Non-pharmacological management of a hemodynamically significant patent ductus arteriosus

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Abstract

The association between the patent ductus arteriosus (PDA) and neonatal morbidity, mortality and poor neurodevelopmental outcome in later childhood has been the focus of intense debate for decades. The lack of evidence supporting therapeutic strategies aimed at achieving PDA closure has led to the widespread adoption of conservative management aimed at mitigating the impact of shunt volume without achieving ductal closure. In this article, we review this management approach, describe the supportive evidence and potential complications associated with this strategy.

Introduction

The association between the patent ductus arteriosus (PDA) and neonatal morbidity, mortality, and poor neurodevelopmental outcome in later childhood has been the focus of intense debate for decades. Despite numerous observational studies and more than 50 randomized controlled trials (RCTs), an agreed consensus on its management in the premature neonatal population remains elusive. Controversy still exists regarding the determination (and definition) of ductal hemodynamic significance, appropriate identification of infants for therapy, selection of treatment regimen, and the exact impact of PDA treatment on meaningful short- and long-term outcomes. The ongoing substantial heterogeneity in clinical practice regarding PDA management was recently highlighted by the European Population-Based Cohort Study (EPICE) study which reported that PDA treatment varied from 10% to 39% between regions, and that this difference could not be explained by differences in perinatal characteristics [1].

There is increasing consensus that shunt volume, rather than periodic estimates of transductal diameter, represents a more holistic and accurate measure of the hemodynamic impact of a PDA. The physiological impact of the duct is governed by Poiseuille's law which states that “At a constant driving pressure the flow rate of liquid through a tube is directly proportional to the fourth power of the radius of the tube and inversely proportional to the length and viscosity of the tube.” Poiseuille's law confirms that the diameter of the blood vessel plays the greatest role of all factors in determining the rate of blood flow through a vessel, as the rate of blood flow through a vessel is directly proportional to the fourth power of the radius of that vessel. In the setting of a PDA, vessel length, the pressure gradient across the vessel, blood viscosity, and the diameter of the vessel all change constantly over the first few days following birth. This dynamic nature of the components which govern flow makes estimation of the volume of the shunt difficult at best (Fig. 1).

Section snippets

The active treatment approach

Over the first days following birth, the transition from fetal to neonatal circulation induces a fall in pulmonary vascular resistance. Shunting from the systemic to pulmonary circulation across the ductus due to this fall in pulmonary vascular resistance leads to pulmonary over-circulation and systemic hypoperfusion. This is the mechanism by which the ductus arteriosus is thought to be associated with a variety of adverse neonatal outcomes including intraventricular hemorrhage (IVH),

Conservative management strategies

Conservative PDA management amalgamates various clinical strategies to mitigate the degree of left-to-right ductal shunting without pursuing active PDA closure through medical or surgical means. This is based on the premise that most PDAs eventually close spontaneously in premature infants prior to hospital discharge. It is, however, prudent to recognize that the conservative approach does not imply “ignoring” the presence of a PDA, nor does it preclude active assessment and management of the

Further considerations

The conservative approach to PDA management is based on the lack of clear evidence of benefit from randomized trials of PDA closure strategies, concern related to the adverse consequences of non-judicious use of medical or surgical treatment, and the assumption that the adverse consequence of shunt volume may be modulated by supportive measures while the natural course of ductal closure over time occurs. The scientific evidence for the components of the conservative approach are based on the

Conclusions

In summary, management of premature neonates with a PDA remains contentious. Justification for the conservative approach to PDA management arose from a large body of evidence found no benefit to ductal closure in prophylactic treatment studies [7]. The conservative approach recommends active management of the PDA shunt, without the administration of drugs that promote PDA closure, and includes fluid restriction, avoidance of anemia, ventilation strategies, and diuretic therapy. It is important

Practice points

  • The association between the PDA and neonatal morbidity, mortality, and poor neurodevelopmental outcome in later childhood is unclear.

  • There is no associated improvement in critical, short- and long-term outcomes following medical or surgical PDA closure.

  • Conservative PDA management amalgamates various clinical strategies to mitigate the degree of left-to-right ductal shunting without pursuing active PDA closure through medical or surgical means.

Research directions

  • Conservative PDA management strategies require a systematic assessment in an RCT setting.

  • Better delineation of problematic PDAs is warranted in a prospective cohort study setting to assess association with important outcomes.

Conflict of interest statement

None declared.

Funding sources

Afif El-Khuffash is in receipt of the following grants: EU FP7/2007–2013 grant (agreement no. 260777, The HIP Trial); the Friends of the Rotunda Research Grant (FoR/EQUIPMENT/101572); Health Research Board Mother and Baby Clinical Trials Network Ireland (CTN-2014-10); Medical Research Charities Group/Health Research Board/Friends of the Rotunda Research Grant (HANDLE Study, MRCG-2013-9).

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