Nitric oxide therapy in persistent pulmonary hypertension of the newborns (PPHN): predictors of survival in a single center experience

Background and aim

Inhaled nitric oxide therapy is an established method for management of PPHN – introduced in our unit 3 years ago. We summarized our experience with iNO treatment in search for predictors of the outcome.

Materials and methods

Thirty newborns (range of gestational age, 25–39 weeks; birth weight range, 700–4500 g; CRIB range, 1–14; mean, 9 pts) admitted to neonatal intensive care unit with clinical features of PPHN and treated with inhaled nitric oxide were analysed. The mean time of NO inhalation was 83 hours (range: 4–192 hours). All infants were ventilated with a Babylog 8000 infant ventilator with NO-Domo adapter. Twenty-two survived, eight died. Arterial blood gases, hemoglobin saturation (pulsoxymetry), respiratory parameters and echocardiography were obtained at least every 12 hours up to 24 hours after discontinuation of the therapy. High pulmonary resistance was defined by tricuspid regurgitation jet V_max > 3 m/s, pulmonary artery blood flow AT/ET < 0.27 and decreased cardiac output CO < 200 ml/kg per min.

Results

The group of survivors did not differ in respect to gestational age and Apgar scores from fatal cases. However, survivors had significantly higher birth weight (3094 ± 940 g vs 2075 ± 1018 g, P < 0.05) and lower CRIB (8 ± 3 vs 12 ± 2 pts, P < 0.001).

The newborns in the survival group had significantly higher hemoglobin saturation (88 ± 8% vs 74 ± 20%, P = 0.03) and blood hydroxycarbonate levels (21.7 ± 3.3 vs 18.7 ± 2.5 mmol/l, P = 0.03) and lower serum lactates values before the initiation of therapy (4.0 ± 3.7 vs 11.5 ± 2.8 mmol/l, P < 0.001). In ECHO evaluation all nonsurvivals presented very severe pulmonary hypertension, while in the other group nine had severe and 13 had moderately elevated resistance in pulmonary circulation. A marked decrease in mean airway pressure (MAP) and oxygenation index (OI) accompanied with an increase in pO₂ was observed since the 6th hour of treatment in the group of survivals. The decline of serum lactates was observed much later (after 24 hours). Such changes were not observed in nonsurvivors. Twelve hours after discontinuation of the therapy, transient increases in MAP and decrease in pO₂ were observed.

Conclusions

Based on the results we conclude that initial values of hemoglobin saturation and blood hydroxycarbonate as well as quick improvement of OI and pO₂ and a decrease in MAP are important predictors of survival PPHN newborns designated for iNO therapy. Additionally, high serum lactate concentration at the beginning of iNO therapy, persistent through the following hours, very strongly indicates a negative outcome.