Intervention Review

Continuous infusion versus intermittent bolus doses of indomethacin for patent ductus arteriosus closure in symptomatic preterm infants

  1. A. Semih Görk1,*,
  2. Richard A Ehrenkranz2,
  3. Michael B Bracken3

Editorial Group: Cochrane Neonatal Group

Published Online: 23 JAN 2008

Assessed as up-to-date: 14 JAN 2010

DOI: 10.1002/14651858.CD006071.pub2

How to Cite

Görk AS, Ehrenkranz RA, Bracken MB. Continuous infusion versus intermittent bolus doses of indomethacin for patent ductus arteriosus closure in symptomatic preterm infants. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD006071. DOI: 10.1002/14651858.CD006071.pub2.

Author Information

  1. 1

    Yale University, Department of Pediatrics, Division of Perinatal Medicine, New Haven, CT, USA

  2. 2

    Yale University, Department of Pediatrics, New Haven, Connecticut, USA

  3. 3

    Yale University Medical School, Department of Epidemiology & Public Health, New Haven, CT, USA

*A. Semih Görk, Department of Pediatrics, Division of Perinatal Medicine, Yale University, 333 Cedar St, PO Box 208064, New Haven, CT, 06520-8064, USA.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 23 JAN 2008




  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要


Indomethacin is a prostaglandin inhibitor used for the prevention and the treatment of patent ductus arteriosus (PDA). Potential adverse effects of indomethacin use in premature infants include reduction in cerebral, mesenteric and renal blood flow and platelet dysfunction. Administering indomethacin continuously over 36-hours has been suggested as a safer and more effective option to prevent such adverse effects compared to bolus administration.


To compare the efficacy and safety of continuous infusion vs. bolus administration of indomethacin in closing a symptomatic PDA in preterm infants.

Search methods

We searched MEDLINE (via PubMed), CINAHL, EMBASE and CENTRAL (The Cochrane Library) through 2009.

Selection criteria

Randomized and quasi-randomized controlled trials comparing continuous indomethacin infusion to bolus doses for closure of a symptomatic PDA in preterm infants with a symptomatic PDA diagnosed clinically and/or by echocardiography.

Data collection and analysis

Data collection and analysis were done in accordance with the recommendations of the CNRG.

Main results

Only two small trials comparing continuous vs. bolus indomethacin were eligible. Analysis of these studies showed that there were no statistically significant differences in PDA closure at day 2 (RR 1.57, 95% CI 0.54, 4.60) and at day 5 (RR 2.77, 95% CI 0.33, 23.14). There was no statistical difference between the bolus and continuous groups for the secondary outcomes of reopening of PDA, neonatal mortality, intraventricular hemorrhage and necrotizing enterocolitis. None of the trials reported on outcomes such as requirement for retreatment with indomethacin or surgical ligation, mortality, bronchopulmonary dysplasia, retinopathy of prematurity, neurodevelopmental outcome and isolated intestinal perforation.

The review demonstrated that there was a decrease in cerebral blood flow velocity after bolus injections and that the difference between the bolus and continuous infusion groups remained significant for 12 - 24 hours. Similar decrease in blood flow to the renal and mesenteric circulations following bolus administration was reported in one study (Christmann 2002). None of the trials detected predefined levels of decreased urine output and increased levels of BUN and creatinine.

Authors' conclusions

The available data is insufficient to draw conclusions regarding the efficacy of continuous indomethacin infusion vs. bolus injections for the treatment of PDA. Although continuous indomethacin seems to cause less alterations in cerebral, renal and mesenteric circulations, the clinical meaning of this effect is unclear. Definitive recommendations about the preferred method of indomethacin administration in premature infants cannot be made based on the current findings of this review.


Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Continuous infusion versus intermittent bolus doses of indomethacin for patent ductus arteriosus closure in symptomatic preterm infants

Patent ductus arteriosus (PDA) occurs when an artery near the heart and lungs stays open and does not close off after birth. Babies born early (preterm) have an increased risk of complications and death due to PDA. Indomethacin has been used to close the PDA; however, it can reduce blood flow in organs such as brain, kidneys and intestine. There is no agreement on the ideal dose and duration of treatment with indomethacin. In order to reduce the adverse effects of indomethacin on blood flow, some investigators have recommended administering the same total dose as a continuous infusion over 36 hours. In this review, the analysis of the two eligible trials found that the data was insufficient to reach a conclusion regarding the effectiveness of the 36-hr continuous infusion method. The blood flow lowering side-effects of indomethacin were reduced by the continuous infusion method, but there was insufficient data to recommend this administration method versus the traditional method.



  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要



Indomethacin是一種前列腺素抑製劑用於預防和治療開放性動脈導管(PDA)上。雖然 3劑量的時間表已被普遍使用,但沒有達成共識的最佳劑量和時間的消炎治療封堵。早產兒使用Indomethacin有潛在的不利影響,如減少腦,腸和腎血流量和血小板功能障礙。有人建議連續輸注超過 36小時,作為一個更安全和更有效的選擇,以防止這種不利影響。










只有兩個小試驗比較連續與間斷輸注Indomethacin有資格納入。分析這些研究顯示,PDA關閉在第2天(RR 1.57,95%CI為 0.54,4.60)和第5天(RR 2.77,95%CI為 0.33,23.14)沒有顯著差異。下列次級結果在間斷給予或連續給予都無統計學差異:PDA再打開,新生兒死亡率,腦室出血,壞死性結腸炎。沒有任何試驗報告了下列結果:如須再度使用indomethacin治療、需要手術、死亡率、支氣管肺發育不良,早產兒視網膜病變,神經發展的結果和單發生腸穿孔。本回顧表明,間斷注射組會下降腦血流速度,而與持續注射組的差異在12  24小時仍然有顯著不同。類似的降低腎血流和腸系膜環血流在間斷注射組也曾被報告(Christmann 2002年)。沒有試驗檢測到符合定義的尿量減少程度與血中尿素氮和肌酐酸濃度增加。





此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。