Defining risk for iatrogenic withdrawal syndrome in critically ill children

描述（由申请人提供）：对接受机械通气支持的危重儿科患者的人道护理需要舒适管理，包括镇静治疗。重症患者很快就会对用于镇静治疗的阿片类药物和苯二氮卓类药物产生耐受性，并需要增加这些药物的剂量以达到相同的治疗效果。反过来，在从原发病中恢复后，药物耐受患者快速撤机或突然停止镇静治疗会导致医源性戒断综合征-这一问题增加了重症监护的个人和经济负担。使用一种新的概念模型，涉及患者，过程和系统水平的风险因素，被认为有助于医源性戒断综合征的发展，我们相信一个新的角度来解决这种可预防的并发症的儿科重症监护是必要的。我们建议使用最近完成的RESTORE研究[U 01 HL 086622和U 01 HL 086649;护士主导的镇静管理对2448例因急性呼吸衰竭需要机械通气的儿童的临床结局的31中心随机分组试验]，发生医源性戒断综合征的受试者与未发生医源性戒断综合征的受试者之间的过程和系统水平数据。通过探索多个层面的变量，这项研究将是有史以来第一次全面评估医源性戒断综合征。该研究将回答关键问题：哪些因素影响从危重病中恢复的儿科患者发生医源性戒断综合征？此外，患者、过程和系统因素的相对贡献可以结合起来，以创建从危重疾病中恢复的儿科患者中临床显著医源性戒断综合征的患者风险的预测统计模型。拟定的研究将在发生医源性戒断综合征的独特临床环境中对医源性戒断综合征现象进行背景分析。这项研究的结果将进一步推进NINR的使命，以更好地了解症状管理和疾病的原因，包括促进个性化干预措施发展的系统（例如家庭单位，人群和/或组织）的行为。

DESCRIPTION (provided by applicant): Humane care for critically ill pediatric patients supported on mechanical ventilation necessitates comfort management that includes sedation therapy. Critically ill patients quickly become tolerant to the opioids and benzodiazepines used for sedation therapy and require increasing doses of these medications to achieve the same therapeutic effect. In turn, after recovery from their primary illnesses, rapid weaning or abrupt cessation of sedative therapy in drug tolerant patients precipitates iatrogenic withdrawal syndrome - a problem that adds to the personal and financial burden of intensive care. Using a novel conceptual model relating patient-, process- and system-level risk factors that are thought to contribute to the development of iatrogenic withdrawal syndrome, we believe a new perspective for addressing this preventable complication of pediatric intensive care is warranted. We propose to use data from the recently completed RESTORE study [U01HL086622 and U01 HL086649; 31-center cluster randomized trial of nurse- led sedation management on clinical outcomes in 2448 children requiring mechanical ventilation for acute respiratory failure] to conduct a secondary analysis comparing patient-, process- and system-level data between those subjects who developed iatrogenic withdrawal syndrome and those who did not. By exploring variables at several levels, this study will be the first comprehensive evaluation of iatrogenic withdrawal syndrome ever completed. The study will answer the key question: What factors impact the development of iatrogenic withdrawal syndrome in pediatric patients recovering from critical illness? Furthermore, the relative contributions of patient, process, and systems factors can be combined to create a predictive statistical model of patient risk for clinically significant iatrogenic withdrawal syndrome in pediatric patients recovering from critica illness. The proposed study will contextualize the phenomenon of iatrogenic withdrawal syndrome within the unique clinical circumstances in which it occurs. The results of this study will further NINR's mission to better understand symptom management and the causes of disease, including the behavior of systems (e.g. family units, populations, and/or organizations) that promote the development of personalized interventions.