Life After Pediatric Sepsis Evaluation, LAPSE

描述（由申请人提供）：LAPSE：儿科脓毒症后的生活评价众所周知，脓毒症是全球儿童死亡的主要原因。然而，与成人医学不同的是，在儿科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。败血症结局数据的缺乏是至关重要的，因为未能识别败血症相关风险的儿童， HRQL/FS恶化可能会延迟关键的康复医学工作，以促进恢复。此外，未能确定脓毒症相关HRQL/FS恶化的机制可能会阻碍为这些儿童开发新的有效干预措施。这项研究将首次测量感染性休克存活儿童HRQL/FS改变的发生率、强度和持续时间，并检查此类不良结局的潜在临床风险因素。目前对儿童败血症相关不良结局的机制了解甚少。然而，在临床上，两种循环往复的脓毒症损伤，即炎症和缺血/缺氧，似乎是多器官功能障碍综合征（MODS）的关键前因，已与脓毒症死亡率和长期发病率。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病后的长期发病率和死亡率密切相关。LAPSE研究假设，脓毒症介导的器官功能障碍的有效措施将预测脓毒症相关的HRQL/FS恶化的程度，并且恢复到基线HRQL/FS将受到儿童慢性共病疾病的复杂性以及父母，家庭和家庭特征的强烈影响。由于改善HRQL可能是医学最重要的目标，本研究计划的长期目标是及时识别脓毒症介导的HRQL/FS恶化的高风险儿童，并最终设计有效的干预措施以最大限度地减少此类风险。本申请的主要目的是全面表征HRQL/FS结局，并严格检查脓毒症相关HRQL/FS恶化的潜在临床风险因素。中心假设是HRQL/FS恶化的程度将根据经验证的器官功能障碍临床标志物预测，父母、家庭和家庭特征以及病前状况将影响HRQL/FS恢复至基线的轨迹。了解儿童感染性休克的现代自然史将有助于制定有针对性的干预措施，以最大限度地提高脓毒症存活儿童的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.