Document Detail

Prolonged versus short course of indomethacin for the treatment of patent ductus arteriosus in preterm infants.
MedLine Citation:
PMID:  14974018     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Indomethacin is a prostaglandin inhibitor used to treat patent ductus arteriosus (PDA) in preterm infants. Although indomethacin produces ductal closure in the majority of cases, it is ineffective in up to 40% of patients. Furthermore, the ductus will re-open in up to 35% of infants who initially respond to the drug. A more prolonged course of indomethacin has been studied regarding the potential to achieve higher rates of ductal closure.
OBJECTIVES: To determine if a prolonged course of indomethacin (compared to a short course) reduces the rate of treatment failure in preterm infants with PDA without unwanted side-effects.
SEARCH STRATEGY: The search included review of personal files, abstracts of conferences, and the following electronic databases: MEDLINE (1966 to April 2003), EMBASE (1974 to April 2003), and Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2003). No language restrictions were applied.
SELECTION CRITERIA: 1) DESIGN AND POPULATION: Randomized or quasi-randomized controlled trials including preterm infants with PDA diagnosed on clinical and/or echocardiographic examination.2) INTERVENTION: Indomethacin treatment by any route given as a long course (four or more doses) vs a short course (three or fewer doses). 3) OUTCOMES: Report of at least one of the following outcomes: failure of PDA to close, need for re-treatment, PDA re-opening, PDA ligation, mortality, duration of assisted ventilation, chronic lung disease (CLD), duration of supplemental oxygen dependence, intraventricular hemorrhage (IVH) (all and severe), diminished urine output, increased serum creatinine, necrotizing enterocolitis (NEC), bleeding diathesis, retinopathy of prematurity (ROP), and duration of hospital stay.
DATA COLLECTION AND ANALYSIS: The three reviewers independently abstracted data from each study. Relative risk (RR) and Risk Difference (RD) with 95% confidence intervals (CI) using the fixed effect model for meta-analysis are reported. When a statistically significant RD was found, the number needed to treat (NNT) or number needed to harm (NNH) was also calculated with 95% CIs. A chi-square test was used to test for heterogeneity of results among included trials.
MAIN RESULTS: Prolonged indomethacin treatment when compared to the short course resulted in a borderline statistically significant difference in PDA re-opening rate favoring the prolonged course [RR 0.54 (95% CI 0.3, 0.99); RD -0.12 (95% CI -0.24, -0.01); NNT = 8 (4, 100). There was no statistically significant treatment effect on PDA closure, re-treatment, or ligation rates. The prolonged course was associated with a decreased incidence of severe IVH [RR 0.49 (95% CI 0.25, 0.98); RD -0.12 (95% CI -0.24, -0.01); NNT 8 (4, 100)] and renal function impairment, as evidenced by a lower proportion of infants having an increased creatinine level [RR 0.52 (95% CI 0.34, 0.81); RD -0.20 (95% CI -0.33, -0.08); NNT 5 (3, 13)]. However, there was a trend for the prolonged course to increase the proportion of infants with CLD in the one trial reporting this outcome [RR 2.24 (95% CI 0.98, 5.12); RD 0.24 (95% CI 0.01, 0.47)].
IMPLICATIONS FOR PRACTICE: Prolonged as compared to short course of indomethacin for the treatment of PDA in preterm infants has a borderline effect on reducing the rate of PDA re-opening and it may be associated with an increased risk for CLD. However, prolonged course of indomethacin appears to reduce the risk of severe intracranial hemorrhage and renal impairment in this population. Definitive recommendations about the preferred duration of indomethacin therapy, i.e. prolonged versus short course, for the treatment of PDA in premature infants cannot be made based on the current findings of this review.
IMPLICATIONS FOR RESEARCH: There is a paucity of data on optimal duration of indomethacin therapy for the treatment of PDA, in particular for ELBW premature infants. Future randomized clinical trials should include this high risk population and investigate the premature infants. Future randomized clinical trials should include this high risk population and investigate the possibility of tailoring duration of therapy (prolonged versus short) to individual response in terms of echocardiographic findings and/or prostaglandin levels, focusing on clinically significant outcomes and potential complications associated with either strategy. In addition, factors which may influence treatment effect need to be taken into account when designing such studies.
C Herrera; J Holberton; P Davis
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Publication Detail:
Type:  Journal Article; Meta-Analysis; Review    
Journal Detail:
Title:  The Cochrane database of systematic reviews     Volume:  -     ISSN:  1469-493X     ISO Abbreviation:  Cochrane Database Syst Rev     Publication Date:  2004  
Date Detail:
Created Date:  2004-02-19     Completed Date:  2004-06-29     Revised Date:  2014-07-28    
Medline Journal Info:
Nlm Unique ID:  100909747     Medline TA:  Cochrane Database Syst Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  CD003480     Citation Subset:  IM    
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MeSH Terms
Ductus Arteriosus, Patent / drug therapy*
Indomethacin / therapeutic use*
Infant, Newborn
Infant, Premature
Infant, Premature, Diseases / drug therapy*
Prostaglandin Antagonists / therapeutic use*
Randomized Controlled Trials as Topic
Reg. No./Substance:
0/Prostaglandin Antagonists; XXE1CET956/Indomethacin
Update In:
Cochrane Database Syst Rev. 2007;(2):CD003480   [PMID:  17443527 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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