Clinical Factors Associated with Ventilator-Free Days in Newborns with Persistent Pulmonary Hypertension of the Newborn: A Retrospective Cohort Study in Thailand

Background/Objectives: Ventilator-free days (VFDs) are a useful composite measure to assess both survival and duration of mechanical ventilation in critically ill patients. This study aimed to determine the factors associated with (VFDs) in neonates with persistent pulmonary hypertension of the newborn (PPHN) and to compare VFDs according to the etiology and severity of PPHN. Methods: We conducted a retrospective cohort study of neonates diagnosed with PPHN between 2013 and 2023. VFDs were defined as days alive and free of mechanical ventilation within the first 28 days. Severe-to-critical PPHN group was defined as an oxygenation index (OI) > 25. Results: Among 175 neonates, the median (interquartile range [IQR]) VFDs were 20 (9–23) days. The factors independently associated with fewer VFDs included maximum OI > 40 (adjusted hazard ratio [aHR] 3.5, 95% confidence interval [CI]: 2.49–4.9), receiving more than two inotropic drugs (aHR 2.27, 95% CI: 1.49–3.45), acute kidney injury (AKI) (aHR 1.54, 95% CI: 1.1–2.17), and ventilator-associated pneumonia (VAP) (aHR 3.42, 95% CI: 1.8–6.48). The median (IQR) number of VFDs in neonates with PPHN secondary to respiratory distress syndrome (RDS), pneumonia/sepsis, meconium aspiration syndrome, and transient tachypnea of the newborn were 16 (0–22), 17 (7–21), 22 (11–24), and 22 (15–24) d, respectively (p = 0.023). Neonates in the severe-to-critical group had markedly fewer VFDs than those in the mild-to-moderate group (8.5 vs. 22 d, p < 0.001). Conclusions: Infants with PPHN from RDS had the fewest VFDs. A maximum OI > 40, use of multiple inotropic agents, AKI, and VAP were associated with a low number of VFDs. Given the retrospective, single-center design, these findings are associative and hypothesis-generating, requiring prospective multi-center validation. Nonetheless, VFDs remain a comprehensive measure of both mortality and respiratory morbidity in this population.