小儿(PARDS)和新生儿(NARDS)急性呼吸窘迫综合征具有不同的年龄特异性特征和定义。在PARDS和NARDS定义之前,儿童和新生儿的表面活性剂治疗ARDS的试验已经进行得很好,结果相互矛盾。这主要是由于研究设计的异质性反映了病理生物学知识的历史缺乏。我们回顾了可用的临床和临床前数据,以建立专家共识,旨在为未来的研究步骤提供信息并促进该领域的知识。8项试验调查了儿童和新生儿使用表面活性剂治疗ARDS的情况,分别。氧合有所改善(7/8儿童试验,新生儿7/10)和死亡率(儿童3/8试验,新生儿的1/10)改善。试验对患者的特征是异质的,表面活性剂类型和给药策略。研究设计中遗漏了关键的病理生物学概念。在四个声明上达成了共识并达成了强有力的共识:1。有足够的临床前和临床数据支持针对PARDS和NARDS的表面活性剂治疗的靶向研究。应根据当前可用的定义并考虑最近的病理生物学知识进行研究。2.PARDS和NARDS应被视为综合征,应根据关键特征进行临床前研究,如直接或间接(主要或次要)性质,临床严重程度,传染性或非传染性起源或患者年龄。3.对于PARDS和NARDS的未来试验,应优先考虑解释性设计,而不是务实设计。4.PARDS和NARDS需要选择不同的临床结果,根据试验阶段和设计,触发器类型,严重等级和/或表面活性剂处理政策。我们提倡进一步精心设计的临床前和临床研究,以研究遵循这些原则的表面活性剂在PARDS和NARDS中的应用。
Pediatric (
PARDS) and neonatal (NARDS) acute respiratory distress syndrome have different age-specific characteristics and definitions. Trials on surfactant for ARDS in children and neonates have been performed well before the
PARDS and NARDS definitions and yielded conflicting results. This is mainly due to heterogeneity in study design reflecting historic lack of pathobiology knowledge. We reviewed the available clinical and preclinical data to create an expert
consensus aiming to inform future research steps and advance the knowledge in this area. Eight trials investigated the use of surfactant for ARDS in children and ten in neonates, respectively. There were improvements in oxygenation (7/8 trials in children, 7/10 in neonates) and mortality (3/8 trials in children, 1/10 in neonates) improved. Trials were heterogeneous for patients\' characteristics, surfactant type and administration strategy. Key pathobiological concepts were missed in study design.
Consensus with strong agreement was reached on four statements: 1. There are sufficient preclinical and clinical data to support targeted research on surfactant therapies for PARDS and NARDS. Studies should be performed according to the currently available definitions and considering recent pathobiology knowledge. 2. PARDS and NARDS should be considered as syndromes and should be pre-clinically studied according to key characteristics, such as direct or indirect (primary or secondary) nature, clinical severity, infectious or non-infectious origin or patients\' age. 3. Explanatory should be preferred over pragmatic design for future trials on
PARDS and NARDS. 4. Different clinical outcomes need to be chosen for PARDS and NARDS, according to the trial phase and design, trigger type, severity class and/or surfactant treatment policy. We advocate for further well-designed preclinical and clinical studies to investigate the use of surfactant for PARDS and NARDS following these principles.