Occurrence of hyperoxia during iNO treatment for persistent pulmonary hypertension of the newborn: a cohort study

Abstract

High concentrations of oxygen are often needed to optimize oxygenation in infants with persistent pulmonary hypertension (PPHN), but this can also increase the risk of hyperoxemia. We determined the occurrence of hyperoxemia in infants treated for PPHN. Medical records of infants ≥ 34 + 0 weeks gestational age (GA) who received inhaled nitric oxide (iNO) were retrospectively reviewed for oxygenation parameters during iNO therapy. Oxygen was manually titrated to target arterial oxygen tension (PaO₂) 10-13 kPa and peripheral oxygen saturation (SpO₂) 92-98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO₂). A total of 181 infants were included. The median FiO₂ was 0.43 (IQR 0.34-0.56) and the maximum FiO₂ was 1.0 in 156/181 (86%) infants, resulting in at least one PaO₂ > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO₂ > 30 kPa. SpO₂ was > 98% in 179/181 (99%) infants for 17.7% (8.2-35.6%) of the iNO time. PaO₂ < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO₂ < 6.7 kPa. SpO₂ was < 92% in 169/181 (93%) infants for 1.6% (0.5-4.3%) of the iNO time. Conclusion: While treatment of PPHN is focused on preventing and reversing hypoxemia, hyperoxemia occurs inadvertently in most patients. What is Known: • High concentrations of oxygen are often needed to prevent hypoxemia-induced deterioration of PPHN, but this can also increase the risk of hyperoxemia. • Infants with persistent pulmonary hypertension may be particularly vulnerable to the toxic effects of oxygen, and hyperoxemia could further induce pulmonary vasoconstriction, potentially worsening the condition. What is New: • Hyperoxemia occurs in the majority of infants with PPHN during treatment with iNO. • Infants with PPHN spent a considerably longer period with saturations above the target range compared to saturations below the target range.

Keywords: Hyperoxia; Newborn; Nitric Oxide; Oxygen therapy; Persistent pulmonary hypertension.

Fig. 1

Flow chart of inclusion and exclusion criteria. The numbers in bold represent the number of infants. iNO, inhaled nitric oxide; GA, gestational age; PaO₂, arterial oxygen tension

Fig. 2

Oxygenation parameters outside the target range. a Proportion of infants (N = 181) with at least one PaO₂ outside the target range during iNO therapy. b Proportion of iNO time with a SpO₂ outside the target range. Values are presented as median (IQR). PaO₂, arterial oxygen tension; SpO₂, oxygen saturation (pulse oximetry); iNO, inhaled nitric oxide