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Meta-Analysis
. 2021 Feb 5;2(2):CD011878.
doi: 10.1002/14651858.CD011878.pub3.

Salbutamol for transient tachypnea of the newborn

Luca Moresco  1 , Matteo Bruschettini  2   3 , Marina Macchi  4 , Maria Grazia Calevo  5
Affiliations
Meta-Analysis

Salbutamol 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 salbutamol (albuterol) for transient tachypnea of the newborn is based on studies showing that β-agonists can accelerate the rate of alveolar fluid clearance. This review was originally published in 2016 and updated in 2020.

Objectives: To assess whether salbutamol compared to placebo, no treatment or any other drugs administered to treat transient tachypnea of the newborn, is effective and safe for infants born at 34 weeks' gestational age with this diagnosis.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2020, Issue 4) in the Cochrane Library; PubMed (1996 to April 2020), Embase (1980 to April 2020); and CINAHL (1982 to April 2020). We applied no language restrictions. We searched the abstracts of the major congresses in the field (Perinatal Society of Australia New Zealand and Pediatric Academic Societies) from 2000 to 2020 and clinical trial registries.

Selection criteria: Randomized controlled trials, quasi-randomized controlled trials and cluster trials comparing salbutamol 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: We used standard Cochrane methodology for data collection and analysis. The primary outcomes considered in this review were duration of oxygen therapy, need for continuous positive airway pressure and need for mechanical ventilation. We used the GRADE approach to assess the certainty of evidence.

Main results: Seven trials, which included 498 infants, met the inclusion criteria. All trials compared a nebulized dose of salbutamol with normal saline. Four studies used one single dose of salbutamol; in two studies, three to four doses were provided; in one study, additional doses were administered if needed. The certainty of the evidence was low for duration of hospital stay and very low for the other outcomes. Among the primary outcomes of this review, four trials (338 infants) reported the duration of oxygen therapy, (mean difference (MD) -19.24 hours, 95% confidence interval (CI) -23.76 to -14.72); one trial (46 infants) reported the need for continuous positive airway pressure (risk ratio (RR) 0.73, 95% CI 0.38 to 1.39; risk difference (RD) -0.15, 95% CI -0.45 to 0.16), and three trials (254 infants) reported the need for mechanical ventilation (RR 0.60, 95% CI 0.13 to 2.86; RD -0.01, 95% CI -0.05 to 0.03). Both duration of hospital stay (4 trials; 338 infants) and duration of respiratory support (2 trials, 228 infants) were shorter in the salbutamol group (MD -1.48, 95% CI -1.8 to -1.16; MD -9.24, 95% CI -14.24 to -4.23, respectively). One trial (80 infants) reported duration of mechanical ventilation and pneumothorax but data could not be extracted due to the reporting of these outcomes (type of units of effect measure and unclear number of events, respectively). Five trials are ongoing.

Authors' conclusions: There was limited evidence to establish the benefits and harms of salbutamol in the management of transient tachypnea of the newborn. We are uncertain whether salbutamol administration reduces the duration of oxygen therapy, duration of tachypnea, need for continuous positive airway pressure and for mechanical ventilation. Salbutamol may slightly reduce hospital stay. Five trials are ongoing. Given the limited and low certainty of the evidence available, we could not determine whether salbutamol was safe or effective for the treatment of transient tachypnea of the newborn.

PubMed Disclaimer

Conflict of interest statement

LM has no interest to declare.

MB has received research funding from ALF grant (non‐profit ‐ Lund University) and Crafoord Foundation (non‐profit) for research projects not related to Cochrane.

MM has no interest to declare.

MGC has no interest to declare.

Figures

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Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.
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3
Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
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Forest plot of comparison: 1 Salbutamol versus placebo, outcome: 1.1 Duration of oxygen therapy (hours).
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Forest plot of comparison: 1 Salbutamol versus placebo, outcome: 1.2 Need for continuous positive airway pressure (yes/no).
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6
Forest plot of comparison: 1 Salbutamol versus placebo, outcome: 1.3 Need for mechanical ventilation (yes/no).
1.1
1.1. Analysis
Comparison 1: Salbutamol versus placebo/no treatment, Outcome 1: Duration of oxygen therapy
1.2
1.2. Analysis
Comparison 1: Salbutamol versus placebo/no treatment, Outcome 2: Need for continuous positive airway pressure (yes/no)
1.3
1.3. Analysis
Comparison 1: Salbutamol versus placebo/no treatment, Outcome 3: Need for mechanical ventilation (yes/no)
1.4
1.4. Analysis
Comparison 1: Salbutamol versus placebo/no treatment, Outcome 4: Duration of hospital stay
1.5
1.5. Analysis
Comparison 1: Salbutamol versus placebo/no treatment, Outcome 5: Duration of tachypnea
1.6
1.6. Analysis
Comparison 1: Salbutamol versus placebo/no treatment, Outcome 6: Initiation of oral feeding
1.7
1.7. Analysis
Comparison 1: Salbutamol versus placebo/no treatment, Outcome 7: Duration of respiratory support (intermittent positive pressure ventilation or continuous positive airway pressure)
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Armangil 2011 {published data only}
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Babaei 2019 {published data only}
    1. Babaei H, Dabiri S, Pirkashani LM, Mohsenpour H. Effects of salbutamol on the treatment of transient tachypnea of the newborn. Iranian Journal of Neonatology 2019;10(1):42-9. [DOI: 10.22038/IJN.2018.31294.1430] - DOI
Kim 2014 {published data only}
    1. Kim MJ, Yoo JH, Jung JA, Byun SY. The effects of inhaled albuterol in transient tachypnea of the newborn. Allergy, Asthma & Immunology Research 2014;6(2):126-30. [DOI: 10.4168/aair.2014.6.2.126] [PMID: ] - DOI - PMC - PubMed
Malakian 2018 {published data only}
    1. Malakian A, Dehdashtian M, Aramesh MR, Aletayeb MH, Heidari S. The effect of inhaled salbutamol on the outcomes of transient tachypnea of the newborn. Journal of the Chinese Medical Association 2018;81(11):990-7. [DOI: 10.1016/j.jcma.2018.01.015] [PMID: ] - DOI - PubMed
Mohammadzadeh 2017 {published data only}
    1. Mohammadzadeh I, Akbarian-Rad Z, Heidari F, Zahedpasha Y, Haghshenas-Mojaveri M. The effect of inhaled salbutamol in transient of tachypnea of the newborn: a randomized clinical trial. Iranian Journal of Pediatrics 2017;27(5):e9633. [DOI: 10.5812/ijp.9633] - DOI
Monzoy‐Ventre 2015 {published data only}
    1. Monzoy-Ventre MA, Rosas-Sumano AB, Hernández-Enríquez NP, Galicia-Flores L. Inhaled salbutamol in newborn infants with transient tachypnea [Salbutamol inhalado en los niños recién nacidos con taquipnea transitoria]. Revista Mexicana de Pediatria 2015;82(1):5-9.
Mussavi 2017 {published data only}
    1. Mussavi M, Asadollahi K, Kayvan M, Sadeghvand S. Effects of nebulized albuterol in transient tachypnea of the newborn a clinical trial. Iranian Journal of Pediatrics 2017;27(3):e8211. [DOI: 10.5812/ijp.8211] - DOI

References to ongoing studies

IRCT2014062518232N1 {published data only}
    1. IRCT2014062518232N1. The effect of salbutamol in treatment of transient tachypnea of newborn. irct.ir/searchresult.php?id=18232&number=1 (first received 7 August 2014).
IRCT2016010225811N1 {published data only}
    1. IRCT2016010225811N1. Investigation of the effects of nebulized ventolin in transient tachypnea of newborn [Investigation of the effects of nebulized ventolin and saline 0.%9 in transient respiratory distress of newborn]. irct.ir/trial/21548 (first received 18 March 2016).
IRCT201711139014N201 {published data only}
    1. IRCT201711139014N201. Effect of inhaler salbutamol versus placebo on treatment of neonatal transient tachypnea: a double blind randomized clinical trial [Effect of inhaler salbutamol versus placebo on treatment of neonatal transient tachypnea]. irct.ir/trial/9639 (first received 15 November 2017).
IRCT20190503043457N1 {published data only}
    1. IRCT20190503043457N1. Comparison of inhaled salbutamol with placebo (water for inj.) on recovery process of newborns' transient tachypnea [Comparison of inhaled salbutamol with placebo (water for inj.) as an add-therapies on the duration of stay of newborns and the recovery process of tachypnea and 02 dependence in transient tachypnea of newborns in NICU in Qom hospitals: a clinical trial study]. en.irct.ir/trial/39273 (first received 28 May 2019).
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    1. NCT03208894. Role of salbutamol and furosemide in TTN [Role of salbutamol and furosemide in transient tachypnea of newborn]. clinicaltrials.gov/ct2/show/NCT03208894 (first received 6 July 2017).

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References to other published versions of this review

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. Art. No: CD011878. [DOI: 10.1002/14651858.CD011878] - DOI - PubMed
Moresco 2016
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