Transcriptomic profiles of multiple organ dysfunction syndrome phenotypes in pediatric critical influenza.

Background: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.

Methods: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS.

Dexmedetomidine for sedation during hematopoietic stem cell harvest apheresis and leukapheresis in the PICU: Guideline development.

Background: Hematopoietic stem cell (HSC) harvest apheresis and leukapheresis are performed in the pediatric intensive care unit (PICU) for high-risk pediatric patients who require procedural sedation. Patients need central access either with their own central lines, ports or require apheresis catheter (CVL) placement. Previously, patients were either awake or emerging from sedation on PICU admission.

Epidemiology and Outcomes of Critically Ill Children at Risk for Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

Objectives: Interventional trials aimed at pediatric acute respiratory distress syndrome prevention require accurate identification of high-risk patients. In this study, we aimed to characterize the frequency and outcomes of children meeting "at risk for pediatric acute respiratory distress syndrome" criteria as defined by the Pediatric Acute Lung Injury Consensus Conference.

Design: Planned substudy of the prospective multicenter, international Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study conducted during 10 nonconsecutive weeks (May 2016-June 2017).

Adherence to Lung-Protective Ventilation Principles in Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

Objectives: To describe mechanical ventilation management and factors associated with nonadherence to lung-protective ventilation principles in pediatric acute respiratory distress syndrome.

Design: A planned ancillary study to a prospective international observational study. Mechanical ventilation management (every 6 hr measurements) during pediatric acute respiratory distress syndrome days 0-3 was described and compared with Pediatric Acute Lung Injury Consensus Conference tidal volume recommendations (< 7 mL/kg in children with impaired respiratory system compliance, < 9 mL/kg in all other children) and the Acute Respiratory Distress Syndrome Network lower positive end-expiratory pressure/higher Fio2 grid recommendations.

The Impact of Preintubation Noninvasive Ventilation on Outcomes in Pediatric Acute Respiratory Distress Syndrome.

Objectives: There is evidence that noninvasive ventilation decreases the need for invasive mechanical ventilation. However, children with pediatric acute respiratory distress syndrome who fail noninvasive ventilation may have worse outcomes than those who are intubated without exposure to noninvasive ventilation. Our objective was to evaluate the impact of preintubation noninvasive ventilation on children with pediatric acute respiratory distress syndrome.

Development of a Standardized Clinical Assessment and Management Plan for Pediatric Acute Respiratory Distress Syndrome.

Pediatric acute respiratory distress syndrome (PARDS) is one of the most challenging patient populations for a clinician to manage with mortality between 8 and 31%. The project was designed to identify patients with PARDS, implement management guidelines with the goal of standardizing practice. Our objectives were to describe the development and implementation of a protocolized approach to identify patients with PARDS and institute ventilator management guidelines.

Correction to: Methods in the design and implementation of the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial.

AbstractFollowing publication of the original article [1], the authors notified us of a typing error in spelling Dr. Asario's name. The original publication has been corrected.

Methods in the design and implementation of the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial.

Background: Few papers discuss the pragmatics of conducting large, cluster randomized clinical trials. Here we describe the sequential steps taken to develop methods to implement the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial that tested the effect of a nurse-implemented, goal-directed, comfort algorithm on clinical outcomes in pediatric patients with acute respiratory failure.

Methods: After development in a single institution, the RESTORE intervention was pilot-tested in two pediatric intensive care units (PICUs) to evaluate safety and feasibility.

Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children With Influenza-related Critical Illness.

Background: Coinfection with influenza virus and methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening necrotizing pneumonia in children. Sporadic incidence precludes evaluation of antimicrobial efficacy. We assessed the clinical characteristics and outcomes of critically ill children with influenza-MRSA pneumonia and evaluated antibiotic use.

Hyperchloremia Is Associated With Complicated Course and Mortality in Pediatric Patients With Septic Shock.

Objective: Hyperchloremia is associated with poor outcome among critically ill adults, but it is unknown if a similar association exists among critically ill children. We determined if hyperchloremia is associated with poor outcomes in children with septic shock.

Design: Retrospective analysis of a pediatric septic shock database.

Endotype Transitions During the Acute Phase of Pediatric Septic Shock Reflect Changing Risk and Treatment Response.

Objective: We previously identified septic shock endotypes A and B based on 100 genes reflecting adaptive immunity and glucocorticoid receptor signaling. The endotypes differ with respect to outcome and corticosteroid responsiveness. We determined whether endotypes change during the initial 3 days of illness, and whether changes are associated with outcomes.

Improved Risk Stratification in Pediatric Septic Shock Using Both Protein and mRNA Biomarkers. PERSEVERE-XP.

Rationale: We previously derived and validated the Pediatric Sepsis Biomarker Risk Model (PERSEVERE) to estimate baseline mortality risk in children with septic shock. The PERSEVERE biomarkers are serum proteins selected from among the proteins directly related to 80 mortality risk assessment genes. The initial approach to selecting the PERSEVERE biomarkers left 68 genes unconsidered.

Glucocorticoid Receptor Polymorphisms and Outcomes in Pediatric Septic Shock.

Objective: Polymorphisms of the glucocorticoid receptor gene are associated with outcome and corticosteroid responsiveness among patients with inflammatory disorders. We conducted a candidate gene association study to test the hypothesis that these polymorphisms are associated with outcome and corticosteroid responsiveness among children with septic shock.

Design: We genotyped 482 children with septic shock for the presence of two glucocorticoid receptor polymorphisms (rs56149945 and rs41423247) associated with increased sensitivity and one glucocorticoid receptor polymorphism (rs6198) associated with decreased sensitivity to corticosteroids.

Pediatric Ventilator-Associated Infections: The Ventilator-Associated INfection Study.

Objective: Suspected ventilator-associated infection is the most common reason for antibiotics in the PICU. We sought to characterize the clinical variables associated with continuing antibiotics after initial evaluation for suspected ventilator-associated infection and to determine whether clinical variables or antibiotic treatment influenced outcomes.

Design: Prospective, observational cohort study conducted in 47 PICUs in the United States, Canada, and Australia.

Pediatric Sepsis Biomarker Risk Model-II: Redefining the Pediatric Sepsis Biomarker Risk Model With Septic Shock Phenotype.

Objective: The Pediatric Sepsis Biomarker Risk Model (PERSEVERE), a pediatric sepsis risk model, uses biomarkers to estimate baseline mortality risk for pediatric septic shock. It is unknown how PERSEVERE performs within distinct septic shock phenotypes. We tested PERSEVERE in children with septic shock and thrombocytopenia-associated multiple organ failure (TAMOF), and in those without new onset thrombocytopenia but with multiple organ failure (MOF).

Accuracy of an Extubation Readiness Test in Predicting Successful Extubation in Children With Acute Respiratory Failure From Lower Respiratory Tract Disease.

Objective: Identifying children ready for extubation is desirable to minimize morbidity and mortality associated with prolonged mechanical ventilation and extubation failure. We determined the accuracy of an extubation readiness test (Randomized Evaluation of Sedation Titration for Respiratory Failure extubation readiness test) in predicting successful extubation in children with acute respiratory failure from lower respiratory tract disease.

Design: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial, a pediatric multicenter cluster randomized trial of sedation.

Combining Prognostic and Predictive Enrichment Strategies to Identify Children With Septic Shock Responsive to Corticosteroids.

Objectives: Prognostic and predictive enrichment strategies are fundamental tools of precision medicine. Identifying children with septic shock who may benefit from corticosteroids remains a challenge. We combined prognostic and predictive strategies to identify a pediatric septic shock subgroup responsive to corticosteroids.

The Association of Central-Line-Associated Bloodstream Infections With Central-Line Utilization Rate and Maintenance Bundle Compliance Among Types of PICUs.

Objective: Central-line-associated bloodstream infections comprise 25% of device-associated infections. Compared with other units, PICUs demonstrate a higher central-line-associated bloodstream infections prevalence. Prior studies have not investigated the association of central-line-associated bloodstream infections prevalence, central-line utilization, or maintenance bundle compliance between specific types of PICUs.

Prospective Testing and Redesign of a Temporal Biomarker Based Risk Model for Patients With Septic Shock: Implications for Septic Shock Biology.

The temporal version of the pediatric sepsis biomarker risk model (tPERSEVERE) estimates the risk of a complicated course in children with septic shock based on biomarker changes from days 1 to 3 of septic shock. We validated tPERSEVERE performance in a prospective cohort, with an a priori plan to redesign tPERSEVERE if it did not perform well. Biomarkers were measured in the validation cohort (n = 168) and study subjects were classified according to tPERSEVERE.

A Multibiomarker-Based Model for Estimating the Risk of Septic Acute Kidney Injury.

Objective: The development of acute kidney injury in patients with sepsis is associated with worse outcomes. Identifying those at risk for septic acute kidney injury could help to inform clinical decision making. We derived and tested a multibiomarker-based model to estimate the risk of septic acute kidney injury in children with septic shock.

Protocolized sedation vs usual care in pediatric patients mechanically ventilated for acute respiratory failure: a randomized clinical trial.

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 experience fewer days of mechanical ventilation than patients receiving usual care.

Design, Setting, And Participants: Cluster randomized trial conducted in 31 US pediatric intensive care units (PICUs).