Defining risk for iatrogenic withdrawal syndrome in critically ill children

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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.