Experience of cases with inhaled nitric oxide and therapeutic hypothermia

Neonates with hypoxic-ischemic encephalopathy (HIE) on therapeutic hypothermia (TH) therapy may show persistent pulmonary hypertension of the newborn (PPHN). In Japan, the reported mortality rate is lower than in the US, possibly due to treatment differences of newborns with moderate to severe HIE and PPHN. This study aimed to determine the feasibility and long-term outcomes of inhaled nitric oxide (iNO) and TH therapy in newborns with moderate to severe HIE and PPHN.

This was a retrospective review of neonates with moderate to severe HIE that were treated with TH from 2008 to 2017 at a large medical center in Japan. We documented their long-term neurological prognosis, measuring their developmental and Gross Motor Function Classification System level at 18 months old.

A total of 37 neonates with moderate to severe HIE underwent TH therapy and six of them were started with iNO therapy for PPHN. iNO with TH was safely administered to all six newborns with moderate to severe HIE with PPHN. In two neonates TH was discontinued because of intraventricular hemorrhage (IVH) and severe hypotension. Neurological outcomes were similar in newborns who were treated with iNO and TH and those who were treated with TH alone.

These initial findings suggest that monitoring hematological and cardiovascular status is important with iNO for severe asphyxia in infants with PPHN. Safer and more feasible protocols are needed for when iNO and TH therapy are administered together.