Dexmedetomidine Versus Morphine During Cooling Therapy in Neonates
Summary
About \~3/ 1000 live-born newborns may suffer from brain injury due to a transient drop in oxygen supply to the brain during the birth process. The degree of brain injury that ensues in the first 72 hours after the injury is directly proportional to the severity of long-term childhood disabilities (e.g., cerebral palsy and developmental delays). Whole-body cooling during the first 3 days of life is proven effective in reducing the severity of brain injury. However, cooling therapy leads to pain, shivering, stress, and discomfort. The best way to alleviate the pain and agitation of cooled newborns is unknown. Standard practice is to provide morphine infusion to reduce pain. Recently, a new drug called "dexmedetomidine" has been tested in small studies and has been found to be safe during cooling in newborns. Dexmedetomidine has added beneficial effects such as anti-inflammation, faster recovery, and shorter hospital stays. This study is going to test the feasibility of conducting a future clinical trial to compare the effects of using Dexmedetomidine versus morphine in the management of cooling-related pain/agitation on the severity of brain injury in the first week of life. The study will also examine the effect of dexmedetomidine compared to morphine on short-term clinical outcomes, parental experiences and developmental outcomes at 1 year.
Timeline
- Start
- 2025-07-01
- Primary completion
- 2027-09-30
- Completion
- 2028-06-30
Publications
- Background Alvik A, Groholt B. Examination of the cut-off scores determined by the Ages and Stages Questionnaire in a population-based sample of 6 month-old Norwegian infants. BMC Pediatr. 2011 Dec 19;11:117. doi: 10.1186/1471-2431-11-117.
- Background Weeke LC, Groenendaal F, Mudigonda K, Blennow M, Lequin MH, Meiners LC, van Haastert IC, Benders MJ, Hallberg B, de Vries LS. A Novel Magnetic Resonance Imaging Score Predicts Neurodevelopmental Outcome After Perinatal Asphyxia and Therapeutic Hypothermia. J Pediatr. 2018 Jan;192:33-40.e2. doi: 10.1016/j.jpeds.2017.09.043.
- Background Craig A, Deerwester K, Fox L, Jacobs J, Evans S. Maternal holding during therapeutic hypothermia for infants with neonatal encephalopathy is feasible. Acta Paediatr. 2019 Sep;108(9):1597-1602. doi: 10.1111/apa.14743. Epub 2019 Mar 5.
- Background Meesters NJ, Dilles T, van Rosmalen J, van den Bosch GE, Simons SHP, van Dijk M. COMFORTneo scale: a reliable and valid instrument to measure prolonged pain in neonates? J Perinatol. 2023 May;43(5):595-600. doi: 10.1038/s41372-023-01628-1. Epub 2023 Feb 6.
- Background van Dijk M, Roofthooft DW, Anand KJ, Guldemond F, de Graaf J, Simons S, de Jager Y, van Goudoever JB, Tibboel D. Taking up the challenge of measuring prolonged pain in (premature) neonates: the COMFORTneo scale seems promising. Clin J Pain. 2009 Sep;25(7):607-16. doi: 10.1097/AJP.0b013e3181a5b52a.
- Background Elliott M, Fairchild K, Zanelli S, McPherson C, Vesoulis Z. Dexmedetomidine During Therapeutic Hypothermia: A Multicenter Quality Initiative. Hosp Pediatr. 2024 Jan 1;14(1):30-36. doi: 10.1542/hpeds.2023-007403.
- Background McAdams RM, Pak D, Lalovic B, Phillips B, Shen DD. Dexmedetomidine Pharmacokinetics in Neonates with Hypoxic-Ischemic Encephalopathy Receiving Hypothermia. Anesthesiol Res Pract. 2020 Feb 25;2020:2582965. doi: 10.1155/2020/2582965. eCollection 2020.
- Background Joshi M, Muneer J, Mbuagbaw L, Goswami I. Analgesia and sedation strategies in neonates undergoing whole-body therapeutic hypothermia: A scoping review. PLoS One. 2023 Dec 7;18(12):e0291170. doi: 10.1371/journal.pone.0291170. eCollection 2023.
- Background Backe P, Bruschettini M, Blomqvist YT, Sibrecht G, Olsson E. Interventions for the Management of Pain and Sedation in Newborns Undergoing Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy: A Systematic Review. Paediatr Drugs. 2023 Jan;25(1):27-41. doi: 10.1007/s40272-022-00546-7. Epub 2022 Dec 8.
- Background Walker SM. Long-term effects of neonatal pain. Semin Fetal Neonatal Med. 2019 Aug;24(4):101005. doi: 10.1016/j.siny.2019.04.005. Epub 2019 Apr 5.
- Background Wu Y, Kapse K, Jacobs M, Niforatos-Andescavage N, Donofrio MT, Krishnan A, Vezina G, Wessel D, du Plessis A, Limperopoulos C. Association of Maternal Psychological Distress With In Utero Brain Development in Fetuses With Congenital Heart Disease. JAMA Pediatr. 2020 Mar 1;174(3):e195316. doi: 10.1001/jamapediatrics.2019.5316. Epub 2020 Mar 2.
- Background Thoresen M, Satas S, Loberg EM, Whitelaw A, Acolet D, Lindgren C, Penrice J, Robertson N, Haug E, Steen PA. Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective. Pediatr Res. 2001 Sep;50(3):405-11. doi: 10.1203/00006450-200109000-00017.
- Background van Marken Lichtenbelt WD, Schrauwen P. Implications of nonshivering thermogenesis for energy balance regulation in humans. Am J Physiol Regul Integr Comp Physiol. 2011 Aug;301(2):R285-96. doi: 10.1152/ajpregu.00652.2010. Epub 2011 Apr 13.
- Background Mohammad K, McIntosh S, Lee KS, Beltempo M, Afifi J, Tremblay S, Shah P, Wilson D, Bodani J, Khurshid F, Makary H, Ng E, Wintermark P; NeoBrainNetwork. Variations in care of neonates during therapeutic hypothermia: call for care practice bundle implementation. Pediatr Res. 2023 Jul;94(1):321-330. doi: 10.1038/s41390-022-02453-6. Epub 2023 Jan 9.
- Background Goswami IR, Whyte H, Wintermark P, Mohammad K, Shivananda S, Louis D, Yoon EW, Shah PS; Canadian Neonatal Network Investigators. Characteristics and short-term outcomes of neonates with mild hypoxic-ischemic encephalopathy treated with hypothermia. J Perinatol. 2020 Feb;40(2):275-283. doi: 10.1038/s41372-019-0551-2. Epub 2019 Nov 13.
- Background 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 Jan 31;2013(1):CD003311. doi: 10.1002/14651858.CD003311.pub3.
- Background Shankaran S. Therapeutic hypothermia for neonatal encephalopathy. Curr Treat Options Neurol. 2012 Dec;14(6):608-19. doi: 10.1007/s11940-012-0200-y.
- Background Kromm GH, Patankar H, Nagalotimath S, Wong H, Austin T. Socioemotional and Psychological Outcomes of Hypoxic-Ischemic Encephalopathy: A Systematic Review. Pediatrics. 2024 Apr 1;153(4):e2023063399. doi: 10.1542/peds.2023-063399.
- Background Pisani F, Orsini M, Braibanti S, Copioli C, Sisti L, Turco EC. Development of epilepsy in newborns with moderate hypoxic-ischemic encephalopathy and neonatal seizures. Brain Dev. 2009 Jan;31(1):64-8. doi: 10.1016/j.braindev.2008.04.001. Epub 2008 May 19.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Dexmedetomidine | Other / unclassified | 0.2 ug/kg | — |
| Comparator | Morphine | Other / unclassified | 4 ug/kg | — |