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...

RATIONALE:A guideline that both evaluates current practice and provides recommendations to address sedation, pain, and delirium management with regard for neuromuscular blockade and withdrawal is not currently available. OBJECTIVE:To develop comprehensive clinical practice guidelines for critically ill infants and children, with specific attention to seven domains of care including pain, sedation/agitation, iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment, and early mobility. DESIGN:The Society of Critical Care Medicine Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility Guideline Taskforce was comprised of 29 national experts who collaborated from 2009 to 2021 via teleconference and/or e-mail at least monthly for planning, literature review, and guideline development, revision, and approval. The full taskforce gathered annually in-person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to. METHODS:Taskforce content experts separated into subgroups addressing pain/ analgesia, sedation, tolerance/iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment (family presence and sleep hygiene), and early mobility. Subgroups created descriptive and actionable Population, Intervention, Comparison, and Outcome questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Subgroups reviewed literature, determined quality of evidence, and formulated recommendations classified as "strong" with "we recommend" or "conditional" with "we suggest. " Good practice statements were used when indirect evidence supported benefit with no or minimal risk. Evidence gaps were noted. Initial recommendations were reviewed by each subgroup and revised as deemed necessary prior to being disseminated for voting by the full taskforce. Individuals who had an overt or potential conflict of interest abstained from relevant votes. Expert opinion alone was not used in substitution for a lack of evidence. RESULTS:The Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility taskforce issued 44 recommendations (14 strong and 30 conditional) and five good practice statements.

CUTE LUNG INJURY IS A MAJORcause of acute respiratory failure in patients who are critically ill and is associated with several clinical disorders, including sepsis, pneumonia, and aspiration. 1 Although lifesaving, traditional ventilation strategies with higher tidal volumes and airway pressures can exacerbate lung inflammation and injury. 2 Acute lung injury produces parenchymal lung damage that is heterogeneous and may place the patient at risk for ventilatorassociated lung injury. When patients are supine, the reduced volume of the nondependent-aerated lung is at risk for alveolar overdistention, 3 and the cyclical ventilation of the dependent lung at low volumes can cause recruitmentderecruitment with subsequent mechanical strain. 4 Prone positioning, as For editorial comment see p 248.

This study uses data from KwaZulu-Natal, South Africa, to examine the factors associated with schoolgirl pregnancy and subsequent educational pathways. We find that prior schooling discontinuities--defined as instances of non-pregnancy-related grade repetition or temporary withdrawals from school--are strongly associated with a young woman's likelihood of later becoming pregnant while enrolled in school, dropping out of school if she becomes pregnant, and not returning to school following a pregnancy-related dropout. Young women who are the primary caregivers to their children are also significantly more likely to leave school than are those who have help with their childcare responsibilities. Given the increasing importance of female school participation in sub-Saharan Africa, programs must be designed to reach girls and their families early to increase incentives for ensuring their timely progression through school and to increase their access to reproductive health information and services.

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