The use of epinephrine (adrenaline) in the management of transient tachypnea of the newborn

Review question: Does epinephrine 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 epinephrine for transient tachypnea of the newborn is based on studies showing that medicines called β-agonists, such as epinephrine, can accelerate the rate of clearance of fluid from small cavities within the lungs called alveoli. This review reported and critically analyzed the available evidence on the effectiveness of epinephrine in the management of transient tachypnea of the newborn.

Study characteristics: In medical literature searches complete to March 2016, we identified and included one trial with 20 newborns comparing epinephrine with placebo.

Results: Epinephrine did not reduce the duration of treatment with oxygen, the need for respiratory support or any other relevant measurements in newborns with transient tachypnea.

Conclusions: Due to the small number of newborns included in the one included trial, this review did not find either a benefit or a detrimental effect of epinephrine and did not provide a definitive answer to the review question.

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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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 strategy: 

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.

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