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Outcome of preterm infants who received rescue inhaled nitric oxide to treat hypoxic respiratory failure

Presented at the Neonatal Society 2018 Spring Meeting (programme).

Noureldein M, Shing H, Nallagonda S, Somisetty S

Luton and Dunstable University Hospital, United Kingdom

Background: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that has been demonstrated its efficacy when used to treat hypoxaemic respiratory failure in term or near term newborns (1,2). Premature newborn infants are not included in the approved indication of iNO use, but in some circumstances, when pulmonary hypertension is associated with severe respiratory failure, iNO has been demonstrated as an effective therapy to improve respiratory failure (3). Aim of the study: to evaluate the efficacy of rescue iNO in improving oxygenation in hypoxic respiratory failure in preterm infants <35-week gestation. Also, to look at mortality, morbidity and neurodevelopmental outcome at 2-year CGA.

Methods: A retrospective review was carried out of all preterm infants <35 weeks admitted to our tertiary NICU who required rescue iNO for hypoxic respiratory failure between Jan 2012 to Dec 2016. Data was collected from local, national electronic and other relevant databases.

Results: We included 24 babies with gestation of 24+1 to 34+2 weeks (mean 27+6 w) and birth weight 540- 2980 g (mean 1321 g). 11/24 had PROM ≥2wks. Mean age at starting iNO was 19 hours (1.7- 240 hrs). There was significant difference in Oxygenation index (OI) before and one hour after administration of iNO (p<0.0001 Wilcoxon test) .16/24 (67%) survived and 8/24 (33%) died, birth weight was significantly higher in survived group (p = 0.0152), but there was no significant difference in gestational age (Mann-Whitney p = 0.6404) between survivors and non-survivors. 9/11 (82%) with PROM ≥2 weeks survived versus 7/13 (54%) with PROM <2weeks (p = 0.2108 Fisher's exact test). 3/16 of survivors had grade IIIIV IVH versus 2/8 of non-survivors in the first two weeks of life. In Survival group, discharge cranial ultrasound showed normal results (10/16). 10/16 (63%) had chronic lung disease, however only 6/16 (37%) discharged on home oxygen. 10/16 (63%) were eligible for 2-year Neurodevelopmental assessment and 5/10 (50%) showed age appropriate development.

Conclusion: Reversal of pulmonary hypertension and hypoxia was rapid and effective in our cohort of preterm infants. Patients with PROM ≥2wks showed dramatic response to iNO and had higher rates of survival. The outcome of this cohort of very sick preterm infants is multifactorial; however survival was 67%, only 37% of them needed home O2 and 50% had normal development at 2 years.

Corresponding author:

1. Sánchez Luna M, Franco ML, Zamora E, Bernardo B. Nitric Oxide for preterm infants. J Pediatr Neonat Individual Med. 2013;2(2):e020217
2. Marc A. Ellsworth, Malinda N. Harris, William A. Carey, Alan R. Spitzer, Reese H. Clark. Off-Label Use of Inhaled Nitric Oxide After Release of NIH Consensus Statement. Pediatrics 2015;135;643
3. Aikio O, Metsola J, Vuolteenaho R, Perhomaa M, Hallman M.Transient defect in nitric oxide generation after rupture of fetal membranes and responsiveness to inhaled nitric oxide in very preterm infants with hypoxic respiratory failure. J Pediatr. 2012 Sep;161(3):397-403.e1

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