Neonatology pp 522-528 | Cite as

Lung Diseases: Surfactant Replacement Therapy

  • Henry L. Halliday


In the past 3 decades introduction of prenatal steroid treatment, postnatal surfactant therapy and assisted ventilation have lead directly to improved neonatal outcomes [1]. Improved survival is directly related to more effective prevention or treatment of respiratory distress syndrome (RDS), which prior to the 1990s had a high mortality. Following unsuccessful clinical trials with nebulized synthetic surfactants, comprised of phospholipids without surfactant proteins, in the 1960s [2] a number of randomized controlled trials in the 1980s demonstrated benefits of surfactants instilled directly into the lungs of preterm infants [3, 4, 5]. These surfactants were of 2 main types: natural (derived from animal lungs or human amniotic fluid) [3] containing surfactant proteins-B and C (SP-B and SP-C) and synthetic [4, 5] (containing phospholipids and other agents to facilitate spreading and adsorption). Both types of surfactant given, either prophylactically (in the delivery room within 15 minutes of birth) [3, 4] or for treatment of RDS [5], increased neonatal survival and reduced pulmonary air leaks such as pneumothoraces and pulmonary interstitial emphysema.


Preterm Infant Respiratory Distress Syndrome Surfactant Therapy Natural Surfactant Surfactant Treatment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Sweet DG, Halliday HL (2009) The use of surfactants in 2009. Arch Dis Child Educ Pract Ed 94: 78–83PubMedCrossRefGoogle Scholar
  2. 2.
    Halliday HL (2008) Surfactants: past, present and future. J Perinatol 28: S47–S56PubMedCrossRefGoogle Scholar
  3. 3.
    Soll RF (2000) Prophylactic natural surfactant extract for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2:CD000511Google Scholar
  4. 4.
    Soll RF (2000) Prophylactic synthetic surfactant for preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2:CD001079Google Scholar
  5. 5.
    Soll RF (2000) Synthetic surfactant for respiratory distress syndrome in preterm infants. Cochrane Database Syst Rev 2: CD001149PubMedGoogle Scholar
  6. 6.
    Sweet DG, Carnielli V, Greisen G et al (2007) European consensus guidelines on the management of neonatal respiratory distress syndrome in preterm infants - 2010 update. Neonatology 97: 402–417CrossRefGoogle Scholar
  7. 7.
    Engle WA, American Academy of Pediatrics Committee on Fetus and Newborn (2008) Surfactant-replacement therapy for respiratory distress syndrome in the preterm and term neonate. Pediatrics 121: 419–432Google Scholar
  8. 8.
    Fetus and Newborn Committee, Canadian Paediatric Society (2005) Recommendations for neonatal surfactant therapy. J Paediatr Child Health 10: 109–116Google Scholar
  9. 9.
    Working Group of the British Association of Perinatal Medicine (1998) Guidelines for good practice in management of neonatal respiratory distress syndrome. publications/rds.pdf (accessed on 12 January 2011)Google Scholar
  10. 10.
    Avery ME, Mead J (1959) Surface properties in relation to atelectasis and hyaline membrane disease. Am J Dis Child 97: 517–523Google Scholar
  11. 11.
    Halliday HL (2003) Respiratory distress syndrome. In: Greenough A, Milner AD (eds) Neonatal respiratory disorders, 2 edn. Arnold, London, pp 247–271Google Scholar
  12. 12.
    Soll RF, Blanco F (2001) Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2:CD000144PubMedGoogle Scholar
  13. 13.
    Soll RF, Morley CJ (2001) Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants. Cochrane Database Syst Rev 2:CD000510Google Scholar
  14. 14.
    Jobe AH, Michell BR, Gunkel JH (1993) Beneficial effects of the combined use of prenatal corticosteroids and postnatal surfactant on preterm infants. Am J Obstet Gynecol 168: 508–513PubMedGoogle Scholar
  15. 15.
    Yost CC, Soll RF (2000) Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2:CD001456PubMedGoogle Scholar
  16. 16.
    Egberts J, Brand R, Walti H et al (1997) Mortality, severe respiratory distress syndrome, and chronic lung disease of the newborn are reduced more after prophylactic than after therapeutic administration of surfactant. Pediatrics 100: e4Google Scholar
  17. 17.
    Walti H, Paris-Llado J, Egberts J et al (2002) Prophylactic administration of porcine-derived lung surfactant is a significant factor in reducing the odds for peri-intraventricular haemorrhage in premature infants. Biol Neonate 81: 182–187PubMedCrossRefGoogle Scholar
  18. 18.
    Kendig JW, Ryan RM, Sinkin RA et al (1998) Comparison of two strategies for surfactant prophylaxis in very premature infants: a multicenter randomized trial. Pediatrics 101: 1006–1012PubMedCrossRefGoogle Scholar
  19. 19.
    Kattwinkel J, Bloom BT, Delmore P et al (1993) Prophylactic administration of calf lung surfactant is more effective than early treatment of respiratory distress syndrome in neonates of 29 through 32 weeks’ gestation. Pediatrics 92: 90–98PubMedGoogle Scholar
  20. 20.
    Morley CJ (1991) Surfactant treatment of premature babies: a review of clinical trials. Arch Dis Child 66: 445–450PubMedCrossRefGoogle Scholar
  21. 21.
    Halliday HL, Robertson B (1994) Surfactant replacement. In: Hanson MA, Spencer JAD, Rodeck CH, Walters D (eds) Fetus and Neonate: Physiology and Clinical Applications, Vol 2, Breathing. Cambridge University Press, Cambridge, pp 265–302Google Scholar
  22. 22.
    Konishi M, Fujiwara T, Naito T et al (1988) Surfactant replacement therapy in neonatal respiratory distress syndrome. A multicenter randomised clinical trial: comparison of high versus low-dose of Surfactant TA. Eur J Pediatr 147: 20–25PubMedCrossRefGoogle Scholar
  23. 23.
    Gortner L, Pohlandt F, Bartmann P et al (1994) High-dose versus low-dose bovine surfactant treatment in very premature infants. Acta Paediatr 83: 135–141PubMedCrossRefGoogle Scholar
  24. 24.
    Halliday HL, Tarnow-Mordi WO, Corcoran JD et al (1993) Multicentre randomised trial comparing high and low dose surfactant regimens for the treatment of respiratory distress syndrome (the Curosurf 4 trial). Arch Dis Child 69: 276–280PubMedCrossRefGoogle Scholar
  25. 25.
    Ramanathan R, Rasmussen MR, Gerstmann DR et al (2004) A randomised, multicenter masked comparison trial of poractant alfa (Curosurf) versus beractant ( Survanta) in the treatment of respiratory distress syndrome in preterm infants. Am J Perinatol 21: 109–119Google Scholar
  26. 26.
    Hallman M (1989) Recycling of surfactant: a review of human amniotic fluid as a source of surfactant for treatment of respiratory distress syndrome. Rev Perinat Med 6: 197–226Google Scholar
  27. 27.
    Ueda T, Ikegami M, Rider ED et al (1994) Distribution of surfactant and ventilation in surfactant-treated preterm lambs. J Appl Physiol 76: 45–55PubMedGoogle Scholar
  28. 28.
    Zola EM, Gunkel JH, Chan RK et al (1993) Comparison of three dosing procedures for administration of bovine surfactant to neonates with respiratory distress syndrome. J Pediatr 122: 453–459PubMedCrossRefGoogle Scholar
  29. 29.
    Valls-i-Soler A, Fernandez-Ruanova B, Lopez-Heredia J et al (1998) A randomised comparison of surfactant dosing via a dual-lumen endotracheal tube in respiratory distress syndrome. Pediatrics 101: E4PubMedCrossRefGoogle Scholar
  30. 30.
    Vento M, Cheung P-Y, Aguar M (2009) The first golden minutes of the extremely-low-gestational-age neonate: a gentle approach. Neonatology 95: 286–298PubMedCrossRefGoogle Scholar
  31. 31.
    Bohlin K, Jonsson B, Gustafsson AS et al (2008) Continuous positive airway pressure and surfactant. Neonatology 93: 309–315PubMedCrossRefGoogle Scholar
  32. 32.
    Stevens TP, Harrington EW, Blennow M et al (2007) Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev 4:CD003063Google Scholar
  33. 33.
    Berggren P, Liljedahl M, Winbladh B et al (2000) Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome. Acta Paediatr 89: 460–464PubMedCrossRefGoogle Scholar
  34. 34.
    Kribs A, Vierzig A, Hunseler C et al (2008) Early surfactant in spontaneously breathing with nCPAP in ELBW infants–a single center four year experience. Acta Paediatr 97: 293–298PubMedCrossRefGoogle Scholar
  35. 35.
    Kattwinkel J, Robinson M, Bloom BT et al (2004) Technique for intrapartum administration of surfactant without requirement for an endotracheal tube. J Perinatol 24: 360–365PubMedCrossRefGoogle Scholar
  36. 36.
    Trevisanuto D, Grazzina N, Ferrasse P et al (2005) Laryngeal mask airway used as a delivery conduit for the administration of surfactant to preterm infants with respiratory distress syndrome. Biol Neonate 87: 217–220PubMedCrossRefGoogle Scholar
  37. 37.
    Dunn MS, Shennan AT, Possmayer F (1990) Single versus multiple- dose surfactant replacement therapy in neonates of 30 to 36 weeks’ gestation with respiratory distress syndrome. Pediatrics 86: 567–571Google Scholar
  38. 38.
    Speer CP, Robertson B, Curstedt T et al (1992) Randomized European multicenter trial of surfactant replacement therapy for severe neonatal respiratory distress syndrome: single versus multiple doses of Curosurf. Pediatrics 89: 13–20PubMedGoogle Scholar
  39. 39.
    Soll RF (1999) Multiple versus single dose natural surfactant extract for severe neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2:CD0000141Google Scholar
  40. 40.
    Kattwinkel J, Bloom BT, Delmore P et al (2000) High- versus lowthreshold surfactant retreatment for neonatal respiratory distress syndrome. Pediatrics 106: 282–288PubMedCrossRefGoogle Scholar
  41. 41.
    Halliday HL (2006) Recent clinical trials of surfactant treatment for neonates. Biol Neonate 89: 323–329PubMedCrossRefGoogle Scholar
  42. 42.
    Moya F, Gadzinowski J, Bancalari E et al (2005) A multicenter, randomized, masked, comparison trial of lucinactant, colfosceril palmitate, and beractant for the prevention of respiratory distress syndrome in very preterm infants. Pediatrics 115: 1018–1029PubMedCrossRefGoogle Scholar
  43. 43.
    Inha S, Lacaze-Masmoneil T, Valls-i-Soler A et al (2005) A randomized, controlled trial of lucinactant versus poractant alfa in very premature infants at high risk for respiratory distress syndrome. Pediatrics 115: 1030–1038CrossRefGoogle Scholar
  44. 44.
    Curstedt T, Johansson J (2006) New synthetic surfactants–how and when?. Biol Neonate 89: 336–339PubMedCrossRefGoogle Scholar
  45. 45.
    Bloom BT, Clark RH (2005) Comparison of Infasurf (calfactant) and Survanta (beractant) in the prevention and treatment of respiratory distress syndrome. Pediatrics 116: 392–399PubMedCrossRefGoogle Scholar
  46. 46.
    Halliday HL (2005) History of surfactant from 1980. Biol Neonate 87: 317–322PubMedCrossRefGoogle Scholar
  47. 47.
    Kattwinkel J (2005) Synthetic surfactants: the search goes on. Pediatrics 115: 1075–1076PubMedCrossRefGoogle Scholar
  48. 48.
    Pfister RH, Soll RF, Wiswell T (2007) Protein containing synthetic surfactant versus animal derived surfactant extract for the prevention and treatment of respiratory distress syndrome. Cochrane Database Syst Rev 4:CD006069Google Scholar
  49. 49.
    Stevens TP, Sinkin RA (2007) Surfactant replacement therapy. Chest 131: 1577–1582PubMedCrossRefGoogle Scholar
  50. 50.
    Ramanathan R (2009) Choosing a right surfactant for respiratory distress syndrome treatment. Neonatology 95: 1–5PubMedCrossRefGoogle Scholar
  51. 51.
    Roberts D, Dalziel S (2006) Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 3:CD004454PubMedGoogle Scholar
  52. 52.
    Jobe AH, Mitchell BR, Gunkel JH (1993) Beneficial effects of the combined use of prenatal corticosteroids and postnatal surfactant on preterm infants. Am J Obstet Gynecol 168: 508–513PubMedGoogle Scholar
  53. 53.
    Dani C, Bertini G, Pezzati M et al (2004) Early extubation and nasal continuous positive airway pressure after surfactant treatment for respiratory distress syndrome among preterm infants 30 weeks’ gestation. Pediatrics 113: e560–563PubMedCrossRefGoogle Scholar
  54. 54.
    Sandri F, Plavka R, Simeoni U et al (2008) The CURPAP study: an international randomized controlled trial to evaluate the efficacy of combining prophylactic surfactant and early nasal continuous positive airway pressure in very preterm infants. Neonatology 94: 60–62PubMedCrossRefGoogle Scholar
  55. 55.
    Verder H, Albertsen P, Ebbesen F et al (1999) Nasal continuous positive airway pressure and early surfactant therapy for respiratory distress syndrome in newborns of less than 30 weeks’ gestation. Pediatrics 103: e24Google Scholar
  56. 56.
    Morley CJ, Davis PG, Doyle LW et al (2008) Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 358: 700–708PubMedCrossRefGoogle Scholar
  57. 57.
    Schmidt B, Roberts R, Davis P et al (2006) Caffeine therapy for apnea of prematurity. N Engl J Med 354: 2112–2121PubMedCrossRefGoogle Scholar
  58. 58.
    Schmidt B, Roberts RS, Davis P et al (2007) Long-term effects of caffeine therapy for apnea of prematurity. N Engl J Med 357: 1893–1902PubMedCrossRefGoogle Scholar
  59. 59.
    El Shahed AI, Dargaville P, Ohlsson A et al (2007) Surfactant for meconium aspiration syndrome in full term/near term infants. Cochrane Database Syst Rev 3:CD002054Google Scholar
  60. 60.
    Dargaville PA, Copnell B, Tingay DG et al (2008) Refining the method of therapeutic lung lavage in meconium aspiration syndrome. Neonatology 94: 160–163PubMedCrossRefGoogle Scholar
  61. 61.
    Lotze A, Mitchell BR, Bulas DJ et al (1998) Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure. J Pediatr 132: 40–47PubMedCrossRefGoogle Scholar
  62. 62.
    Herting E, Gefeller O, Land M et al (2000) Surfactant treatment of neonates with respiratory failure and group B streptococcal infection. Pediatrics 106: 957–964PubMedCrossRefGoogle Scholar
  63. 63.
    Halliday HL, Speer CP (1995) Strategies for surfactant therapy in established neonatal respiratory distress syndrome. In: Robertson B, Taeusch HW (eds) Surfactant Therapy for Lung Disease. Marcell Dekker, New York, pp 443–459Google Scholar
  64. 64.
    Aziz A, Ohlsson A (2008) Surfactant for pulmonary hemorrhage in neonates. Cochrane Database Syst Rev 2:CD005254Google Scholar
  65. 65.
    Pandit PB, Dunn MS, Kelly EN et al (1995) Surfactant replacement in neonates with early chronic lung disease. Pediatrics 95: 851–854PubMedGoogle Scholar
  66. 66.
    Yeh TF, Lin HC, Chang CH et al (2008) Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: a pilot study. Pediatrics 121:e1310– e1318PubMedCrossRefGoogle Scholar
  67. 67.
    Finer NN (2004) Surfactant use for neonatal lung injury: beyond respiratory distress syndrome. Paediatr Respir Rev 5 (suppl A): S289–S297PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Henry L. Halliday
    • 1
    • 2
  1. 1.Regional Neonatal UnitRoyal Maternity HospitalBelfastNorthern Ireland
  2. 2.Department of Child HealthQueen’s University BelfastBelfastNorthern Ireland

Personalised recommendations