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Exogenous surfactant: intubated present, nebulized future?

World Journal of Pediatrics volume 7, pages 11–15 (2011)Cite this article

Abstract

Background

Exogenous surfactant is currently administered via intra-tracheal instillation, a method which can increase the possibility of clinical instability in the peri-surfactant administration period. Since its introduction, there has been an increase in understanding of the pathology of respiratory distress syndrome and surfactant biology. This includes development of a potential nebulized surfactant which has the potential to increase the number, safety and timely administration of the medication in preterm infants.

Data sources

Based on recent original publications in the field of surfactant biology, we reviewed our experience with surfactant administration and discussed the available evidence on nebulized surfactant and outlined potential barriers toward widespread introduction of this therapy.

Results

Surfactant has revolutionized modern neonatal management and nebulized surfactant is attractive and a vector for administration. However, issues regarding costeffectiveness, development of nebulizer devices capable of administration, deposition of medication in the airway and dosing strategies remain unresolved.

Conclusions

Nebulized surfactant has the potential to be a therapeutic breakthrough by eliminating the potent volu-and-baro-traumatic effects of mechanical ventilation in the peri-surfactant period. Nebulization would likely lead to increased administration immediately after birth and more emphasis on noninvasive ventilator strategies. These features will aid clinical implementation of nebulized surfactant as a standard of treatment after introduction.

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References

  1. Halliday HL. Recent clinical trials of surfactant treatment for neonates. Biol Neonate 2006;89:323–329.

    CAS  Article  PubMed  Google Scholar 

  2. Stevens TP, Sinkin RA. Surfactant replacement therapy. Chest 2007;131:1577–1582.

    Article  PubMed  Google Scholar 

  3. Morley CJ, Bangham AD, Miller N, Davis JA. Dry artificial lung surfactant and its effect on very premature babies. Lancet 1981;1:64–68.

    CAS  Article  PubMed  Google Scholar 

  4. Bangham AD. Lung surfactant: how it does and does not work. Lung 1987;165:17–25.

    CAS  Article  PubMed  Google Scholar 

  5. Hawgood S. Surfactant protein B: structure and function. Biol Neonate 2004;85:285–289.

    CAS  Article  PubMed  Google Scholar 

  6. Broussard D, Larson JE, Cohen JC, Lundblad LK. Developmental changes in respiratory mechanics in the neonatal rat. Exp Lung Res 2006;32:263–273.

    Article  PubMed  Google Scholar 

  7. Ramanathan R. Surfactants in the management of respiratory distress syndrome in extremely premature infants. J Pediatr Pharmacol Ther 2006;11:132–144.

    Google Scholar 

  8. Finer NN. Surfactant use for neonatal lung injury: beyond respiratory distress syndrome. Paediatr Respir Rev 2004;5Suppl A:S289–297.

    Article  PubMed  Google Scholar 

  9. Greenough A. Expanded use of surfactant replacement therapy. Eur J Pediatr 2000;159:635–640.

    CAS  Article  PubMed  Google Scholar 

  10. 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 2005;293:470–476.

    CAS  Article  PubMed  Google Scholar 

  11. Gregory TJ, Steinberg KP, Spragg R, Gadek JE, Hyers TM, Longmore WJ, et al. Bovine surfactant therapy for patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 1997;155:1309–1315.

    CAS  PubMed  Google Scholar 

  12. Auten RL, Notter RH, Kendig JW, Davis JM, Shapiro DL. Surfactant treatment of full-term newborns with respiratory failure. Pediatrics 1991;87:101–107.

    CAS  PubMed  Google Scholar 

  13. Chinese Collaborative Study Group for Neonatal Respiratory Diseases. Treatment of severe meconium aspiration syndrome with porcine surfactant: a multicentre, randomized, controlled trial. Acta Paediatr 2005;94:896–902.

    Article  Google Scholar 

  14. Soll RF, Dargaville P. Surfactant for meconium aspiration syndrome in full term infants. Cochrane Database Syst Rev 2000;(2):CD002054.

  15. Yost CC, Soll RF. Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2000;(2):CD001456.

  16. Soll RF, Blanco F. Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2001;(2):CD000144.

  17. Sinha S, Moya F, Donn SM. Surfactant for respiratory distress syndrome: are there important clinical differences among preparations? Curr Opin Pediatr 2007;19:150–154.

    Article  PubMed  Google Scholar 

  18. Ainsworth SB, Beresford MW, Milligan DW, Shaw NJ, Matthews JN, Fenton AC, et al. Pumactant and poractant alfa for treatment of respiratory distress syndrome in neonates born at 25–29 weeks’ gestation: a randomised trial. Lancet 2000; 355:1387–1392.

    CAS  Article  PubMed  Google Scholar 

  19. Merritt TA, Kheiter A, Cochrane CG. Positive end-expiratory pressure during KL4 surfactant instillation enhances intrapulmonary distribution in a simian model of respiratory distress syndrome. Pediatr Res 1995;38:211–217.

    CAS  Article  PubMed  Google Scholar 

  20. Thomson MA. Continuous positive airway pressure and surfactant; combined data from animal experiments and clinical trials. Biol Neonate 2002;81Suppl 1:16–19.

    CAS  Article  PubMed  Google Scholar 

  21. Hilgendorff A, Reiss I, Ruppert C, Hanfstingl T, Seliger AS, Gunther A, et al. Positive end-expiratory pressure modifies response to recombinant and natural exogenous surfactant in ventilated immature newborn rabbits. Biol Neonate 2006;90: 210–216.

    Article  PubMed  Google Scholar 

  22. Horbar JD, Carpenter JH, Buzas J, Soll RF, Suresh G, Bracken MB, et al. Timing of initial surfactant treatment for infants 23 to 29 weeks’ gestation: is routine practice evidence based? Pediatrics 2004;113:1593–602.

    Article  PubMed  Google Scholar 

  23. Finer NN, Rich W, Craft A, Henderson C. Comparison of methods of bag and mask ventilation for neonatal resuscitation. Resuscitation 2001;49:299–305.

    CAS  Article  PubMed  Google Scholar 

  24. American Academy of Pediatrics/American Heart Association. Use of Resuscitation Devices for Positive Pressure Ventilation in Textbook of Neonatal Resuscitation. In: Kattwinkel J, eds. Textbook of Neonatal Resuscitation, 5th ed. Elk Grove Village, 2006: 3-1–3-58.

  25. Marshall TA, Deeder R, Pai S, Berkowitz GP, Austin TL. Physiologic changes associated with endotracheal intubation in preterm infants. Crit Care Med 1984;12:501–503.

    CAS  Article  PubMed  Google Scholar 

  26. Lane B, Finer N, Rich W. Duration of intubation attempts during neonatal resuscitation. J Pediatr 2004;145:67–70.

    Article  PubMed  Google Scholar 

  27. Bradley JS, Billows GL, Olinger ML, Boha SP, Cordell WH, Nelson DR. Prehospital oral endotracheal intubation by rural basic emergency medical technicians. Ann Emerg Med 1998; 32:26–32.

    CAS  Article  PubMed  Google Scholar 

  28. Falck AJ, Escobedo MB, Baillargeon JG, Villard LG, Gunkel JH. Proficiency of pediatric residents in performing neonatal endotracheal intubation. Pediatrics 2003;112:1242–1247.

    Article  PubMed  Google Scholar 

  29. Leone TA, Rich W, Finer NN. Neonatal intubation: success of pediatric trainees. J Pediatr 2005;146:638–641.

    Article  PubMed  Google Scholar 

  30. Geller D. The science of aerosol delivery in cystic fibrosis. Pediatr Pulmonol 2008;43:S5–S17.

    Article  Google Scholar 

  31. Zanen P, Laube BL. Targeting the Lungs with Theraputic Aerosols. In: Bisgaard H, O’Callaghan CO, Smaldone GC, eds. Drug Delivery to the Lung. New York: NY Marcel Dekker Inc, 2002: 211–225.

    Google Scholar 

  32. Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol 2003;56:588–599.

    CAS  Article  PubMed  Google Scholar 

  33. Laube BL, Jashnani R, Dalby RN, Zeitlin PL. Targeting aerosol deposition in patients with cystic fibrosis: effects of alterations in particle size and inspiratory flow rate. Chest 2000;118:1069–1076.

    CAS  Article  PubMed  Google Scholar 

  34. Stocks J, Hislop A. Structure and function of the respiratory system. Developmental aspects and their relevance to aerosol therapy. In: Bisgaard H, O’Callaghan C, Smaldone G, eds. Drug delivery to the lung. New York: Marcel Dekker, 2002: 47–104.

    Google Scholar 

  35. Mazela J, Merritt TA, Finer NN. Aerosolized surfactants. Curr Opin Pediatr 2007;19:155–162.

    Article  PubMed  Google Scholar 

  36. Jorch G, Hartl H, Roth B, Kribs A, Gortner L, Schaible T, et al. Surfactant aerosol treatment of respiratory distress syndrome in spontaneously breathing premature infants. Pediatr Pulmonol 1997;24:222–224.

    CAS  Article  PubMed  Google Scholar 

  37. Berggren E, Liljedahl M, Winbladh B, Andreasson B, Curstedt T, Robertson B, et al. Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome. Acta Paediatr 2000;89:460–464.

    CAS  Article  PubMed  Google Scholar 

  38. Finer NN, Merritt TA, Bernstein G, Job L, Mazela J, Liu G. A multicenter pilot study of Aerosurf™ delivered via nasal continuous positive airway pressure (nCPAP) to prevent respiratory distress syndrome in preterm neonates. Pediatr Res 2006;59:PAS2006:4840.138

    Google Scholar 

  39. Arroe M, Pedersen-Bjergaard L, Albertsen P, Bode S, Greisen G. Inhalation of aerosolized surfactant (Exosurf) to neonates treated with continuous positive airway pressure. Prenat Neonat Med 1998;3:346–352.

    Google Scholar 

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Affiliations

  1. State University of New York at Stony Brook, Stony Brook, New York, 11791, USA

    Shetal Shah

  2. Department of Pediatrics, Division of Neonatology, State University of New York at Stony Brook, Health Science Center tower 11th Floor 060, Stony Brook, New York, 11791, USA

    Shetal Shah

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Correspondence to Shetal Shah.

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Shah, S. Exogenous surfactant: intubated present, nebulized future?. World J Pediatr 7, 11–15 (2011). https://doi.org/10.1007/s12519-010-0201-4

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  • DOI: https://doi.org/10.1007/s12519-010-0201-4

Key words

  • nebulization
  • neonatal respiratory disease
  • surfactant