Life After Pediatric Sepsis Evaluation, LAPSE

描述(申请人提供)：败血症：儿科败血症后的生活评估众所周知，败血症是全球儿童死亡的主要原因。然而，与成人医学不同的是，在儿童脓毒症后的长期健康相关生活质量(HRQL)和功能状态(FS)方面存在很大的知识差距。这种败血症结局数据的缺乏是至关重要的，因为未能识别出与脓毒症相关的风险儿童 HRQL/FS的恶化可能会延误关键康复药物的交付，以促进康复。此外，未能确定败血症相关的HRQL/FS恶化的机制可能会阻碍针对这些儿童的新的、有效的干预措施的发展。这项研究将首次测量败血症休克存活儿童中HRQL/FS改变的发生率、强度和持续时间，并检查此类不良后果的潜在临床危险因素。目前，儿童败血症相关不良结局的潜在机制尚不清楚。然而，在临床上，两种循环往复式脓毒症损伤，即炎症和缺血/缺氧，似乎是多器官功能障碍综合征(MODS)的关键前驱因素，该综合征与脓毒症死亡率和长期发病率有关。器官衰竭负担，特别是心血管和肺功能障碍，已被证明与成人危重疾病后的长期发病率和死亡率密切相关。这项失误的研究假设，经过验证的脓毒症介导的器官功能障碍的测量将预测脓毒症相关的HRQL/FS恶化的程度，而恢复到基线HRQL/FS将受到儿童慢性合并症的复杂性以及父母、家庭和家庭特征的强烈影响。由于改善HRQL可能是医学上最重要的目标，本研究计划的长期目标是及时识别脓毒症所致HRQL/FS恶化的高危儿童，并最终设计有效的干预措施，将此类风险降至最低。该应用的主要目的是全面描述HRQL/FS的结果，并严格检查脓毒症相关的HRQL/FS恶化的潜在临床危险因素。中心假设是，HRQL/FS恶化的程度将基于器官功能障碍的有效临床标志物，父母、家庭和家庭特征以及病前状况将影响回到基线HRQL/FS的轨迹。了解儿童感染性休克的当代自然病史将有助于制定针对性的干预措施，以最大限度地提高败血症患儿的HRQL/FS。

DESCRIPTION (provided by applicant): LAPSE: Life After Pediatric Sepsis Evaluation It is well known that sepsis represents the leading cause of childhood mortality worldwide. However, as distinct from adult medicine, there exists a large knowledge gap regarding long-term health-related quality of life (HRQL) and functional status (FS) following pediatric sepsis. This lack of sepsis outcomes data is critical because failure to identify children at risk for sepsis-associated HRQL/FS deterioration may delay delivery of crucial rehabilitation medicine efforts to facilitate recovery. Moreover, failure to identify mechanisms of sepsis- associated HRQL/FS deterioration may impede development of novel, effective interventions for these children. For the first time this investigation will measure the incidence, intensity and duration of HRQL/FS alterations among children surviving septic shock, and examine potential clinical risk factors for such adverse outcomes. Mechanisms underlying adverse sepsis-associated outcomes among children are poorly understood at this time. Clinically however, two circular reciprocating sepsis insults, namely inflammation and ischemia/dysoxia, appear to be key antecedents for multiple organ dysfunction syndrome (MODS) that has been linked to sepsis mortality and perhaps long term morbidity. Organ failure burden, particularly cardiovascular and pulmonary dysfunction, has been shown to be strongly associated with long term morbidity and mortality following adult critical illness. The LAPSE investigation hypothesizes that validated measures of sepsis-mediated organ dysfunction will predict magnitude of sepsis-associated deterioration in HRQL/FS, and that recovery towards baseline HRQL/FS will be strongly influenced by complexity of children's chronic comorbid conditions and parent, family and home characteristics. As improving HRQL may be the most important goal of medicine, the long-term goal of this research program is to timely identify children at high risk of sepsis-mediated HRQL/FS deterioration and to ultimately design effective interventions to minimize such risk. The primary objectives of this application are to comprehensively characterize HRQL/FS outcomes and to critically examine the potential clinical risk factors for sepsis-associated HRQL/FS deterioration. The central hypothesis is that magnitude of HRQL/FS deterioration will be predicated on validated clinical markers of organ dysfunction, and that parent, family and home characteristics as well as premorbid conditions will influence trajectory back to baseline HRQL/FS. Knowledge of the contemporary natural history of pediatric septic shock will facilitate development of targeted interventions to maximize HRQL/FS among children surviving sepsis.