Morbidity and Mortality in Critically Ill Children. II. A Qualitative Patient-Level Analysis of Pathophysiologies and Potential Therapeutic Solutions*

OBJECTIVE: To describe at the individual patient level the pathophysiologic processes contributing to morbidity and mortality in pediatric intensive care units (PICUs) and therapeutic additions and advances that could potentially prevent or reduce morbidity and mortality. DESIGN: Qualitative content analysis of intensivists’ conclusions on pathophysiologic processes and needed therapeutic advances formulated by structured medical record review. SETTING: Eight children’s hospitals affiliated with the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. PATIENTS: A randomly selected cohort of critically ill children with a new functional morbidity or mortality at hospital discharge. New morbidity was assessed using the Functional Status Scale and defined as worsening by two or more points in a single domain from pre-illness baseline. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 292 children, 175 (59.9%) had a new morbidity and 117 (40.1%) died. The most common pathophysiology was impaired substrate delivery (n=158, 54.1%) manifesting as global or regional hypoxia or ischemia due to low cardiac output or cardiac arrest. Other frequent pathophysiologies were inflammation (n=104, 35.6%) related to sepsis, respiratory failure, acute respiratory distress syndrome or multiple organ dysfunction; and direct tissue injury (n=64, 21.9%) including brain and spinal cord trauma. Chronic conditions were often noted (n=156, 53.4%) as contributing to adverse outcomes. Drug therapies (n=149, 51.0%) including chemotherapy, inotropes, vasoactive agents and sedatives were the most frequently proposed needed therapeutic advances. Other frequently proposed therapies included cell regeneration (n=115, 39.4%) mainly for treatment of neuronal injury, and improved immune and inflammatory modulation (n=79, 27.1%). CONCLUSIONS: Low cardiac output and cardiac arrest, inflammation-related organ failures, and central nervous system trauma were the most common pathophysiologies leading to morbidity and mortality in PICUs. A research agenda focused on better understanding and treatment of these conditions may have high potential to directly impact patient outcomes.