Objectives: To develop evidence-based recommendations for clinicians caring for children (including infants, school-aged children, and adolescents) with septic shock and other sepsis-associated organ dysfunction. Design: A panel of 49 international experts, representing 12 international organizations, as well as three methodologists and three public members was convened. Panel members assembled at key international meetings (for those panel members attending the conference), and a stand-alone meeting was held for all panel members in November 2018. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. Teleconferences and electronic-based discussion among the chairs, co-chairs, methodologists, and group heads, as well as within subgroups, served as an integral part of the guideline development process. Methods: The panel consisted of six subgroups: recognition and management of infection, hemodynamics and resuscitation, ventilation, endocrine and metabolic therapies, adjunctive therapies, and research priorities. We conducted a systematic review for each Population, Intervention, Control, and Outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak, or as a best practice statement. In addition, “in our practice” statements were included when evidence was inconclusive to issue a recommendation, but the panel felt that some guidance based on practice patterns may be appropriate. Results: The panel provided 77 statements on the management and resuscitation of children with septic shock and other sepsis-associated organ dysfunction. Overall, six were strong recommendations, 52 were weak recommendations, and nine were best-practice statements. For 13 questions, no recommendations could be made; but, for 10 of these, “in our practice” statements were provided. In addition, 49 research priorities were identified. Conclusions: A large cohort of international experts was able to achieve consensus regarding many recommendations for the best care of children with sepsis, acknowledging that most aspects of care had relatively low quality of evidence resulting in the frequent issuance of weak recommendations. Despite this challenge, these recommendations regarding the management of children with septic shock and other sepsis-associated organ dysfunction provide a foundation for consistent care to improve outcomes and inform future research.

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BACKGROUNDHigh-flow oxygen therapy through a nasal cannula has been increasingly used in infants with bronchiolitis, despite limited high-quality evidence of its efficacy. The efficacy of high-flow oxygen therapy through a nasal cannula in settings other than intensive care units (ICUs) is unclear. METHODSIn this multicenter, randomized, controlled trial, we assigned infants younger than 12 months of age who had bronchiolitis and a need for supplemental oxygen therapy to receive either high-flow oxygen therapy (high-flow group) or standard oxygen therapy (standard-therapy group). Infants in the standard-therapy group could receive rescue high-flow oxygen therapy if their condition met criteria for treatment failure. The primary outcome was escalation of care due to treatment failure (defined as meeting ≥3 of 4 clinical criteria: persistent tachycardia, tachypnea, hypoxemia, and medical review triggered by a hospital early-warning tool). Secondary outcomes included duration of hospital stay, duration of oxygen therapy, and rates of transfer to a tertiary hospital, ICU admission, intubation, and adverse events. RESULTSThe analyses included 1472 patients. The percentage of infants receiving escalation of care was 12% (87 of 739 infants) in the high-flow group, as compared with 23% (167 of 733) in the standard-therapy group (risk difference, −11 percentage points; 95% confidence interval, −15 to −7; P<0.001). No significant differences were observed in the duration of hospital stay or the duration of oxygen therapy. In each group, one case of pneumothorax (<1% of infants) occurred. Among the 167 infants in the standard-therapy group who had treatment failure, 102 (61%) had a response to high-flow rescue therapy. CONCLUSIONSAmong infants with bronchiolitis who were treated outside an ICU, those who received high-flow oxygen therapy had significantly lower rates of escalation of care due to treatment failure than those in the group that received standard oxygen therapy. Original ArticleThe New England Journal of Medicine 1122T h e ne w e ngl a nd jou r na l o f m e dicine B ronchiolitis, an acute lower airway lung disease that is generally caused by respiratory viruses, is the most common reason worldwide for nonelective hospital admission in infants. In the United States, bronchiolitis is responsible for $1.7 billion in hospitalization costs annually.1,2 In Australia and New Zealand, there has been a population-based increase in admissions to the intensive care unit (ICU) for bronchiolitis, with associated increases in hospital costs. 3Numerous studies have investigated the role of medical therapies 4 in infants with bronchiolitis; none of these interventions have shown efficacy. 5The American Academy of Pediatrics guidelines recommend only supportive therapy that includes oxygen therapy for hypoxemia, respiratory support, and the maintenance of hydration. 5,6 Respiratory support as provided in emergency and ward settings has been limited to oxygen delivered through a standard nasal cannula, at a rate of up to 2 li...