Worsened short-term clinical outcomes in a cohort of patients with iNO-unresponsive PPHN: a case for improving iNO responsiveness

Abstract

To identify distinguishing characteristics of neonates with persistent pulmonary hypertension of the newborn (PPHN) unresponsive to inhaled nitric oxide (iNO) and evaluate the use of milrinone in this cohort. STUDY DESIGN: Retrospective chart review of 99 neonates with PPHN treated with iNO over a five-year period at a quaternary neonatal intensive care unit. RESULTS: Neonates with iNO-unresponsive PPHN had an increased number of ventilator days (10 vs 7 days, p = 0.02), greater length of hospital stay (30 vs 22 days, p = 0.02), and increased risk of death or ECMO than iNO-responsive neonates (p = 0.03). Inhaled NO non-responders treated with milrinone had improved oxygenation (p < 0.03) and no change in systemic hemodynamics. CONCLUSION: Neonates with iNO-unresponsive PPHN had worse clinical outcomes than iNO responders. Milrinone may be a safe and effective adjuvant therapy, although large-scale studies are lacking. Identifying early predictors of iNO response and novel strategies to enhance iNO responsiveness should be prioritized.

Comparison of the efficacy of inhaled versus infused milrinone in the management of persistent pulmonary hypertension of the newborn in resource‐limited settings: A randomized clinical trial

“…23 Dillard et al reported that infants who were nonrespondent to iNO and received adjuvant milrinone had a better prognosis, better oxygenation, and fewer hemodynamic changes. 28 Nevertheless, in some cases, the addition of milrinone to iNO had no significant effects on the improvement of treatment. 29 Overall, injectable milrinone, which showed satisfactory outcomes in the present study, can be used as an adjuvant or alternative therapy to PPHN management, especially in centers with limited access to iNO.…”

“…According to previous research, injectable milrinone may improve the prognosis of infants with iNO-resistant PPHN. 23,28 Mat Bah et al…”

“…Mat Bah et al reported a poorer prognosis in iNO‐resistant PPHN neonates, especially those with the idiopathic type 23 . Dillard et al reported that infants who were nonrespondent to iNO and received adjuvant milrinone had a better prognosis, better oxygenation, and fewer hemodynamic changes 28 . Nevertheless, in some cases, the addition of milrinone to iNO had no significant effects on the improvement of treatment 29 .…”

Comparison of the Efficacy of Inhaled Versus Infused Milrinone in the Management of Persistent Pulmonary Hypertension in Infants in Resource-Limited Settings A Randomized Clinical Trial

“…El-Ghandour et al (29) showed that the combination of oral sildena l and intravenous milrinone did not increase the side effects and was more effective than monotherapy with any of the drugs. Also, previous studies have shown that injectable milrinone may improve prognosis in infants with iNO-resistant PPHN (24,30) . Mat Bah et al reported a worse prognosis among iNO-resistant PPHN neonates, especially in the idiopathic type (24) .…”

“…Mat Bah et al reported a worse prognosis among iNO-resistant PPHN neonates, especially in the idiopathic type (24) . Also, Dillard et al reported that infants who were non-respondent to iNO and received adjuvant milrinone had a better prognosis, better oxygenation, and less hemodynamic change (30) . However, in some cases, the addition of milrinone to iNO has shown no signi cant effect in improving treatment (31) .…”