Indomethacin or ibuprofen in the treatment of patent ductus arteriosus

The persistence of patent ductus arteriosus (PDA) in preterm infants is inversely related to gestational age and birth weight and can result in serious hemodynamic changes. These changes may determine respiratory, gastrointestinal and renal morbidities and possibly death if not treated within the first week of life. Therefore, diagnosis and appropriate treatment of the PDA is essential to prevent these morbidities.
PDA usually presents with at least one or more symptoms, including bounding pulses with wide pulse pressure, hyperdynamic precardium, heart murmur, worsening respiratory status, edema and/or oliguria. However, the echocardiogram remains the gold standard in confirming the presence of hemodynamically significant PDA. The timing of the echocardiogram plays a central role in making a decision to treat, since about one-third of PDAs will begin to close spontaneously within the first 24 h of life and will not require treatment.
The treatment options available are a conservative approach, pharmacological treatment with cyclo-oxygenase (COX) inhibitors and surgical ligation. Current clinical experience suggests that the conservative approach, which includes fluid restriction and ventilator support, could be associated with a high failure rate, while surgical ligation may be invasive and is associated with significant morbidities. Therefore, pharmacotherapy is the therapy of choice for safe and effective treatment of PDA.
The two available pharmacological agents approved by the FDA are IV indomethacin and IV ibuprofen lysine. Clinical trials have indicated that both drugs are equally effective in closing the PDA in preterm infants. However, differences exist in the effect on cerebral and renal blood flow when using these two drugs. In fact, indomethacin decreases cerebral blood flow and oxygen consumption to a greater degree than ibuprofen lysine. This is associated with a preventative effect in the occurrence of intraventricular hemorrhage (IVH), whereas ibuprofen lysine has no such protective effect. On the other hand, indomethacin more profoundly decreases renal blood flow compared to ibuprofen lysine, resulting in significant oliguria and an increase in serum creatinine levels.
The optimal time to treat the PDA is when treatment with COX inhibitors will be most effective while avoiding treatment of infants who may have spontaneous closure of the ductus. Therefore, prophylaxis treatment is only indicated in situations where the risk of IVH is very high. If prophylaxis is desired, indomethacin is the treatment of choice. The current trend is to treat early presymptomatic therapeutic PDA at 2 to 7 days of age after echocardiogram confirmation. Indomethacin and ibuprofen lysine have been shown to be equally effective in closure rates when given at this time. However, ibuprofen lysine will be preferable because of its better toxicity profile. Medical therapy should still be attempted for PDA closure beyond 7 days of age, although treatment may be ineffective, while surgical ligation should be reserved for resistant symptomatic PDA that did not respond to medical and pharmacologic therapy.

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