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...

Our ex vivo study demonstrates serial losses of several drugs commonly used during ECMO therapy. Therapeutic concentrations of fentanyl, voriconazole, antimicrobials and heparin cannot be guaranteed in patients on ECMO.

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