Using of dexmedetomidine in term neonates with hypoxic-ischemic encephalopathy

Authors

DOI:

https://doi.org/10.26641/2307-0404.2019.2.170123

Keywords:

hypoxia, ischemia, encephalopathy, dexmedetomidine, neonates, mechanical ventilation

Abstract

Related Article:
This is a corrected version. See correction statement in: https://medpers.dmu.edu.ua/en/2021-vol-xxvi/n-3
doi: https://doi.org/10.26641/2307-0404.2021.3.242347

The negative impacts of standard pharmacologic sedative agents suggest that alternative agents should be investigated. Dexmedetomidine could be the new option for sedation in newborns with hypoxic-ischemic encephalopathy requiring mechanical ventilation. The aim – to compare cerebral blood flow indexes and results of treatment for hypoxic-ischemic encephalopathy between groups of full-term infants who received dexmedetomidine (study group) and other sedatives (control group) during therapeutic hypothermia period. Data of 205 term infants with hypoxic-ischemic encephalopathy by Sarnat scale stage II-III were collected during ≤72 hours of life. Infants of the study group (n = 46) received dexmedetomidine during mechanical ventilation for pharmacological sedation. Control group infants (n = 159) received morphine, sodium oxybutiras, and diazepam in standard recommended doses. A comparative analysis of the effect of dexmedetomidine and other drugs on cerebral perfusion and outcomes of hypoxic-ischemic encephalopathy was performed. A significant difference between groups in days of trachea extubation (p=0.022) was found; the chance for babies to be extubated before the 7th day of treatment was significantly higher in the dexmedetomidine group 68% versus 33% in the control group (p=0.018) with HR 0.48 (95% CI 0.27-0.86, p=0.011). Also, the NIRS index rScO2 differed significantly between the studied and control groups on the 1st day of treatment (65% versus 79%, p=0.012) and on the 2nd day of treatment (74% versus 81%, p=0.035). Mean arterial pressure was higher in the dexmedetomidine group compared to the control group – (58 [51-65] mm Hg versus 53 [46-60] mm Hg, p<0.001), with a lower dose of dobutamine (EV -1.87, 95% CI from -3.25 to -0.48, p=0.009). In the dexmedetomidine group, the rate of seizures was significantly lower on the 1st day of obser­vation (4.3% versus 48.3%, p <0.001); the incidence of unfavorable outcome such as cerebral leukomalacia was also 7 times lower in the dexmedetomidine group compared to the control group (2.2% versus 15.1%, p=0.018). The determined peculiarities give grounds to use dexmedetomidine in the daily practice of the neonatal intensive care, but additional data needs to be collected before any further conclusions can be drawn.

Author Biography

D. Surkov

MI «Dnipropetrovsk Regional Children's Clinical Hospital» DRС»
neonatal intensive care unit
Kosmichna, 13, Dnipro, 49100, Ukraine

References

Tkachik SJ. [Forecasting and preventive main­tenance perinatal pathologies at anomalies patrimonial activity]. Health of Woman. 2016;4(110):168-70. Ukrainian.

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):2066-76. doi: https://doi.org/10.1111/bcp.13293

Chrysostomou C, Schulman SR, Herrera Castel­lanos M, Cofer BE, Mitra S, da Rocha MG, et al. A phase II/III, multicenter, safety, efficacy, and pharmacokinetic study of dexmedetomidine in preterm and term neonates. J. Pediatr. 2014;164(2):276-282.e1-3. doi: https://doi.org/10.1016/j.jpeds.2013.10.002

Forster DE, Koumoundouros E, Saxton V, Fedai G, Holberton J. Cerebral blood flow velocities and cerebro­vascular resistance in normal‐term neonates in the first 72 hours. J. Paediatr Child Health. 2018;54(1):61-68. doi: https://doi.org/10.1111/jpc.13663

Hyttel-Sorensen S, Pellicer A, Alderliesten T, Austin T, van Bel F, Benders M, et al. Cerebral near infrared spectroscopy oximetry in extremely preterm infants: phase II randomised clinical trial. BMJ. 2015;350(2):g7635. doi: https://doi.org/10.1136/bmj.g7635

Allanson E, Tunçalp Ö, Gardosi J, Pattinson RC, Erwich JJ, Flenady VJ, et al. Classifying the causes of perinatal death. Bull World Health Organ. 2016;94(2):79–79A. doi: https://doi.org/10.2471/BLT.15.168047

Weerink MA, Struys MM, Hannivoort LN, Barends CR, Absalom AR, Colin P. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet. 2017;56(8):893-913. doi: https://doi.org/10.1007/s40262-017-0507-7

Arnaez J, García-Alix A, Arca G, Valverde E, Ca­serío S, Moral MT, et al. Grupo de Trabajo EHI-ESP. Incidence of hypoxic-ischaemic encephalopathy and use of therapeutic hypothermia in Spain. An Pediatr (Barc). 2018;89(1):12-23. doi: https://doi.org/10.1016/j.anpedi.2017.06.008

Kurosawa A, Sato Y, Sasakawa T, Kunisawa T, Iwasaki H. Dexmedetomidine inhibits epileptiform acti­vity in rat hippocampal slices. Int J Clin Exp Med. 2017;10(4):6704-6711. ISSN:1940-5901/IJCEM0046980.

Su F, GastonguayMR, Nicolson SC, DiLiber­to M, Ocampo-Pelland A, Zuppa AF. Dexmedetomidine phar­macology in neonates and infants after open heart surgery. Anesth Analg. 2016;122(5):1556-66. doi: https://doi.org/10.1213/ANE.0000000000000869

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

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

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.

Garvey AA, Kooi EM, Smith A, Dempsey EM. Interpretation of cerebral oxygenation changes in the preterm infant. Children (Basel). 2018;5(7). pii: E94. doi: https://doi.org/10.3390/children5070094

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;385:430-40. doi: https://doi.org/10.1016/S0140-6736(14)61698-6

Herold F, Wiegel P, Scholkmann F, Müller NG. Applications of functional near-infrared spectroscopy (fNIRS) neuroimaging in exercise-cognition science: a systematic, methodology-focused review. J Clin Med. 2018;7(12). pii: E466. doi: https://doi.org/10.3390/jcm7120466

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: https://doi.org/10.1002/14651858.CD012361

Torbenson VE, Tolcher MC, Nesbitt KM, Col­by CE, EL-Nashar SA, Gostout BS, et al. Intrapartum factors associated with neonatal hypoxic ischemic encephalopathy: a case-controlled study. BMC Pregnancy Childbirth. 2017;17:415-422. doi: https://doi.org/10.1186/s12884-017-1610-3

Lee AC, Kozuki N, Blencowe H, Vos T, Baha­lim A, Darmstadt GL, et al. Intrapartum-related neonatal encephalopath incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res. 2013;74(1):50-72. doi: https://doi.org/10.1038/pr.2013.206

Kumar AS, Chandrasekaran A, Asokan R, Gopi­nathan K. Prognostic value of resistive index in neonates with hypoxic ischemic encephalopathy. Indian Pediatr. 2016;53:1079-1082. PMID: 27889713.

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):171-82. doi: https://doi.org/10.1093/bja/aev226

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

Borenstein-Levin L, Synnes A, Grunau RE, Miller SP, Yoon EW, Shah PS. Narcotics and sedative use in preterm neonates. J Pediatr. 2017;180:92-98.e1. doi: https://doi.org/10.1016/j.jpeds.2016.08.031

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: https://doi.org/10.1016/j.jpeds.2015.02.056

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. doi: https://doi.org/10.1371/journal.pone.0171498

Wu J, Vogel T, Gao X, Lin B, Kulwin C, Chen J. Neuroprotective effect of dexmedetomidine in a murine model of traumatic brain injury. Scientific Reports. 2018;8:4935.

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):8079-86. doi: https://doi.org/10.3892/mmr.2018.8898

O'Mara K, Weiss MD. Dexmedetomidine for sedation of neonates with HIE undergoing therapeutic hypothermia: a single-center experience. AJP Rep. 2018;8(3):e168-e173.

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

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):506-16. doi: https://doi.org/10.1093/bja/aex222

Simiyu IN, Mchaile DN, Katsongeri K, Phile­mon RN, Msuya SE. Prevalence, severity and early outco­mes of hypoxic ischemic encephalopathy among new­borns at a tertiary hospital, in northern Tanzania. BMC Pediatr. 2017;17(1):131. doi: https://doi.org/10.1186/s12887-017-0876-y

Pullen LC. Dexmedetomidine effective sedative for neonates [Internet]. 2013 [cited 2019 Feb 19]. Avai­lable from: https://www.medscape.com/viewarticle/818075

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: https://doi.org/10.1016/j.pedneo.2014.07.005

Baik N, Urlesberger B, Schwaberger B, Schmöl­zer GM, Mileder L, Avian A, Pichler G. Reference ranges for cerebral tissue oxygen saturation index in term neonates during immediate neonatal transition after birth. Neonatology. 2015;108(4):283-286. doi: https://doi.org/10.1159/000438450

Simon-Pimmel J, Lorton F, Masson D, Bou­vier D, Hanf M, Gras-Le Guen C. Reference ranges for serum S100B neuroprotein specific to infants under four months of age. Clinical Biochemistry. 2017;50(18):1056-60. doi: https://doi.org/10.1016/j.clinbiochem.2017.08.014

Zamora CA, Oshmyansky A, Bembea M, Berko­witz I, Alqahtani E, Liu S, et al. Resistive index varia­bility in anterior cerebral artery measurements during daily transcranial duplex sonography. J Ultrasound Med. 2016;35:2459-65. doi: https://doi.org/10.7863/ultra.15.09046

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: https://doi.org/10.1002/14651858.CD012468.pub2

Sood BG, McLaughlin K, Cortez J. Near-infrared spectroscopy: applications in neonates. Semin Fetal Neonatal Med. 2015;20(3):164-72. doi: https://doi.org/10.1016/j.siny.2015.03.008

Sorokan ST, Jefferies AL, Miller SP. Canadian Paediatric Society, Fetus and Newborn Committee. Ima­ging the term neonatal brain. Paediatr Child Health. 2018;23(5):322-8. doi: https://doi.org/10.1093/pch/pxx161

Su F, Nicolson SC, Zuppa AF. A dose-response study of dexmedetomidine administered as the primary sedative in infants following open heart surgery. Pediatr Crit Care Med. 2013;14(5):499-507. doi: https://doi.org/10.1097/PCC.0b013e31828a8800

UNICEF. Neonatal mortality [Internet]. 2018 [cited 2019 Jan 31]. Available from: https://data.uni­cef.org/topic/child-survival/neonatal-mortality/

Van Meurs KP, Bonifacio SL. Brain-focused care in the neonatal intensive care unit: the time has come. J Pediatr (RioJ). 2017;93(5):439-441. doi: https://doi.org/10.1016/j.jped.2017.03.002

Wang Y, Han R, Zuo Z. Dexmedetomidine-indu­ced neuroprotection: is it translational? Transl Perioper Pain Med. 2016;1(4):15-19. PMID: 28217717; PMCID: PMC5310645.

Wenhao W. Model-based evaluation of dose regi­mens in preterm and term neonates for dexmedetomidine and vancomycin. Digitala Vetenskapliga Arkivet [Internet]. 2017 Available from: http://www.diva-portal.org/smash/­record.jsf?pid=diva2%3A1140628&dswid=1932

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2019-11-06

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Surkov D. Using of dexmedetomidine in term neonates with hypoxic-ischemic encephalopathy. Med. perspekt. [Internet]. 2019Nov.6 [cited 2024Apr.20];24(2):24-33. Available from: https://journals.uran.ua/index.php/2307-0404/article/view/170123

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CLINICAL MEDICINE