Pediatr Emerg Med J.  2023 Oct;10(4):109-117. 10.22470/pemj.2023.00745.

Intranasal drug delivery in pediatric emergency departments: brief review and future outlook

Affiliations
  • 1Department of General Surgery, Virginia Commonwealth University Health System, Richmond, VA, United States
  • 2Independent Researcher, Brooklyn, NY, United States
  • 3SUNY Downstate College of Medicine, Brooklyn, NY, United States
  • 4Department of Family Medicine, The Brooklyn Hospital Center, Brooklyn, NY, United States

Abstract

This review aims to provide an overview and update of current literature on the use of intranasal (IN) drug delivery in pediatric emergency medicine (PEM), in terms of the anatomy, physiology, pharmacokinetics, limitations, drug delivery methods, necessary training, safety, contraindications, effectiveness, current indications and trends, and implications for clinical practice and future developments in IN drug administration. We evaluate how IN medication use in PEM has recently evolved, what recent research has revealed about the utility of IN drug delivery in PEM, and what the future of IN drug delivery might look like.

Keyword

Administration, Intranasal; Analgesia; Conscious Sedation; Emergency Service, Hospital; Fentanyl

Reference

References

1. Pansini V, Curatola A, Gatto A, Lazzareschi I, Ruggiero A, Chiaretti A. Intranasal drugs for analgesia and sedation in children admitted to pediatric emergency department: a narrative review. Ann Transl Med. 2021; 9:189.
2. Poonai N, Canton K, Ali S, Hendrikx S, Shah A, Miller M, et al. Intranasal ketamine for procedural sedation and analgesia in children: a systematic review. PLoS One. 2017; 12:e0173253.
3. AlSarheed MA. Intranasal sedatives in pediatric dentistry. Saudi Med J. 2016; 37:948–956.
4. Ryan PM, Kienstra AJ, Cosgrove P, Vezzetti R, Wilkinson M. Safety and effectiveness of intranasal midazolam and fentanyl used in combination in the pediatric emergency department. Am J Emerg Med. 2019; 37:237–40.
5. Zhang G, McCrary MR, Wei L. Intranasal medication delivery in children for brain disorders. In: Chen J, Wang J, Wei L, Zhang J, editors. Therapeutic intranasal delivery for stroke and neurological disorders. Springer series in translational stroke research. Springer, Cham: 2019.
6. Djupesland PG, Messina JC, Mahmoud RA. The nasal approach to delivering treatment for brain diseases: an anatomic, physiologic, and delivery technology overview. Ther Deliv. 2014; 5:709–33.
7. Xi J, Si X, Zhou Y, Kim J, Berlinski A. Growth of nasal and laryngeal airways in children: implications in breathing and inhaled aerosol dynamics. Respir Care. 2014; 59:263–73.
8. Antunes JL, Amado J, Veiga F, Paiva-Santos AC, Pires PC. Nanosystems, Drug Molecule functionalization and intranasal delivery: an update on the most promising strategies for increasing the therapeutic efficacy of antidepressant and anxiolytic drugs. Pharmaceutics. 2023; 15:998.
9. Crowe TP, Hsu WH. Evaluation of recent intranasal drug delivery systems to the central nervous system. Pharmaceutics. 2022; 14:629.
10. Helwany M, Bordoni B. Neuroanatomy, cranial nerve 1 (olfactory) [Updated 2022 Aug 8]. In: StatPearls [Internet]. StatPearls Publishing; 2022 [cited 2023 Apr 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK556051/.
11. Chapman CD, Frey WH 2nd, Craft S, Danielyan L, Hallschmid M, Schio¨th HB, et al. Intranasal treatment of central nervous system dysfunction in humans. Pharm Res. 2013; 30:2475–84.
12. Keller LA, Merkel O, Popp A. Intranasal drug delivery: opportunities and toxicologic challenges during drug development. Drug Deliv Transl Res. 2022; 12:735–57.
13. Bruinsmann FA, Richter Vaz G, de Cristo Soares Alves A, Aguirre T, Raffin Pohlmann A, Stanisc¸uaski Guterres S, et al. Nasal drug delivery of anticancer drugs for the treatment of glioblastoma: preclinical and clinical trials. Molecules. 2019; 24:4312.
14. Wang J, Shi Y, Yu S, Wang Y, Meng Q, Liang G, et al. Intranasal administration of dantrolene increased brain concentration and duration. PLoS One. 2020; 15:e0229156.
15. Wolfe TR, Braude DA. Intranasal medication delivery for children: a brief review and update. Pediatrics. 2010; 126:532–7.
16. Rees CA, Brousseau DC, Ahmad FA, Bennett J, Bhatt S, Bogie A, et al. Intranasal fentanyl and discharge from the emergency department among children with sickle cell disease and vaso-occlusive pain: a multicenter pediatric emergency medicine perspective. Am J Hematol. 2023; 98:620–7.
17. Monzani A, Savastio S, Manzo A, Scalogna A, Pozzi E, Sainaghi PP, et al. Not only for caregivers: intranasal glucagon for severe hypoglycaemia in a simulation study. Acta Diabetol. 2022; 59:1479–84.
18. Settles JA, Gerety GF, Spaepen E, Suico JG, Child CJ. Nasal glucagon delivery is more successful than injectable delivery: a simulated severe hypoglycemia rescue. Endocr Pract. 2020; 26:407–15.
19. Choudhary D, Dhillon R, Chadha K, Cross K, Carnevale FP. National survey to describe the current patterns of procedural sedation practices among pediatric emergency medicine practitioners in the United States. Pediatr Emerg Care. 2022; 38:e321–8.
20. Oliveira J E Silva L, Lee JY, Bellolio F, Homme JL, Anderson JL. Intranasal ketamine for acute pain management in children: a systematic review and meta-analysis. Am J Emerg Med. 2020; 38:1860–6.
21. Chang JG, Regen RB, Peravali R, Harlan SS, Smeltzer MP, Kink RJ. Intranasal fentanyl and midazolam use in children 3 years of age and younger in the emergency department. J Emerg Med. 2021; 61:731–9.
22. Graudins A, Meek R, Egerton-Warburton D, Oakley E, Seith R. The PICHFORK (Pain in Children Fentanyl or Ketamine) trial: a randomized controlled trial comparing intranasal ketamine and fentanyl for the relief of moderate to severe pain in children with limb injuries. Ann Emerg Med. 2015; 65:248–254.e1.
23. Kendall J, Maconochie I, Wong IC, Howard R; DIASAFE study. A novel multipatient intranasal diamorphine spray for use in acute pain in children: pharmacovigilance data from an observational study. Emerg Med J. 2015; 32:269–73.
24. Abebe Y, Hetmann F, Sumera K, Holland M, Staff T. The effectiveness and safety of paediatric prehospital pain management: a systematic review. Scand J Trauma Resusc Emerg Med. 2021; 29:170.
25. Bauman BH, McManus JG Jr. Pediatric pain management in the emergency department. Emerg Med Clin North Am. 2005; 23:393–ix.
26. U.S. Food & Drug Administration (FDA). FDA alerts health care professionals of potential risks associated with compounded ketamine nasal spray [Internet]. U.S. FDA; 2022 [cited 2023 May 1]. Available from: https://www.fda.gov/drugs/humandrug-compounding/fda-alerts-health-care-professionals-potential-risks-associated-compounded-ketamine-nasal-spray.
27. Swisher AR, Kshirsagar RS, Adappa ND, Liang J. Dupilumab adverse events in nasal polyp treatment: analysis of FDA adverse event reporting system. Laryngoscope. 2022; 132:2307–13.
28. Ahsanuddin S, Povolotskiy R, Tayyab R, Nasser W, Barinsky GL, Grube JG, et al. Adverse events associated with intranasal sprays: an analysis of the Food and Drug Administration database and literature review. Ann Otol Rhinol Laryngol. 2021; 130:1292–301.
29. Gondek S, Schroeder ME, Sarani B. Assessment and resuscitation in trauma management. Surg Clin North Am. 2017; 97:985–98.
30. Bouida W, Bel Haj Ali K, Ben Soltane H, Msolli MA, Boubaker H, Sekma A, et al. Effect on opioids requirement of early administration of intranasal ketamine for acute traumatic pain. Clin J Pain. 2020; 36:458–62.
31. Erdo´´ F, Bors LA, Farkas D, Gizurarson S. Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res Bull. 2018; 143:155–170.
32. Kendall JM, Reeves BC, Latter VS; Nasal Diamorphine Trial Group. Multicentre randomised controlled trial of nasal diamorphine for analgesia in children and teenagers with clinical fractures. BMJ. 2001; 322:261–5.
33. Chafe R, Harnum D, Porter R. Improving the treatment and assessment of moderate and severe pain in a pediatric emergency department. Pain Res Manag. 2016; 2016:4250109.
34. Ruest S, Anderson A. Management of acute pediatric pain in the emergency department. Curr Opin Pediatr. 2016; 28:298–304.
35. Nemeth M, Jacobsen N, Bantel C, Fieler M, Su¨mpelmann R, Eich C. Intranasal analgesia and sedation in pediatric emergency care-a prospective observational study on the implementation of an institutional protocol in a tertiary children’s hospital. Pediatr Emerg Care. 2019; 35:89–95.
36. Lane RD, Schunk JE. Atomized intranasal midazolam use for minor procedures in the pediatric emergency department. Pediatr Emerg Care. 2008; 24:300–3.
37. Sado-Filho J, Viana KA, Correˆa-Faria P, Costa LR, Costa PS. Randomized clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation. PLoS One. 2019; 14:e0213074.
38. Alp H, Elmacı AM, Alp EK, Say B. Comparison of intranasal midazolam, intranasal ketamine, and oral chloral hydrate for conscious sedation during paediatric echocardiography: results of a prospective randomised study. Cardiol Young. 2019; 29:1189–1195.
39. Li A, Yuen VM, Goulay-Dufay¨ S, Sheng Y, Standing JF, Kwok PCL, et al. Pharmacokinetic and pharmacodynamic study of intranasal and intravenous dexmedetomidine. Br J Anaesth. 2018; 120:960–8.
40. Borland ML, Clark LJ, Esson A. Comparative review of the clinical use of intranasal fentanyl versus morphine in a paediatric emergency. Emerg Med Australas. 2008; 20:515–20.
41. Hadley G, Maconochie I, Jackson A. A survey of intranasal medication use in the paediatric emergency setting in England and Wales. Emerg Med J. 2010; 27:553–4.
42. Fowler M, Ali S, Gouin S, Drendel AL, Poonai N, Yaskina M, et al. Knowledge, attitudes and practices of Canadian pediatric emergency physicians regarding short-term opioid use: a descriptive, cross-sectional survey. CMAJ Open. 2020; 8:E148–55.
43. Waseem M, Asad H, Shariff MA, Epstein E, Umar Y, Leber M. Parent and physician preference for anxiolytic medication prior to laceration repair in young children. Cureus. 2022; 14:e32412.
44. Lorente S, Romero A, Mart´lnez M, Mart´lnez-Mej´las A. Effectiveness of procedural sedation and analgesia in pediatric emergencies. A cross-sectional study. J Emerg Nurs. 2023; 49:75–85.
45. Rassy D, Ba´ rcena B, Pe´rez-Osorio IN, Espinosa A, Peo´n AN, Terrazas LI, et al. Intranasal methylprednisolone effectively reduces neuroinflammation in mice with experimental autoimmune encephalitis. J Neuropathol Exp Neurol. 2020; 79:226–37.
46. Hayes SH, Liu Q, Selvakumaran S, Haney MJ, Batrakova EV, Allman BL, et al. Brain targeting and toxicological assessment of the extracellular vesicle-packaged antioxidant catalase-SKL following intranasal administration in mice. Neurotox Res. 2021; 39:1418–29.
47. Yang Y, Zhang X, Wu S, Zhang R, Zhou B, Zhang X, et al. Enhanced nose-to-brain delivery of siRNA using hyaluronan-enveloped nanomicelles for glioma therapy. J Control Release. 2022; 342:66–80.
48. Touitou E, Duchi S, Natsheh H. A new nanovesicular system for nasal drug administration. Int J Pharm. 2020; 580:119243.
49. Hetrick SE, McKenzie JE, Bailey AP, Sharma V, Moller CI, Badcock PB, et al. New generation antidepressants for depression in children and adolescents: a network meta-analysis. Cochrane Database Syst Rev. 2021; 5:CD013674.
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