Effects of Prophylactic Indomethacin on Vasopressor-Dependent Hypotension in Extremely Preterm Infants

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Abstract

Objective

To determine whether a moderate-to-large patent ductus arteriosus (PDA) is responsible for vasopressor-dependent hypotension, occurring at the end of the first postnatal week.

Study design

We performed a retrospective, double cohort controlled study of infants delivered at ≤27+6 weeks' gestation (n = 313). From January 2004 through April 2011, all infants were treated with prophylactic indomethacin ([PINDO] epoch). From May 2011 through December 2015, no infant was treated with indomethacin until at least 8 postnatal days (conservative epoch). Echocardiograms were performed on postnatal days 6 or 7. Hypotension was managed by a predefined protocol. The primary outcome was the incidence of dopamine-dependent hypotension, defined as having received at least 6 μg/kg/min dopamine for at least 24 hours during postnatal days 4-7.

Results

As expected, the incidence of moderate-to-large PDA at the end of the first week differed significantly between epochs (PINDO = 8%; conservative = 64%). In multivariate analyses, infants in the PINDO epoch had a significantly lower incidence of vasopressor-dependent hypotension (11%) than infants in the conservative epoch (21%; OR = 0.40, 95% CI 0.20-0.82). Infants in the PINDO epoch also required less mean airway pressure, had a lower respiratory severity score, and lower mode of ventilation score than infants in the conservative epoch during postnatal days 4-7. The effects of PINDO on both the incidence of vasopressor-dependent hypotension and the need for respiratory support were no longer significant when analyses were adjusted for “presence or absence of a moderate-to-large PDA.”

Conclusion

PINDO decreases vasopressor-dependent hypotension and the need for respiratory support at the end of the first postnatal week. These effects are mediated by closure of the PDA.

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