The trials conducted to date, although not designed to assess harm, do provide some useful information on adverse effects of non‐steroidal treatment. Transient alterations in cerebral perfusion6
during indometacin administration have been shown, but prophylactic treatment is more likely to decrease the incidence of periventricular leucomalacia10
and led to improved long‐term outcome at 4.5 and 8 years.33
In addition, any renal impairment during medical treatment is entirely reversible.7
These studies do not provide any plausible rationale for complete avoidance of medical intervention. The adverse effects of PDA ligation are well recognised and include both reversible complications, such as pneumothorax, infection or haemorrhage, and irreversible complications, including chylothorax and vocal cord paralysis,34
which may lead to major patient morbidity and even mortality. Not uncommonly the postoperative course is characterised by a post‐ligation cardiac syndrome consisting of oxygenation failure due to pulmonary oedema, systolic hypotension and the need for cardiotropic support, which typically occur 8–12 hours after the procedure.35
Previously we have shown that surgical intervention was associated with myocardial dysfunction secondary to increased left ventricular afterload coinciding with the clinical deterioration. Kabra et al
have recently highlighted an association between PDA ligation and an increased risk of bronchopulmonary dysplasia, severe retinopathy of prematurity and neurosensory impairment.36
It is impossible to determine whether this relationship reflects causality or whether need for PDA ligation is merely a marker for illness severity. Unfortunately their study did not consider the heterogeneity of clinical and echocardiographic changes that may occur with varying severity of ductal disease.
In summary, the stage at which the physiological effects of the ductus arteriosus change from benefit to harm remains unclear. Future clinical trials of treatment should be less pragmatic but more focused with strict inclusion criteria that ensure infants are randomised only if there is clear clinical and echocardiographic evidence of an HSDA. Recruited infants should be stratified according to the severity of ductal disease, in a fashion as suggested in table 1. The desired endpoints should be more tangible and reflective of the nature of the primary problem—for example, hypotension, duration of ventilation. The phenomenon of the “HSDA” is a continuum from physiological normality to a pathological disease state with clinical instability and varying effects on bodily organs. Although the overall desire is to improve long‐term outcomes, the starting point should be to provide excellence in intensive care, focused cardiorespiratory monitoring and early targeted intervention.
With this backdrop, we propose an individualistic and rational approach in which information obtained from echocardiographic assessment is analysed in conjunction with clinical parameters to make more focused clinical decisions.