Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants

The way an infant's blood is circulated changes soon after birth. Initially, premature infants have an opening (a patent ductus arteriosus, PDA) between the large blood vessel to the lungs and the large blood vessel that carries oxygenated blood to the rest of the body. Early symptomatic treatment of PDA, when clinical signs first appear, helps reduce the amount of time an infant needs assisted breathing (mechanical ventilation) and the likelihood of chronic lung disease and damaging inflammation of the gut (necrotising enterocolitis). Standard therapy includes restricting fluids, diuretics and cyclooxygenase inhibitors like indomethacin or ibuprofen. The PDA is closed surgically if these medical treatments do not work. Only one randomised controlled study could be included in this review (including 154 preterm infants that needed breathing support). Indomethacin and surgery gave similar benefits. There were no differences in deaths during the hospital stay, chronic lung disease, necrotising enterocolitis, cerebral or other bleeding. Surgery was more effective in closing the PDA (three needed to treat for one to benefit) but it was associated with complications (pneumothorax and retinopathy of prematurity). The one study found was carried out over 30 years ago. Clinical practice has changed a great deal and surgical closure of a PDA is safer. Therefore, whether the results of the study are applicable today is debatable. Updates of this review in July 2007 and February 2012 did not identify any additional randomised controlled studies for inclusion, but three observational studies indicated an increased risk for one or more of the following outcomes associated with PDA ligation: chronic lung disease, retinopathy of prematurity and neurosensory impairment.

Authors' conclusions: 

There are insufficient data to conclude whether surgical ligation or medical treatment with indomethacin is preferred as the initial treatment for symptomatic PDA in preterm infants.

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Background: 

A patent ductus arteriosus (PDA) with significant left to right shunt increases morbidity and mortality in preterm infants. Early closure of the ductus arteriosus may be achieved pharmacologically or by surgery. The preferred initial treatment of a symptomatic PDA, surgical ligation or treatment with indomethacin, is not clear.

Objectives: 

To compare the effect of surgical ligation of PDA versus medical treatment with cyclooxygenase inhibitors (indomethacin, ibuprofen or mefenamic acid), each used as the initial treatment, on neonatal mortality in preterm infants with a symptomatic PDA.

Search strategy: 

For this update we searched The Cochrane Library 2012, Issue 2, MEDLINE, EMBASE, CINAHL, Clinicaltrials.gov, Controlled-trials.com, Proceedings of the Annual Meetings of the Pediatric Academic Societies (2000 to 2011) (Abstracts2ViewTM) and Web of Science on 8 February 2012.

Selection criteria: 

Randomised or quasi-randomised trials in preterm or low birth weight neonates with symptomatic PDA and comparing surgical ligation with medical treatment with cyclooxygenase inhibitors, each used as the initial treatment for closure of PDA.

Data collection and analysis: 

The authors independently assessed methodological quality and extracted data for the included trial. We used RevMan 5.1 for analyses of the data.

Main results: 

One study reporting on 154 neonates was found eligible. No significant difference between surgical closure and indomethacin treatment was found for in-hospital mortality, chronic lung disease, necrotising enterocolitis, sepsis, creatinine level or intraventricular haemorrhage. There was a significant increase in the surgical group in the incidence of pneumothorax (risk ratio (RR) 2.68; 95% confidence interval (CI) 1.45 to 4.93; risk difference (RD) 0.25; 95% CI 0.11 to 0.38; number needed to treat to harm (NNTH) 4 (95% CI 3 to 9)) and retinopathy of prematurity stage III and IV (RR 3.80; 95% CI 1.12 to 12.93; RD 0.11; 95% CI 0.02 to 0.20; NNTH 9 (95% CI 5 to 50)) compared to the indomethacin group. There was a statistically significant decrease in failure of ductal closure rate in the surgical group as compared to the indomethacin group (RR 0.04; 95% CI 0.01 to 0.27; RD -0.32; 95% CI -0.43 to -0.21, number needed to treat to benefit (NNTB) 3 (95% CI 2 to 4)). No new trials were identified for inclusion in the 2012 update.

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