Importance Protocolized sedation improves clinical outcomes in critically-ill adults, but its effect in children is unknown. Objective To determine whether critically-ill children managed with a nurse-implemented, goal-directed sedation protocol (RESTORE) would experience fewer days of mechanical ventilation than patients receiving usual care. Design, Setting, and Participants Cluster-randomized trial conducted in 31 U.S. Pediatric Intensive Care Units (PICUs). Children (n=2449; mean age 4.7 years, range 2 weeks to 17 years) mechanically ventilated for acute respiratory failure were enrolled 2009–2013 and followed until 72 hours after opioids were discontinued, 28 days, or hospital discharge. Interventions Intervention PICUs (17 sites, n=1225 patients) managed sedation using a protocol that included targeted sedation, arousal assessments, extubation readiness testing, sedation adjustment every 8 hours, and sedation weaning. Control PICUs (14 sites, n=1224 patients) managed sedation per usual care without a protocol. Main Outcome and Measures The primary outcome was duration of mechanical ventilation. Secondary outcomes included time to recovery from acute respiratory failure, duration of weaning from mechanical ventilation, neurological testing, PICU and hospital lengths of stay, in-hospital mortality, sedation-related adverse events, sedative exposure including measures of wakefulness, pain, and agitation, and occurrence of iatrogenic withdrawal. Results Duration of mechanical ventilation was not statistically significantly different between the two groups (median; interquartile range: intervention: 6.5 days; 4.1–11.2 vs. control: 6.5; 3.7–12.1). Sedation-related adverse events including inadequate pain and sedation management, clinically significant iatrogenic withdrawal, and unplanned endotracheal tube/invasive line removal were not statistically significantly different between the two groups. Intervention patients experienced more post-extubation stridor (7% vs. 4%; P=0.03) and fewer stage 2+ immobility-related pressure ulcers (<1% vs. 2%; P=0.001). In exploratory analyses, intervention patients had fewer days of opioid administration (median; interquartile range: 9; 5–15 vs. 10; 4–21; P=0.01), were exposed to fewer sedative classes (2; 2–3 vs. 3; 2–4; P<0.001), and were awake and calm for a greater percentage of study days while intubated (86%; 67–100% vs. 75%; 50–100%; P=0.004), than control patients. However, patients in the intervention group had a greater percentage of days with any report of a pain score ≥4 (50%; 27%-67% vs. 23%; 0–46%; P<0.001) and any report of agitation with a State Behavior Scale score of +1/+2 (60%; 33–80% vs. 40%; 13–67%, P=0.003), than control patients. Conclusions and Relevance Among children undergoing mechanical ventilation for acute respiratory failure, the use of a nurse-implemented, goal-directed sedation protocol compared with usual care did not reduce the duration of mechanical ventilation. Exploratory analyses of secondary outcomes suggest a complex relatio...

Objective To describe the relationship between altered white matter microstructure and neurodevelopment in children with d-transposition of the great arteries (d-TGA). Study design We report correlations between regional white matter microstructure as measured by fractional anisotropy (FA) and cognitive outcome in a homogeneous group of adolescents with d-TGA. Subjects with d-TGA (n=49) and controls (n=29) underwent diffusion tensor imaging and neurocognitive testing. In the group with d-TGA, we correlated neurocognitive scores with FA in 14 composite regions of interest in which subjects with d-TGA had lower FA than controls. Results Among the patients with d-TGA, mathematics achievement correlated with left parietal FA (r=0.39, p=0.006), inattention/hyperactivity symptoms with right precentral FA (r=−0.39, p=0.006) and left parietal FA (r=−0.30, p=0.04), executive function with right precentral FA (r=−0.30, p=0.04), and visual-spatial skills with right frontal FA(r=0.30, p=0.04). We also found an unanticipated correlation between memory and right posterior limb of the internal capsule FA (r=0.29, p=0.047). Conclusion Within the group with d-TGA, regions of reduced white matter microstructure are associated with cognitive performance in a pattern similar to healthy adolescents and adults. Diminished white matter microstructure may contribute to cognitive compromise in adolescents who underwent open-heart surgery in infancy.

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