The use of dexmedetomidine in pediatrics has grown over the last decade as research has shown the benefits of its use in procedural sedation, anxiety management, and pediatric palliative care [1].  

In contrast to other anesthetic drugs, dexmedetomidine is unique in that its pharmacological profile mimics natural sleep patterns [2]. After dexmedetomidine administration, children with obstructive sleep apnea were able to compensate for airway obstruction, demonstrating airway responses similar to those seen in natural sleep [3]. Dexmedetomidine is also an attractive choice for procedures to evaluate the airway preoperatively in pediatrics, such as drug-induced sleep endoscopy or dynamic airway imaging [4]. Intranasal dexmedetomidine premedication can reduce the minimum alveolar concentration of sevoflurane required to efficiently conduct certain respiratory surgical interventions [5]. The drug also has been shown to decrease laryngeal and tracheal irritation during mask placement or intubation [6].  

Dexmedetomidine is a sympathomimetic agent classified as an α2 agonist. In conjunction with a strong preservation of vagal activity, sympathomimetics such as dexmedetomidine create an anti-inflammatory effect and promotes healthy immune system balance [8]. In a clinical trial on mechanically ventilated patients, treatment with dexmedetomidine was associated with a significantly lower mortality rate [8]. Dexmedetomidine used in hamsters was associated with an improvement in microcirculatory flow, increasing functional capillary density and possibly minimizing detrimental gas exchange during septic shock [8]. In Japanese rabbits, dexmedetomidine preconditioning inhibits the inflammatory response, stabilizing the blood-spinal cord barrier and improving neuronal viability [9].  

Electroencephalogram studies in pediatric populations show dexmedetomidine elicits neural activity similar to natural, non-REM (Rapid Eye Movement) sleep [10]. A randomized clinical trial with elderly patients had similar results; those treated with dexmedetomidine reported better sleep quality, increased sleep efficiency, and longer total sleep time [11]. In both dexmedetomidine-induced sedation and natural sleep, thalamic cortical activity was decreased. However, unlike propofol, dexmedetomidine did not diminish the functional connectivity of brain areas implicated in physiological arousal, possibly explaining the rapid recovery of awareness after dexmedetomidine [12]. By increasing the phosphorylation of protein kinase B and cAMP (cyclic adenosine monophosphate), dexmedetomidine upregulates anti-apoptotic factors and creates an overall neuroprotective effect [13].  

Cardiac surgery is often associated with a risk of injury to the kidneys. In a double-blinded clinical study with 60 pediatric patients undergoing cardiac angiography, dexmedetomidine decreased markers of acute renal injury. The authors suggest by preventing the elevation of vasoconstrictor agents such as plasma endothelin-1 and renin, dexmedetomidine may be beneficial in protecting against nephropathies [14]. Another research group proposed that reno-protection may arise from dexmedetomidine decreasing the systemic inflammatory response and thereby reducing renal cell death [1,15].  

Currently, one of most pressing clinical questions in pediatric anesthesia is anesthetic neurotoxicity. Dexmedetomidine has shown to have neuroprotective, reno-protective and cardioprotective effects, but further research replicating these effects for use of dexmedetomidine for pediatrics is needed.  

References 

1. Mahmoud, M., Barbi, E., & Mason, K. P. (2020). Dexmedetomidine: What’s new for Pediatrics? A Narrative review. Journal of Clinical Medicine, 9(9), 2724. https://doi.org/10.3390/jcm9092724  
2. Akeju, O., Kim, S.-E., Vazquez, R., Rhee, J., Pavone, K. J., Hobbs, L. E., Purdon, P. L., & Brown, E. N. (2016). Spatiotemporal Dynamics of Dexmedetomidine-induced Electroencephalogram Oscillations. PLOS ONE, 11(10), e0163431. https://doi.org/10.1371/journal.pone.0163431 
3. Mahmoud, M., Ishman, S. L., McConnell, K., Fleck, R., Shott, S., Mylavarapu, G., Gutmark, E., Zou, Y., Szczesniak, R., & Amin, R. S. (2017). Upper Airway Reflexes are Preserved during Dexmedetomidine Sedation in Children with Down syndrome and Obstructive Sleep Apnea. Journal of Clinical Sleep Medicine, 13(05), 721–727. https://doi.org/10.5664/jcsm.6592 
4. Chatterjee, D., Friedman, N., Shott, S., & Mahmoud, M. (2014). Anesthetic Dilemmas for Dynamic Evaluation of the Pediatric upper Airway. Seminars in Cardiothoracic and Vascular Anesthesia, 18(4), 371–378. https://doi.org/10.1177/1089253214548804  
5. Yao, Y., Qian, B., Lin, Y., Wu, W., Ye, H., & Chen, Y. (2015). Intranasal Dexmedetomidine Premedication Reduces Minimum Alveolar Concentration Of Sevoflurane For Laryngeal Mask Airway Insertion And Emergence Delirium In Children: A Prospective, Randomized, Double-blind, Placebo-controlled Trial. Pediatric Anesthesia, 25(5), 492–498. https://doi.org/10.1111/pan.12574  
6. He, L., Wang, X., & Zheng, S. (2014). Effects Of Dexmedetomidine On Sevoflurane Requirement For 50% Excellent Tracheal Intubation In Children: A Randomized, Double-blind Comparison. Pediatric Anesthesia, 24(9), 987–993. https://doi.org/10.1111/pan.12430   
7. Geng, J., Qian, J., Cheng, H., Ji, F., & Liu, H. (2016). The Influence of Perioperative Dexmedetomidine on Patients Undergoing Cardiac Surgery: A Meta-analysis. PLOS ONE, 11(4), e0152829. https://doi.org/10.1371/journal.pone.0152829  
8. Ferreira, J. A., & Bissell, B. D. (2018). Misdirected Sympathy: The Role Of Sympatholysis In Sepsis And Septic Shock. Journal of Intensive Care Medicine, 33(2), 74–86. https://doi.org/10.1177/0885066616689548  
9. Liu, J., Zhang, S., Fan, X., Yuan, F., Dai, J., & Hu, J. (2019). Dexmedetomidine Preconditioning Ameliorates Inflammation And Blood–spinal Cord Barrier Damage After Spinal Cord Ischemia-reperfusion Injury By Down-regulation High Mobility Group Box 1-toll-like Receptor 4-nuclear Factor Κb Signaling Pathway. Spine, 44(2), E74–E81. https://doi.org/10.1097/BRS.0000000000002772  
10. Mason, K. P., O’Mahony, E., Zurakowski, D., & Libenson, M. H. (2009). Effects Of Dexmedetomidine Sedation On The EEG In Children: Dexmedetomidine And EEG Effects In Children. Pediatric Anesthesia, 19(12), 1175–1183. https://doi.org/10.1111/j.1460-9592.2009.03160.x  
11. Wu, X.-H., Cui, F., Zhang, C., Meng, Z.-T., Wang, D.-X., Ma, J., Wang, G.-F., Zhu, S.-N., & Ma, D. (2016). Low-dose Dexmedetomidine Improves Sleep Quality Pattern In Elderly Patients After Noncardiac Surgery In The Intensive Care Unit. Anesthesiology, 125(5), 979–991. https://doi.org/10.1097/ALN.0000000000001325  
12. Guldenmund, P., Vanhaudenhuyse, A., Sanders, R. D., Sleigh, J., Bruno, M. A., Demertzi, A., Bahri, M. A., Jaquet, O., Sanfilippo, J., Baquero, K., Boly, M., Brichant, J. F., Laureys, S., & Bonhomme, V. (2017). Brain Functional Connectivity Differentiates Dexmedetomidine From Propofol And Natural Sleep. British Journal of Anaesthesia, 119(4), 674–684. https://doi.org/10.1093/bja/aex257  
13. Bell, M. T., Puskas, F., Bennett, D. T., Herson, P. S., Quillinan, N., Fullerton, D. A., & Reece, T. B. (2014). Dexmedetomidine, an α-2a Adrenergic Agonist, Promotes Ischemic Tolerance in a Murine model of Spinal Cord Ischemia-Reperfusion. The Journal of Thoracic and Cardiovascular Surgery, 147(1), 500–507. https://doi.org/10.1016/j.jtcvs.2013.07.043  
14. Bayram, A., Ülgey, A., Baykan, A., Narin, N., Narin, F., Esmaoglu, A., & Boyaci, A. (2014). The Effects Of Dexmedetomidine On Early-stage Renal Functions In Pediatric Patients Undergoing Cardiac Angiography Using Non-ionic Contrast Media: A Double-blind, Randomized Clinical Trial. Pediatric Anesthesia, 24(4), 426–432. https://doi.org/10.1111/pan.12348  
15. Ji, F., Li, Z., Young, J. N., Yeranossian, A., & Liu, H. (2013). Post-bypass Dexmedetomidine Use And Postoperative Acute Kidney Injury In Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass. PLOS ONE, 8(10), e77446. https://doi.org/10.1371/journal.pone.0077446