Supplementary Material for: Use of Continuous Physiological Monitor Data to Evaluate Doxapram Therapy in Preterm Infants

<b><i>Introduction:</i></b> Evaluation of pharmacotherapy during intensive care treatment is commonly based on subjective, intermittent interpretations of physiological parameters. Real-time visualization and analysis may improve drug effect evaluation. We aimed to evaluate the effects of the respiratory stimulant doxapram objectively in preterm infants using continuous physiological parameters. <b><i>Methods:</i></b> In this longitudinal observational study, preterm infants who received doxapram therapy were eligible for inclusion. Physiological data (1 Hz) were used to assess respiration and to evaluate therapy effects. The oxygen saturation (SpO₂)/fraction of inspired oxygen (FiO₂) ratio and the area under the 89% SpO₂ curve (duration × saturation depth below target) were calculated as measures of hypoxemia. Regression analyses were performed in 1-h timeframes to discriminate therapy failure (intubation or death) from success (no intubation). <b><i>Results:</i></b> Monitor data of 61 patients with a median postmenstrual age (PMA) at doxapram initiation of 28.7 (IQR 27.6–30.0) weeks were available. The success rate of doxapram therapy was 56%. Doxapram pharmacodynamics were reflected in an increased SpO₂ and SpO₂/FiO₂ ratio as well as a decrease in episodes with saturations below target (SpO₂ &lt;89%). The SpO₂/FiO₂ ratio, corrected for PMA and mechanical ventilation before therapy start, discriminated best between therapy failure and success (highest AUC ROC of 0.83). <b><i>Conclusion:</i></b> The use of continuous physiological monitor data enables objective and detailed interpretation of doxapram in preterm infants. The SpO₂/FiO₂ ratio is the best predictive parameter for therapy failure or success. Further implementation of real-time data analysis and treatment algorithms would provide new opportunities to treat newborns.

<b><i>引言：</i></b> 重症监护治疗期间的药物疗效评估通常基于对生理参数的主观、间歇性解读。实时可视化与分析或可优化药物效应评估流程。本研究旨在借助连续生理参数，客观评估呼吸兴奋剂多沙普仑（doxapram）对早产儿（preterm infants）的治疗效果。
<b><i>方法：</i></b> 本项纵向观察性研究纳入接受多沙普仑治疗的早产儿。研究采用频率为1 Hz的生理数据评估呼吸状态与治疗效应。以血氧饱和度（SpO₂）/吸入氧分数（FiO₂）比值，以及89% SpO₂曲线下面积（即低于目标值的持续时长×饱和度下降幅度）作为低氧血症的评估指标。通过1小时时间窗内的回归分析，区分治疗失败（需插管或死亡）与治疗成功（无需插管）两类结局。
<b><i>结果：</i></b> 本研究共纳入61例患者，其开始多沙普仑治疗时的中位月经后孕周（postmenstrual age, PMA）为28.7周（四分位距Interquartile Range, IQR 27.6~30.0周）。多沙普仑的治疗成功率为56%。多沙普仑的药效动力学特征体现为SpO₂及SpO₂/FiO₂比值升高，同时饱和度低于目标值（SpO₂<89%）的发作频次减少。经治疗前PMA与机械通气状态校正后的SpO₂/FiO₂比值，对治疗失败与成功的区分效果最优（受试者工作特征曲线下面积Area Under the Receiver Operating Characteristic Curve, AUC ROC最高达0.83）。
<b><i>结论：</i></b> 连续生理监护数据的应用可实现对早产儿多沙普仑治疗效果的客观且精细化解读。SpO₂/FiO₂比值是预测治疗成败的最优指标。进一步推广实时数据分析与治疗算法的应用，将为新生儿治疗带来新的机遇。