Four Patterns of Response to Inhaled Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn

Abstract

Objective. To determine the clinical role of inhaled nitric oxide (iNO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). Study Design. Prospective open observational clinical study. Setting. A regional cardiac and pediatric intensive care unit. Methods. Twenty-five consecutive near-term neonates (>35 weeks gestation) with severe PPHN (oxygenation index [OI]> 25) were given a trial of iNO of 20 ppm for 20 minutes. Neonates who showed a greater than 20% improvement in Pao 2 as well as a decrease in the OI to below 40 were defined as responders and continued on this therapy. Results. Four patterns of response emerged to the iNO therapy: Pattern 1 neonates (n = 2) did not respond to the initial trial of iNO—one survived. Pattern 2 neonates (n = 9) responded to the initial trial of iNO, but failed to sustain this response over 36 hours, as defined by a rise in the OI to >40. Six survived, five with extracorporeal membrane oxygenation. Pattern 3 neonates (n = 11) responded to the initial trial of iNO, sustained this response, and were successfully weaned from iNO within 5 days—all survived to discharge. Pattern 4 neonates (n = 3) responded to the initial trial of iNO, but developed a sustained dependence on iNO for 3 to 6 weeks. All three died and lung histology revealed severe pulmonary hypoplasia and dysplasia. These neonates (pattern 4) not only required iNO for a longer period of time than did the sustained responders (pattern 3), but they required significantly higher doses of iNO during their first 5 days of iNO therapy. Conclusions. Early responses to iNO may not be sustained. Neonates with pulmonary hypoplasia and dysplasia may have a decreased sensitivity and differing time course of response to iNO when compared with patients who have PPHN in fully developed lungs.

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

“…Thus, some of the neonates who were labeled as non-responders in our study may have had a late response to iNO. Alternatively, it is documented that some neonates who have an initial response to iNO fail to sustain that response over time [27,33,34], and this may have been the case in some of our patients who were labeled as responders. Some studies classified any neonate who required ECMO during the hospitalization as iNO non-responsive [8].…”

Use of vasopressin in persistent pulmonary hypertension of the newborn: A case series

“…Inhaled nitric oxide selectively reduces PVR; however, there are data suggesting approximately 30% of patients with PPHN are non-responders. 14 Sildenafil and milrinone reduce PVR via their actions as phosphodiesterase 5 and 3 inhibitors, respectively. However, their effects on SVR can induce systemic hypotension and decreased end organ perfusion.…”

Efficacy of inhaled nitric oxide in preterm infants ≤ 34 weeks: a systematic review and meta—analysis of randomized controlled trials

“…Therefore, theoretically, NO can effectively prevent or treat BPD. Clinically, NO has been shown to be a specific drug for improving short-term oxygenation in neonates and a treatment for persistent pulmonary hypertension ( Goldman et al, 1996 ; Dani et al, 2017 ). A meta-analysis showed that iNO improved short-term oxygenation and decreased ECMO use in term or near-term infants ( Barrington et al, 2017a ).…”