Dexmedetomidine is an alpha agonist (or, a sympathomimetic drug that selectively increases the activity of alpha adrenergic receptors) with sedative, anxiolytic (inhibiting anxiety), hypnotic, analgesic, and sympatholytic (inhibiting the sympathetic nervous system) properties. This drug is particularly notable in its selectivity for the alpha-2 receptor, as opposed to the alpha-1 receptor, with a selectivity of 1600 to 1 compared to clonidine’s 220 to 1, which is another alpha agonist. [1] This selectivity is significant because, while alpha-1 receptors’ physiological action, or agonism, is the constriction of vascular smooth muscle, contraction of the radial muscle of the eye, and contraction of the vas deferens smooth muscle; alpha-2 receptors’ agonism is the inhibition of norepinephrine (the “fight or flight” response neuromodulator) release, centrally induced sedation via the locus coeruleus (a small brainstem nucleus and the primary source of norepinephrine), centrally mediated pain modification via the dorsal horn (an intermediary processing center in the spinal cord which receives the norepinephrine from the locus coeruleus), and the inhibition of insulin release from pancreatic beta cells. [2] In effect, this makes dexmedetomidine an excellent candidate for premedication to be offered to patients prior to a surgical operation to help decrease preoperative anxiety, enhance perioperative sedation, and lessen postoperative pain without significantly increasing the risk of hypertension or other unwanted physiological effects.
It is particularly important to manage anxiety in pediatric patients about to undergo a surgical procedure (at 60% of whom experience some form of preoperative anxiety) because such anxiety can cause difficulty in separating the child from their parents and uncooperative behavior that can make venipuncture and mask application difficult. Beyond this, severe, untreated anxiety has strong physiological effects that can lead to difficult induction, increased pain post-operation, greater analgesic requirements, emergence agitation, and postoperative psychological effects and behavioral issues. Although there are non-pharmaceutical techniques to help soothe a pediatric patient’s anxiety and stress about the operation, clinicians still frequently rely upon sedatives in pediatric cases because reducing preoperative anxiety is so critical to ensuring a good outcome to the operation and minimizing the pain experienced by the young patient as much as possible. [3]
Thus, in 2014, Peng et al. conducted a review and meta-analysis of randomized control trials testing the relative efficacy of premedication with dexmedetomidine, midazolam, or a placebo in pediatric patients. Midazolam was considered because it was at the time of writing a popularly administered premedication for these patients but has undesirable effects (including restlessness, paradoxical reactions, cognitive impairment, postoperative behavioral changes, and respiratory depression), whereas dexmedetomidine does not cause respiratory depression and has much rarer and less severe side effects overall, especially when not administered intravenously. [3,4] The meta-analysis revealed that, when compared with midazolam, premedication with dexmedetomidine resulted in a statistically significant increase in satisfactory separation from parents and a decrease in the use of postoperative rescue analgesia. Furthermore, children treated with dexmedetomidine had a lower heart rate before induction, and the premedication provided superior intravenous cannulation compared to placebo. Based on these merits, the authors concluded that, while additional studies are necessary to evaluate dosing schemes and the long term effects of using dexmedetomidine to treat preoperative anxiety in children, dexmedetomidine was in many ways superior to midazolam in addressing various perioperative concerns caused by this anxiety and was also, overall, a safer alternative for these vulnerable patients. [3]
The benefits of dexmedetomidine premedication is not limited to pediatric surgical patients. In fact, a recent (2022) randomized double-blind clinical study demonstrated that premedication with dexmedetomidine resulted in less stress and enhanced sedation for adult patients undergoing tracheal intubation. [5] As clinicians become more aware of the benefits of this drug as premedication, and as research continues to carve out optimal procedures for its administration, it seems likely that dexmedetomidine will enter standard use in promoting sedation and reducing perioperative anxiety and pain through preoperative application.
References
(1) Reel, B.; Maani, C. V. Dexmedetomidine. In StatPearls; StatPearls Publishing: Treasure Island (FL), 2023.
(2) Giovannitti, J. A.; Thoms, S. M.; Crawford, J. J. Alpha-2 Adrenergic Receptor Agonists: A Review of Current Clinical Applications. Anesthesia Progress 2015, 62 (1), 31–38. https://doi.org/10.2344/0003-3006-62.1.31.
(3) Peng, K.; Wu, S.; Ji, F.; Li, J. Premedication with Dexmedetomidine in Pediatric Patients: A Systematic Review and Meta-Analysis. Clinics (Sao Paulo) 2014, 69 (11), 777–786. https://doi.org/10.6061/clinics/2014(11)12.
(4) Dexmedetomidine (Intravenous Route) Side Effects – Mayo Clinic. https://www.mayoclinic.org/drugs-supplements/dexmedetomidine-intravenous-route/side-effects/drg-20537766.
(5) Xiong, J.; Gao, J.; Pang, Y.; Zhou, Y.; Sun, Y.; Sun, Y. Dexmedetomidine Premedication Increases Preoperative Sedation and Inhibits Stress Induced by Tracheal Intubation in Adult: A Prospective Randomized Double-Blind Clinical Study. BMC Anesthesiol 2022, 22 (1), 398. https://doi.org/10.1186/s12871-022-01930-z.