Supplementary Material for: Characterisation of the Oxygenation Response to Inspired Oxygen Adjustments in Preterm Infants

<b><i>Background:</i></b> Oxygen saturation (SpO<sub>2</sub>) targeting in the preterm infant may be improved with a better understanding of the SpO<sub>2</sub> responses to changes in inspired oxygen (FiO<sub>2</sub>). <b><i>Objective:</i></b> We investigated the first-order FiO<sub>2</sub>-SpO<sub>2</sub> relationship, aiming to quantify the parameters governing that relationship, the influences on these parameters and their variability. <b><i>Methods:</i></b> In recordings of FiO<sub>2</sub> and SpO<sub>2</sub> from preterm infants on continuous positive airway pressure and supplemental oxygen, we identified unique FiO<sub>2</sub> adjustments and mapped the subsequent SpO<sub>2</sub> responses. For responses identified as first-order, the delay, time constant and gain parameters were determined. Clinical and physiological predictors of these parameters were sought in regression analysis, and intra- and inter-subject variability was evaluated. <b><i>Results:</i></b> In 3,788 h of available data from 47 infants at 31 (28-33) post-menstrual weeks [median (interquartile range)], we identified 993 unique FiO<sub>2</sub> adjustments followed by a first-order SpO<sub>2</sub> response. All response parameters differed between FiO<sub>2</sub> increments and decrements, with increments having a shorter delay, longer time constant and higher gain [2.9 (1.7-4.8) vs. 1.3 (0.58-2.6), p < 0.05]. Gain was also higher in less mature infants and in the setting of recent SpO<sub>2</sub> instability, and was diminished with increasing severity of lung dysfunction. Intra-subject variability in all parameters was prominent. <b><i>Conclusions:</i></b> First-order SpO<sub>2</sub> responses show variable gain, influenced by the direction of FiO<sub>2</sub> adjustment and the severity of lung disease, as well as substantial intra-subject parameter variability. These findings should be taken into account in adjustment of FiO<sub>2</sub> for SpO<sub>2</sub> targeting in preterm infants.