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. 2016 May 23;2016(5):CD011877.
doi: 10.1002/14651858.CD011877.pub2.

Epinephrine for transient tachypnea of the newborn

Luca Moresco  1 , Maria Grazia Calevo, Federica Baldi, Amnon Cohen, Matteo Bruschettini
Affiliations

Epinephrine for transient tachypnea of the newborn

Luca Moresco et al. Cochrane Database Syst Rev. .

Abstract

Background: Transient tachypnea of the newborn is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of life in term and late preterm newborns. Although transient tachypnea of the newborn is usually a self limited condition, it is associated with wheezing syndromes in late childhood. The rationale for the use of epinephrine (adrenaline) for transient tachypnea of the newborn is based on studies showing that β-agonists can accelerate the rate of alveolar fluid clearance.

Objectives: To assess whether epinephrine compared to placebo, no treatment or any other drugs (excluding salbutamol) is effective and safe in the treatment of transient tachypnea of the newborn in infants born at 34 weeks' gestational age or more.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 3), MEDLINE (1996 to March 2016), EMBASE (1980 to March 2016) and CINAHL (1982 to March 2016). We applied no language restrictions. We searched the abstracts of the major congresses in the field (Perinatal Society of Australia and New Zealand and Pediatric Academic Societies) from 2000 to 2015.

Selection criteria: Randomized controlled trials, quasi-randomized controlled trials and cluster trials comparing epinephrine versus placebo or no treatment or any other drugs administered to infants born at 34 weeks' gestational age or more and less than three days of age with transient tachypnea of the newborn.

Data collection and analysis: For the included trial, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, duration of oxygen therapy (hours), need for continuous positive airway pressure and need for mechanical ventilation, duration of mechanical ventilation, etc.) and assessed the risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). The primary outcomes considered in this review were duration of oxygen therapy (hours), need for continuous positive airway pressure and need for mechanical ventilation.

Main results: One trial, which included 20 infants, met the inclusion criteria of this review. Study authors administered three doses of nebulized 2.25% racemic epinephrine or placebo. We found no differences between the two group in the duration of supplemental oxygen therapy (mean difference (MD) -6.60, 95% confidence interval (CI) -54.80 to 41.60 hours) and need for mechanical ventilation (risk ratio (RR) 0.67, 95% CI 0.08 to 5.88; risk difference (RD) -0.07, 95% CI -0.46 to 0.32). Among secondary outcomes, we found no differences in terms of initiation of oral feeding. The quality of the evidence was limited due to the imprecision of the estimates.

Authors' conclusions: At present there is insufficient evidence to determine the efficacy and safety of epinephrine in the management of transient tachypnea of the newborn.

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Conflict of interest statement

All review authors declared to have no competing financial conflict of interest.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
3
3
Forest plot of comparison: 1 Epinephrine versus placebo, outcome: 1.1 Duration of oxygen therapy (hours).
4
4
Forest plot of comparison: 1 Epinephrine versus placebo, outcome: 1.2 Need for mechanical ventilation (yes/no).
1.1
1.1. Analysis
Comparison 1 Epinephrine versus placebo, no treatment or any other drugs, Outcome 1 Duration of oxygen therapy (hours).
1.2
1.2. Analysis
Comparison 1 Epinephrine versus placebo, no treatment or any other drugs, Outcome 2 Need for mechanical ventilation (yes/no).
1.3
1.3. Analysis
Comparison 1 Epinephrine versus placebo, no treatment or any other drugs, Outcome 3 Initiation of oral feeding (days).
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD011877

References

References to studies included in this review

Kao 2008 {published data only}
    1. Kao B, Stewart de Ramirez SA, Belfort MB, Hansen A. Inhaled epinephrine for the treatment of transient tachypnea of the newborn. Journal of Perinatology 2008;28(3):205‐10. [PUBMED: 18200024] - PubMed

Additional references

Avery 1966
    1. Avery ME, Gatewood OB, Brumley G. Transient tachypnea of newborn. Possible delayed resorption of fluid at birth. American Journal of Diseases of Children 1966;111(4):380‐5. [PUBMED: 5906048] - PubMed
Barker 2002
    1. Barker PM, Olver RE. Invited review: clearance of lung liquid during the perinatal period. Journal of Applied Physiology 2002;93(4):1542‐8. [DOI: 10.1152/japplphysiol.00092.2002] - DOI - PubMed
Brown 1983
    1. Brown MJ, Olver RE, Ramsden CA, Strang LB, Walters DV. Effects of adrenaline and of spontaneous labour on the secretion and absorption of lung liquid in the fetal lamb. Journal of Physiology 1983;344:137‐52. [PUBMED: 6655575] - PMC - PubMed
Clark 2005
    1. Clark RH. The epidemiology of respiratory failure in neonates born at an estimated gestational age of 34 weeks or more. Journal of Perinatology 2005;25(4):251‐7. [PUBMED: 15605071] - PubMed
Cochrane EPOC Group 2013
    1. Effective Practice, Organisation of Care (EPOC). Data extraction and management. EPOC Resources for review authors. Oslo: Norwegian Knowledge Centre for the Health Services; 2013. epoc.cochrane.org/epoc‐specific‐resources‐review‐authors (accessed 15 May 2016).
Davies 2004
    1. Davies JC. Ion transport in lung disease. Pediatric Pulmonology 2004;26:147‐8. [PUBMED: 15029633] - PubMed
Di Marco 2012
    1. Marco F, Guazzi M, Sferrazza Papa GF, Vicenzi M, Santus P, Busatto P. Salmeterol improves fluid clearance from alveolar‐capillary membrane in COPD patients: a pilot study. Pulmonary Pharmacology & Therapeutics 2012;25(1):119‐23. [PUBMED: 22245487] - PubMed
Egger 1997
    1. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphical test. BMJ 1997;315(7109):629‐34. [PUBMED: 9310563] - PMC - PubMed
Faxelius 1983
    1. Faxelius G, Hagnevik K, Lagercrantz H, Lundell B, Irestedt L. Catecholamine surge and lung function after delivery. Archives of Disease in Childhood 1983;58(4):262‐6. [PUBMED: 6847229] - PMC - PubMed
Frank 2000
    1. Frank JA, Wang Y, Osorio O, Matthay MA. Beta‐adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats. Journal of Applied Physiology 2000;89(4):1255‐65. [PUBMED: 11007557] - PubMed
Guglani 2008
    1. Guglani L, Lakshminrusimha S, Ryan RM. Transient tachypnea of the newborn. Pediatrics in Review 2008;29(11):e59‐65. [PUBMED: 18977854] - PubMed
Guyatt 2011a
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction‐GRADE evidence profiles and summary of findings tables. Journal of Clinical Epidemiology 2011;64(4):383‐94. [PUBMED: 21195583] - PubMed
Guyatt 2011b
    1. Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso‐Coello P, et al. GRADE guidelines: 4. Rating the quality of evidence ‐ study limitations (risk of bias). Journal of Clinical Epidemiology 2011;64(4):407‐15. [PUBMED: 21247734] - PubMed
Guyatt 2011c
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence ‐ inconsistency. Journal of Clinical Epidemiology 2011;64(12):1294‐302. [PUBMED: 21803546] - PubMed
Guyatt 2011d
    1. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso‐Coello P, Rind D, et al. GRADE guidelines 6. Rating the quality of evidence ‐ imprecision. Journal of Clinical Epidemiology 2011;64(12):1283‐93. [PUBMED: 21839614] - PubMed
Guyatt 2011e
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence ‐ indirectness. Journal of Clinical Epidemiology 2011;64(12):1303‐10. [PUBMED: 21802903] - PubMed
Hansen 2008
    1. Hansen AK, Wisborg K, Uldbjerg N, Henriksen TB. Risk of respiratory morbidity in term infants delivered by elective caesarean section: cohort study. BMJ 2008;336(7635):85‐7. [PUBMED: 18077440] - PMC - PubMed
Higgins 2003
    1. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. [PUBMED: 12958120] - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Irestedt 1982
    1. Irestedt L, Lagercrantz H, Hjemdahl P, Hägnevik K, Belfrage P. Fetal and maternal plasma catecholamine levels at elective cesarean section under general or epidural anesthesia versus vaginal delivery. American Journal of Obstetrics & Gynecology 1982;142(8):1004‐10. [PUBMED: 7072768] - PubMed
Karabayir 2010
    1. Karabayir N. Intravenous furosemide therapy in transient tachypnea of the newborn. Pediatrics International 2010;52(5):851. [PUBMED: 20880312] - PubMed
Kassab 2013
    1. Kassab M, Khriesat WM, Bawadi H, Anabrees J. Furosemide for transient tachypnoea of the newborn. Cochrane Database of Systematic Reviews 2013, Issue 6. [DOI: 10.1002/14651858.CD003064.pub2] - DOI - PubMed
Kumar 1996
    1. Kumar A, Bhat BV. Epidemiology of respiratory distress of newborns. Indian Journal of Pediatrics 1996;63(1):93‐8. [PUBMED: 10829971] - PubMed
Lawson 1978
    1. Lawson EE, Brown ER, Torday JS, Madansky DL, Taeusch HW Jr. The effect of epinephrine on tracheal fluid flow and surfactant efflux in fetal sheep. American Review of Respiratory Disease 1978;118(6):1023‐6. [PUBMED: 581724] - PubMed
Liem 2007
    1. Liem JJ, Huq SI, Ekuma O, Becker AB, Kozyrskyj AL. Transient tachypnea of the newborn may be an early clinical manifestation of wheezing symptoms. Journal of Pediatrics 2007;151(1):29‐33. [PUBMED: 17586187] - PubMed
Ma 2010
    1. Ma XL, Xu XF, Chen C, Yan CY, Liu YM, Liu L, et al. Epidemiology of respiratory distress and the illness severity in late preterm or term infants: a prospective multi‐center study. Chinese Medical Journal 2010;123(20):2776‐80. [PUBMED: 21034581] - PubMed
Miller 1980
    1. Miller LK, Calenoff L, Boehm JJ, Riedy MJ. Respiratory distress in the newborn. JAMA 1980;243(11):1176‐9. [PUBMED: 7359671] - PubMed
Minakata 1998
    1. Minakata Y, Suzuki S, Grygorczyk C, Dagenais A, Berthiaume Y. Impact of β‐adrenergic agonist on Na+ channel and Na+‐K+‐ATPase expression in alveolar type II cells. American Journal of Physiology 1998;275(2 Pt 1):L414‐22. [PUBMED: 9700104] - PubMed
Moresco 2015
    1. Moresco L, Bruschettini M, Cohen A, Gaiero A, Calevo MG. Salbutamol for transient tachypnea of the newborn. Cochrane Database of Systematic Reviews 2015, Issue 9. [DOI: 10.1002/14651858.CD011878] - DOI - PubMed
Morrison 1995
    1. Morrison JJ, Rennie JM, Milton PJ. Neonatal respiratory morbidity and mode of delivery at term: influence of timing of elective caesarean section. British Journal of Obstetrics and Gynaecology 1995;102(2):101‐6. [PUBMED: 7756199] - PubMed
Niisato 1999
    1. Niisato N, Ito Y, Marunaka Y. cAMP stimulates Na(+) transport in rat fetal pneumocyte: involvement of a PTK‐ but not a PKA‐dependent pathway. American Journal of Physiology 1999;277(4 Pt 1):L727‐36. [PUBMED: 10516213] - PubMed
Olver 1986
    1. Olver RE, Ramsden CA, Strang LB, Walters DV. The role of amiloride‐blockable sodium transport in adrenaline‐induced lung liquid reabsorption in the fetal lamb. Journal of Physiology 1986;376:321‐40. [PUBMED: 3795077] - PMC - PubMed
Perkins 2006
    1. Perkins GD, McAuley DF, Thickett DR, Gao F. The Beta‐Agonist Lung injury TrIal (BALTI): a randomized placebo‐controlled clinical trial. American Journal of Respiratory and Critical Care Medicine 2006;173(3):281‐7. [PUBMED: 16254268] - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Sakuma 1994
    1. Sakuma T, Okaniwa G, Nakada T, Nishimura T, Fujimura S, Matthay MA. Alveolar fluid clearance in the resected human lung. American Journal of Respiratory and Critical Care Medicine 1994;150(2):305‐10. [PUBMED: 8049807] - PubMed
Sakuma 1996
    1. Sakuma T, Suzuki S, Usuda K, Handa M, Okaniwa G, Nakada T, et al. Preservation of alveolar epithelial fluid transport mechanisms in rewarmed human lung after severe hypothermia. Journal of Applied Physiology 1996;80(5):1681‐6. [PUBMED: 8727555] - PubMed
Sartori 2002
    1. Sartori C, Allemann Y, Duplain H, Lepori M, Egli M, Lipp E, et al. Salmeterol for prevention of high‐altitude pulmonary edema. New England Journal of Medicine 2002;346(21):1631‐6. [PUBMED: 12023995] - PubMed
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A, editors. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. www.guidelinedevelopment.org/handbook (accessed 15 May 2016).
Strang 1989
    1. Strang LB. Solute and water transport across the pulmonary epithelium: a new chapter in lung physiology inaugurated by Alfred Jost. Biology of the Neonate 1989;55(6):355‐65. [PUBMED: 2663091] - PubMed
Stroustrup 2012
    1. Stroustrup A, Trasande L, Holzman IR. Randomized controlled trial of restrictive fluid management in transient tachypnea of the newborn. Journal of Pediatrics 2012;160(1):38‐43.e1. [PUBMED: 21839467] - PMC - PubMed
Tudehope 1979
    1. Tudehope DI, Smyth MH. Is "transient tachypnoea of the newborn" always a benign disease? Report of 6 babies requiring mechanical ventilation. Australian Paediatric Journal 1979;15(3):160‐5. [PUBMED: 518409] - PubMed
Walters 1978
    1. Walters DV, Olver RE. The role of catecholamines in lung liquid absorption at birth. Pediatric Research 1978;12(3):239‐42. [PUBMED: 205826] - PubMed
Weintraub 2013
    1. Weintraub AS, Cadet CT, Perez R, Lorenzo E, Holzman IR, Stroustrup A. Antibiotic use in newborns with transient tachypnea of the newborn. Neonatology 2013;103(3):235‐40. [PUBMED: 23428585] - PubMed

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