neurocognitive dysfunction compared to other sedatives.[12] Whether this observation has a beneficial psychological impact is unclear.[11] From an economic perspective, dexmedetomidine is associated with lower ICU costs, largely due to a shorter time to extubation.[13]
Procedural sedation
Dexmedetomidine can also be used for procedural sedation such as during colonoscopy.[14] It can be used as an adjunct with other sedatives like
benzodiazepines,
opioids, and
propofol to enhance sedation and help maintain hemodynamic stability by decreasing the requirement of other sedatives.[15][16] Dexmedetomidine is also used for procedural sedation in children.[17]
It has also been used as an adjunct infusion during general anesthesia. In this application, it has been shown to decrease post-operative delirium, pain, nausea and opioid use.[19][20][21][22]
Other
Dexmedetomidine may be useful for the treatment of the negative cardiovascular effects of acute
amphetamines and
cocaineintoxication and
overdose.[23][24] Dexmedetomidine has also been used as an adjunct to
neuroaxial anesthesia for lower limb procedures.[25] It has been successfully used to treat opioid withdrawal symptoms.[26]
In 2022 it was approved by the FDA for the treatment of agitation in schizophrenia and bipolar disorder.[27]
Side effects
There are no known contraindication to the use of dexmedetomidine. It has a biphasic effect on blood pressure with lower readings at lower drug concentrations and higher readings at higher concentrations.[28] Common side effects include: hypotension, hypertension, with slight decreases in heart rate, arrhythmias, and hypoxia.[29][30] Toxic doses may cause first-degree or second-degree
atrioventricular block. These adverse events usually occur briefly after administering a loading dose of the drug. Thus, adverse effects may be reduced by omitting a loading dose.[30]
Interactions
Dexmedetomidine may enhance the effects of other sedatives and anesthetics when co-administered. Similarly, drugs that lower blood pressure and heart rate, such as
beta blockers, may also have enhanced effects when co-administered with dexmedetomidine.[31]
Pharmacology
Pharmacodynamics
Dexmedetomidine is a highly selective
α2-adrenergic agonist. It possesses an α2:α1 selectivity ratio of 1620:1, making it eight times more selective for the α2-receptor than clonidine.[32] Unlike opioids and other sedatives such as propofol, dexmedetomidine is able to achieve its effects without causing respiratory depression. Dexmedetomidine induces sedation by decreasing activity of noradrenergic neurons in the
locus ceruleus in the
brain stem, thereby increasing the downstream activity of inhibitory
gamma-aminobutyric acid (GABA) neurons in the
ventrolateral preoptic nucleus.[33] In contrast[clarification needed], other sedatives like propofol and benzodiazepines directly increase activity of
gamma-aminobutyric acid neurons.[34] Through action on this endogenous sleep-promoting pathway the sedation produced by dexmedetomidine more closely mirrors natural
sleep (specifically stage 2
non-rapid eye movement sleep), as demonstrated by EEG studies.[33][35] As such, dexmedetomidine provides less amnesia than benzodiazepines.[34] Dexmedetomidine also has analgesic effects at the spinal cord level and other supraspinal sites.[34]
Intravenous dexmedetomidine exhibits linear pharmacokinetics with a rapid
distribution half-life of approximately 6 minutes in healthy volunteers, and a longer and more variable distribution half-life in ICU patients.[39] The terminal
elimination half-life of intravenous dexmedetomidine ranged 2.1 to 3.1 hours in healthy adults and 2.2 to 3.7 hours in ICU patients.[5]Plasma protein binding of dexmedetomidine is about 94% (mostly albumin).[3]
Dexmedetomidine is metabolized by the liver, largely by
glucuronidation (34%) as well as by oxidation via
CYP2A6 and other
Cytochrome P450 enzymes.[5] As such, it should be used with caution in people with liver disease.[31]
The majority of metabolized dexmedetomidine is excreted in the urine (~95%).[medical citation needed]
Dexmedetomidine was approved in 1999 by the US Food and Drug Administration (FDA) as a short-term sedative and analgesic (<24 hours) for critically ill or injured people on mechanical ventilation in the
intensive care unit (ICU). The rationale for its short-term use was due to concerns over withdrawal side effects such as rebound high blood pressure. These effects have not been consistently observed in research studies, however.[40]
Veterinary use
Dexmedetomidine, under the trade name Dexdomitor (
Orion Corporation), was approved in the European Union in for use in cats and dogs in 2002, for sedation and induction of general anesthesia.[41] The FDA approved dexmedetomidine for use in dogs in 2006 and cats in 2007.[42]
In 2015, the European Medicines Agency and the FDA approved an oromucosal gel form of dexmedetomidine marketed as Sileo (
Zoetis) for use in dogs for relief of noise aversion.[43][44]
^
abMacLaren R, Preslaski CR, Mueller SW, Kiser TH, Fish DN, Lavelle JC, Malkoski SP (March 2015). "A randomized, double-blind pilot study of dexmedetomidine versus midazolam for intensive care unit sedation: patient recall of their experiences and short-term psychological outcomes". Journal of Intensive Care Medicine. 30 (3): 167–175.
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^Ahmed SS, Unland T, Slaven JE, Nitu ME, Rigby MR (September 2014). "Successful use of intravenous dexmedetomidine for magnetic resonance imaging sedation in autistic children". Southern Medical Journal. 107 (9): 559–564.
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^Richards JR, Albertson TE, Derlet RW, Lange RA, Olson KR, Horowitz BZ (May 2015). "Treatment of toxicity from amphetamines, related derivatives, and analogues: a systematic clinical review". Drug and Alcohol Dependence. 150: 1–13.
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abcPanzer O, Moitra V, Sladen RN (July 2009). "Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists". Critical Care Clinics. 25 (3): 451–69, vii.
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^Huupponen E, Maksimow A, Lapinlampi P, Särkelä M, Saastamoinen A, Snapir A, et al. (February 2008). "Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep". Acta Anaesthesiologica Scandinavica. 52 (2): 289–294.
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^Gozalo-Marcilla M, Gasthuys F, Luna SP, Schauvliege S (April 2018). "Is there a place for dexmedetomidine in equine anaesthesia and analgesia? A systematic review (2005-2017)". Journal of Veterinary Pharmacology and Therapeutics. 41 (2): 205–217.
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^"Recent Animal Drug Approvals". U.S. Department of Health and Human Services. 2 June 2016.
Archived from the original on 12 July 2016. Retrieved 3 July 2016. For the treatment of noise aversion in dogs