Intranasal Dexmedetomidine for Pain Management During Screening for Retinopathy of Prematurity

Summary

Background: Preterm infants undergo serial eye examinations during their hospital stay to monitor for the development of a specific disease termed "retinopathy of prematurity". While those examinations are known to cause significant pain and stress, the current standard of care (sucrose and local anesthesia) is not adequate in terms of alleviation of pain. Purpose: The goal of this clinical trial is to test the effectiveness of dexmedetomidine for pain management in preterm infants undergoing routine eye examinations. The main questions it aims to answer are: * Does dexmedetomidine reduce the pain scores of preterm infants during and shortly after eye assessments in comparison to placebo (saline 0.9%). * Does dexmedetomidine cause more adverse effects than placebo. In this crossover study participants will receive either dexmedetomidine or saline 0.9% intranasally 30 minutes before the examination, on top of the current standard of care. The participants will be monitored closely for 5 hours to note differences in adverse effects. The researchers will use video monitoring to assess the pain scores using a standardized and validated scoring system.

Timeline

Start

2023-12-11

Primary completion

2025-12

Completion

2025-12

Publications

• Background Wood EH, Chang EY, Beck K, Hadfield BR, Quinn AR, Harper CA 3rd. 80 Years of vision: preventing blindness from retinopathy of prematurity. J Perinatol. 2021 Jun;41(6):1216-1224. doi: 10.1038/s41372-021-01015-8. Epub 2021 Mar 5.
• Background Chiang MF, Quinn GE, Fielder AR, Ostmo SR, Paul Chan RV, Berrocal A, Binenbaum G, Blair M, Peter Campbell J, Capone A Jr, Chen Y, Dai S, Ells A, Fleck BW, Good WV, Elizabeth Hartnett M, Holmstrom G, Kusaka S, Kychenthal A, Lepore D, Lorenz B, Martinez-Castellanos MA, Ozdek S, Ademola-Popoola D, Reynolds JD, Shah PK, Shapiro M, Stahl A, Toth C, Vinekar A, Visser L, Wallace DK, Wu WC, Zhao P, Zin A. International Classification of Retinopathy of Prematurity, Third Edition. Ophthalmology. 2021 Oct;128(10):e51-e68. doi: 10.1016/j.ophtha.2021.05.031. Epub 2021 Jul 8.
• Background Nayak R, Nagaraj KN, Gururaj G. Prevention of Pain During Screening for Retinopathy of Prematurity: A Randomized Control Trial Comparing Breast Milk, 10% Dextrose and Sterile Water. Indian J Pediatr. 2020 May;87(5):353-358. doi: 10.1007/s12098-020-03182-6. Epub 2020 Jan 27.
• Background Mitchell AJ, Green A, Jeffs DA, Roberson PK. Physiologic effects of retinopathy of prematurity screening examinations. Adv Neonatal Care. 2011 Aug;11(4):291-7. doi: 10.1097/ANC.0b013e318225a332.
• Background Padhi TR, Sareen D, Pradhan L, Jalali S, Sutar S, Das T, Modi RR, Behera UC. Evaluation of retinopathy of prematurity screening in reverse Kangaroo Mother Care: a pilot study. Eye (Lond). 2015 Apr;29(4):505-8. doi: 10.1038/eye.2014.340. Epub 2015 Jan 23.
• Background Valeri BO, Holsti L, Linhares MB. Neonatal pain and developmental outcomes in children born preterm: a systematic review. Clin J Pain. 2015 Apr;31(4):355-62. doi: 10.1097/AJP.0000000000000114.
• 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 Nesargi SV, Nithyanandam S, Rao S, Nimbalkar S, Bhat S. Topical anesthesia or oral dextrose for the relief of pain in screening for retinopathy of prematurity: a randomized controlled double-blinded trial. J Trop Pediatr. 2015 Feb;61(1):20-4. doi: 10.1093/tropej/fmu058. Epub 2014 Nov 5.
• Background Marsh VA, Young WO, Dunaway KK, Kissling GE, Carlos RQ, Jones SM, Shockley DH, Weaver NL, Ransom JL, Gal P. Efficacy of topical anesthetics to reduce pain in premature infants during eye examinations for retinopathy of prematurity. Ann Pharmacother. 2005 May;39(5):829-33. doi: 10.1345/aph.1E476. Epub 2005 Mar 29.
• Background Disher T, Cameron C, Mitra S, Cathcart K, Campbell-Yeo M. Pain-Relieving Interventions for Retinopathy of Prematurity: A Meta-analysis. Pediatrics. 2018 Jul;142(1):e20180401. doi: 10.1542/peds.2018-0401. Epub 2018 Jun 1.
• Background Dempsey E, McCreery K. Local anaesthetic eye drops for prevention of pain in preterm infants undergoing screening for retinopathy of prematurity. Cochrane Database Syst Rev. 2011 Sep 7;2011(9):CD007645. doi: 10.1002/14651858.CD007645.pub2.
• Background Campbell-Yeo M, Benoit B. Use of morphine before retinopathy of prematurity examinations. Lancet. 2018 Dec 15;392(10164):2521-2523. doi: 10.1016/S0140-6736(18)32324-9. Epub 2018 Nov 30. No abstract available.
• Background Alselaimy R, Al Tawil L, Abouammoh MA. Anesthesia in retinopathy of prematurity. Saudi J Ophthalmol. 2022 Oct 14;36(3):251-259. doi: 10.4103/sjopt.sjopt_229_21. eCollection 2022 Jul-Sep.
• Background Hartley C, Moultrie F, Hoskin A, Green G, Monk V, Bell JL, King AR, Buckle M, van der Vaart M, Gursul D, Goksan S, Juszczak E, Norman JE, Rogers R, Patel C, Adams E, Slater R. Analgesic efficacy and safety of morphine in the Procedural Pain in Premature Infants (Poppi) study: randomised placebo-controlled trial. Lancet. 2018 Dec 15;392(10164):2595-2605. doi: 10.1016/S0140-6736(18)31813-0. Epub 2018 Nov 30.
• Background Sindhur M, Balasubramanian H, Srinivasan L, Kabra NS, Agashe P, Doshi A. Intranasal fentanyl for pain management during screening for retinopathy of prematurity in preterm infants: a randomized controlled trial. J Perinatol. 2020 Jun;40(6):881-887. doi: 10.1038/s41372-020-0608-2. Epub 2020 Feb 13.
• Background McDonald D, Palsgraf H, Shah P. Dexmedetomidine - An emerging option for sedation in neonatal patients. J Perinatol. 2022 Jul;42(7):845-855. doi: 10.1038/s41372-022-01351-3. Epub 2022 Feb 23.
• Background O'Mara K, Gal P, Wimmer J, Ransom JL, Carlos RQ, Dimaguila MA, Davanzo CC, Smith M. Dexmedetomidine versus standard therapy with fentanyl for sedation in mechanically ventilated premature neonates. J Pediatr Pharmacol Ther. 2012 Jul;17(3):252-62. doi: 10.5863/1551-6776-17.3.252.
• Background 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 Jan;96(1):134-41. doi: 10.1097/00000542-200201000-00026.
• Background Lewis J, Bailey CR. Intranasal dexmedetomidine for sedation in children; a review. J Perioper Pract. 2020 Jun;30(6):170-175. doi: 10.1177/1750458919854885. Epub 2019 Jun 27.
• Background Bua J, Massaro M, Cossovel F, Monasta L, Brovedani P, Cozzi G, Barbi E, Demarini S, Travan L. Intranasal dexmedetomidine, as midazolam-sparing drug, for MRI in preterm neonates. Paediatr Anaesth. 2018 Aug;28(8):747-748. doi: 10.1111/pan.13454. No abstract available.
• Background Yuen VM, Hui TW, Irwin MG, Yao TJ, Wong GL, Yuen MK. Optimal timing for the administration of intranasal dexmedetomidine for premedication in children. Anaesthesia. 2010 Sep;65(9):922-9. doi: 10.1111/j.1365-2044.2010.06453.x.
• Background Stevens BJ, Gibbins S, Yamada J, Dionne K, Lee G, Johnston C, Taddio A. The premature infant pain profile-revised (PIPP-R): initial validation and feasibility. Clin J Pain. 2014 Mar;30(3):238-43. doi: 10.1097/AJP.0b013e3182906aed.
• Background Slater R, Hartley C, Moultrie F, Adams E, Juszczak E, Rogers R, Norman JE, Patel C, Stanbury K, Hoskin A, Green G; Poppi Trial Team. A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol. Wellcome Open Res. 2016 Nov 15;1:7. doi: 10.12688/wellcomeopenres.10005.2.

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