Intensive care unit sedation

Studies suggest dexmedetomidine for sedation in mechanically ventilated adults may reduce time to extubation and ICU stay.^[9][10]

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 can be used for sedation required for awake fibreoptic nasal intubation in patients with a difficult airway.^[18]

Adjunct in general anesthesia

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 cocaine intoxication 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]

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]

Pharmacokinetics

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]}

It can be absorbed sublingually.^[27]