Rescue Inhaled Nitric Oxide in Extremely Low Birth Weight Infants: An Exercise in Futility?

Background: Despite the use of surfactant, antenatal steroids, and optimized ventilation, Extremely Low Birth Weight (ELBW) infants face significant morbidity in the form of bronchopulmonary dysplasia (BPD). The use of prophylactic inhaled nitric oxide (INO) in these patients has been studied in several trials and is not recommended. However, INO is used as a rescue therapy for hypoxic respiratory failure when other treatment options have failed. Our objective was to compare the respiratory outcomes of ELBW infants who received rescue INO during admission to similar patients who did not. Methods: With Institutional Review Board approval, data were retrospectively extracted from the medical records of all infants with birth weight ≤ 1,000 g admitted to the Rush University Children9s Hospital NICU from January 2015 to December 2017 who survived > 72 h. Patients with major congenital malformations were excluded. 150 patients were identified, of which 15 received INO. 3 patients were excluded as INO was discontinued quickly within 72 h for absence of a clinical response and no evidence of pulmonary hypertension on echocardiogram. 12 patients, who received rescue INO for hypoxic respiratory failure were compared to the remaining 138 patients. Death and tracheostomy rates were compared using Fisher Exact/Chi-Square and Odds Ratios. Demographic data and other clinical markers were evaluated by t-test or Fisher Exact to assess similarity of the groups. Results: INO recipients had lower birth weight (645 ± 175 g vs 778 ± 142 g, P =0.02) with similar birth gestational age (25.5 ± 1.6 weeks vs 25.6 ± 1.6 weeks, P =0.82) with lower weight for gestation z-scores (-0.94 ± 1.34 vs 0.06 ± 1.14, P =0.03). INO recipients had a significantly higher rate of death (92% vs 4%, P P =0.01, OR 13.6, 95% CI 1.72-106.9) compared to non-recipients. The combined outcome of death or tracheostomy was 100% vs 6% ( P Conclusions: Use of rescue INO in ELBW infants was associated with significantly worse mortality and respiratory outcomes compared to non-recipients, with 100% of recipients dying or requiring tracheostomy. Given these poor outcomes, use of rescue INO in this population for hypoxic respiratory failure cannot be recommended. Additional studies may identify a specific subset of patients with reversible pulmonary hypertension who may benefit from INO.