Perspective of the Surviving Sepsis Campaign on the Management of Pediatric Sepsis in the Era of Coronavirus Disease 2019.

Severe acute respiratory syndrome coronavirus 2 is a novel cause of organ dysfunction in children, presenting as either coronavirus disease 2019 with sepsis and/or respiratory failure or a hyperinflammatory shock syndrome. Clinicians must now consider these diagnoses when evaluating children for septic shock and sepsis-associated organ dysfunction. The Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children provide an appropriate framework for the early recognition and initial resuscitation of children with sepsis or septic shock caused by all pathogens, including severe acute respiratory syndrome coronavirus 2. However, the potential benefits of select adjunctive therapies may differ from non-coronavirus disease 2019 sepsis.

A Novel Framework Using Remote Telesimulation With Standardized Parents to Improve Research Staff Preparedness for Informed Consent in Pediatric Critical Care Research.

OBJECTIVES: The Heart And Lung Failure-Pediatric INsulin Titration study was experiencing poor subject enrollment due to low rates of informed consent. Heart And Lung Failure-Pediatric INsulin Titration investigators collaborated with the Perelman School of Medicine Standardized Patient Program to explore the novel use of telesimulation with standardized parents to train research staff to approach parents of critically ill children for informed consent. We describe the feasibility, learner acceptance, and financial costs of this novel intervention and performed a post hoc analysis to determine if this intervention improved study consent rates. DESIGN: Observational, comparative effectiveness study. SETTING: Heart And Lung Failure-Pediatric INsulin Titration study enrolling sites. SUBJECTS: Research staff (at the remote site). INTERVENTIONS: Individual 90-minute Skype telesimulation sessions with standardized parent and simulation facilitator (at the training site). MEASUREMENTS AND MAIN RESULTS: Forty telesimulation sessions with 79 Heart And Lung Failure-Pediatric INsulin Titration research staff (participants) at 24 remote sites were conducted. Despite some technical delays, 40 out of 40 simulations (100%) were completed. Based on feedback surveys, 100% of respondents agreed (81% strongly agreed) that telesimulation sessions achieved intended learning objectives to prepare research staff to approach parents of eligible critically ill children to obtain informed consent. Additionally, 100% of respondents agreed (74% strongly agreed) that they would use lessons from the telesimulation when approaching parents to obtain informed consent for research. Telesimulation with standardized parents achieved lower financial costs (approximately $85 per session) compared with traditional in-person site visits for training research staff. There was no significant improvement in study consent rates with the intervention (pre: 46% vs post: 48%; p = 0.78). CONCLUSIONS: Remote telesimulation with standardized parents is feasible, acceptable, and associated with lower financial costs to prepare research staff to obtain informed consent from parents of critically ill children eligible for clinical research trials. Despite this novel approach, Heart And Lung Failure-Pediatric INsulin Titration study consent rates did not improve, suggesting that other factors influence parental consent and decision making in complex multicenter clinical research trials.

Clinical Manifestations and Outcomes of Critically Ill Children and Adolescents with Coronavirus Disease 2019 in New York City.

OBJECTIVES: To describe the clinical manifestations and outcomes of critically ill children with coronavirus disease-19 (COVID-19) in New York City. STUDY DESIGN: Retrospective observational study of children 1 month to 21 years admitted March 14 to May 2, 2020, to 9 New York City pediatric intensive care units (PICUs) with severe acute respiratory syndrome coronavirus 2 infection. RESULTS: Of 70 children admitted to PICUs, median age was 15 (IQR 9, 19) years; 61.4% male; 38.6% Hispanic; 32.9% black; and 74.3% with comorbidities. Fever (72.9%) and cough (71.4%) were the common presenting symptoms. Twelve patients (17%) met severe sepsis criteria; 14 (20%) required vasopressor support; 21 (30%) developed acute respiratory distress syndrome (ARDS); 9 (12.9%) met acute kidney injury criteria; 1 (1.4%) required renal-replacement therapy, and 2 (2.8%) had cardiac arrest. For treatment, 27 (38.6%) patients received hydroxychloroquine; 13 (18.6%) remdesivir; 23 (32.9%) corticosteroids; 3 (4.3%) tocilizumab; and 1 (1.4%) anakinra; no patient was given immunoglobulin or convalescent plasma. Forty-nine (70%) patients required respiratory support: 14 (20.0%) noninvasive mechanical ventilation, 20 (28.6%) invasive mechanical ventilation (IMV), 7 (10%) prone position, 2 (2.8%) inhaled nitric oxide, and 1 (1.4%) extracorporeal membrane oxygenation. Nine (45%) of the 20 patients requiring IMV were extubated by day 14 with median IMV duration of 218 (IQR 79, 310.4) hours. Presence of ARDS was significantly associated with duration of PICU and hospital stay, and lower probability of PICU and hospital discharge at hospital day 14 (P < .05 for all). CONCLUSIONS: Critically ill children with COVID-19 predominantly are adolescents, have comorbidities, and require some form of respiratory support. The presence of ARDS is significantly associated with prolonged PICU and hospital stay.

Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children.

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.

Long-Term Neurobehavioral and Quality of Life Outcomes of Critically Ill Children after Glycemic Control.

OBJECTIVES: To investigate adaptive skills, behavior, and quality health-related quality of life in children from 32 centers enrolling in the Heart And Lung Failure-Pediatric INsulin Titration randomized controlled trial. STUDY DESIGN: This prospective longitudinal cohort study compared the effect of 2 tight glycemic control ranges (lower target, 80-100 mg/dL vs higher target, 150-180 mg/dL) 1-year neurobehavioral and health-related quality of life outcomes. Subjects had confirmed hyperglycemia and cardiac and/or respiratory failure. Patients aged 2-16 years old enrolled between April 2012 and September 2016 were studied at 1 year after intensive care discharge. The primary outcome, adaptive skills, was assessed using the Vineland Adaptive Behavior Scale. Behavior and health-related quality of life outcomes were assessed as secondary outcomes using the Pediatric Quality of Life and Child Behavior Checklist at baseline and 1-year follow-up. Group differences were evaluated using regression models adjusting for age category, baseline overall performance, and risk of mortality. RESULTS: Of 369 eligible children, 358 survived after hospital discharge and 214 (60%) completed follow-up. One-year Vineland Adaptive Behavior Scale-II composite scores were not different (mean ± SD, 79.9 ± 25.5 vs 79.4 ± 26.9, lower vs higher target; P = .20). Improvement in Pediatric Quality of Life total health from baseline was greater in the higher target group (adjusted mean difference, 8.2; 95% CI, 1.1-15.3; P = .02). CONCLUSIONS: One-year adaptive behavior in critically ill children with lower vs higher target glycemic control did not differ. The higher target group demonstrated improvement from baseline in overall health. This study affirms the lack of benefit of lower glucose targeting. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01565941.

Early Enteral Nutrition Is Associated With Improved Clinical Outcomes in Critically Ill Children: A Secondary Analysis of Nutrition Support in the Heart and Lung Failure-Pediatric Insulin Titration Trial.

OBJECTIVES: The impact of early enteral nutrition on clinical outcomes in critically ill children has not been adequately described. We hypothesized that early enteral nutrition is associated with improved clinical outcomes in critically ill children. DESIGN: Secondary analysis of the Heart and Lung Failure-Pediatric Insulin Titration randomized controlled trial. SETTING: Thirty-five PICUs. PATIENTS: Critically ill children with hyperglycemia requiring inotropic support and/or invasive mechanical ventilation who were enrolled for at least 48 hours with complete nutrition data. INTERVENTIONS: Subjects received nutrition via guidelines that emphasized enteral nutrition and were classified into early enteral nutrition (enteral nutrition within 48 hr of study randomization) and no early enteral nutrition (enteral nutrition after 48 hr of study randomization, or no enteral nutrition at any time). MEASUREMENTS AND MAIN RESULTS: Of 608 eligible subjects, 331 (54%) received early enteral nutrition. Both early enteral nutrition and no early enteral nutrition groups had similar daily caloric intake over the first 8 study days (median, 36 vs 36 kcal/kg/d; p = 0.93). After controlling for age, body mass index z scores, primary reason for ICU admission, severity of illness, and mean Vasopressor-Inotrope Score at the time of randomization, and adjusting for site, early enteral nutrition was associated with lower 90-day hospital mortality (8% vs 17%; p = 0.007), more ICU-free days (median, 20 vs 17 d; p = 0.02), more hospital-free days (median, 8 vs 0 d; p = 0.003), more ventilator-free days (median, 21 vs 19 d; p = 0.003), and less organ dysfunction (median maximum Pediatric Logistic Organ Dysfunction, 11 vs 12; p < 0.001). CONCLUSIONS: In critically ill children with hyperglycemia requiring inotropic support and/or mechanical ventilation, early enteral nutrition was independently associated with better clinical outcomes.

Impact of Tight Glycemic Control on Neurodevelopmental Outcomes at 1 Year of Age for Children with Congenital Heart Disease: A Randomized Controlled Trial.

OBJECTIVE: To assess the association of postoperative tight glycemic control and hypoglycemia in children undergoing cardiac surgery with neurodevelopmental outcomes at 1 year of age. STUDY DESIGN: A 2-center, prospective, randomized trial of postoperative tight glycemic control vs standard care was conducted in 980 children undergoing cardiac surgery. Neurodevelopmental outcomes were assessed at nine to 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), the Adaptive Behavior Assessment System, Second Edition, the Ages and Stages Questionnaire, Third Edition, and the Brief Infant Toddler Social-Emotional Assessment. RESULTS: Neurodevelopmental follow-up was performed on 237 patients with a mean age of 13 months. No significant treatment group differences were found in the Bayley-III and Adaptive Behavior Assessment System, Second Edition composite scores or percentage at risk based on the Ages and Stages Questionnaire, Third Edition and the Brief Infant Toddler Social-Emotional Assessment. Patients who experienced moderate to severe hypoglycemia (n = 8) had lower Bayley-III composite scores compared with patients with no to mild hypoglycemia, even after controlling for factors known to be associated with poorer neurodevelopmental outcomes. CONCLUSION: For infants undergoing cardiac surgery, tight glycemic control did not impact neurodevelopmental outcomes compared with standard care. These data suggest a possible association between moderate to severe hypoglycemia and poorer neurodevelopmental outcomes at 1 year of age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00443599.