Digoxin for preventing or treating neonatal respiratory distress syndrome.
BACKGROUND
Lendrum 1955 suggested that pulmonary edema secondary to congestive heart failure may contribute to neonatal respiratory distress syndrome (RDS). Based on this hypothesis, investigators began to use digitalis glycosides to improve myocardial contractility and decrease congestive heart failure. The first use of digitalis glycosides in infants with RDS was reported by Stahlman 1959. Stahlman reported a reduction in mortality in an uncontrolled trial of digitalis in infants with RDS.


OBJECTIVE
To assess the effect of digoxin on mortality in premature infants at risk for or with RDS.


METHODS
Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: digoxin; limits: age groups, newborn infants; publication type, clinical trial), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language.When updated in December 2008, the search was expanded to include Medline, CINHAL, and Embase (MeSH terms and text words: digoxin or digitalis; limits: age group, all infants; publication type: clinical trial).


METHODS
Randomized and quazi-randomized controlled trials of digoxin in either the prevention or treatment of RDS are included in this overview.


METHODS
Data regarding clinical outcomes were excerpted from the trial reports by one review author (RS) and checked by the second review author (EO). Data were analyzed according to the standards of the Cochrane Neonatal Review Group.


RESULTS
Two randomized controlled trials have studied the effects of digoxin in the prevention and treatment of RDS. No improvement in respiratory status or mortality was noted. Meta-analysis of the effect of digoxin given to infants at risk of or with RDS on mortality does not suggest any benefit of digoxin treatment (typical relative risk 1.27 95% CI 0.78 to 2.07; typical risk difference 0.06, 95% CI -0.06 to 0.17).


CONCLUSIONS
Although hemodynamic disturbances play a role in the overall pathogenesis of respiratory distress syndrome, the specific contribution of early congestive heart failure (unrelated to hemodynamically significant patent ductus arteriosus) does not appear to be a significant factor in RDS. Treatment with digoxin has no proven value in infants solely affected with RDS.
Division of Neonatal-Perinatal Medicine, University of Vermont, Fletcher Allen Health Care, Smith 552A, 111 Colchester Avenue, Burlington, Vermont, USA, 05401.
Roger
R
Soll
Eren
E
Ozek
D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004077:Digoxin / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D016032:Randomized Controlled Trials as Topic; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy*
D002316:Cardiotonic Agents; D004077:Digoxin
J Pediatr. 1969 Feb;74(2):310-4
4883855
Cochrane Database Syst Rev. 2011 Jan 19;(1):CD001080
21249645
Cochrane Database Syst Rev. 2000;(2):CD001080
10796245
Can Med Assoc J. 1963 Nov 9;89:995-7
14076169
J Pediatr. 1955 Aug;47(2):149-56
13243213