Hypoxic-ischemic encephalopathy in full-term neonates: current state of the problem

D.M. Surkov


The article presents a systematic review of the researches on hypoxic-ischemic encephalopathy (HIE), which develops in infants after perinatal ischemia. It remains a significant challenge for neonatal intensive care because of high mortality and neurological disabilities in children, despite some progress in diagnosis, monitoring and treatment. The main goal of therapy is to support adequate cerebral perfusion and to prevent secondary neuronal damage, including the apoptosis development. Among the methods for the diagnosis and monitoring of neurological disorders in neonates, the main ones are: brain ultrasound and Doppler evaluation of cerebral blood flow patterns, near-infrared spectrometry monitoring in conjunction with amplitude-integrated electroencephalography. At the moment, the only method of intensive care with proven neuroprotection is therapeutic hypothermia 33–35 °C for 72 hours. Nevertheless, its efficacy is still insufficient, reducing the combined outcome of death or severe neurodevelopmental impairment from 65 to 40–50 %. While the benefits of therapeutic hypothermia provide proof that outcomes can be better, additional treatments to further improve outcomes are needed. The new mode of ventilation, neurally adjusted ventilatory assist, is promising for respiratory support in newborns with HIE. The ideal fluid for the blood volume replacement in newborns hasn’t yet been found. Crystalloids because of low replacement coefficient have unstable impact on cardiac output. The use of albumin is restricted due to high blood-brain barrier permeability in HIE. The possibility of using 6% hydroxyethyl starch 130/0.42 has been considered, as recent studies have not demonstrated additional risks compared to crystalloids. Dopamine is still considered as a drug of choice in infants, but several studies show the benefits of dobutamine effects on systemic and cerebral hemodynamics. Searching for other agents for secondary neuroprotection has shown some benefits of erythropoietin, but the number of observations is limited. Other drugs are still ongoing preclinical and clinical studies of phase I and II.


review; newborns; hypoxia; encephalopathy; neuroprotection


Johnston MV, Fatemi A, Wilson MA, Northington F. Treatment advances in neonatal neuroprotection and neurointensive care. Lancet Neurol. 2011;10:372–382. doi: 10.1016/S1474-4422(11)70016-3.

Pfister RH, Bingham P, Edwards EM, Horbar JD, Kenny MJ, Inder T, et al. The Vermont Oxford Neonatal Encephalopathy Registry: rationale, methods, and initial results. BMC Pediatr. 2012;12:84-93. doi: 10.1186/1471-2431-12-84.

Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, et al. Global, regional, and national causes of child mortality in 2000-2013, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015;385:430-440. doi: 10.1016/S0140-6736(14)61698-6.

Parikh P, Juul SE. Neuroprotective strategies in neonatal brain injury. The Journal of Pediatrics. 2018;192:22-32. doi: 10.1016/j.jpeds.2017.08.031.

Tagin M, Abdel-Hady H, Rahman S, Azzopardi DV, Gunn AJ. Neuroprotection for perinatal hypoxic ischemic encephalopathy in low- and middle-income countries. Journal of Pediatrics. 2015;167(1):25–28. doi: 10.1016/j.jpeds.2015.02.056.

Levene MI, de Vries L. Hypoxic-ischemic encephalopathy. In: Martin RJ, Fanaroff AA, Walsh MC, editors. Fanaroff and Martin's neonatal-perinatal medicine: diseases of the fetus and infant. 9th Ed. St. Louis, Missoury: Elseiver Mosby Inc.; 2011. p. 952-975.

Zanelli SA, Stanley DP. Hypoxic-ischemic encephalopathy [Internet]. 2018 [Epub 2018 Jul 18]. Available from:

Hill A, Volpe JJ. Neurologic Disorders. In: Avery GB, Fletcher MA, MacDonald MG, editors. Neonatology: Pathophysiology and management of the newborn. Philadelphia, New York: Lippincott-Raven; 1994. p. 1117-1138.

Kaur C, Rathnasamy G, Ling EA. Roles of activated microglia in hypoxia, induced neuroinflammation in the developing brain and the retina. Journal of Neuroimmune Pharmacology. 2013;8:66-78.

Howlett JA, Northington FJ, Gilmore MM, Tekes A, Huisman TA, Parkinson C, et al. Cerebrovascular autoregulation and neurologic injury in neonatal hypoxic-ischemic encephalopathy. Pediatric Research. 2013;74(5):525–535. doi: 10.1038/pr.2013.132.

Burton VJ, Gerner G, Cristofalo E, Chung SE, Jennings JM, Parkinson C, et al. A pilot cohort study of cerebral autoregulation and 2-year neurodevelopmental outcomes in neonates with hypoxic-ischemic encephalopathy who received therapeutic hypothermia. BMC Neurology. 2015;15:209. doi: 10.1186/s12883-015-0464-4.

Pardo AC. Autoregulation in infants with neonatal encephalopathy. Pediatric Neurology Briefs. 2015;29(10):75. doi: 10.15844/pedneurbriefs-29-10-2.

Vutskits L. Cerebral blood flow in the neonate. Pediatric Anesthesia. 2014;24:22-29. doi:10.1111/pan.12307.

Parikh P, Juul SE. Novel targets for neuroprotection in neonatal brain injury. Atlas of Science [Internet]. 2018 [Epub 2018 Oct 30]. Available from:

Dalili H, Sheikh M, Hardani AK, Nili F, Shariat M, Nayeri F. Comparison of the Combined versus Conventional Apgar Scores in Predicting Adverse Neonatal Outcomes. PLoS One. 2016;11(2):e0149464. doi: 10.1371/journal.pone.0149464.

Aliyu I, Lawal T, Onankpa B. Hypoxic-ischemic encephalopathy and the Apgar scoring system: The experience in a resource-limited setting. Journal of Clinical Science. 2018;15(1):18-21. doi: 10.4103/jcls.jcls_102_17.

Martinello K, Hart AR, Yap S, Mitra S, Robertson NJ. Management and investigation of neonatal encephalopathy: 2017 update. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2017:fetalneonatal-2015-309639.

Иова А.С. Оценка тяжести внутрижелудочковых кровоизлияний у новорожденных [Интернет]. 2005 [цитировано 2019 фев. 12]. Доступно с:

Glass HC. Neonatal seizures: advances in mechanisms and management. Clinics in Perinatology. 2014;41:177–190.

Gerner GJ, Burton VJ, Poretti A, Bosemani T, Cristofalo E, Tekes A, et al. Transfontanellar duplex brain ultrasonography resistive indices as a prognostic tool in neonatal hypoxic-ischemic encephalopathy before and after treatment with therapeutic hypothermia. Journal of Perinatology. 2016;36(3):202-206. doi: 10.1038/jp.2015.169.

Chalak LF, Sánchez PJ, Adams-Huet B, Laptook AR, Heyne RJ. Biomarkers for severity of neonatal hypoxic-ischemic encephalopathy and outcomes in newborns receiving hypothermia therapy. Journal of Pediatrics. 2014;164:468-474.

Douglas-Escobar M, Weiss MD. Biomarkers of hypoxic-ischemic encephalopathy in newborns. Frontiers in Neurology. 2012;3:144. doi: 10.3389/fneur.2012.00144.

Douglas-Escobar M, Yang C, Bennett J, Shuster J, Theriaque D, Leibovici A, et al. A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy. Pediatric Research. 2010;68(6):531–536.

Massaro AN, Chang T, Kadom N, Tsuchida T, Scafidi J, Glass P, et al. Biomarkers of brain injury in neonatal encephalopathy treated with hypothermia. Journal of Pediatrics. 2012;1(3):434–440.

Massaro AN, Chang T, Baumgart S, McCarter R, Nelson KB, Glass P. Biomarkers S100b and NSE predict outcome in hypothermia-treated encephalopathic newborns. Pediatric Critical Care Medicine. 2014;15(7):615–622.

Chaparro-Huerta V, Flores-Soto ME, Merin Sigala ME, Barrera de León JC, de Lourdes Lemus-Varela M, de GuadalupeTorres-Mendoza BM. Proinflammatory cytokines, enolase and S-100 as early biochemical indicators of hypoxic-ischemic encephalopathy following perinatal asphyxia in newborns. Pediatrics and Neonatology. 2017;58(1):70-76.

Abbasoglu A, Sarialioglu F, Yazici N, Bayraktar N, Haberal A, Erbay A. Serum neuron-specific enolase levels in preterm and term newborns and in infants 1-3 months of age. Pediatrics and Neonatology. 2015;56(2):114-119. doi: 10.1016/j.pedneo.2014.07.005.

Zaigham M, Lundberg F, Olofsson P. Protein S100B in umbilical cord blood as a potential biomarker of hypoxic-ischemic encephalopathy in asphyxiated newborns. Early Human Development. 2017;112:48-53.

Toso PA, González AJ, Pérez ME, Kattan J, Fabres JG. Clinical utility of early amplitude integrated EEG in monitoring term newborns at risk of neurological injury. J Pediatr (Rio J). 2014;90(2):143-148. doi: 10.1016/j.jped.2013.07.004.

Merchant N, Azzopardi D. Early predictors of outcome in infants treated with hypothermia for hypoxic-ischemic encephalopathy. Dev Med Child Neurol. 2015;57(3):8-16. doi: 10.1111/dmcn.12726.

de Vries LS, Toet MC. Amplitude integrated electroencephalography in the full-term newborn. Clin Perinatol. 2006;33(3):619-632.

del Río R, Ochoa C, Alarcon A, Arnáez J, Blanco D, García-Alix A. Amplitude integrated electroencephalogram as a prognostic tool in neonates with hypoxic-ischemic encephalopathy: a systematic review. PLoS One. 2016;11(11): e0165744. doi: 10.1371/journal.pone.0165744.

Chandrasekaran M, Chaban B, Montaldo P, Thayyil S. Predictive value of amplitude-integrated EEG (aEEG) after rescue hypothermic neuroprotection for hypoxic ischemic encephalopathy: a meta-analysis. J Perinatol. 2017;37(6):684-689. doi: 10.1038/jp.2017.14.

Guan B, Dai C, Zhang Y, Zhu L, He X, Wang N, Liu H. Early diagnosis and outcome prediction of neonatal hypoxic-ischemic encephalopathy with color Doppler ultrasound. Diagn Interv Imaging. 2017;98(6):469-475. doi: 10.1016/j.diii.2016.12.001.

Vesoulis ZA, Liao SM, Mathur AM. Late failure of cerebral autoregulation in hypoxic-ischemic encephalopathy is associated with brain injury: a pilot study. Physiol Meas. 2018;39(12):125004. doi: 10.1088/1361-6579/aae54d.

Massaro AN, Govindan RB, Vezina G, Chang T, Andescavage NN, Wang Y, et al. Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia. J Neurophysiol. 2015;114(2): 818–824. doi: 10.1152/jn.00353.2015.

Carrasco M, Perin J, Jennings JM, Parkinson C, Gilmore MM, Chavez-Valdez R, et al. Cerebral Autoregulation and Conventional and Diffusion Tensor Imaging Magnetic Resonance Imaging in Neonatal Hypoxic-Ischemic Encephalopathy. Pediatr Neurol. 2018;82:36-43. doi: 10.1016/j.pediatrneurol.2018.02.004.

Mokri B. The Monro-Kellie hypothesis: applications in CSF volume depletion. Neurology. 2001;56(12):1746-1748.

Царенко С.В. Нейрореаниматология: интенсивная терапия черепно-мозговой травмы. 3-е изд., испр. и доп. Москва: Медицина; 2009. 383 с.

Avellino AM, Carson BS. Increased intracranial pressure. In Current Management in Child Neurology, Third Edition. Edited by Bernard L. Maria. BC Decker Inc. 2005:563-568

Zahka KG. Principles of neonatal cardiovascular hemodynamics. In: Martin RJ, Fanaroff AA, Walsh MC, editors. Fanaroff and Martin's neonatal-perinatal medicine: diseases of the fetus and infant. 9th Ed. St. Louis, Missoury: Elseiver Mosby Inc.; 2011. p. 952-975.

Vrancken SL, van Heijst AF, de Boode WP. Neonatal Hemodynamics: From Developmental Physiology to Comprehensive Monitoring. Front Pediatr. 2018;6:87.doi: 10.3389/fped.2018.00087.

Kent AL, Chaudhari T. Determinants of neonatal blood pressure. Current Hypertension Reports. 2013;15(5):426-432. doi: 10.1007/s11906-013-0375-y .

Kusaka T, Okubo K, Nagano K, Isobe K, Itoh S. Cerebral distribution of cardiac output in newborn infants. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2005;90:77-78.

Lalzad A, Wong F, Schneider M. Neonatal cranial ultrasound: are current safety guidelines appropriate? Ultrasound in Medicine and Biology. 2017;43(3):553-560. doi: 10.1016/j.ultrasmedbio.2016.11.002.

Gupta P, Sodhi KS, Saxena AK, Khandelwal N, Singhi P. Neonatal cranial sonography: A concise review for clinicians. J Pediatr Neurosci. 2016;11(1): 7–13. doi: 10.4103/1817-1745.181261.

Ааslid R. Transcranial Doppler sonography. Wien: Springer-Verlag. 1986; 39 р.

Czosnyka M, Matta BF, Smielewski P, Kirkpatrick PJ, Pickard JD. Cerebral perfusion pressure in head-injured patients: a noninvasive assessment using transcranial Doppler ultrasonography. J. Neurosurg. 1998;88(5):802-808.

Fister P, Grosek Š. Hemodynamic monitoring in neonates. In: Barría RM, editor. Selected Topics in Neonatal Care. IntechOpen; 2018. p. 27-43. doi: 10.5772/intechopen.69215.

Wu T-W, Tamrazi B, Hsu K-H, Ho E, Reitman AJ, Borzage M, et al. Cerebral lactate concentration in neonatal hypoxic-ischemic encephalopathy: in relation to time, characteristic of injury, and serum lactate concentration. Front Neurol. 2018;9:293. doi: 10.3389/fneur.2018.00293

Greisen G, Leung T, Wolf M. Has the time come to use near-infrared spectroscopy as a routine clinical tool in preterm infants undergoing intensive care? Philos Trans A Math Phys Eng Sci. 2011;369(1955): 4440–4451. doi: 10.1098/rsta.2011.0261

Dix LM, van Bel F, Lemmers PM. Monitoring cerebral oxygenation in neonates: an update. Front Pediatr. 2017;5:46. doi: 10.3389/fped.2017.00046.

Gumulak R, Lucanova LC, Zibolen M. Use of near-infrared spectroscopy (NIRS) in cerebral tissue oxygenation monitoring in neonates. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2017;161(2):128-133. doi: 10.5507/bp.2017.012.

Weiner GM, Zaichkin J, Kattwinkel J, editors. Textbook of Neonatal Resuscitation. 7th ed. Elk Grove Village, IL: American Academy of Pediatrics and American Heart Association; 2016. 328 p.

WHO, Maternal, newborn, child and adolescent health. Guidelines on Basic Newborn Resuscitation. Geneva, Switzerland; 2012. 61 p.

Silveira RC, Procianoy RS. Hypothermia therapy for newborns with hypoxic ischemic encephalopathy. J Pediatr (Rio J). 2015;91(6 Suppl 1):78-83. doi: 10.1016/j.jped.2015.07.004.

Cotten SM, Shankaran S. Hypothermia for hypoxic–ischemic encephalopathy. Expert Rev Obstet Gynecol. 2010;5(2): 227–239. doi: 10.1586/eog.10.7

Fukuda H , Tomimatsu T , Watanabe N , Mu JW , Kohzuki M , Endo M, et al. Post-ischemic hypothermia blocks caspase-3 activation in the newborn rat brain after hypoxia–ischemia. Brain Res. 2001;910(1–2):187–191. doi: 10.1016/S0006-8993(01)02659-2.

Natarajan G, Pappas A, Shankaran S. Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE). Semin Perinatol. 2016;40(8):549-555. doi: 10.1053/j.semperi.2016.09.007.

Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013;(1):CD003311. doi: 10.1002/14651858.CD003311.pub3.

Shankaran S, Laptook AR, Pappas A, McDonald SA, Das A, Tyson JE, et al. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial. JAMA. 2014;312(24):2629-2639. doi: 10.1001/jama.2014.16058.

Laptook AR, Shankaran S, Tyson JE, Munoz B, Bell EF, Goldberg RN, et al. Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial. JAMA. 2017;318(16):1550-1560. doi: 10.1001/jama.2017.14972.

Verma P, Kalraiya A. Respiratory compliance of newborns after birth and their short-term outcomes. Int J Contemp Pediatr. 2017;4(2):620-624. doi: 10.18203/2349-3291.ijcp20170720.

Goldsmith JP, Karotkin E, Suresh G, Keszler M. Assisted Ventilation of the Neonate, 6th Edition. Evidence-Based Approach to Newborn Respiratory Care. Elsevier; 2017. 640 p.

Stein H, Firestone K. Application of neurally adjusted ventilatory assist in neonates. Semin Fetal Neonatal Med. 2014;19(1):60-69. doi: 10.1016/j.siny.2013.09.005.

Rossor TE, Shetty S, Greenough A. Neurally adjusted ventilatory assist for neonatal respiratory support.Cochrane Database of Systematic Reviews. 2016;6:CD012251. doi: 10.1002/14651858.CD012251.

Kadivar M, Mosayebi Z, Sangsari R, Soltan Alian H, Jedari Attari S. Neurally Adjusted Ventilatory Assist in Neonates: A Research Study. Journal of Comprehensive Pediatrics. 2018;9(3):e62297. doi: 10.5812/compreped.62297.

Лебединский К.М. Кровообращение и анестезия: оценка и коррекция системной гемодинамики во время операции и анестезии. СПб.: Человек; 2012. 1076 с.

Polglase GR, Ong T, Hillman NH. Cardiovascular Alterations and Multiorgan Dysfunction After Birth Asphyxia. Clin Perinatol. 2016;43(3):469-83. doi: 10.1016/j.clp.2016.04.006.

Tanigasalam V, Plakkal N, Vishnu Bhat B, Chinnakali P. Does fluid restriction improve outcomes in infants with hypoxic ischemic encephalopathy? A pilot randomized controlled trial. J Perinatol. 2018;38(11):1512-1517. doi: 10.1038/s41372-018-0223-7.

Finn D, Roehr CC, Ryan CA, Dempsey EM. Optimizing intravenous volume resuscitation of the newborn in the delivery room: practical considerations and gaps in knowledge. Neonatology. 2017;112:163-171. doi: 10.1159/000475456.

László I., Demeter G., Öveges N, Érces D, Kaszaki J, Tánczos K, et al. Volume-replacement ratio for crystalloids and colloids during bleeding and resuscitation: an animal experiment. Intensive Care Medicine Experimental. 2017;5:52. doi: 10.1186/s40635-017-0165-y.

Ambalavanan N. Fluid, electrolyte, and nutrition management of the newborn [Internet]. 2018 [Epub 2018 Oct 18]. Available from:

Ek CJ, D'Angelo B, Baburamani AA, Lehner C, Leverin AL, Smith PL, et al. Brain barrier properties and cerebral blood flow in neonatal mice exposed to cerebral hypoxia-ischemia. Journal of Cerebral Blood Flow & Metabolism. 2015;35(5):818-827. doi: 10.1038/jcbfm.2014.255.

Myburgh JA, Finfer S, Bellomo R, Billot L, Cass A, Gattas D, et al. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012;367(20):1901-11. doi: 10.1056/NEJMoa1209759

Annane D, Siami S, Jaber S, Martin C, Elatrous S, Declère AD, et al. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013;310(17):1809-1817. doi: 10.1001/jama.2013.280502.

Estrada CA, Murugan R. Hydroxyethyl starch in severe sepsis: end of starch era? Crit Care. 2013;17(2):310. doi: 10.1186/cc12531.

Phillips DP, Kaynar AM, Kellum JA, Gomez H. Crystalloids vs. colloids: KO at the twelfth round? Crit Care. 2013;17(3):319. doi: 10.1186/cc12708.

Lewis SR, Pritchard MW, Evans DJ, Butler AR, Alderson P, Smith AF, et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev. 2018;8:CD000567. doi: 10.1002/14651858.CD000567.pub7.

Sümpelmann R, Witt L, Brütt M, Osterkorn D, Koppert W, Osthaus WA. Changes in acid-base, electrolyte and hemoglobin concentrations during infusion of hydroxyethyl starch 130/0.42/6:1 in normal saline or in balanced electrolyte solution in children. Pediatr Anesth. 2010;20(1):100-104. doi:10.1111/j.1460-9592.2009.03197.x.

Sümpelmann R, Kretz FJ, Luntzer R, de Leeuw TG, Mixa V, Gäbler R, et al. Hydroxyethyl starch 130/0.42/6:1 for perioperative plasma volume replacement in 1130 children: results of an European prospective multicenter observational postauthorization safety study (PASS). Paediatr Anesth. 2012;22(4):371-378. doi: 10.1111/j.1460-9592.2011.03776.x.

Gray R. Which colloid to choose for neonates, infants and children. Southern African Journal of Anaesthesia and Analgesia. 2015;21(1):56-58.

Priebe H.J. Should hydroxyethyl starch be banned? The Lancet. 2018;392:117-118. doi: 10.1016/S0140-6736(18)31172-3.

Standl T, Lochbuehler H, Galli C, Reich A, Dietrich G, Hagemann H, et al. HES 130/0.4 (Voluven) or human albumin in children younger than 2 yr undergoing non-cardiac surgery. A prospective, randomized, open-label, multicentre trial. European Journal of Anaesthesiology. 2008;25(6):437-445. doi: 10.1017/S0265021508003888.

Van der Linden P, Dumoulin M, Van Lerberghe C, Torres CS, Willems A, Faraoni D, et al. Efficacy and safety of 6% hydroxyethyl starch 130/0.4 (Voluven) for perioperative volume replacement in children undergoing cardiac surgery: a propensity-matched analysis. Critical Care. 2015;19:87. doi: 10.1186/s13054-015-0830-z.

Sahni M, Jain S. Hypotension in Neonates. NeoReviews. 2016;17(10):e579-e587. doi: 10.1542/neo.17-10-e579.

Bhayat SI, Gowda HM, Eisenhut M. Should dopamine be the first line inotrope in the treatment of neonatal hypotension? Review of the evidence. World Journal of Clinical Pediatrics. 2016;5(2):212–222. doi: 10.5409/wjcp.v5.i2.212.

Gupta S, Donn SM. Neonatal hypotension: dopamine or dobutamine? Seminars in Fetal and Neonatal Medicine. 2014;19(1):54-59. doi: 10.1016/j.siny.2013.09.006.

Mayock DE, Gleason CA. Pain and sedation in the NICU. NeoReviews. 2013;14;e22-e31. doi: 10.1542/neo.14-1-e22.

Carbajal R, Eriksson M, Courtois E, Boyle E, Avila-Alvarez A, Andersen RD, et al; EUROPAIN Survey Working Group. Sedation and analgesia practices in neonatal intensive care units (EUROPAIN): results from a prospective cohort study. Lancet Respir Med. 2015;3(10):796-812. doi: 10.1016/S2213-2600(15)00331-8.

Romantsik O, Calevo MG, Norman E, Bruschettini M. Clonidine for sedation and analgesia for neonates receiving mechanical ventilation. Cochrane Database Syst Rev. 2017;5:CD012468. doi: 10.1002/14651858.CD012468.pub2.

Mahmoud M, Mason KP. Dexmedetomidine: review, update, and future considerations of paediatric perioperative and periprocedural applications and limitations. BJA: British Journal of Anaesthesia. 2015;115(2):171-182. doi: 10.1093/bja/aev226.

Pullen LC. Dexmedetomidine Effective Sedative for Neonates [Internet]. 2013 [cited 2019 Feb 19]. Available from:

Weatherall M, Aantaa R, Conti G, Garratt C, Pohjanjousi P, Lewis MA, et al. A multinational, drug utilization study to investigate the use of dexmedetomidine (Dexdor®) in clinical practice in the EU. Br J Clin Pharmacol. 2017;83(9):2066-2076. doi: 10.1111/bcp.13293.

Ibrahim M, Jones LJ, Lai N, Tan K. Dexmedetomidine for analgesia and sedation in newborn infants receiving mechanical ventilation (Protocol). Cochrane Database Syst Rev. 2016;9:CD012361. doi: 10.1002/14651858.CD012361.

Estkowski LM, Morris JL, Sinclair EA. Characterization of dexmedetomidine dosing and safety in neonates and infants. J Pediatr Pharmacol Ther. 2015;20(2):112-118. doi: 10.5863/1551-6776-20.2.112.

Perez-Zoghbi JF, Zhu W, Grafe MR, Brambrink AM. Dexmedetomidine-mediated neuroprotection against sevoflurane-induced neurotoxicity extends to several brain regions in neonatal rats. BJA: British Journal of Anaesthesia. 2017;119(3):506–516. doi: 10.1093/bja/aex222.

Zhang MH, Zhou XM, Cui JZ, Wang KJ, Feng Y, Zhang HA. Neuroprotective effects of dexmedetomidine on traumatic brain injury: Involvement of neuronal apoptosis and HSP70 expression. Mol Med Rep. 2018;17(6):8079-8086. doi: 10.3892/mmr.2018.8898.

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