Current Issues and Challenges in the Use of Aerosolized Surfactant for Respiratory Distress Syndrome in the Newborns

Dion Darius Samsudin


BACKGROUND: Surfactant replacement therapy is a recognized treatment for respiratory distress syndrome (RDS) in the newborns. Over the past 30 years, human and animal trials have been performed regarding administration of aerosolized surfactant to the injured lung, however the result has been unsatisfactory when compared with instilled surfactant delivery via endotracheal tube (ETT). This review aims to investigate the current issues, challenges and future recommendation of aerosolized surfactant therapy.

CONTENT: Five randomized clinical trials in humans and 13 animal trials met the inclusion criteria and were reviewed. Most animal trials agree that this method of treatment is feasible. However, human trials presented conflicting results, and generally showed it to be ineffective. When compared with surfactant delivery via ETT, aerosolized surfactant is less effective in improving respiratory function.

SUMMARY: The current data from human trials does not support the implementation of aerosolized surfactant therapy to treat newborns with RDS. Further research is necessary to improve nebulization, delivery, distribution and deposition in the lung, to investigate aerosolized surfactant delivery via ETT and to determine the appropriate dose.

KEYWORDS: surfactant, aerosol, prematurity, respiratory distress syndrome

Full Text:



Zuo YY, Veldhuizen RA, Neumann AW, Petersen NO, Possmayer F. Current perspectives in pulmonary surfactant-inhibition, enhancement and evaluation. Biochim Biophys Acta. 2008; 1778: 1947-77, CrossRef.

West JB. Respiratory physiology: the essentials. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2005, NLMID.

Cole FS, Nogee LM, Hamvas A. Defects in surfactant synthesis: clinical implications. Pediatr Clin North Am. 2006; 53: 911-27, CrossRef.

Stevens TP, Sinkin RA. Surfactant replacement therapy. Chest. 2007; 131: 1577-82, CrossRef.

Gupta S, Donn S. Novel approaches to surfactant administration. Crit Care Res Pract. 2012; 2012: 278483, CrossRef.

Lissauer T, Fanaroff AA. Neonatology at a glance. Malden: Blackwell Publishing; 2006, NLMID.

Goldenberg RL, Culhane JF, Lams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008; 371: 75-84, CrossRef.

Slattery M, Morrison J. Preterm delivery. Lancet. 2002; 360: 1489-97, CrossRef.

Beck S, Wojdyla D, Say L, Betran A, Merialdi M, Requejo J, et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ. 2010; 88: 31-8, CrossRef.

Pudjiadi A, Hegar B, Handryastuti S, Idris N, Gandaputra E, Harmoniati E. Pedoman pelayanan medis IDAI. Jakarta: Ikatan Dokter Anak Indonesia; 2009.

Haram K, Mortensen J, Wollen A. Preterm delivery: an overview. Acta Obstet Gynecol Scand. 2003; 82: 687-704, CrossRef.

Lal MK, Sinha S. Surfactant respiratory therapy using surfaxin/sinapultide. Ther Adv Respir Dis. 2008; 2: 339-44, CrossRef.

Lorraine BW, Michael AM. The acute respiratory distress syndrome. N Engl J Med. 2000; 342: 1334-49, CrossRef.

Notter R. Lung surfactants: Basic science and clinical applications. New York: Marcel Dekker, Inc; 2000, NLMID.

Sinha S, Gupta S, Donn S. Immediate respiratory management of the preterm infant. Semin Fetal Neonatal Med. 2008; 13: 24-9, CrossRef.

Agrons GA, Courtney SE, Stocker JT, Markowitz RI. Lung disease in premature neonates: radiologic-pathologic correlation. Radiographics. 2005; 25: 1047-73, CrossRef.

Ballard PL, Merrill JD, Truog WE, Godinez RI, Godinez MH, McDevitt TM, et al. Surfactant function and composition in premature infants treated with inhaled nitric oxide. Pediatrics. 2007; 120: 346-53, CrossRef.

Avery ME, Mead J. Surface properties in relation to atelectasis and hyaline membrane disease. Am J Dis Child. 1959; 97: 517-23, CrossRef.

Merenstein GB, Gardner SL. Handbook of neonatal intensive care. 4th ed St. Louis, Missouri: Mosby-Year Book, Inc; 1998, NLMID.

Vavasseur C, Foran A, Murphy JF. Consensus statements on the borderlands of neonatal viability: from uncertainty to grey areas. Ir Med J. 2007; 100: 561-4, PMID.

Brumley GW, Hodson WA, Avery ME. Lung phospholipids and surface tension correlations in infants with and without hyaline membrane disease and in adults. Pediatrics. 1967; 40: 13-9, PMID.

Fujiwara T, Maeta H, Chida S, Morita T, Watabe Y, Abe T. Artificial surfactant therapy in hyaline-membrane disease. Lancet. 1980; 1: 55-9, CrossRef.

Kobayashi T, Kataoka H, Ueda T, Murakami S, Takada Y, Kokubo M. Effects of surfactant supplement and end-expiratory pressure in lung-lavaged rabbits. J Appl Physiol Respir Environ Exerc Physiol. 1984; 57: 995-1001, PMID.

Berggren E, Lachmann B, Curstedt T, Grossmann G, Robertson B. Gas exchange and lung morphology after surfactant replacement in experimental adult respiratory distress syndrome induced by repeated lung lavage. Acta Anaesthesiol Scand. 1986; 30: 321-8, CrossRef.

Rey M, Segerer H, Kiessling C, Obladen M. Surfactant bolus instillation: effects of different doses on blood pressure and cerebral blood flow velocities. Biol Neonate. 1994; 66: 16-21, CrossRef.

Schipper JA, Mohammad GI, van Straaten HL, Koppe JG. The impact of surfactant replacement therapy on cerebral and systemic circulation and lung function. Eur J Pediatr. 1997; 156: 224-7, CrossRef.

Kendig JW, Ryan RM, Sinkin RA, Maniscalco WM, Notter RH, Guillet R, et al. Comparison of two strategies for surfactant prophylaxis in very premature infants: a multicenter randomized trial. Pediatrics. 1998; 101: 1006-12, CrossRef.

Nuntnarumit P, Bada HS, Yang W, Korones SB. Cerebral blood flow velocity changes after bovine natural surfactant instillation. J Perinatol. 2000; 20: 240-3, CrossRef.

Halliday H. Recent clinical trials of surfactant treatment for neonates. Biol Neonate. 2006; 89: 323-9, CrossRef.

Engle WA. Surfactant-replacement therapy for respiratory distress in the preterm and term neonate. Pediatrics. 2008; 121: 419-3, CrossRef.

Vidyasagar D, Velaphi S, Bhat V. Surfactant replacement therapy in developing countries. neonatology. 2011; 99: 355-66, CrossRef.

Stevens TP, Blennow M, Myers EH, Soll R. 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. 2007; 4: CD003063, PMID.

Halliday H. Surfactants: past, present and future. J Perinatol. 2008; 28: S47-56, CrossRef.

Lewis JF. In vivo studies of aerosolized exogenous surfactant. Aerosol Sci Technol. 1995; 22: 354-63, CrossRef.

Ware L, Matthay M. The acute respiratory distress syndrome. N Engl J Med. 2000; 342: 1334-49, CrossRef.

Lopez E, Gascoin G, Flamant C, Merhi M, Tourneux P, Baud O. Exogenous surfactant therapy in 2013: What is next? who, when and how should we treat newborns infants in the future? BMC Pediatr. 2013; 13: 165, CrossRef.

Espinosa FF, Kamm RD. Bolus dispersal through the lungs in surfactant replacement therapy. J Appl Physiol. 1999; 86: 391-410, PMID.

Pillow J, Micnocchieri S. Innovation in surfactant therapy II: Surfactant administration by aerosolization. Neonatology. 2012; 101: 337-44, PMID.

Femitha P, Joy R, Adhisivam B, Prasad K, Gane BD, Bhat V. Surfactant replacement therapy (SRT) in respiratory distress syndrome (RDS). Curr Pediatr Res. 2012; 16: 134-6, article.

Ramanathan R. Surfactant therapy in preterm infants with respiratory distress syndrome and in near-term or term newborns with acute RDS. J Perinatol. 2006; 26: S51-6, CrossRef.

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: 222-4, CrossRef.

Arroe M, Pedersen-Bjergaard L, Albertsen P, Bode S, Greisen G, Jonsbo F, et al. Inhalation of aerosolized surfactant (Exosurf(R)) to neonates treated with nasal continuous positive airway pressure. Prenatal Neonatal Med. 1998; 3: 346-52.

Finer NN, Merritt TA, Bernstein 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.

Gardenhire DS, Rau JL. Rau's respiratory care pharmacology. 7th ed. St. Louis, Mo: Mosby/Elsevier; 2008, NLMID.

Smedsaas-Löfvenberg A, Nilsson K, Moa G, Axelsson I. Nebulization of drugs in a nasal CPAP system. Acta Paediatr. 1999; 88: 89-92, CrossRef.

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: 460-4, CrossRef.

Mathai SCS, Raju CU, Kanitkar M. Management of respiratory distress in the newborn. Med J Armed Forces India. 2007; 63: 269-72, CrossRef.

Finer N, Merritt T, Bernstein G, Job L, Mazela J, Segal R. An open label, pilot study of aerosurf (R) combined with nCPAP to prevent RDS in preterm neonates. J Aerosol Med Pulm Drug Deliv. 2010; 5: 303-9, CrossRef.

Tashiro K, Yamada K, Li W, Matsumoto Y, Kobayashi T. Aerosolized and instilled surfactant therapies for acute lung injury caused by intratracheal endotoxin in rats. Crit Care Med. 1996; 24: 488-94, CrossRef.

Cui X, Tashiro K, Matsumoto H, Tsubokawa Y, Kobayashi T. Aerosolized surfactant and dextran for experimental acute respiratory distress syndrome caused by acidified milk in rats. Acta Anaesthesiol Scand. 2003; 47: 853-60, CrossRef.

Bahlmann H, Sun B, Nilsson G, Curstedt T, Robertson B. Aerosolized surfactant in lung-lavaged adult rats: factors influencing the therapeutic response. Acta Anaesthesiol Scand. 2000; 44: 612-22, CrossRef.

Tashiro K, Yamada K, Konzaki T, Yamamoto K, Ohmura S, Kobayashi T, et al. Aerosolized surfactant therapy for endotoxin-induced experimental acute respiratory distress syndrome in rats. Br J Anaesth. 2001; 87: 266-71, CrossRef.

Li W, Chen W, Kobayashi T. Aerosolized surfactant reverses respiratory failure in lung-lavaged rats. Acta Anaesthesiol Scand. 1994; 38: 82-8, CrossRef.

Fok TF, Al-Essa M, Dolovich M, Rasid F, Kirpalani H. Nebulisation of surfactants in an animal model of neonatal respiratory distress. Arch Dis Child Fetal Neonatal Ed. 1998; 78: F3-F9, CrossRef.

Ellyett KM, Broadbent RS, Fawcett ER, Campbell AJ. Surfactant aerosol treatment of respiratory distress for spontaneously breathing premature rabbit. Pediatr Res. 1996; 39: 953-7, CrossRef.

Dijk PH, Heikamp A, Bambang Oetomo S. Surfactant nebulization prevents the adverse effects of surfactant therapy on blood pressure and cerebral blood flow in rabbits with severe respiratory failure. Intensive Care Med. 1997; 23: 1077-81, CrossRef.

Lewis JF, Ikegami M, Jobe A, Tabor B. Aerosolized surfactant treatment of preterm lambs. J Appl Physiol. 1991; 70: 869-76, PMID.

Henry MD, Rebello CM, Ikegami M, Jobe AH, Langenback EG, Davis JM. Ultrasonic nebulized in comparison with instilled surfactant treatment of preterm lambs. Am J Respir Crit Care Med. 1996; 154: 366-75, CrossRef.

Lewis JF, Ikegami M, Jobe AH, Absolom D. Physiologic responses and distribution of aerosolized surfactant (Survanta) in a nonuniform pattern of lung injury. Am Rev Respir Dis. 1993; 147: 1364-70, CrossRef.

Lewis JF, McCaig L. Aerosolized versus instilled exogenous surfactant in a nonuniform pattern of lung injury. Am Rev Respir Dis. 1993; 148: 1187-93, CrossRef.

Lewis JF, Tabor B, Ikegami M, Jobe AH, Joseph M, Absolom D. Lung function and surfactant distribution in saline-lavaged sheep given instilled vs. nebulized surfactant. J Appl Physiol. 1993; 74: 1256-64, PMID.

Rau JL. Design principles of liquid nebulization devices currently in use. Respir Care. 2002; 47: 1257-75, PMID.

Asmus MJ, Milavetz G, Tice AL, Teresi ME. In vitro characteristics of tobramycin aerosol from ultrasonic and jet nebulizers. Pharmacotherapy. 2001; 21: 534-9, CrossRef.

Steckel H, Eskandar F. Factors affecting aerosol performance during nebulization with jet and ultrasonic nebulizers. Eur J Pharm Sci. 2003; 19: 443-55, CrossRef.

Adjei AL, Altiere RJ, Amin H, Asgharian B, Bernstein JA, Bhat M, et al. Inhalation aerosols: physical and biological basis of therapy. 2nd ed. New York: Informa Healthcare; 2007, NLMID.

Dolovich MA. Influence of inspiratory flow rate, particle size, and airway caliber on aerosolized drug delivery to the lung. Respir Care. 2000; 45: 597-608, PMID.

Ma CC, Ma S. The role of surfactant in respiratory distress syndrome. Open Respir Med J. 2012; 6: 44-53, CrossRef.

Fuller H, Dolovich M, Chambers C, Newhouse M. Aerosol delivery during mechanical ventilation: a predictive in-vitro lung model. J Aerosol Med. 1992; 5: 251-9, CrossRef.

Holm BA. Editorial: Surfactant replacement therapy, new level of understanding. Am Rev Respir Dis. 1993; 148: 834-6, CrossRef.


Copyright (c) 2013 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.


Indexed by:






The Prodia Education and Research Institute