Intranasal Sufentanil for Analgesia of Severe Sickle Cell Vaso-occlusive Pain Crisis in the Pediatric

Summary

Sickle cell disease (SCD) is characterized by an abnormal hemoglobin, the main protein in the red blood cell. From the first months of life, acute obstruction of the vessels of the microcirculation manifests as intense and unpredictable recurrent episodes of severe pain. In the Emergency Department (ED), patients presenting with a vaso-occlusive crisis (VOC) required a rapid evaluation and administration of pain relief therapies and hydration. this strategy is based on an intranasal (IN) administration of Sufentanil at the initial management of children with VOC, followed by morphine intravenous (IV) relay as soon as possible, compared to the usual care procedure with IV morphine as soon as possible. The hypothesis is that the use of this IN opioid at the beginning of the management of children with VOC can reduce the time before being pain relieved. Indeed, the IN administration make it easier and faster to administer.

Timeline

Start

2024-05-02

Primary completion

2026-05-30

Completion

2027-05-29

Publications

• Background Prise en charge de la drépanocytose chez l'enfant et l'adolescent. Haute Autorité de Santé. Accessed March 3, 2021. https://www.has-sante.fr/jcms/c_272479/fr/prise-en-charge-de-la-drepanocytose-chez-l-enfant-et-l-adolescent
• Background Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517.
• Background Gonzalez ER, Bahal N, Hansen LA, Ware D, Bull DS, Ornato JP, Lehman ME. Intermittent injection vs patient-controlled analgesia for sickle cell crisis pain. Comparison in patients in the emergency department. Arch Intern Med. 1991 Jul;151(7):1373-8.
• Background Dampier CD, Smith WR, Wager CG, Kim HY, Bell MC, Miller ST, Weiner DL, Minniti CP, Krishnamurti L, Ataga KI, Eckman JR, Hsu LL, McClish D, McKinlay SM, Molokie R, Osunkwo I, Smith-Whitley K, Telen MJ; Sickle Cell Disease Clinical Research Network (SCDCRN). IMPROVE trial: a randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies. Clin Trials. 2013 Apr;10(2):319-31. doi: 10.1177/1740774513475850.
• Background Treadwell MJ, Bell M, Leibovich SA, Barreda F, Marsh A, Gildengorin G, Morris CR. A Quality Improvement Initiative to Improve Emergency Department Care for Pediatric Patients with Sickle Cell Disease. J Clin Outcomes Manag. 2014 Feb;21(2):62-70.
• Background Shenoi R, Ma L, Syblik D, Yusuf S. Emergency department crowding and analgesic delay in pediatric sickle cell pain crises. Pediatr Emerg Care. 2011 Oct;27(10):911-7. doi: 10.1097/PEC.0b013e3182302871.
• Background Kavanagh PL, Sprinz PG, Wolfgang TL, Killius K, Champigny M, Sobota A, Dorfman D, Barry K, Miner R, Moses JM. Improving the Management of Vaso-Occlusive Episodes in the Pediatric Emergency Department. Pediatrics. 2015 Oct;136(4):e1016-25. doi: 10.1542/peds.2014-3470. Epub 2015 Sep 21.
• Background Brandow AM, Nimmer M, Simmons T, Charles Casper T, Cook LJ, Chumpitazi CE, Paul Scott J, Panepinto JA, Brousseau DC. Impact of emergency department care on outcomes of acute pain events in children with sickle cell disease. Am J Hematol. 2016 Dec;91(12):1175-1180. doi: 10.1002/ajh.24534. Epub 2016 Sep 3.
• Background Mathias MD, McCavit TL. Timing of opioid administration as a quality indicator for pain crises in sickle cell disease. Pediatrics. 2015 Mar;135(3):475-82. doi: 10.1542/peds.2014-2874. Epub 2015 Feb 9.
• Background Galeotti C, Courtois E, Carbajal R. How French paediatric emergency departments manage painful vaso-occlusive episodes in sickle cell disease patients. Acta Paediatr. 2014 Dec;103(12):e548-54. doi: 10.1111/apa.12773. Epub 2014 Oct 2.
• Background Corrigan M, Wilson SS, Hampton J. Safety and efficacy of intranasally administered medications in the emergency department and prehospital settings. Am J Health Syst Pharm. 2015 Sep 15;72(18):1544-54. doi: 10.2146/ajhp140630.
• Background Dale O. Intranasal administration of opioids/fentanyl - Physiological and pharmacological aspects. European Journal of Pain Supplements. 2010;4(3):187-190. doi:10.1016/j.eujps.2010.06.001
• Background Dale O, Hjortkjaer R, Kharasch ED. Nasal administration of opioids for pain management in adults. Acta Anaesthesiol Scand. 2002 Aug;46(7):759-70. doi: 10.1034/j.1399-6576.2002.460702.x.
• Background Wolfe TR, Braude DA. Intranasal medication delivery for children: a brief review and update. Pediatrics. 2010 Sep;126(3):532-7. doi: 10.1542/peds.2010-0616. Epub 2010 Aug 9.
• Background Helmers JH, Noorduin H, Van Peer A, Van Leeuwen L, Zuurmond WW. Comparison of intravenous and intranasal sufentanil absorption and sedation. Can J Anaesth. 1989 Sep;36(5):494-7. doi: 10.1007/BF03005373.
• Background Haynes G, Brahen NH, Hill HF. Plasma sufentanil concentration after intranasal administration to paediatric outpatients. Can J Anaesth. 1993 Mar;40(3):286. doi: 10.1007/BF03037044. No abstract available.
• Background Nielsen BN, Friis SM, Romsing J, Schmiegelow K, Anderson BJ, Ferreiros N, Labocha S, Henneberg SW. Intranasal sufentanil/ketamine analgesia in children. Paediatr Anaesth. 2014 Feb;24(2):170-80. doi: 10.1111/pan.12268. Epub 2013 Oct 1.
• Background Murphy A, O'Sullivan R, Wakai A, Grant TS, Barrett MJ, Cronin J, McCoy SC, Hom J, Kandamany N. Intranasal fentanyl for the management of acute pain in children. Cochrane Database Syst Rev. 2014 Oct 10;2014(10):CD009942. doi: 10.1002/14651858.CD009942.pub2.
• Background Lemoel F, Contenti J, Cibiera C, Rapp J, Occelli C, Levraut J. Intranasal sufentanil given in the emergency department triage zone for severe acute traumatic pain: a randomized double-blind controlled trial. Intern Emerg Med. 2019 Jun;14(4):571-579. doi: 10.1007/s11739-018-02014-y. Epub 2019 Jan 1.
• Background Setlur A, Friedland H. Treatment of pain with intranasal fentanyl in pediatric patients in an acute care setting: a systematic review. Pain Manag. 2018 Sep 1;8(5):341-352. doi: 10.2217/pmt-2018-0016. Epub 2018 Oct 3.
• Background Hronova K, Pokorna P, Posch L, Slanar O. Sufentanil and midazolam dosing and pharmacogenetic factors in pediatric analgosedation and withdrawal syndrome. Physiol Res. 2016 Dec 21;65(Suppl 4):S463-S472. doi: 10.33549/physiolres.933519.
• Background Bayrak F, Gunday I, Memis D, Turan A. A comparison of oral midazolam, oral tramadol, and intranasal sufentanil premedication in pediatric patients. J Opioid Manag. 2007 Mar-Apr;3(2):74-8. doi: 10.5055/jom.2007.0043.
• Background Crellin D, Ling RX, Babl FE. Does the standard intravenous solution of fentanyl (50 microg/mL) administered intranasally have analgesic efficacy? Emerg Med Australas. 2010 Feb;22(1):62-7. doi: 10.1111/j.1742-6723.2010.01257.x.
• Background Borland M, Jacobs I, King B, O'Brien D. A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in children in the emergency department. Ann Emerg Med. 2007 Mar;49(3):335-40. doi: 10.1016/j.annemergmed.2006.06.016. Epub 2006 Oct 25.
• Background Sin B, Jeffrey I, Halpern Z, Adebayo A, Wing T, Lee AS, Ruiz J, Persaud K, Davenport L, de Souza S, Williams M. Intranasal Sufentanil Versus Intravenous Morphine for Acute Pain in the Emergency Department: A Randomized Pilot Trial. J Emerg Med. 2019 Mar;56(3):301-307. doi: 10.1016/j.jemermed.2018.12.002. Epub 2019 Jan 9.
• Background Fantacci C, Fabrizio GC, Ferrara P, Franceschi F, Chiaretti A. Intranasal drug administration for procedural sedation in children admitted to pediatric Emergency Room. Eur Rev Med Pharmacol Sci. 2018 Jan;22(1):217-222. doi: 10.26355/eurrev_201801_14120.
• Background Chiaretti A, Barone G, Rigante D, Ruggiero A, Pierri F, Barbi E, Barone G, Riccardi R. Intranasal lidocaine and midazolam for procedural sedation in children. Arch Dis Child. 2011 Feb;96(2):160-3. doi: 10.1136/adc.2010.188433. Epub 2010 Oct 27.
• Background Inthavong K, Fung MC, Yang W, Tu J. Measurements of droplet size distribution and analysis of nasal spray atomization from different actuation pressure. J Aerosol Med Pulm Drug Deliv. 2015 Feb;28(1):59-67. doi: 10.1089/jamp.2013.1093. Epub 2014 Jun 10.
• Background Barrett MJ, Cronin J, Murphy A, McCoy S, Hayden J, an Fhaili S, Grant T, Wakai A, McMahon C, Walsh S, O'Sullivan R. Intranasal fentanyl versus intravenous morphine in the emergency department treatment of severe painful sickle cell crises in children: study protocol for a randomised controlled trial. Trials. 2012 May 30;13:74. doi: 10.1186/1745-6215-13-74.

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Indications