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

Abstract

Objective To determine if a moderate-to-large 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, PINDO infants had a significantly lower incidence of vasopressor-dependent hypotension (11%) than Conservative infants (21%)(OR=0.40, 95% CI: 0.20–0.82). PINDO infants also required less Mean Airway Pressure, had a lower Respiratory Severity Score and lower Mode of Ventilation Score than Conservative infants 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.

Prophylactic Indomethacin Compared with Delayed Conservative Management of the Patent Ductus Arteriosus in Extremely Preterm Infants: Effects on Neonatal Outcomes

“…Infants were included in the current study if they were born between January 2005 and August 2016, delivered at ≤27 6/7 weeks gestation, and admitted to the intensive care nursery at the University of California San Francisco within 24 hours of birth. Detailed descriptions of our approach to respiratory and hemodynamic support have been previously published (5, 12–14). …”

“…Early pharmacologic treatment of the PDA is effective in closing the PDA, decreasing the incidence of hemorrhagic pulmonary edema (1–3) and hypotension, and decreasing the need for early ventilator and inotropic support (4, 5). However, long-term benefits appear to be lacking (2, 4, 6–9).…”

Treatment and Nontreatment of the Patent Ductus Arteriosus: Identifying Their Roles in Neonatal Morbidity

“…As was seen in the earlier RCTs, there were no differences between the “treatment” and “no treatment” groups in the rates of death, NEC, and severe ROP. On the other hand, when PDA “rescue” treatment was delayed beyond 8 days, there was a significant increase in the need for ventilator and inotropic support at the end of the first week (51), as well as an increase in the incidence of BPD and BPD/Death in the “no treatment” group (49, 50). Although “treating” the PDA early in the first week had a significant effect on decreasing the incidence of BPD and BPD/Death, each week that “rescue” treatment was delayed reduced its effectiveness in preventing the occurrence of BPD and BPD/Death (49).…”

Early prediction of a significant patent ductus arteriosus in infants <32 weeks gestational age

“…Individual parameters of ductal features (Transductal diameter and ductal velocity), magnitude of ductal shunts, and features of myocardial performance (E/A ratio and isovolumetric relaxation time) were graded from 1 to 3 depending on the magnitude of severity. Of these parameters, ductal diameter was the most important factor for determining therapeutic intervention [23]. It has been shown that ductal diameter greater than 1.5 mm at a mean of 19 hours after birth predicted later clinically apparent PDA that required treatment in a cohort of extremely premature, ventilated newborns [24].…”