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 is 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 within the lungs called the alveoli. 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 March 2016, we identified and included three clinical trials with 140 newborns comparing salbutamol with placebo. Two 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 one additional trial that is still underway.
Results: Salbutamol reduced the duration of treatment with oxygen in newborns with transient tachypnea (reported in one study); whereas it did not affect the need for respiratory support or any other relevant outcomes.
Conclusions: The results of this systematic review were consistent with either a benefit or a detrimental effect of salbutamol and did not provide a definitive answer to the review question.
At present there is insufficient evidence to determine the efficacy and safety of salbutamol in the management of transient tachypnea of the newborn. The quality of evidence was low due to paucity of included trials, small sample sizes and overall poor methodologic quality.
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.
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 in the treatment of transient tachypnea of the newborn in infants born at 34 weeks' gestational age or more.
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 New Zealand and Pediatric Academic Societies) from 2000 to 2015 and clinical trial registries.
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.
For each of the included trials, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, duration of oxygen therapy, 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, need for continuous positive airway pressure and need for mechanical ventilation.
Three trials, which included 140 infants, met the inclusion criteria. All three trials compared a nebulized dose of salbutamol with placebo; in one of the three trials newborns were assigned to two different doses of the intervention. We found differences in the duration of oxygen therapy (mean difference (MD) -43.10 hours, 95% confidence interval (CI) -81.60 to -4.60). There were no differences in 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; 1 study, 46 infants) or the need for mechanical ventilation (RR 1.50, 95% CI 0.06 to 34.79; RD 0.03, 95% CI -0.08 to 0.14; 1 study, 46 infants). Tests for heterogeneity were not applicable for any of the analyses as only one study was included. Among secondary outcomes, we found no differences in terms of duration of hospital stay and tachypnea. The quality of the evidence was very low due to the imprecision of the estimates. One trial is ongoing.