Safety and Effectiveness of Indomethacin versus Ibuprofen for Treatment of Patent Ductus Arteriosus

Katakam, Lakshmi; Cotten, C. Michael; Goldberg, Ronald N.; Dang, C N; Smith, Patrick B.

doi:10.1055/s-0029-1243371

Cited by 27 publications

(18 citation statements)

References 14 publications

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“…Both intravenous indomethacin (RR 2.39, 95% CI 2.05 to 2.78) and intravenous ibuprofen (RR 2.40, 95% CI 2.03 to 2.84) closed a PDA more effectively than placebo. Other studies [98, 99] have shown a similar efficacy of the two drugs. The two drugs also have a similar failure rate for PDA closure, ranging between 0-50%; Ohlsson et al [100] performed a meta-analysis on data from 19 trials (n=956 infants) for failure rates after 1-3 doses of ibuprofen compared to indomethacin.…”

Section: Management Of Neonatal Pdamentioning

confidence: 56%

Patent Ductus Arteriosus in Premature Neonates

Mezu‐Ndubuisi

Agarwal

Raghavan

et al. 2012

Drugs

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Persistent patency of the ductus arteriosus is a major cause of morbidity and mortality in premature infants. In infants born prior to 28 weeks of gestation, a hemodynamically-significant patent ductus arteriosus (PDA) can cause cardiovascular instability, exacerbate respiratory distress syndrome, prolong the need for assisted ventilation, and increase the risk of bronchopulmonary dysplasia, intraventricular hemorrhage, renal dysfunction, intraventricular hemorrhage, cerebral palsy, and mortality. In this article, we review the pathophysiology, clinical features, and assessment of hemodynamic significance, and provide a rigorous appraisal of the quality of evidence to support current medical and surgical management of PDA of prematurity. Cyclo-oxygenase inhibitors such as indomethacin and ibuprofen remain the mainstay of medical therapy for PDA, and can be used both for prophylaxis as well as rescue therapy to achieve PDA closure. Surgical ligation is also effective and is used in infants who do not respond to medical management. Although both medical and surgical treatment have proven efficacy in closing the ductus, both modalities are associated with significant adverse effects. Because the ductus does undergo spontaneous closure in some premature infants, improved and early identification of infants most likely to develop a symptomatic PDA could help in directing treatment to the at-risk infants and allow others to receive expectant management.

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Section: Management Of Neonatal Pdamentioning

confidence: 56%

Patent Ductus Arteriosus in Premature Neonates

Mezu‐Ndubuisi

Agarwal

Raghavan

et al. 2012

Drugs

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“…Two studies reported using prophylactic intravenous ibuprofen within 6 to 8 h after birth, with bowel perforation occurring in 8.0 to 8.3% of the infants, 8,21 whereas another study reported bowel perforation in 8.0% when ibuprofen (treatment) was used at a median age of 6 days. 22 Bowel perforation has also been reported in isolated infants within 48 h of oral ibuprofen prophylaxis, or with treatment of PDA. 16,23 The GA and birth weight reported in these studies are similar to our study.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 Further, our data suggest that the incidence of SIP with ibuprofen is similar to the 2 to 8% incidence reported with indomethacin use previously. 22,24 Although most studies have not reported the timing of perforation in relation to the medical treatment of PDA, Shorter et al 25 noted focal perforation about 7 days following the last dose of indomethacin treatment of PDA. The mean age of first dose of indomethacin in this study was 4 days.…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal complications associated with ibuprofen therapy for patent ductus arteriosus

Rao

Bryowsky

Mao³

et al. 2011

J Perinatol

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Objective: To review intestinal complications associated with ibuprofen treatment of patent ductus arteriosus (PDA).Study Design: Data from preterm infants treated with ibuprofen were retrospectively reviewed. w 2 test and Fischer's exact test were used for univariate analyses. Multivariate analyses with logistic regression modeling were used to identify risk factors.Result: One hundred and two infants were treated with ibuprofen for PDA. Nine (9/102, 8.8%) infants developed spontaneous intestinal perforation (SIP), whereas 93/102 (91.2%) did not. The mean (±s.d.) gestational age (GA) at birth in infants with and without SIP was 25.2 ( ± 1.3) vs 27.6 ( ± 2.4) weeks (P ¼ 0.02) and the median (interquartile) length of stay (LOS) was 109.5 (91.0 to 116.5) vs 75.0 (53.0 to 94.5) days (P ¼ 0.002), respectively. The mean ( ± s.d.) age at starting ibuprofen was 3.3 ( ± 1.3) vs 5.8 (±3.5) days in infants with and without SIP, respectively (P ¼ 0.03). In logistic regression analyses, increasing GA and later initiation of ibuprofen treatment were protective against risk of SIP; odds ratio, 95% confidence interval (OR, 95% CI) ¼ 0.26 (0.09 to 0.75), P ¼ 0.01 and 0.63 (0.41 to 0.95), P ¼ 0.03, respectively.Conclusion: Infants at lower GA are at risk of SIP when treated early with ibuprofen for symptomatic PDA.

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“…Intestinal complications (necrotizing enterocolitis or spontaneous intestinal perforation) and side effects occurred in less than 10% of cases, but were more frequent following indomethacin. Katakam et al 11 analyzed safety and effectiveness of Indomethacin vs. ibuprofen for the treatment of patent ductus arteriosus. The rates of closure were similar, 62% for indomethacin vs. 58% for ibuprofen.…”

Section: ■ Bibliographic Searchmentioning

confidence: 99%

Ibuprofen and indomethacin for the closure of the patent ductus arteriosus

Pacifici¹

2016

Medical Express

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The ductus arteriosus connects the pulmonary artery with the aorta and allows right ventricular blood to bypass the unexpanded lungs. In mature infants, the ductus arteriosus closes after birth. Patent ductus arteriosus occurs in 70% of preterm infants with a birth weight < 1,000 grams. Failure of the ductus arteriosus to close has been associated with intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular leukomalacia, renal failure, and persistent pulmonary hypertension. The drugs used to treat the patent ductus arteriosus are ibuprofen and indomethacin which are potent non-selective inhibitors of cyclo-oxygenase (COX) and therefore inhibit prostaglandin E2 synthesis. Prostaglandin E2 relaxes smooth muscle and tends to inhibit the closure of the patent ductus arteriosus. Intravenous ibuprofen and indomethacin inhibit prostaglandin E2 synthesis and thereby close the patent ductus arteriosus with similar efficacy. Indomethacin reduces the blood flow velocity in kidneys, intestine and brain. Ibuprofen has less effect on blood flow velocity in these organs. There is a significant increase in serum creatinine after indomethacin administration but not after ibuprofen and infants treated with ibuprofen have higher creatinine clearance. Oliguria (urine output < 1 ml/kg/h) occurs more frequently with indomethacin than with ibuprofen. Indomethacin requires furosemide for urine output more often than ibuprofen. Ibuprofen reduces the risk of necrotizing enterocolitis and transient renal insufficiency and it is the drug of choice for closing the patent ductus arteriosus. Ibuprofen and indomethacin may be administered orally. In conclusion, intravenous ibuprofen and indomethacin close the patent ductus arteriosus at the same rate, but indomethacin is more toxic than ibuprofen.

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Safety and Effectiveness of Indomethacin versus Ibuprofen for Treatment of Patent Ductus Arteriosus

Cited by 27 publications

References 14 publications

Patent Ductus Arteriosus in Premature Neonates

Patent Ductus Arteriosus in Premature Neonates

Gastrointestinal complications associated with ibuprofen therapy for patent ductus arteriosus

Ibuprofen and indomethacin for the closure of the patent ductus arteriosus

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