PaCO₂ in surfactant, positive pressure, and oxygenation randomised trial (SUPPORT)

Objective: To determine the association of arterial partial pressure of carbon dioxide PaCO₂with severe intraventricular haemorrhage (sIVH), bronchopulmonary dysplasia (BPD), and neurodevelopmental impairment (NDI) at 18-22 months in premature infants. Design: Secondary exploratory data analysis of Surfactant, Positive Pressure, and Oxygenation Randomised Trial (SUPPORT). Setting Patients: Multiple referral neonatal intensive care units. 1316 infants 24 0/7 to 27 6/7 weeks gestation randomised to different oxygenation (SpO₂target 85-89% vs 91-95%) and ventilation strategies. Main outcome measures: Blood gases from postnatal day 0 to day14 were analysed. Five PaCO₂variables were defined: minimum (Min), maximum (Max), SD, average (time-weighted), and a four level categorical variable (hypercapnic (highest quartile of Max PaCO₂), hypocapnic (lowest quartile of Min PaCO₂), fluctuators (hypercapnia and hypocapnia), and normocapnic (middle two quartiles of Max and Min PaCO₂)). PaCO₂variables were compared for infants with and without sIVH, BPD and NDI (±death). Multivariable logistic regression models were developed for adjusted results. Results: sIVH, BPD and NDI (±death) were associated with hypercapnic infants and fluctuators. Association of Max PaCO₂and outcomes persisted after adjustment (per 10 mm Hg increase: sIVH/death: OR 1.27 (1.13 to 1.41); BPD/death: OR 1.27 (1.12 to 1.44); NDI/death: OR 1.23 (1.10 to 1.38), death: OR 1.27 (1.12 to 1.44), all p<0.001). No interaction was found between PaCO₂category and SpO₂treatment group for sIVH/death, NDI/death or death. Max PaCO₂was positively correlated with maximum FiO₂(r_s0.55, p<0.0001) and ventilator days (rs0.61, p<0.0001). Conclusions: Higher PaCO₂was an independent predictor of sIVH/death, BPD/death and NDI/death. Further trials are needed to evaluate optimal PaCO₂targets for high-risk infants.