Dexmedetomidine for Sedation of Neonates with HIE Undergoing Therapeutic Hypothermia: A Single-Center Experience

Abstract

Hypoxic-ischemic encephalopathy (HIE) is a significant cause of morbidity and mortality in neonates. Therapeutic hypothermia reduces the risk of death or disability. Providing optimal sedation while neonates are undergoing therapeutic hypothermia is likely beneficial but may present therapeutic challenges. There are limited data describing the use of dexmedetomidine for sedation in patients undergoing therapeutic hypothermia. The objective of this study is to evaluate the efficacy and short-term safety of dexmedetomidine infusion for sedation in term neonates undergoing therapeutic hypothermia for HIE.

Keywords

hypoxic-ischemic encephalopathy - sedation - dexmedetomidine - neonate

Statement of Financial Support

Children's Miracle Network.

• References

• 1 Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 2010; 86 (06) 329-338
• 2 Azzopardi DV, Strohm B, Edwards AD. , et al; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009; 361 (14) 1349-1358
• 3 Gluckman PD, Wyatt JS, Azzopardi D. , et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365 (9460): 663-670
• 4 Shankaran S, Laptook AR, Ehrenkranz RA. , et al; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353 (15) 1574-1584
• 5 Wassink G, Lear CA, Gunn KC, Dean JM, Bennet L, Gunn AJ. Analgesics, sedatives, anticonvulsant drugs, and the cooled brain. Semin Fetal Neonatal Med 2015; 20 (02) 109-114
• 6 Thoresen M, Satas S, Løberg EM. , et al. Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective. Pediatr Res 2001; 50 (03) 405-411
• 7 Angeles DM, Wycliffe N, Michelson D. , et al. Use of opioids in asphyxiated term neonates: effects on neuroimaging and clinical outcome. Pediatr Res 2005; 57 (06) 873-878
• 8 Festekjian A, Ashwal S, Obenaus A, Angeles DM, Denmark TK. The role of morphine in a rat model of hypoxic-ischemic injury. Pediatr Neurol 2011; 45 (02) 77-82
• 9 McAdams RM, Juul SE. Neonatal encephalopathy: update on therapeutic hypothermia and other novel therapeutics. Clin Perinatol 2016; 43 (03) 485-500
• 10 Laudenbach V, Mantz J, Lagercrantz H, Desmonts JM, Evrard P, Gressens P. Effects of alpha(2)-adrenoceptor agonists on perinatal excitotoxic brain injury: comparison of clonidine and dexmedetomidine. Anesthesiology 2002; 96 (01) 134-141
• 11 Paris A, Mantz J, Tonner PH, Hein L, Brede M, Gressens P. The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the alpha2A-adrenoceptor subtype. Anesth Analg 2006; 102 (02) 456-461
• 12 Ma D, Hossain M, Rajakumaraswamy N. , et al. Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor subtype. Eur J Pharmacol 2004; 502 (1-2): 87-97
• 13 Tobias JD. Bradycardia during dexmedetomidine and therapeutic hypothermia. J Intensive Care Med 2008; 23 (06) 403-408
• 14 Ezzati M, Broad K, Kawano G. , et al. Pharmacokinetics of dexmedetomidine combined with therapeutic hypothermia in a piglet asphyxia model. Acta Anaesthesiol Scand 2014; 58 (06) 733-742
• 15 Chang LL, Wynn JL, Pacella MJ. , et al. Enteral feeding as an adjunct to hypothermia in neonates with hypoxic-ischemic encephalopathy. Neonatology 2018; 113 (04) 347-352
• 16 Douglas-Escobar M, Weiss MD. Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr 2015; 169 (04) 397-403
• 17 Dahmani S, Paris A, Jannier V. , et al. Dexmedetomidine increases hippocampal phosphorylated extracellular signal-regulated protein kinase 1 and 2 content by an alpha 2-adrenoceptor-independent mechanism: evidence for the involvement of imidazoline I1 receptors. Anesthesiology 2008; 108 (03) 457-466
• 18 Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med 2004; 32 (06) 1322-1326