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Salbutamol for transient tachypnea of the newborn (Review)

  Moresco L, Bruschettini M, Macchi M, Calevo MG  

  Moresco L, Bruschettini M, Macchi M, Calevo MG.  

Salbutamol for transient tachypnea of the newborn.
Cochrane Database of Systematic Reviews 2021, Issue 2. Art. No.: CD011878.
DOI: 10.1002/14651858.CD011878.pub3.

  www.cochranelibrary.com  

 
Salbutamol for transient tachypnea of the newborn (Review)
Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Informed decisions.
 
 
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[Intervention Review]

Salbutamol for transient tachypnea of the newborn

Luca Moresco1, Matteo Bruschettini2,3, Marina Macchi4, Maria Grazia Calevo5

1Pediatric and Neonatology Unit, Ospedale San Paolo, Savona, Italy. 2Department of Clinical Sciences Lund, Paediatrics, Lund University,
Skåne University Hospital, Lund, Sweden. 3Cochrane Sweden, Lund University, Skåne University Hospital, Lund, Sweden. 4University of
Milan, Milano, Italy. 5Epidemiology, Biostatistics Unit, IRCCS, Istituto Giannina Gaslini, Genoa, Italy

Contact address: Matteo Bruschettini, matteo.bruschettini@med.lu.se, matbrus@gmail.com.

Editorial group: Cochrane Neonatal Group.

Publication status and date: New search for studies and content updated (conclusions changed), published in Issue 2, 2021.

Citation: Moresco L, Bruschettini M, Macchi M, Calevo MG. Salbutamol for transient tachypnea of the newborn. Cochrane Database of
Systematic Reviews 2021, Issue 2. Art. No.: CD011878. DOI: 10.1002/14651858.CD011878.pub3.

Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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,
Salbutamol for transient tachypnea of the newborn (Review) 1
Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
 Cochrane Trusted evidence.
Informed decisions.
 
 
Library Better health. Cochrane Database of Systematic Reviews

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.

PLAIN LANGUAGE SUMMARY

The use of salbutamol (albuterol) in the management of transient tachypnea of the newborn

Review question: does salbutamol reduce the duration of oxygen therapy and the need for respiratory support in newborns with transient
tachypnea?

Background: transient tachypnea (abnormally rapid breathing) of the newborn is characterized by high respiratory rate (more than 60
breaths per minute) and signs of respiratory distress (difficulty in breathing); it typically appears within the first two hours of life in
infants born at or after 34 weeks' gestational age. Although transient tachypnea of the newborn usually improves without treatment, it
is associated with wheezing syndromes in late childhood. The idea behind using salbutamol for transient tachypnea of the newborn is
based on studies showing that medicines called β-agonists, such as epinephrine (also known as adrenaline), can accelerate the rate of
clearance of fluid from small cavities (alveoli) within the lungs. This review reported and critically analyzed the available evidence on the
effectiveness of salbutamol in the management of transient tachypnea of the newborn.

Study characteristics: in medical literature searches complete to April 2020, we identified and included seven clinical trials with 498
newborns comparing salbutamol with placebo. Six studies evaluated a single, nebulized (where the medicine is given in a fine mist) dose
of salbutamol, and one study evaluated two different dosages. We found five additional trials that are still underway.

Key results: 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.

Certainty of evidence was low for the outcome, duration of hospital stay, and very low for duration of oxygen therapy and of tachypnea,
need for continuous positive airway pressure and for mechanical ventilation. 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.

Salbutamol for transient tachypnea of the newborn (Review) 2

Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.