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Table of Contents
Vol. 101, No. 3, 2012
Issue release date: March 2012
Section title: Systematic Review and Meta-Analysis
Free Access
Neonatology 2012;101:183–191
(DOI:10.1159/000329822)

Surfactant Lavage Therapy for Meconium Aspiration Syndrome: A Systematic Review and Meta-Analysis

Choi H.J.a, g · Hahn S.b, d, g · Lee J.d · Park B.-J.a, d, g · Lee S.M.e · Kim H.-S.c · Bae C.-W.f
Departments of aPreventive Medicine, bMedicine and cPediatrics, Seoul National University College of Medicine, dMedical Research Collaborating Center, Seoul National University Hospital, eDepartment of Pediatrics, Yonsei University College of Medicine, fDepartment of Pediatrics, Kyung Hee University School of Medicine, and gNational Evidence-Based Healthcare Collaborating Agency, Seoul, Korea
email Corresponding Author

Abstract

Background: Lung lavage with diluted surfactant has emerged as an innovative treatment for meconium aspiration syndrome (MAS). However, the treatment effect has not yet been fully established. Objective: To investigate the effects of surfactant lavage therapy for MAS by a systematic meta-analysis. Methods: Relevant studies were identified by database searches in MEDLINE (from 1950), EMBASE (from 1980), and CENTRAL, up to June 2010, and by additional hand searches. Meta-analyses were separately conducted for randomized controlled trials (RCTs) and non-randomized controlled studies (NRSs). Risk of bias was assessed and clinical as well as statistical heterogeneities were also investigated in explaining the potential bias. Results: Two RCTs (87 patients) and eight NRSs (178 patients) were identified. From the results of the meta-analysis of RCTs, surfactant lavage significantly decreased death or the need for extracorporeal membrane oxygenation (RR 0.34, 95% CI 0.11, 0.99). An interventional benefit was indicated for other outcomes, although it was not statistically significant based only on the two RCTs. Results from the analysis of outcomes from NRSs are consistent with those from RCTs and demonstrated a beneficial effect, which could be considered as supporting evidence. Conclusions: Lung lavage with diluted surfactant appeared to improve the clinical outcome in infants with MAS. Given that less than 100 infants were included in the two RCTs, the findings of this study may still be regarded as insufficient evidence. Further research will be needed to confirm the benefit as well as to refine the lavage technique.

© 2011 S. Karger AG, Basel


  

Key Words

  • Meconium
  • Meconium aspiration syndrome
  • Surfactant
  • Pulmonary surfactant
  • Bronchoalveolar lavage
  • Neonate

References

  1. Fleischer A, Anyaegbunam A, Guidetti D, Randolph G, Merkatz IR: A persistent clinical problem: profile of the term infant with significant respiratory complications. Obstet Gynecol 1992;79:185–190.
  2. Dargaville PA, Copnell B: The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome. Pediatrics 2006;117:1712–1721.
  3. The Neonatal Inhaled Nitric Oxide Study Group: Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med 1997;336:597–604.
  4. Tran N, Lowe C, Sivieri EM, Shaffer TH: Sequential effects of acute meconium obstruction on pulmonary function. Pediatr Res 1980;14:34–38.
  5. Davey AM, Becker JD, Davis JM: Meconium aspiration syndrome: physiological and inflammatory changes in a newborn piglet model. Pediatr Pulmonol 1993;16:101–108.
  6. Bae CW, Takahashi A, Chida S, Sasaki M: Morphology and function of pulmonary surfactant inhibited by meconium. Pediatr Res 1998;44:187–191.
  7. Moses D, Holm BA, Spitale P, Liu MY, Enhorning G: Inhibition of pulmonary surfactant function by meconium. Am J Obstet Gynecol 1991;164:477–481.
  8. Findlay RD, Taeusch HW, Walther FJ: Surfactant replacement therapy for meconium aspiration syndrome. Pediatrics 1996;97:48–52.
  9. Chinese Collaborative Study Group for Neonatal Respiratory D: Treatment of severe meconium aspiration syndrome with porcine surfactant: a multicentre, randomized, controlled trial. Acta Paediatr 2005;94:896–902.
  10. El Shahed AI, Dargaville P, Ohlsson A, Soll RF: Surfactant for meconium aspiration syndrome in full term/near term infants. Cochrane Database Syst Rev 2007:CD002054.
  11. Cleary GM, Wiswell TE: Meconium-stained amniotic fluid and the meconium aspiration syndrome. An update. Pediatr Clin North Am 1998;45:511–529.
  12. Lam BC, Yeung CY: Surfactant lavage for meconium aspiration syndrome: a pilot study. Pediatrics 1999;103:1014–1018.
  13. Wiswell TE, Knight GR, Finer NN, Donn SM, Desai H, Walsh WF, Sekar KC, Bernstein G, Keszler M, Visser VE, Merritt TA, Mannino FL, Mastrioianni L, Marcy B, Revak SD, Tsai H, Cochrane CG: A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome. Pediatrics 2002;109:1081–1087.
  14. Chang HY, Hsu CH, Kao HA, Hung HY, Chang JH, Peng CC, Jim WT: Treatment of severe meconium aspiration syndrome with dilute surfactant lavage. J Formos Med Assoc 2003;102:326–330.
  15. Salvia-Roiges MD, Carbonell-Estrany X, Figueras-Aloy J, Rodriguez-Miguelez JM: Efficacy of three treatment schedules in severe meconium aspiration syndrome. Acta Paediatr 2004;93:60–65.
  16. Dargaville PA, Mills JF, Copnell B, Loughnan PM, McDougall PN, Morley CJ: Therapeutic lung lavage in meconium aspiration syndrome: a preliminary report. J Paediatr Child Health 2007;43:539–545.
  17. Dargaville PA, Mills JF: Surfactant therapy for meconium aspiration syndrome: current status. Drugs 2005;65:2569–2591.
  18. Higgins J, Green S (eds): Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 (updated Sept 2009). The Cochrane Collaboration, 2009 (available from www.cochrane-handbook.org).
  19. Norris SL, Atkins D: Challenges in using nonrandomized studies in systematic reviews of treatment interventions. Ann Intern Med 2005;142:1112–1119.
  20. Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–634.
  21. Dargaville PA, Copnell B, Mills JF, Haron I, Lee JK, Tingay DG, Rohana J, Mildenhall LF, Jeng MJ, Narayanan A, Battin MR, Kuschel CA, Sadowsky JL, Patel H, Kilburn CJ, Carlin JB, Morley CJ: Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome. J Pediatr 2011;158:383–389.
  22. Schlösser RL, Veldman A, Fischer D, Allendorf A, von Loewenich V: Lavage with exogenous surfactant in neonatal meconium aspiration syndrome. Z Geburtshilfe Neonatol 2002;206:15–18.
  23. Lee SM, Kim HM, Jeon JH, Park MS, Park KI, Namgung R, Lee C: Effect of surfactant lavage in severe meconium aspiration syndrome. Korean J Pediatr 2008;51:367–371.

    External Resources

  24. Kowalska K, Szymankiewicz M, Gadzinowski J: An effectiveness of surfactant lung lavage in meconium aspiration syndrome treatment – preliminary report. Przeglad Lekarski 2002;59(suppl 1):21–24.

    External Resources

  25. Kawano T: Effect of surfactant lavage to the babies with meconium aspiration syndrome. Acta Neonatol Jpn 1999;35:32–40.
  26. Lotze A, Mitchell BR, Bulas DI, Zola EM, Shalwitz RA, Gunkel JH, et al: Multicenter study of surfactant (Beractant) use in the treatment of term infants with severe respiratory failure. J Pediatr 1998;132:40–47.
  27. Cleary GM, Antunes MJ, Ciesielka DA, Higgins ST, Spitzer AR, Chander A: Exudative lung injury is associated with decreased levels of surfactant proteins in a rat model of meconium aspiration. Pediatrics 1997;100:998–1003.
  28. Kattwinkel J: Surfactant lavage for meconium aspiration: a word of caution. Pediatrics 2002;109:1167–1168.
  29. Kinsella JP: Meconium aspiration syndrome: is surfactant lavage the answer? Am J Respir Crit Care Med 2003;168:413–414.
  30. Hung HY, Jim WT, Hsu CH, Chang JH, Peng CC, Shih SL, Chang HY, Kao HA: Small versus large volume dilute surfactant lavage for meconium aspiration syndrome. Acta Paediatr Taiwan 2006;47:181–186.

    External Resources

  

Author Contacts

Seokyung Hahn, PhD
Department of Medicine
Seoul National University College of Medicine
28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea)
Tel. +82 2 740 8911, E-Mail hahns@snu.ac.kr

  

Article Information

Received: March 8, 2011
Accepted after revision: May 31, 2011
Published online: November 8, 2011
Number of Print Pages : 9
Number of Figures : 1, Number of Tables : 4, Number of References : 30

  

Publication Details

Neonatology (Fetal and Neonatal Research)

Vol. 101, No. 3, Year 2012 (Cover Date: March 2012)

Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661-7800 (Print), eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Lung lavage with diluted surfactant has emerged as an innovative treatment for meconium aspiration syndrome (MAS). However, the treatment effect has not yet been fully established. Objective: To investigate the effects of surfactant lavage therapy for MAS by a systematic meta-analysis. Methods: Relevant studies were identified by database searches in MEDLINE (from 1950), EMBASE (from 1980), and CENTRAL, up to June 2010, and by additional hand searches. Meta-analyses were separately conducted for randomized controlled trials (RCTs) and non-randomized controlled studies (NRSs). Risk of bias was assessed and clinical as well as statistical heterogeneities were also investigated in explaining the potential bias. Results: Two RCTs (87 patients) and eight NRSs (178 patients) were identified. From the results of the meta-analysis of RCTs, surfactant lavage significantly decreased death or the need for extracorporeal membrane oxygenation (RR 0.34, 95% CI 0.11, 0.99). An interventional benefit was indicated for other outcomes, although it was not statistically significant based only on the two RCTs. Results from the analysis of outcomes from NRSs are consistent with those from RCTs and demonstrated a beneficial effect, which could be considered as supporting evidence. Conclusions: Lung lavage with diluted surfactant appeared to improve the clinical outcome in infants with MAS. Given that less than 100 infants were included in the two RCTs, the findings of this study may still be regarded as insufficient evidence. Further research will be needed to confirm the benefit as well as to refine the lavage technique.

© 2011 S. Karger AG, Basel


  

Author Contacts

Seokyung Hahn, PhD
Department of Medicine
Seoul National University College of Medicine
28 Yongon-dong, Chongno-gu, Seoul 110-744 (Korea)
Tel. +82 2 740 8911, E-Mail hahns@snu.ac.kr

  

Article Information

Received: March 8, 2011
Accepted after revision: May 31, 2011
Published online: November 8, 2011
Number of Print Pages : 9
Number of Figures : 1, Number of Tables : 4, Number of References : 30

  

Publication Details

Neonatology (Fetal and Neonatal Research)

Vol. 101, No. 3, Year 2012 (Cover Date: March 2012)

Journal Editor: Halliday H.L. (Belfast), Speer C.P. (Würzburg)
ISSN: 1661-7800 (Print), eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


Article / Publication Details

First-Page Preview
Abstract of Systematic Review and Meta-Analysis

Received: 3/8/2011
Accepted: 5/31/2011
Published online: 11/8/2011
Issue release date: March 2012

Number of Print Pages: 9
Number of Figures: 1
Number of Tables: 4

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Fleischer A, Anyaegbunam A, Guidetti D, Randolph G, Merkatz IR: A persistent clinical problem: profile of the term infant with significant respiratory complications. Obstet Gynecol 1992;79:185–190.
  2. Dargaville PA, Copnell B: The epidemiology of meconium aspiration syndrome: incidence, risk factors, therapies, and outcome. Pediatrics 2006;117:1712–1721.
  3. The Neonatal Inhaled Nitric Oxide Study Group: Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med 1997;336:597–604.
  4. Tran N, Lowe C, Sivieri EM, Shaffer TH: Sequential effects of acute meconium obstruction on pulmonary function. Pediatr Res 1980;14:34–38.
  5. Davey AM, Becker JD, Davis JM: Meconium aspiration syndrome: physiological and inflammatory changes in a newborn piglet model. Pediatr Pulmonol 1993;16:101–108.
  6. Bae CW, Takahashi A, Chida S, Sasaki M: Morphology and function of pulmonary surfactant inhibited by meconium. Pediatr Res 1998;44:187–191.
  7. Moses D, Holm BA, Spitale P, Liu MY, Enhorning G: Inhibition of pulmonary surfactant function by meconium. Am J Obstet Gynecol 1991;164:477–481.
  8. Findlay RD, Taeusch HW, Walther FJ: Surfactant replacement therapy for meconium aspiration syndrome. Pediatrics 1996;97:48–52.
  9. Chinese Collaborative Study Group for Neonatal Respiratory D: Treatment of severe meconium aspiration syndrome with porcine surfactant: a multicentre, randomized, controlled trial. Acta Paediatr 2005;94:896–902.
  10. El Shahed AI, Dargaville P, Ohlsson A, Soll RF: Surfactant for meconium aspiration syndrome in full term/near term infants. Cochrane Database Syst Rev 2007:CD002054.
  11. Cleary GM, Wiswell TE: Meconium-stained amniotic fluid and the meconium aspiration syndrome. An update. Pediatr Clin North Am 1998;45:511–529.
  12. Lam BC, Yeung CY: Surfactant lavage for meconium aspiration syndrome: a pilot study. Pediatrics 1999;103:1014–1018.
  13. Wiswell TE, Knight GR, Finer NN, Donn SM, Desai H, Walsh WF, Sekar KC, Bernstein G, Keszler M, Visser VE, Merritt TA, Mannino FL, Mastrioianni L, Marcy B, Revak SD, Tsai H, Cochrane CG: A multicenter, randomized, controlled trial comparing Surfaxin (Lucinactant) lavage with standard care for treatment of meconium aspiration syndrome. Pediatrics 2002;109:1081–1087.
  14. Chang HY, Hsu CH, Kao HA, Hung HY, Chang JH, Peng CC, Jim WT: Treatment of severe meconium aspiration syndrome with dilute surfactant lavage. J Formos Med Assoc 2003;102:326–330.
  15. Salvia-Roiges MD, Carbonell-Estrany X, Figueras-Aloy J, Rodriguez-Miguelez JM: Efficacy of three treatment schedules in severe meconium aspiration syndrome. Acta Paediatr 2004;93:60–65.
  16. Dargaville PA, Mills JF, Copnell B, Loughnan PM, McDougall PN, Morley CJ: Therapeutic lung lavage in meconium aspiration syndrome: a preliminary report. J Paediatr Child Health 2007;43:539–545.
  17. Dargaville PA, Mills JF: Surfactant therapy for meconium aspiration syndrome: current status. Drugs 2005;65:2569–2591.
  18. Higgins J, Green S (eds): Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2 (updated Sept 2009). The Cochrane Collaboration, 2009 (available from www.cochrane-handbook.org).
  19. Norris SL, Atkins D: Challenges in using nonrandomized studies in systematic reviews of treatment interventions. Ann Intern Med 2005;142:1112–1119.
  20. Egger M, Davey Smith G, Schneider M, Minder C: Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–634.
  21. Dargaville PA, Copnell B, Mills JF, Haron I, Lee JK, Tingay DG, Rohana J, Mildenhall LF, Jeng MJ, Narayanan A, Battin MR, Kuschel CA, Sadowsky JL, Patel H, Kilburn CJ, Carlin JB, Morley CJ: Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome. J Pediatr 2011;158:383–389.
  22. Schlösser RL, Veldman A, Fischer D, Allendorf A, von Loewenich V: Lavage with exogenous surfactant in neonatal meconium aspiration syndrome. Z Geburtshilfe Neonatol 2002;206:15–18.
  23. Lee SM, Kim HM, Jeon JH, Park MS, Park KI, Namgung R, Lee C: Effect of surfactant lavage in severe meconium aspiration syndrome. Korean J Pediatr 2008;51:367–371.

    External Resources

  24. Kowalska K, Szymankiewicz M, Gadzinowski J: An effectiveness of surfactant lung lavage in meconium aspiration syndrome treatment – preliminary report. Przeglad Lekarski 2002;59(suppl 1):21–24.

    External Resources

  25. Kawano T: Effect of surfactant lavage to the babies with meconium aspiration syndrome. Acta Neonatol Jpn 1999;35:32–40.
  26. Lotze A, Mitchell BR, Bulas DI, Zola EM, Shalwitz RA, Gunkel JH, et al: Multicenter study of surfactant (Beractant) use in the treatment of term infants with severe respiratory failure. J Pediatr 1998;132:40–47.
  27. Cleary GM, Antunes MJ, Ciesielka DA, Higgins ST, Spitzer AR, Chander A: Exudative lung injury is associated with decreased levels of surfactant proteins in a rat model of meconium aspiration. Pediatrics 1997;100:998–1003.
  28. Kattwinkel J: Surfactant lavage for meconium aspiration: a word of caution. Pediatrics 2002;109:1167–1168.
  29. Kinsella JP: Meconium aspiration syndrome: is surfactant lavage the answer? Am J Respir Crit Care Med 2003;168:413–414.
  30. Hung HY, Jim WT, Hsu CH, Chang JH, Peng CC, Shih SL, Chang HY, Kao HA: Small versus large volume dilute surfactant lavage for meconium aspiration syndrome. Acta Paediatr Taiwan 2006;47:181–186.

    External Resources