{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T05:36:30Z","timestamp":1781242590757,"version":"3.54.1"},"reference-count":80,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Hypoxic-ischemic encephalopathy (HIE) is a common cause of significant neonatal morbidity and mortality. The stronghold of the treatment for moderate-to-severe HIE is therapeutic hypothermia (TH) which provides a neuroprotective effect. However, it also is associated with pain and stress. Moreover, neonates with HIE are subjected to a significant number of painful procedures. Untreated pain during the early neonatal period may entail future challenges such as impaired brain growth and development as well as impaired pain sensitivity later in life. Hereby, the provision of adequate sedation and alleviation of pain and discomfort is essential. There are currently no universally accepted guidelines for sedation and pain management for this patient population. In this review, we highlight non-pharmacologic and pharmacologic methods currently in use to provide comfort and sedation to patients with HIE undergoing TH.<\/jats:p>","DOI":"10.3390\/children12020253","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:34:26Z","timestamp":1739943266000},"page":"253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sedation and Pain Management in Neonates Undergoing Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy"],"prefix":"10.3390","volume":"12","author":[{"given":"Artemiy","family":"Kokhanov","sequence":"first","affiliation":[{"name":"Phoenix Children\u2019s, Phoenix, AZ 85016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Chen","sequence":"additional","affiliation":[{"name":"MemorialCare Miller Women\u2019s and Children\u2019s Hospital Long Beach, Long Beach, CA 90806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"751.e1","DOI":"10.1016\/j.ajog.2022.06.002","article-title":"Trends of neonatal hypoxic-ischemic encephalopathy prevalence and associated risk factors in the United States, 2010 to 2018","volume":"227","author":"Acun","year":"2022","journal-title":"Am. J. Obstet Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1136\/archdischild-2020-320902","article-title":"Trends in the incidence and management of hypoxic-ischaemic encephalopathy in the therapeutic hypothermia era: A national population study","volume":"106","author":"Shipley","year":"2021","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1159\/000518654","article-title":"Temporal trends in the severity and mortality of neonatal hypoxic-ischemic encephalopathy in the era of hypothermia","volume":"118","author":"Arnaez","year":"2021","journal-title":"Neonatology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ezenwa, B.N., Olorunfemi, G., Fajolu, I., Adeniyi, T., Oleolo-Ayodeji, K., Kene-Udemezue, B., Olamijulo, J.A., and Ezeaka, C. (2021). Trends and predictors of in-hospital mortality among babies with hypoxic ischaemic encephalopathy at a tertiary hospital in Nigeria: A retrospective cohort study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0250633"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/pr.2013.206","article-title":"Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990","volume":"74","author":"Lee","year":"2013","journal-title":"Pediatr. Res."},{"key":"ref_6","first-page":"CD003311","article-title":"Cooling for newborns with hypoxic ischaemic encephalopathy","volume":"2013","author":"Jacobs","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.pedneo.2016.11.001","article-title":"Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy","volume":"58","author":"Chiang","year":"2017","journal-title":"Pediatr. Neonatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s11910-019-0916-0","article-title":"Therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy","volume":"19","author":"Wassink","year":"2019","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5430","DOI":"10.2174\/0929867326666190506124836","article-title":"Therapeutic hypothermia and neuroprotection in acute neurological disease","volume":"26","author":"Kurisu","year":"2019","journal-title":"Curr. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1097\/ANC.0b013e31829d8baf","article-title":"Monitoring of pain and stress in an infant with asphyxia during induced hypothermia: A case report","volume":"13","author":"Hoffman","year":"2013","journal-title":"Adv. Neonatal Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/JPN.0b013e31829dc2d3","article-title":"Sleep-wake cycling in a neonate admitted to the NICU: A video-EEG case study during hypothermia treatment","volume":"27","author":"Axelin","year":"2013","journal-title":"J. Perinat. Neonatal Nurs."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104828","DOI":"10.1016\/j.earlhumdev.2019.104828","article-title":"Therapeutic hypothermia and N-PASS; results from implementation in a level 3 NICU","volume":"137","author":"Johansen","year":"2019","journal-title":"Early Hum. Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1152\/advan.00126.2014","article-title":"Recent advances in thermoregulation","volume":"39","author":"Tansey","year":"2015","journal-title":"Adv. Physiol. Educ."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.siny.2014.10.005","article-title":"Physiological responses to hypothermia","volume":"20","author":"Wood","year":"2015","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_15","first-page":"1","article-title":"Thermogenesis in human brown adipose tissue and skeletal muscle induced by sympathomimetic stimulation","volume":"278","author":"Astrup","year":"1986","journal-title":"Acta Endocrinol. Suppl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R285","DOI":"10.1152\/ajpregu.00652.2010","article-title":"Implications of nonshivering thermogenesis for energy balance regulation in humans","volume":"301","author":"Schrauwen","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1203\/00006450-200109000-00017","article-title":"Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective","volume":"50","author":"Thoresen","year":"2001","journal-title":"Pediatr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1097\/j.pain.0000000000000784","article-title":"Translational studies identify long-term impact of prior neonatal pain experience","volume":"158","author":"Walker","year":"2017","journal-title":"Pain"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Williams, M.D., and Lascelles, B.D.X. (2020). Early neonatal pain\u2014A review of clinical and experimental implications on painful conditions later in life. Front. Pediatr., 8.","DOI":"10.3389\/fped.2020.00030"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"101005","DOI":"10.1016\/j.siny.2019.04.005","article-title":"Long-term effects of neonatal pain","volume":"24","author":"Walker","year":"2019","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Joshi, M., Muneer, J., Mbuagbaw, L., and Goswami, I. (2023). Analgesia and sedation strategies in neonates undergoing whole-body therapeutic hypothermia: A scoping review. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0291170"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101264","DOI":"10.1016\/j.siny.2021.101264","article-title":"Management of comfort and sedation in neonates with neonatal encephalopathy treated with therapeutic hypothermia","volume":"26","author":"McPherson","year":"2021","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_23","first-page":"CD006275","article-title":"Non-pharmacological management of infant and young child procedural pain","volume":"6","author":"Bucsea","year":"2023","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.neures.2008.10.007","article-title":"The calming effect of a maternal breast milk odor on the human newborn infant","volume":"63","author":"Nishitani","year":"2009","journal-title":"Neurosci. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3406\/enfan.1997.3049","article-title":"\u00c9tudes exploratoires des relations intersensorielles olfaction-douleur","volume":"50","author":"Mellier","year":"1997","journal-title":"Enfance"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1097\/00004703-200504000-00003","article-title":"The calming effect of a familiar odor on full-term newborns","volume":"26","author":"Rattaz","year":"2005","journal-title":"J. Dev. Behav. Pediatr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1080\/14767058.2022.2041594","article-title":"Feeding during therapeutic hypothermia is safe and may improve outcomes in newborns with perinatal asphyxia","volume":"35","author":"Alburaki","year":"2022","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/S2352-4642(21)00026-2","article-title":"Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: A retrospective, UK population-based cohort study","volume":"5","author":"Gale","year":"2021","journal-title":"Lancet Child. Adolesc. Health"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"F230","DOI":"10.1136\/archdischild-2018-315393","article-title":"Optimising nutrition during therapeutic hypothermia","volume":"104","author":"Ojha","year":"2019","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.srhc.2019.03.004","article-title":"Parental participation during therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy","volume":"20","author":"Biskop","year":"2019","journal-title":"Sex. Reprod. Healthc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1111\/apa.14743","article-title":"Maternal holding during therapeutic hypothermia for infants with neonatal encephalopathy is feasible","volume":"108","author":"Craig","year":"2019","journal-title":"Acta Paediatr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.jpeds.2015.04.055","article-title":"Neonatal pain and infection relate to smaller cerebellum in very preterm children at school age","volume":"167","author":"Ranger","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chau, C.M.Y., Ranger, M., Bichin, M., Park, M.T.M., Amaral, R.S.C., Chakravarthy, M., Poskitt, K., Synnes, A.R., Miller, S.P., and Grunau, R.E. (2019). Hippocampus, amygdala, and thalamus volumes in very preterm children at 8 years: Neonatal pain and genetic variation. Front. Behav. Neurosci., 13.","DOI":"10.3389\/fnbeh.2019.00051"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jpeds.2015.12.024","article-title":"Smaller cerebellar growth and poorer neurodevelopmental outcomes in very preterm infants exposed to neonatal morphine","volume":"172","author":"Zwicker","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1016\/S0140-6736(04)16251-X","article-title":"Effects of morphine analgesia in ventilated preterm neonates: Primary outcomes from the NEOPAIN randomised trial","volume":"363","author":"Anand","year":"2004","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Azzopardi, D., Brocklehurst, P., Edwards, D., Halliday, H., Levene, M., Thoresen, M., Whitelaw, A., and TOBY Study Group (2008). The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: A randomised controlled trial. BMC Pediatr., 8.","DOI":"10.1186\/1471-2431-8-17"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.pediatrneurol.2004.06.015","article-title":"Moderate hypothermia in neonatal encephalopathy: Safety outcomes","volume":"32","author":"Eicher","year":"2005","journal-title":"Pediatr. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1056\/NEJMcps050929","article-title":"Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy","volume":"353","author":"Shankaran","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1001\/archpediatrics.2011.43","article-title":"Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: A randomized controlled trial","volume":"165","author":"Jacobs","year":"2011","journal-title":"Arch. Pediatr. Adolesc. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e771","DOI":"10.1542\/peds.2009-2441","article-title":"Systemic hypothermia after neonatal encephalopathy: Outcomes of neo.nEURO.network RCT","volume":"126","author":"Simbruner","year":"2010","journal-title":"Pediatrics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1172\/JCI119153","article-title":"Dramatic neuronal rescue with prolonged selective head cooling after ischemia in fetal lambs","volume":"99","author":"Gunn","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/nrn.2016.128","article-title":"Lasting impact of general anaesthesia on the brain: Mechanisms and relevance","volume":"17","author":"Vutskits","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Sabir, H., Dingley, J., Scull-Brown, E., Chakkarapani, E., and Thoresen, M. (2018). Fentanyl induces cerebellar internal granular cell layer apoptosis in healthy newborn pigs. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00294"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1136\/archdischild-2019-317050","article-title":"Pre-emptive opioid sedation during therapeutic hypothermia","volume":"105","author":"Montaldo","year":"2020","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41390-022-02453-6","article-title":"Variations in care of neonates during therapeutic hypothermia: Call for care practice bundle implementation","volume":"94","author":"Mohammad","year":"2023","journal-title":"Pediatr. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41372-019-0533-4","article-title":"Opioid and benzodiazepine use during therapeutic hypothermia in encephalopathic neonates","volume":"40","author":"Berube","year":"2020","journal-title":"J. Perinatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1038\/s41372-018-0126-7","article-title":"Association between sedation-analgesia and neurodevelopment outcomes in neonatal hypoxic-ischemic encephalopathy","volume":"38","author":"Natarajan","year":"2018","journal-title":"J. Perinatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1089\/ther.2018.0052","article-title":"Preemptive morphine during therapeutic hypothermia after neonatal encephalopathy: A secondary analysis","volume":"10","author":"Liow","year":"2020","journal-title":"Ther. Hypothermia Temp. Manag."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"100892","DOI":"10.1016\/j.eclinm.2021.100892","article-title":"Morphine and fentanyl exposure during therapeutic hypothermia does not impair neurodevelopment","volume":"36","author":"Gundersen","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7764","DOI":"10.1080\/14767058.2021.1937106","article-title":"Fentanyl analgesia in asphyxiated newborns treated with therapeutic hypothermia","volume":"35","author":"Lugli","year":"2022","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/jcph.775","article-title":"Decreased morphine clearance in neonates with hypoxic ischemic encephalopathy receiving hypothermia","volume":"57","author":"Frymoyer","year":"2017","journal-title":"J. Clin. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Favi\u00e9, L.M.A., Groenendaal, F., van den Broek, M.P.H., Rademaker, C.M.A., de Hann, T.R., van Straaten, H.L.M., Dijk, P.H., van Heijst, A., Dudink, J., and Dijkman, K.P. (2019). Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0211910"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Lugli, L., Garetti, E., Goffredo, B.M., Candia, F., Crestani, S., Spada, C., Guidotti, I., Bedetti, L., Miselli, F., and Della Casa, E.M. (2023). Continuous fentanyl infusion in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia: Background, aims, and study protocol for time-concentration profiles. Biomedicines, 11.","DOI":"10.3390\/biomedicines11092395"},{"key":"ref_54","first-page":"CD011107","article-title":"Alpha-2 adrenergic agonists for the prevention of shivering following general anaesthesia","volume":"2015","author":"Lewis","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41372-021-01151-1","article-title":"Clonidine for sedation in infants during therapeutic hypothermia with neonatal encephalopathy: Pilot study","volume":"42","author":"Gauda","year":"2022","journal-title":"J. Perinatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"242","DOI":"10.4103\/0019-5049.82666","article-title":"A comparative study of the effect of clonidine and tramadol on post-spinal anaesthesia shivering","volume":"55","author":"Shukla","year":"2011","journal-title":"Indian. J. Anaesth."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e168","DOI":"10.1055\/s-0038-1669938","article-title":"Dexmedetomidine for sedation of neonates with hie undergoing therapeutic hypothermia: A single-center experience","volume":"8","author":"Weiss","year":"2018","journal-title":"AJP Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1213\/00000539-199110000-00016","article-title":"Clonidine decreases plasma catecholamines and improves outcome from incomplete ischemia in the rat","volume":"73","author":"Hoffman","year":"1991","journal-title":"Anesth. Analg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1097\/00000542-199108000-00022","article-title":"Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Reversal by the alpha 2-adrenergic antagonist atipamezole","volume":"75","author":"Hoffman","year":"1991","journal-title":"Anesthesiology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1213\/00000539-199302000-00012","article-title":"Brain alpha 2-adrenergic receptor binding during incomplete cerebral ischemia in the rat","volume":"76","author":"Hoffman","year":"1993","journal-title":"Anesth. Analg."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1053\/ejpn.2001.0401","article-title":"Hypoxic-ischaemic brain damage in immature rats: Effects of adrenoceptor modulation","volume":"5","author":"Yuan","year":"2001","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"ref_62","first-page":"270","article-title":"Clonidine in paediatrics\u2014A review","volume":"53","author":"Basker","year":"2009","journal-title":"Indian. J. Anaesth."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e849","DOI":"10.1542\/peds.2008-0978","article-title":"Clonidine as an adjunct therapy to opioids for neonatal abstinence syndrome: A randomized, controlled trial","volume":"123","author":"Agthe","year":"2009","journal-title":"Pediatrics"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6643171","DOI":"10.1155\/2021\/6643171","article-title":"Dexmedetomidine alleviates hypoxia-induced synaptic loss and cognitive impairment via inhibition of microglial nox2 activation in the hippocampus of neonatal rats","volume":"2021","author":"Chen","year":"2021","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1097\/00000542-200201000-00026","article-title":"Effects of alpha(2)-adrenoceptor agonists on perinatal excitotoxic brain injury: Comparison of clonidine and dexmedetomidine","volume":"96","author":"Laudenbach","year":"2002","journal-title":"Anesthesiology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ejphar.2004.08.044","article-title":"Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor subtype","volume":"502","author":"Ma","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1213\/01.ane.0000194301.79118.e9","article-title":"The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the alpha2A-adrenoceptor subtype","volume":"102","author":"Paris","year":"2006","journal-title":"Anesth. Analg."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jclinane.2017.04.003","article-title":"The protective effects of dexmedetomidine on ischemic brain injury: A meta-analysis","volume":"40","author":"Jiang","year":"2017","journal-title":"J. Clin. Anesth."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.jpeds.2013.10.002","article-title":"A phase II\/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates","volume":"164","author":"Chrysostomou","year":"2014","journal-title":"J. Pediatr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3233\/NPM-210737","article-title":"Effect of dexmedetomidine on heart rate in neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia","volume":"15","author":"Elliott","year":"2022","journal-title":"J. Neonatal Perinatal Med."},{"key":"ref_71","first-page":"232","article-title":"Effectiveness and safety of dexmedetomidine in neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia","volume":"29","author":"Acun","year":"2024","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1038\/s41372-021-00998-8","article-title":"Dexmedetomidine versus intermittent morphine for sedation of neonates with encephalopathy undergoing therapeutic hypothermia","volume":"41","author":"Cosnahan","year":"2021","journal-title":"J. Perinatol."},{"key":"ref_73","first-page":"352","article-title":"Dexmedetomidine versus fentanyl for neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia","volume":"27","author":"Naveed","year":"2022","journal-title":"J. Pediatr. Pharmacol. Ther."},{"key":"ref_74","first-page":"22","article-title":"Is dexmedetomidine a potential neuroprotective agent for term neonates with hypoxic-ischemic encephalopathy?","volume":"7","author":"Surkov","year":"2019","journal-title":"Pediatr. Anesth. Crit. Care J.\u2014PACCJ"},{"key":"ref_75","first-page":"2582965","article-title":"Dexmedetomidine pharmacokinetics in neonates with hypoxic-ischemic encephalopathy receiving hypothermia","volume":"2020","author":"McAdams","year":"2020","journal-title":"Anesthesiol. Res. Pract."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Baserga, M., DuPont, T.L., Ostrander, B., Minton, S., Sheffield, M., Balch, A.H., Timothy, T.M., and Watt, K.M. (2021). Dexmedetomidine use in infants undergoing cooling due to neonatal encephalopathy (Dice trial): A randomized controlled trial: Background, aims and study protocol. Front. Pain Res., 2.","DOI":"10.3389\/fpain.2021.770511"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1159\/000368180","article-title":"Anticonvulsant effectiveness and hemodynamic safety of midazolam in full-term infants treated with hypothermia","volume":"107","author":"Huitema","year":"2015","journal-title":"Neonatology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1161\/01.STR.0000128029.50221.fa","article-title":"Topiramate extends the therapeutic window for hypothermia-mediated neuroprotection after stroke in neonatal rats","volume":"35","author":"Liu","year":"2004","journal-title":"Stroke"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1203\/PDR.0b013e3181d4ff4d","article-title":"Phenobarbital augments hypothermic neuroprotection","volume":"67","author":"Barks","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"15089","DOI":"10.1073\/pnas.222550499","article-title":"Antiepileptic drugs and apoptotic neurodegeneration in the developing brain","volume":"99","author":"Bittigau","year":"2002","journal-title":"Proc. Natl. Acad. Sci. 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