Inhaled nitric oxide a "rescue therapy" for preterm infants with Persistent Pulmonary Hypertension

Turkey: A study published in the Journal of Health Sciences and Medicine concluded that infants of gestational age < 34 weeks with Persistent Pulmonary Hypertension (PHT) respond well to inhaled nitric oxide (iNO) and are associated with a significant proportion of survival. The study added that usage of iNO could be a rescue therapy in preterm infants in the presence of PHT due to oligohydramnios.

Nitric oxide (NO) relaxes the smooth muscles and plays an essential role in controlling pulmonary artery pressure and bronchial tone. There is a higher risk of mortality and morbidity in persistent increased pulmonary vascular resistance, clinically characterized by hypoxemic respiratory failure (HRF). In such a condition, there is persistent pulmonary Hypertension in the newborn (PPHN).

Inhaled nitric oxide (iNO) has been related to increased survival in hypoxemic or near-term infants. The literature mentions that many studies have failed to demonstrate iNO benefits in preterm infants (before 34 weeks). This may be due to insufficient standardization and a lack of disease stratification.

Considering this, a study was conducted by Dr. Gonca Vardar from the University of Health Sciences, Turkey, to evaluate whether iNO is effective concerning acute oxygenation and clinical status in premature infants with persistent pulmonary Hypertension.

The critical point of the study are:

• The study included 25 infants.

• 48% of infants (n = 12) positively responded to iNO administration for PHT.

• Responders had higher oligohydramnios and were significant [41.7% vs. 0%]. The p-value was 0.015.

• The rate of mortality was lower, with a p-value of 0.039 (66% vs. 100%).

• Before iNO treatment, SpO2/FiO2 ratio predicted the response to iNO in preterm infants with PHT.

• The ROC analysis yielded an area under curve AUC for SpO2/FiO2 ratio before iNO of AUCSpO2/ FiO2 before was 0.756 with a P value of 0.03.

• Before iNO treatment, a cut-off value of 79 points by the SpO2/FiO2 ratio predicted the response to iNO treatment.

• The sensitivity and specificity recorded were 83 % and 70 %.

FDA approved iNO for use in term and near-term infants with PPHN in the year 1999. Recent data on the incidence of PHT in term and late preterm infants is reported to be 1-2 per 1000 live births.

The researchers wrote, "In our study, the median maximum dose for iNO was observed as 20 (20-35) among positive responders, compared to 40 (40-40) in negative responders. So it could be noted that iNO has a good safety profile used at 20ppm." They mentioned, "We found the most significant factor, oligohydramnios which was related to a positive response to iNO in our study. In pregnancies complicated by PPROM and oligohydramnios, very low nitrite and nitrate levels are associated with HRF. During iNO initiation, nitrite and nitrate concentrations increase.

The study's findings were consistent with those mentioned in the literature.

The researchers explained that both lower and higher doses are equally effective, while higher doses provide no additional advantages and benefits. Methemoglobinemia is the absolute contra-indication of iNO.

Further reading:

Vardar G, Aksoy Okan M, Karadağ N, et al. Controversies in neonatology: The efficacy of inhaled nitric oxide in preterm infants with persistent pulmonary Hypertension. J Health Sci Med 2022; 5(5): 1303-1311