Department of Paediatrics, Division of Paediatric Critical Care Medicine, Beatrix Children's Hospital, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Department of Epidemiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
Trials. 2022 Jan 31;23(1):96. doi: 10.1186/s13063-021-05927-w.
Paediatric acute respiratory distress syndrome (PARDS) is a manifestation of severe, life-threatening lung injury necessitating mechanical ventilation with mortality rates ranging up to 40-50%. Neuromuscular blockade agents (NMBAs) may be considered to prevent patient self-inflicted lung injury in PARDS patients, but two trials in adults with severe ARDS yielded conflicting results. To date, randomised controlled trials (RCT) examining the effectiveness and efficacy of NMBAs for PARDS are lacking. We hypothesise that using NMBAs for 48 h in paediatric patients younger than 5 years of age with early moderate-to-severe PARDS will lead to at least a 20% reduction in cumulative respiratory morbidity score 12 months after discharge from the paediatric intensive care unit (PICU).
This is a phase IV, multicentre, randomised, double-blind, placebo-controlled trial performed in level-3 PICUs in the Netherlands. Eligible for inclusion are children younger than 5 years of age requiring invasive mechanical ventilation with positive end-expiratory pressure (PEEP) ≥ 5 cm HO for moderate-to-severe PARDS occurring within the first 96 h of PICU admission. Patients are randomised to continuous infusion of rocuronium bromide or placebo for 48 h. The primary endpoint is the cumulative respiratory morbidity score 12 months after PICU discharge, adjusted for confounding by age, gestational age, family history of asthma and/or allergy, season in which questionnaire was filled out, day-care and parental smoking. Secondary outcomes include respiratory mechanics, oxygenation and ventilation metrics, pulmonary and systemic inflammation markers, prevalence of critical illness polyneuropathy and myopathy and metrics for patient outcome including ventilator free days at day 28, length of PICU and hospital stay, and mortality DISCUSSION: This is the first paediatric trial evaluating the effects of muscular paralysis in moderate-to-severe PARDS. The proposed study addresses a huge research gap identified by the Paediatric Acute Lung Injury Consensus Collaborative by evaluating practical needs regarding the treatment of PARDS. Paediatric critical care practitioners are inclined to use interventions such as NMBAs in the most critically ill. This liberal use must be weighed against potential side effects. The proposed study will provide much needed scientific support in the decision-making to start NMBAs in moderate-to-severe PARDS.
ClinicalTrials.gov NCT02902055 . Registered on September 15, 2016.
儿科急性呼吸窘迫综合征（PARDS）是一种严重的、危及生命的肺部损伤表现，需要机械通气，死亡率高达 40-50%。神经肌肉阻滞剂（NMBAs）可用于预防 PARDS 患者的自我造成的肺损伤，但两项针对严重 ARDS 成人的试验得出了相互矛盾的结果。迄今为止，缺乏针对 PARDS 的 NMBA 有效性和疗效的随机对照试验（RCT）。我们假设，在 5 岁以下、早期中重度 PARDS 的儿科患者中使用 NMBA 治疗 48 小时，将导致儿科重症监护病房（PICU）出院后 12 个月累积呼吸发病率评分至少降低 20%。
这是一项在荷兰 3 级 PICU 进行的 IV 期、多中心、随机、双盲、安慰剂对照试验。符合纳入标准的是在 PICU 入院后 96 小时内，需要接受正呼气末压（PEEP）≥5cmH2O 的中重度 PARDS 患儿，需要接受有创机械通气。患者随机接受罗库溴铵或安慰剂持续输注 48 小时。主要终点是 PICU 出院后 12 个月的累积呼吸发病率评分，通过年龄、胎龄、哮喘和/或过敏家族史、填写问卷的季节、日托和父母吸烟情况进行混杂因素调整。次要结局包括呼吸力学、氧合和通气指标、肺和全身炎症标志物、危重病多发性神经病和肌病的发生率以及患者结局指标，包括第 28 天无呼吸机天数、PICU 和住院时间以及死亡率。
这是第一项评估中重度 PARDS 中肌肉麻痹效果的儿科试验。该研究通过评估治疗 PARDS 的实际需求，解决了由儿科急性肺损伤共识协作组确定的巨大研究空白。儿科重症监护医生倾向于在最危重的患者中使用 NMBA 等干预措施。这种自由使用必须与潜在的副作用进行权衡。该研究将为中度至重度 PARDS 中开始使用 NMBA 的决策提供急需的科学支持。
ClinicalTrials.gov NCT02902055。于 2016 年 9 月 15 日注册。
