Safety of pulmonary surfactant therapy in acute respiratory distress syndrome in children
Keywords:
Acute respiratory distress syndrome, children, lung surfactant, adverse events.Abstract
Introduction: Pulmonary surfactants, together with other therapeutic measures, constitute a treatment of choice for various respiratory conditions.
Objective: To demonstrate the safety of the treatment with Surfacen® in acute respiratory distress syndrome in children.
Material and Methods: A multicenter, open, controlled, randomized Phase III clinical trial with two treatment groups. Group A received conventional oxygen therapy and mechanical ventilation combined with Surfacen® at a dosage of 100 mg every eight hours for three days. Group B received conventional treatment. Children 28 days of life to 18 years of age, of either sex, with the diagnosis of acute respiratory distress syndrome were included. The occurrence of adverse events, intensity, attitude followed after the appearance, outcome, and relationship between causality and mortality at day 28 were identified and quantified.
Results: A total of 42 children were included: twenty children in group A and twenty-two ones in group B. In group A, 23 adverse events were reported in nine patients, while 97 adverse events were reported in 18 patients from group B. Hypertension was the most frequent adverse event. In group A, 73.9 % of adverse events of severe intensity were reported, 86.9 % remained unchanged after the administration of the drug, and 73.9 % had a remote causality with respect to the surfactant. Mortality at day 28 was 41.5 %; 20 % in group A, and 62 % in group B.
Conclusions: Surfacen® was safe and well tolerated since a small number of adverse events related to its administration were reported.Downloads
References
1. Castro Pastrana L. Farmacovigilancia, tecnovigilancia y hemovigilancia: tareas obligatorias durante la pandemia. Entorno Especial 2020 UDLAP [Internet]. México: Universidad de las Américas Puebla; 2020 [Citado 2021/04/25]. Dosponible en: https://issuu.com/webudlap/docs/farmacovigilancia-tecnovigilancia-hemovigilancia-e
2. Rodríguez Moya VS, Barrese PY, Iglesias AN, Díaz Casañas E. Síndrome de dificultad respiratoria aguda en niños. Medisur [Internet]. 2018 [Citado 2021/03/21];17(1):126-35. Disponible en: http://www.medisur.sld.cu/index.php/medisur/article/view/3601
3. López AC, Alfonso DA, Durán MR, Villegas DC. Uso de Surfacen en recién nacidos con dificultad respiratoria. Rev Cubana Pediatr. 2015;87(3):295-307.
4. Barrese Pérez Y, Hidalgo Sánchez AO, Ávila Albuerne Y, Uranga Piña R, Díaz Casañas E, Fernández Limia O. Surfactante pulmonar exógeno en adultos con síndrome de dificultad respiratoria aguda. Neumol Cir Torax [Internet]. 2015 [Citado 2021/07/09];74(3):172-8. Disponible en: http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0028-37462015000300002&lng=es
5. Rodríguez Moya VS, Machado Lubián MC, Barrese Pérez Y, Ávila Albuerne Y, Uranga Piña R, Blanco Hidalgo O, et al. Cuban Exogenous Pulmonary Surfactant in Treatment of Pediatric Acute Respiratory Distress Syndrome. MEDICC. 2017;19(2-3):24-31. Disponible en: https://doi.org/10.37757/MR2017.V19.N2-3.5
6. Barrese Pérez Y, Hidalgo Sánchez Á, Ávila Albuerne Y, Uranga Piña R, Díaz Casañas E, Fernández Limia O. Seguridad del tratamiento con surfactante pulmonar en el síndrome de dificultad respiratoria aguda en adultos. Arch Méd Camagüey [Internet].2015 [Citado 2021/07/09];19(6):[Aprox. 2 p.]. Disponible en: http://revistaamc.sld.cu/index.php/amc/article/view/3798
7. Morilla Guzmán A, Díaz Casañas E, Ávila Albuerne Y, Barrese Pérez Y, Fernández Limia O, Uranga Piña R. Seguridad del tratamiento con Surfacen® en recién nacidos pretérminos con síndrome de dificultad respiratoria. Rev Cubana Pediatr. [Internet] 2019 [Citado 2021/07/09];91(2):[Aprox. 2 p.]. Disponible en: http://revpediatria.sld.cu/index.php/ped/article/view/700
8. Barrese Pérez Y, Lim Alonso N, Díaz Casañas E, Uranga Piña R, Ávila Albuerne Y. Evaluación de la seguridad del uso poscomercial del surfactante cubano, SURFACEN®, en el tratamiento del síndrome de dificultad respiratoria aguda del adulto. Neumol Cir Torax [Internet]. 2019 [Citado 2021/07/09];78(3):296-303. Disponible en: http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0028-37462019000300296&lng=es
9. Centro para el Control Estatal de los Medicamentos, Equipos y Dispositivos Médicos. Regulación No. 45-2007. Requerimientos para la notificación y el reporte de eventos adversos graves e inesperados en los ensayos clínicos [Internet]. La habana: Ministerio de Salud Pública; 2007[Citado 2021/07/09]. Disponible en: http://www.cecmed.cu/sites/default/files/adjuntos/Reglamentacion/reg_45-7_requerimientos_para_la_notificación_y_el_reporte_de_eventos_ adversos_graves_e_inesperados_en_los_ensayos_clínicos_0.pdf
10. Centro para el Control Estatal de los Medicamentos, Equipos y Dispositivos Médicos. Ministerio de Salud Pública de Cuba. Directrices sobre Buenas Prácticas Clínicas en Cuba. La Habana: ECIMED; 2000. Disponible en: http://www.cecmed.cu/sites/default/files/adjuntos/Reglamentacion/Dir_BPC.pdf
11. Asociación Médica Mundial. Declaración de Helsinki. Principios éticos para las investigaciones médicas en seres humanos [Internet]. París: Asociación Médica Mundial; 2020 [Citado 2021/07/09]. Disponible en: http://www.wma.net/es/30publications/10policies/b3/
12. Organización de las Naciones Unidas para la Educación, la Ciencia y la Cultura. Declaración Universal sobre Bioética y Derechos humanos [Internet]. París: Organización de las Naciones Unidas para la Educación, la Ciencia y la Cultura; 2020 [Citado 2021/07/09]. Disponible en: https://www.sergas.es/Asistencia-sanitaria/Documents/599/146180S.pdf
13. Zhang LN, Sun JP, Xue XY, Wang JX. Exogenous pulmonary surfactant for acute respiratory distress syndrome in adults: A systematic review and meta-analysis. Exp Ther Med [Internet]. 2013;5(1):237-42. Disponible en: http://doi.org/10.3892/etm.2012.746
14. Shah S. Exogenous surfactant: intubated present, nebulized future?. World J Pediatr [Internet]. 2011 [Citado 2021/03/18];7(1):11-5. Disponible en: http://wjpch.com/article.asp?article_id=428
15. Willson DF, Thomas NJ, Markovitz BP, Bauman LA, DiCarlo JV, Pon S, et al. Effect of exogenous surfactant (Calfactant) in pediatric acute lung injury: a randomized controlled trial. JAMA [Internet]. 2005 [Citado 2021/04/18/];293(4):470-6. Disponible en: http://jama.jamanetwork.com/article.aspx?articleid=200218&resultclick=1
16. Raghavendran K, Willson D, Notter RH. Surfactant Therapy of ALI and ARDS. Critical Care Clin [Internet]. 2011 [Citado 2021/04/20];27(3):525-59. Disponible en: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153076/
17. Cheifetz IM. Pediatric ARDS. Respiratory Care [Internet]. 2017 [Citado 2021/03/24];62(6):718-31. Disponible en: https://doi.org/10.4187/respcare.05591
18. Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome Advances in Diagnosis and Treatment. JAMA [Internet]. 2018 [Citado 21/3/2021];319(7):698-710. Disponible en: https://doi.org/10.1001/jama.2017.21907
19. Wilson DF, Chess PR, Notter RH. Surfactant for pediatric acute lung injury. Pediatr Clin North Am [Internet]. 2008 [Citado 2021/04/21];55(3):545-75. Disponible en: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275446/
20. Kesecioglu J, Beale R, Stwart TE, Findlay GP, Rouby JJ, Holzapfel L, et al. Exogenus natural surfactant for treatment of acute lung injury and the acute respiratory distress syndrome. Am J Resp Critical Care Med [Internet]. 2009 [Citado 22/4/2021];180:989-94. Disponible en: http://www.atsjournals.org/doi/full/10.1164/rccm.200812-1955OC
21. Willson DF, Thomas NJ. Surfactant composition and biophysical properties are important in clinical studies. Am J Resp Critical Care Med [Internet]. 2010 [Citado 24/4/2021];181(7):762. Disponible en: http://www.atsjournals.org/doi/pdf/10.1164/ajrccm.181.7.762a
22. Silva BF, Oliveira RC, Freitas CT, Pereira da Silva AN, Farias SA, Balthar BA, et al. Exogenous surfactant prevents hyperoxiainduced lung injury in adult mice. Intensive Care Med Exp [Internet]. 2019;7(19):1-12 Disponible en: https://doi.org/10.1186/s40635-019-0233-6
23. Williams GW, Berg NK, Reskallah A, Yuan X, Eltzschig HK. Acute Respiratory Distress Syndrome Contemporary Management and Novel Approaches during COVID-19. Clin Focus Review. 2021;134(2):270-82.
24. Fernando SM, Ferreyro BL, Urner M, Munshi L, Fan E. Diagnosis and management of acute respiratory distress syndrome. Canadian Medical Association J [Internet]. 2021;193(21):E761-E768. Disponible en: https://doi.org/10.1503/cmaj.202661
25. Eugene H, Shah V. Guidelines for surfactant replacement therapy in neonates. Paediatr Child Health [Internet]. 2021 [Citado 21/4/2021];26(1):35-41. Disponible en: https://doi.org/ 10.1093/pch/pxaa116
26. Hernandis CR. Tratamiento del paciente crítico con síndrome de distrés respiratorio agudo. Revista Sanitaria de Investigación. 2021;2(2):42-6.
27. Marsegliaa L, D'Angeloa G, Granese R, Falsaperlac R, Reiterd R, Corselloe G, et al. Role of oxidative stress in neonatal respiratory distress syndrome. Free Radical Biology and Medicine [Internet]. 2019;142:132-7. Disponible en: https://doi.org/10.1016/j.freeradbiomed.2019.04.029
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