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.

Twitter is a tool for physicians to increase engagement of learners and the public, share scientific information, crowdsource new ideas, conduct, discuss and challenge emerging research, pursue professional development and continuing medical education, expand networks around specialized topics and provide moral support to colleagues. However, new users or skeptics may well be wary of its potential pitfalls. The aims of this commentary are to discuss the potential advantages of the Twitter platform for dialogue among physicians, to explore the barriers to accurate and high-quality healthcare discourse and, finally, to recommend potential safeguards physicians may employ against these threats in order to participate productively.

Objective Septic shock heterogeneity has important implications for clinical trial implementation and patient management. We previously addressed this heterogeneity by identifying 3 putative subclasses of children with septic shock based exclusively on a 100-gene expression signature. Here we attempted to prospectively validate the existence of these gene expression-based subclasses in a validation cohort. Design Prospective observational study involving microarray-based bioinformatics. Setting Multiple pediatric intensive care units in the United States. Patients Separate derivation (n=98) and validation (n=82) cohorts of children with septic shock. Interventions None other than standard care. Measurements and Main Results Gene expression mosaics of the 100 class-defining genes were generated for 82 individual patients in the validation cohort. Using computer-based image analysis, patients were classified into 1 of 3 subclasses (“A”, “B”, or “C”) based on color and pattern similarity relative to reference mosaics generated from the original derivation cohort. After subclassification, the clinical database was mined for phenotyping. Subclass A patients had higher illness severity relative to subclasses B and C, as measured by maximal organ failure, fewer ICU-free days, and a higher PRISM score. Patients in subclass A were characterized by repression of genes corresponding to adaptive immunity and glucocorticoid receptor signaling. Separate subclass assignments were conducted by 21 individual clinicians, using visual inspection. The consensus classification of the clinicians had modest agreement with the computer algorithm. Conclusions We have validated the existence of subclasses of children with septic shock based on a biologically relevant, 100-gene expression signature. The subclasses have relevant clinical differences.