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.

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.

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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 strategy: 

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.

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