Dexmedetomidine in Neurocritical Care
Journal of Cellular & Molecular Anesthesia,
Vol. 5 No. 4 (2020),
14 December 2020
,
Page 251-258
https://doi.org/10.22037/jcma.v5i4.30725
Abstract
Early and appropriate management of brain insults has significantly reduced patient morbidity and mortality. Neuromonitoring, neuroprotection and secondary brain injury prevention are the essential principals of brain injury management.
In this literature review we have elaborated the neuroprotective role of dexmedetomidine (DEX), predominantly in different animal models of brain insults and reports in patients cared in a neurocritical care setting. We undertook an electronic literature search of articles published in English prior to July 2019. This search resulted in inclusion of 59 studies from medical databanks such as PubMed, Scopus, EMBSCO, CINAHL, ISC and the Cochrane Library. The keywords used were brain, α2 agonist, neurocritical care and dexmedetomidine.
DEX may have a neuroprotective effect in a broad spectrum of brain pathologies such as traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), ischemic stroke, intracerebral hemorrhage (ICH), and cerebral hypoxia. However, its neuroprotective role in status epilepticus (SE) is less clear. Further animal and human studies are needed before we could consider DEX as a neuroprotective agent in this patient population. Due to its favorable properties outlined in this review, DEX could be considered a favorable sedative agent in the neurocritical care settings.
- dexmedetomidine
- Neurocritical care
- Neuroprotection
How to Cite
References
Stocchetti N, Taccone FS, Citerio G, Pepe PE, Le Roux PD, Oddo M, et al. Neuroprotection in acute brain injury: an up-to-date review. Crit Care. 2015;19(1):186.
Zoerle T, Carbonara M, Zanier ER, Ortolano F, Bertani G, Magnoni S, et al. Rethinking Neuroprotection in Severe Traumatic Brain Injury: Toward Bedside Neuroprotection. Front Neurol. 2017;8:354.
Gao J, Wei L, Xu G, Ren C, Zhang Z, Liu Y. Effects of dexmedetomidine vs sufentanil during percutaneous tracheostomy for traumatic brain injury patients: A prospective randomized controlled trial. Medicine (Baltimore). 2019;98(35):e17012.
Jeon SB, Koh Y, Choi HA, Lee K. Critical care for patients with massive ischemic stroke. J Stroke. 2014;16(3):146-60.
Cosar M, Eser O, Fidan H, Sahin O, Buyukbas S, Ela Y, et al. The neuroprotective effect of dexmedetomidine in the hippocampus of rabbits after subarachnoid hemorrhage. Surg Neurol. 2009;71(1):54-9; discussion 9.
Ma D, Hossain M, Rajakumaraswamy N, Arshad M, Sanders RD, Franks NP, et al. Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor subtype. Eur J Pharmacol. 2004;502(1-2):87-97.
Castillo RL, Ibacache M, Cortínez I, Carrasco-Pozo C, Farías JG, Carrasco RA, et al. Dexmedetomidine Improves Cardiovascular and Ventilatory Outcomes in Critically Ill Patients: Basic and Clinical Approaches. Front Pharmacol. 2019;10:1641.
Oddo M, Crippa IA, Mehta S, Menon D, Payen JF, Taccone FS, et al. Optimizing sedation in patients with acute brain injury. Crit Care. 2016;20(1):128.
Marehbian J, Muehlschlegel S, Edlow BL, Hinson HE, Hwang DY. Medical Management of the Severe Traumatic Brain Injury Patient. Neurocrit Care. 2017;27(3):430-46.
Luo CL, Chen XP, Yang R, Sun YX, Li QQ, Bao HJ, et al. Cathepsin B contributes to traumatic brain injury-induced cell death through a mitochondria-mediated apoptotic pathway. J Neurosci Res. 2010;88(13):2847-58.
Sanders RD, Xu J, Shu Y, Januszewski A, Halder S, Fidalgo A, et al. Dexmedetomidine attenuates isoflurane-induced neurocognitive impairment in neonatal rats. Anesthesiology. 2009;110(5):1077-85.
Wu J, Vogel T, Gao X, Lin B, Kulwin C, Chen J. Neuroprotective effect of dexmedetomidine in a murine model of traumatic brain injury. Sci Rep. 2018;8(1):4935.
Winkler EA, Minter D, Yue JK, Manley GT. Cerebral Edema in Traumatic Brain Injury: Pathophysiology and Prospective Therapeutic Targets. Neurosurg Clin N Am. 2016;27(4):473-88.
Shen M, Wang S, Wen X, Han XR, Wang YJ, Zhou XM, et al. Dexmedetomidine exerts neuroprotective effect via the activation of the PI3K/Akt/mTOR signaling pathway in rats with traumatic brain injury. Biomed Pharmacother. 2017;95:885-93.
Liu HD, Li W, Chen ZR, Hu YC, Zhang DD, Shen W, et al. Expression of the NLRP3 inflammasome in cerebral cortex after traumatic brain injury in a rat model. Neurochem Res. 2013;38(10):2072-83.
Maccioli GA. Dexmedetomidine to facilitate drug withdrawal. Anesthesiology. 2003;98(2):575-7.
Tang JF, Chen PL, Tang EJ, May TA, Stiver SI. Dexmedetomidine controls agitation and facilitates reliable, serial neurological examinations in a non-intubated patient with traumatic brain injury. Neurocrit Care. 2011;15(1):175-81.
Meagher DJ. Delirium: optimising management. BMJ. 2001;322(7279):144-9.
Mayberg MR, Okada T, Bark DH. The significance of morphological changes in cerebral arteries after subarachnoid hemorrhage. J Neurosurg. 1990;72(4):626-33.
Ayoglu H, Gul S, Hanci V, Bahadir B, Bektas S, Mungan AG, et al. The effects of dexmedetomidine dosage on cerebral vasospasm in a rat subarachnoid haemorrhage model. J Clin Neurosci. 2010;17(6):770-3.
Song Y, Lim BJ, Kim DH, Ju JW, Han DW. Effect of Dexmedetomidine on Cerebral Vasospasm and Associated Biomarkers in a Rat Subarachnoid Hemorrhage Model. J Neurosurg Anesthesiol. 2019;31(3):342-9.
Turan N, Miller BA, Huie JR, Heider RA, Wang J, Wali B, et al. Effect of Progesterone on Cerebral Vasospasm and Neurobehavioral Outcomes in a Rodent Model of Subarachnoid Hemorrhage. World Neurosurg. 2018;110:e150-e9.
Nagoshi N, Nakashima H, Fehlings MG. Riluzole as a neuroprotective drug for spinal cord injury: from bench to bedside. Molecules. 2015;20(5):7775-89.
Yin D, Zhou S, Xu X, Gao W, Li F, Ma Y, et al. Dexmedetomidine attenuated early brain injury in rats with subarachnoid haemorrhage by suppressing the inflammatory response: The TLR4/NF-κB pathway and the NLRP3 inflammasome may be involved in the mechanism. Brain Res. 2018;1698:1-10.
Wang Y, Han R, Zuo Z. Dexmedetomidine post-treatment induces neuroprotection via activation of extracellular signal-regulated kinase in rats with subarachnoid haemorrhage. Br J Anaesth. 2016;116(3):384-92.
Okazaki T, Hifumi T, Kawakita K, Shishido H, Ogawa D, Okauchi M, et al. Association between dexmedetomidine use and neurological outcomes in aneurysmal subarachnoid hemorrhage patients: A retrospective observational study. J Crit Care. 2018;44:111-6.
Dahmani S, Rouelle D, Gressens P, Mantz J. Effects of dexmedetomidine on hippocampal focal adhesion kinase tyrosine phosphorylation in physiologic and ischemic conditions. Anesthesiology. 2005;103(5):969-77.
Kuhmonen J, Pokorný J, Miettinen R, Haapalinna A, Jolkkonen J, Riekkinen P, Sr., et al. Neuroprotective effects of dexmedetomidine in the gerbil hippocampus after transient global ischemia. Anesthesiology. 1997;87(2):371-7.
Goyagi T, Nishikawa T, Tobe Y, Masaki Y. The combined neuroprotective effects of lidocaine and dexmedetomidine after transient forebrain ischemia in rats. Acta Anaesthesiol Scand. 2009;53(9):1176-83.
Fang B, Li XQ, Bi B, Tan WF, Liu G, Zhang Y, et al. Dexmedetomidine attenuates blood-spinal cord barrier disruption induced by spinal cord ischemia reperfusion injury in rats. Cell Physiol Biochem. 2015;36(1):373-83.
Venn RM, Bryant A, Hall GM, Grounds RM. Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in post-operative patients needing sedation in the intensive care unit. Br J Anaesth. 2001;86(5):650-6.
Basu A, Lazovic J, Krady JK, Mauger DT, Rothstein RP, Smith MB, et al. Interleukin-1 and the interleukin-1 type 1 receptor are essential for the progressive neurodegeneration that ensues subsequent to a mild hypoxic/ischemic injury. J Cereb Blood Flow Metab. 2005;25(1):17-29.
Jiang WW, Wang QH, Liao YJ, Peng P, Xu M, Yin LX. Effects of dexmedetomidine on TNF-α and interleukin-2 in serum of rats with severe craniocerebral injury. BMC Anesthesiol. 2017;17(1):130.
Kim E, Kim HC, Lee S, Ryu HG, Park YH, Kim JH, et al. Dexmedetomidine confers neuroprotection against transient global cerebral ischemia/reperfusion injury in rats by inhibiting inflammation through inactivation of the TLR-4/NF-κB pathway. Neurosci Lett. 2017;649:20-7.
Li Y, Liu S. The Effect of Dexmedetomidine on Oxidative Stress Response Following Cerebral Ischemia-Reperfusion in Rats and the Expression of Intracellular Adhesion Molecule-1 (ICAM-1) and S100B. Med Sci Monit. 2017;23:867-73.
Hanci V, Yurdakan G, Yurtlu S, Turan I, Sipahi EY. Protective effect of dexmedetomidine in a rat model of α-naphthylthiourea-induced acute lung injury. J Surg Res. 2012;178(1):424-30.
MacLellan CL, Langdon KD, Churchill KP, Granter-Button S, Corbett D. Assessing cognitive function after intracerebral hemorrhage in rats. Behav Brain Res. 2009;198(2):321-8.
Xiong L, Reijmer YD, Charidimou A, Cordonnier C, Viswanathan A. Intracerebral hemorrhage and cognitive impairment. Biochim Biophys Acta. 2016;1862(5):939-44.
Guo YC, Song XK, Xu YF, Ma JB, Zhang JJ, Han PJ. The expression and mechanism of BDNF and NGB in perihematomal tissue in rats with intracerebral hemorrhage. Eur Rev Med Pharmacol Sci. 2017;21(15):3452-8.
Hwang L, Choi IY, Kim SE, Ko IG, Shin MS, Kim CJ, et al. Dexmedetomidine ameliorates intracerebral hemorrhage-induced memory impairment by inhibiting apoptosis and enhancing brain-derived neurotrophic factor expression in the rat hippocampus. Int J Mol Med. 2013;31(5):1047-56.
Walker MC. Pathophysiology of status epilepticus. Neurosci Lett. 2018;667:84-91.
Scott RC. Status epilepticus in the developing brain: Long-term effects seen in humans. Epilepsia. 2009;50 Suppl 12:32-3.
Holmes GL. Effect of Seizures on the Developing Brain and Cognition. Semin Pediatr Neurol. 2016;23(2):120-6.
Miskin C, Hasbani DM. Status epilepticus: immunologic and inflammatory mechanisms. Semin Pediatr Neurol. 2014;21(3):221-5.
Borham LE, Mahfoz AM, Ibrahim IAA, Shahzad N, AA AL, Labib AA, et al. The effect of some immunomodulatory and anti-inflammatory drugs on Li-pilocarpine-induced epileptic disorders in Wistar rats. Brain Res. 2016;1648(Pt A):418-24.
Halonen T, Kotti T, Tuunanen J, Toppinen A, Miettinen R, Riekkinen PJ. Alpha 2-adrenoceptor agonist, dexmedetomidine, protects against kainic acid-induced convulsions and neuronal damage. Brain Res. 1995;693(1-2):217-24.
Whittington RA, Virag L, Vulliemoz Y, Cooper TB, Morishima HO. Dexmedetomidine increases the cocaine seizure threshold in rats. Anesthesiology. 2002;97(3):693-700.
Kan MC, Wang WP, Yao GD, Li JT, Xie T, Wang W, et al. Anticonvulsant effect of dexmedetomidine in a rat model of self-sustaining status epilepticus with prolonged amygdala stimulation. Neurosci Lett. 2013;543:17-21.
Xu KL, Liu XQ, Yao YL, Ye MR, Han YG, Zhang T, et al. Effect of dexmedetomidine on rats with convulsive status epilepticus and association with activation of cholinergic anti-inflammatory pathway. Biochem Biophys Res Commun. 2018;495(1):421-6.
Byon HJ, Ok SH, Lee SH, Kang S, Cho Y, Han JY, et al. Dexmedetomidine Inhibits Phenylephrine-induced Contractions via Alpha-1 Adrenoceptor Blockade and Nitric Oxide Release in Isolated Rat Aortae. Int J Med Sci. 2017;14(2):143-9.
Mirski MA, Rossell LA, McPherson RW, Traystman RJ. Dexmedetomidine decreases seizure threshold in a rat model of experimental generalized epilepsy. Anesthesiology. 1994;81(6):1422-8.
Kubota T, Fukasawa T, Kitamura E, Magota M, Kato Y, Natsume J, et al. Epileptic seizures induced by dexmedetomidine in a neonate. Brain Dev. 2013;35(4):360-2.
Talke P, Stapelfeldt C, Garcia P. Dexmedetomidine does not reduce epileptiform discharges in adults with epilepsy. J Neurosurg Anesthesiol. 2007;19(3):195-9.
Busl KM, Greer DM. Hypoxic-ischemic brain injury: pathophysiology, neuropathology and mechanisms. NeuroRehabilitation. 2010;26(1):5-13.
Eser O, Fidan H, Sahin O, Cosar M, Yaman M, Mollaoglu H, et al. The influence of dexmedetomidine on ischemic rat hippocampus. Brain Res. 2008;1218:250-6.
Endesfelder S, Makki H, von Haefen C, Spies CD, Bührer C, Sifringer M. Neuroprotective effects of dexmedetomidine against hyperoxia-induced injury in the developing rat brain. PLoS One. 2017;12(2):e0171498.
Ren X, Ma H, Zuo Z. Dexmedetomidine Postconditioning Reduces Brain Injury after Brain Hypoxia-Ischemia in Neonatal Rats. J Neuroimmune Pharmacol. 2016;11(2):238-47.
Yang T, Feng X, Zhao Y, Zhang H, Cui H, Wei M, et al. Dexmedetomidine Enhances Autophagy via α2-AR/AMPK/mTOR Pathway to Inhibit the Activation of NLRP3 Inflammasome and Subsequently Alleviates Lipopolysaccharide-Induced Acute Kidney Injury. Front Pharmacol. 2020;11:790.
Ming T, Yuan M, Kong Q, Huang Q, Xia Z, Wu X. Dexmedetomidine alleviates blunt chest trauma and hemorrhagic shock‑resuscitation‑induced acute lung injury through inhibiting the NLRP3 inflammasome. Mol Med Rep. 2020;22(3):2507-15.
- Abstract Viewed: 275 times
- PDF Downloaded: 258 times