Pediatric Drugs

, Volume 4, Issue 8, pp 485–492 | Cite as

Lung Surfactants for Neonatal Respiratory Distress Syndrome

Animal-Derived or Synthetic Agents?
  • Gautham K. Suresh
  • Roger F. Soll
Current Opinion


Exogenous surfactant therapy is widely used in the management of neonatal respiratory distress syndrome. Two types of surfactants are available: synthetic surfactants, and those derived from animal sources (‘natural’ surfactants). Both of these surfactants have been shown to be effective. In this article, we review the evidence to compare the two types of surfactants in terms of their physical properties, physiologic effects, and clinical outcomes.

Natural surfactants have been shown to have advantages over synthetic surfactants in their physical properties and physiologic effects in animals, as well as in humans. A systematic review of 11 randomized clinical trials comparing natural and synthetic surfactants demonstrated that the use of natural surfactant preparations results in greater clinical benefits compared with synthetic surfactants. These benefits include a more rapid improvement in oxygenation and lung compliance after surfactant therapy, a decrease in the risk of mortality (typical relative risk 0.87; typical risk difference −0.02), and a decrease in the risk of pneumothorax (typical relative risk 0.63; typical risk difference −0.04). Although the use of natural surfactants results in a slightly increased risk of intraventricular hemorrhage (typical relative risk 1.09; typical risk difference 0.03), there is no increase in the risk of grade 3 or 4 intraventricular hemorrhage.

There are theoretical but unproven risks of natural surfactants, such as transmission of infectious agents, immunogenicity and impurities in composition. The use of natural surfactants is preferred in most situations. In addition, clinicians should determine the costs of different types of surfactants in their individual practice settings and use this information in decision-making.


DPPC Patent Ductus Arteriosus Intraventricular Hemorrhage Surfactant Protein Synthetic Surfactant 
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.



Dr Soll has acted as a paid consultant and invited speaker for several of the pharmaceutical companies that manufacture surfactant preparations (Abbott Laboratories, Ross Laboratories, Chiesi Pharmaceuticals, Dey Laboratories, Burroughs Wellcome). He is the principal investigator or co-principal investigator of two of the randomized controlled trials cited in this review.


  1. 1.
    Horbar JD, Wright EC, Onstad L. Decreasing mortality associated with the introduction of surfactant therapy: an observational study of neonates weighing 601 to 1300 grams at birth. The Members of the National Institute of Child Health and Human Development Neonatal Research Network. Pediatrics 1993; 92(2): 191–6PubMedGoogle Scholar
  2. 2.
    Schwartz RM, Luby AM, Scanlon JW, et al. Effect of surfactant on morbidity, mortality, and resource use in newborn infants weighing 500 to 1500g. N Engl J Med 1994; 330(21): 1476–80PubMedCrossRefGoogle Scholar
  3. 3.
    Soll RF. Surfactant treatment of the very preterm infant. Biol Neonate 1998; 74Suppl. 1: 35–42PubMedCrossRefGoogle Scholar
  4. 4.
    Soll RF. Synthetic surfactant for respiratory distress syndrome in preterm infants (Cochrane Review). In: The Cochrane Library. Issue 2. Oxford: Update Software, 2001Google Scholar
  5. 5.
    Soll RF. Prophylactic natural surfactant extract for preventing morbidity and mortality in preterm infants (Cochrane Review). In: The Cochrane Library. Issue 2. Oxford: Update Software, 2001Google Scholar
  6. 6.
    Soll RF. Prophylactic synthetic surfactant for preventing morbidity and mortality in preterm infants (Cochrane Review). In: The Cochrane Library. Issue 2. Oxford: Update Software, 2001Google Scholar
  7. 7.
    Wiseman LR, Bryson HM. Porcine-derived lung surfactant: a review of the therapeutic efficacy and clinical tolerability of a natural surfactant preparation (Curosurf) in neonatal respiratory distress syndrome [published erratum appears in Drugs 1995 Jan; 49 (1): 70]. Drugs 1994; 48(3): 386–403PubMedCrossRefGoogle Scholar
  8. 8.
    Kattwinkel J. Surfactant: evolving issues. Clin Perinatol 1998; 25(1): 17–32PubMedGoogle Scholar
  9. 9.
    Robertson B, Halliday HL. Principles of surfactant replacement. Biochim Biophys Acta 1998; 1408(2–3): 346–61PubMedGoogle Scholar
  10. 10.
    Hallman M, Merritt TA, Jarvenpaa AL, et al. Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomized prospective clinical trial. J Pediatr 1985; 106: 963–9PubMedCrossRefGoogle Scholar
  11. 11.
    Merritt TA, Hallman M, Berry C, et al. Randomized, placebo-controlled trial of human surfactant given at birth versus rescue administration in very low birth weight infants with lung immaturity. J Pediatr 1991; 118 (4 Pt 1): 581–94PubMedCrossRefGoogle Scholar
  12. 12.
    Cochrane CG, Revak SD, Merritt TA, et al. The efficacy and safety of KL4-surfactant in preterm infants with respiratory distress syndrome. Am J Respir Crit Care Med 1996; 153(1): 404–10PubMedGoogle Scholar
  13. 13.
    Cochrane CG, Revak SD, Merritt TA, et al. Bronchoalveolar lavage with KL4-surfactant in models of meconium aspiration syndrome. Pediatr Res 1998; 44(5): 705–15PubMedCrossRefGoogle Scholar
  14. 14.
    Hafner D, Germann PG. Additive effects of phosphodiesterase-4 inhibition on effects of rSP-C surfactant. Am J Respir Crit Care Med 2000; 161: 1495–500PubMedGoogle Scholar
  15. 15.
    Spragg RG, Smith RM, Harris K, et al. Effect of recombinant SP-C surfactant in a porcine lavage model of acute lung injury. J Appl Physiol 2000; 88: 674–81PubMedGoogle Scholar
  16. 16.
    Hall SB, Venkitaraman AR, Whitsett JA, et al. Importance of hydrophobic apoproteins as constituents of clinical exogenous surfactants. Am Rev Respir Dis 1992; 145: 24–30PubMedCrossRefGoogle Scholar
  17. 17.
    Halliday HL. Controversies: synthetic or natural surfactant: the case for natural surfactant. J Perinat Med 1996; 24(5): 417–26PubMedCrossRefGoogle Scholar
  18. 18.
    Corcoran JD, Berggren P, Sun B, et al. Comparison of surface properties and physiological effects of a synthetic and a natural surfactant in preterm rabbits. Arch Dis Child Fetal Neonatal Ed 1994; 71(3): F165–169PubMedCrossRefGoogle Scholar
  19. 19.
    Egan EA, Notter RH, Kwong MS, et al. Natural and artificial lung surfactant replacement therapy in premature lambs. J Appl Physiol 1983; 55(3): 875–83PubMedGoogle Scholar
  20. 20.
    Cummings JJ, Holm BA, Hudak BB, et al. A controlled clinical comparison of four different surfactant preparations in surfactant-deficient preterm lambs. Am Rev Respir Dis 1992; 145: 999–1004PubMedCrossRefGoogle Scholar
  21. 21.
    Halliday HL, Nilsson R, Robertson B, et al. Automated image analysis of the alveolar expansion pattern in immature rabbits treated with artificial or natural surfactant. Br J Exp Pathol 1987; 68: 727–32PubMedGoogle Scholar
  22. 22.
    Morley CJ, Robertson B, Lachmann B, et al. Artificial and natural surfactant: comparative study of the effect on premature rabbit lungs. Arch Dis Child 1980; 55: 758–65PubMedCrossRefGoogle Scholar
  23. 23.
    Bongrani S, Fornasier M, Papotti M, et al. Lung gas volumes and expiratory time constant in immature newborn rabbits treated with natural or synthetic surfactant or detergents. Biol Neonate 1994; 65: 406–15PubMedCrossRefGoogle Scholar
  24. 24.
    Tooley WH, Clements JA, Muramatsu K, et al. Lung function in prematurely delivered rabbits treated with a synthetic surfactant. Am Rev Respir Dis 1987; 136(3): 651–6PubMedCrossRefGoogle Scholar
  25. 25.
    Durand D, Clyman RI, Heymann MA. Effects of a protein-free, synthetic surfactant on survival and pulmonary function in preterm lambs. J Pediatr 1985; 107: 775–80PubMedCrossRefGoogle Scholar
  26. 26.
    Alvarado M, Hingre R, Hakason D, et al. Clinical trial of Survanta versus Exosurf in infants <1500g with respiratory distress syndrome [abstract]. Pediatr Res 1993; 33: 314AGoogle Scholar
  27. 27.
    Horbar JD, Wright LL, Soll RF, et al. A multicenter randomized trial comparing two surfactants for the treatment of neonatal respiratory distress syndrome. J Pediatr 1993; 123(5): 757–66PubMedCrossRefGoogle Scholar
  28. 28.
    Modanlou HD, Beharry K, Padilla G, et al. Comparative efficacy of Exosurf and Survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity. J Perinatol 1997; 17(6): 455–60PubMedGoogle Scholar
  29. 29.
    Pearlman SA, Leef KH, Stefano JL, et al. A randomized trial comparing Exosurf versus Survanta in the treatment of neonatal RDS [abstract]. Pediatr Res 1993; 33: 340AGoogle Scholar
  30. 30.
    Sehgal SS, Ewing CK, Richards T, et al. Modified bovine surfactant (Survanta) versus a protein-free surfactant (Exosurf) in the treatment of respiratory distress syndrome in preterm infants: apilot study. J Nat Med Assoc 1994; 86(1): 46–52Google Scholar
  31. 31.
    Rollins M, Jenkins J, Tubman R, et al. Comparison of clinical responses to natural and synthetic surfactants. J Perinat Med 1993; 21(5): 341–7PubMedCrossRefGoogle Scholar
  32. 32.
    Stenson BJ, Glover RM, Parry GJ, et al. Static respiratory compliance in the newborn (III): early changes after exogenous surfactant treatment. Arch Dis Child Fetal Neonatal Ed 1994; 70(1): F19–24PubMedCrossRefGoogle Scholar
  33. 33.
    Choukroun ML, Lianas B, Apere H, et al. Pulmonary mechanics in ventilated preterm infants with respiratory distress syndrome after exogenous surfactant administration: a comparison between two surfactant preparations. Pediatr Pulmonol 1994; 18(5): 273–8PubMedCrossRefGoogle Scholar
  34. 34.
    Bassiouny MR, Remo C, Cherian E. Comparison of the changes in the a/A oxygen ratio after administration of two surfactants for the treatment of neonatal respiratory distress syndrome. J Trop Pediatr 1997; 43(1): 38–41PubMedCrossRefGoogle Scholar
  35. 35.
    Ainsworth SB, Beresford MW, Milligan DW, et al. Pumactant and poractant alfa for treatment of respiratory distress syndrome in neonates born at 25–29 weeks’ gestation: a randomised trial [published erratum appears in Lancet 2000 Aug 12; 356 (9229): 600]. Lancet 2000; 355(9213): 1387–92PubMedCrossRefGoogle Scholar
  36. 36.
    da Costa DE, Pai MG, Al Khusaiby SM. Comparative trial of artificial and natural surfactants in the treatment of respiratory distress syndrome of prematurity: experiences in a developing country. Pediatr Pulmonol 1999; 27(5): 312–7PubMedCrossRefGoogle Scholar
  37. 37.
    Hudak ML, Farrell EE, Rosenberg AA, et al. A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome. J Pediatr 1996; 128(3): 396–406PubMedCrossRefGoogle Scholar
  38. 38.
    Kukkonen AK, Virtanen M, Jarvenpaa AL, et al. Randomized trial comparing natural and synthetic surfactant: increased infection rate after natural surfactant. Acta Paediatr 2000; 89: 556–61PubMedCrossRefGoogle Scholar
  39. 39.
    Vermont-Oxford Neonatal Network. A multicenter, randomized trial comparing synthetic surfactant with modified bovine surfactant extract in the treatment of neonatal respiratory distress syndrome. Pediatrics 1996; 97(1): 1–6Google Scholar
  40. 40.
    Hudak ML, Martin DJ, Egan EA, et al. A multicenter randomized masked comparison trial of synthetic surfactant versus calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome. Pediatrics 1997; 100(1): 39–50PubMedCrossRefGoogle Scholar
  41. 41.
    Soll RF, Blanco F. Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome (Cochrane Review). In: The Cochrane Library. Issue 2. Oxford: Update Software, 2001Google Scholar
  42. 42.
    Cotton RB, Olsson T, Law AB, et al. The physiologic effects of surfactant treatment on gas exchange in newborn premature infants with hyaline membrane disease. Pediatr Res 1993; 34(4): 495–501PubMedCrossRefGoogle Scholar
  43. 43.
    Grauaug A, Kohan R, Sly P, et al. Exosurf and Survanta: are there advantages of one over the other when used as rescue therapy [abstract]. Pediatr Res 1994; 35: 335AGoogle Scholar
  44. 44.
    Lloyd J, Todd DA, John E. Serial phospholipid analysis in preterm infants: comparison of Exosurf and Survanta. Early Hum Dev 1999; 54(2): 157–68PubMedCrossRefGoogle Scholar
  45. 45.
    Murdoch E, Kempley ST. Randomized trial examining cerebral haemodynamics following artificial or animal surfactant. Acta Paediatr 1998; 87(4): 411–5PubMedCrossRefGoogle Scholar
  46. 46.
    Bartmann P, Bamberger U, Pohlandt F, et al. Immunogenicity and immunomodulatory activity of bovine surfactant (SF-RI 1). Acta Paediatr 1992; 81(5): 383–8PubMedCrossRefGoogle Scholar
  47. 47.
    Whitsett JA, Hull WM, Luse S. Failure to detect surfactant protein-specific antibodies in sera of premature infants treated with Survanta, a modified bovine surfactant. Pediatrics 1991; 87(4): 505–10PubMedGoogle Scholar
  48. 48.
    Chida S, Phelps DS, Soll RF, et al. Surfactant proteins and anti-surfactant antibodies in sera from infants with respiratory distress syndrome with and without surfactant treatment. Pediatrics 1991; 88(1): 84–9PubMedGoogle Scholar
  49. 49.
    Strayer DS, Merritt TA, Hallman M. Surfactant replacement: immunological considerations. Eur J Respir Dis 1989; 3: 91–96SGoogle Scholar
  50. 50.
    Robertson B, Curstedt T, Tubman R, et al. A 2-year follow up of babies enrolled in a European multicentre trial of porcine surfactant replacement for severe neonatal respiratory distress syndrome. Collaborative European Multicentre Study Group. Eur J Pediatr 1992; 151(5): 372–6PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Gautham K. Suresh
    • 1
  • Roger F. Soll
    • 1
  1. 1.Department of PediatricsUniversity of Vermont College of MedicineBurlingtonUSA

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