A Simple and Robust Bedside Model for Mortality Risk in Pediatric Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: Despite declining mortality, acute respiratory distress syndrome is still involved in up to one third of pediatric intensive care deaths. The recently convened Pediatric Acute Lung Injury Consensus Conference has outlined research priorities for the field, which include the need for accurate bedside risk stratification of patients. We aimed to develop a simple yet robust model of mortality risk among pediatric patients with acute respiratory distress syndrome to facilitate the targeted application of high-risk investigational therapies and stratification for enrollment in clinical trials. DESIGN: Prospective, multicenter cohort. SETTING: Five academic PICUs. PATIENTS: Three hundred eight children greater than 1 month and less than or equal to 18 years old, admitted to the ICU, with bilateral infiltrates on chest radiograph and PaO2/FIO2 ratio less than 300 in the clinical absence of left atrial hypertension. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty clinical variables were recorded in the following six categories: demographics, medical history, oxygenation, ventilation, radiographic imaging, and multiple organ dysfunction. Data were measured 0-24 and 48-72 hours after acute respiratory distress syndrome onset (day 1 and 3) and examined for associations with hospital mortality. Among 308 enrolled patients, mortality was 17%. Children with a history of cancer and/or hematopoietic stem cell transplant had higher mortality (47% vs 11%; p < 0.001). Oxygenation index, the PaO2/FIO2 ratio, extrapulmonary organ dysfunction, Pediatric Risk of Mortality-3, and positive cumulative fluid balance were each associated with mortality. Using two statistical approaches, we found that a parsimonious model of mortality risk using only oxygenation index and cancer/hematopoietic stem cell transplant history performed as well as other more complex models that required additional variables. CONCLUSIONS: In the PICU, oxygenation index and cancer/hematopoietic stem cell transplant history can be used on acute respiratory distress syndrome day 1 or day 3 to predict hospital mortality without the need for more complex models. These findings may simplify risk assessment for clinical trials, counseling families, and high-risk interventions such as extracorporeal life support.

Extracorporeal membrane oxygenation in children receiving haematopoietic cell transplantation and immune effector cell therapy: an international and multidisciplinary consensus statement.

Use of extracorporeal membrane oxygenation (ECMO) in children receiving haematopoietic cell transplantation (HCT) and immune effector cell therapy is controversial and evidence-based guidelines have not been established. Remarkable advancements in HCT and immune effector cell therapies have changed expectations around reversibility of organ dysfunction and survival for affected patients. Herein, members of the Extracorporeal Life Support Organization (ELSO), Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network (HCT and cancer immunotherapy subgroup), the Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT), the supportive care committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC), and the Pediatric Intensive Care Oncology Kids in Europe Research (POKER) group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) provide consensus recommendations on the use of ECMO in children receiving HCT and immune effector cell therapy. These are the first international, multidisciplinary consensus-based recommendations on the use of ECMO in this patient population. This Review provides a clinical decision support tool for paediatric haematologists, oncologists, and critical care physicians during the difficult decision-making process of ECMO candidacy and management. These recommendations can represent a base for future research studies focused on ECMO selection criteria and bedside management.

Plasma total fibroblast growth factor 23 levels are associated with acute kidney injury and mortality in children with acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) has high rates of mortality and multisystem morbidity. Pre-clinical data suggest that fibroblast growth factor 23 (FGF23) may contribute to pulmonary pathology, and FGF23 is associated with mortality and morbidity, including acute kidney injury (AKI), in non-ARDS cohorts. Here, we assess whether FGF23 is associated with AKI and/or mortality in a cohort of 161 pediatric ARDS patients. Plasma total (intact + C-terminal) FGF23 and intact FGF23 concentrations were measured within 24 hours of ARDS diagnosis (Day 1), and associations with Day 3 AKI and 60-day mortality were evaluated. 35 patients (22%) developed AKI by 3 days post-ARDS diagnosis, and 25 (16%) died by 60 days post-ARDS diagnosis. In unadjusted models, higher Day 1 total FGF23 was associated with Day 3 AKI (odds ratio (OR) 2.22 [95% confidence interval (CI) 1.62, 3.03], p<0.001), but Day 1 intact FGF23 was not. In a model adjusted for demographics and disease severity, total FGF23 remained associated with AKI (OR 1.52 [95% CI 1.02, 2.26], p = 0.039). In unadjusted models, both higher Day 1 total and intact FGF23 were associated with 60-day mortality (OR 1.43 [95% CI 1.07, 1.91], p = 0.014; and OR 1.44 [95% CI 1.02, 2.05], p = 0.039, respectively). In the adjusted model, only total FGF23 remained associated with 60-day mortality (OR 1.62 [95% CI 1.07, 2.45], p = 0.023). In a subgroup analysis of patients with Day 1 plasma IL-6 concentrations available, inflammation partially mediated the association between total FGF23 and AKI. Our data suggest both inflammation-dependent and inflammation-independent associations between total FGF23 and clinical outcomes in pediatric ARDS patients.

Safe and Effective Prophylaxis with Bimonthly Intravenous Pentamidine in the Pediatric Hematopoietic Stem Cell Transplant Population.

BACKGROUND: Without prophylaxis, Pneumocystis jiroveci pneumonia (PCP) develops in 5%-15% of pediatric hematopoietic stem cell transplant (HCT) patients with mortality above 50%. Trimethoprim-sulfamethoxazole is a standard PCP prophylaxis; pentamidine is frequently used as second-line prophylaxis because of trimethoprim-sulfamethoxazole's potential for cytopenias. Monthly intravenous (IV) pentamidine has variable efficacy with PCP infection rates of 0%-10% in pediatric patients, and higher breakthrough rates in those younger than 2 years. We hypothesized that bimonthly (twice monthly) pentamidine might have equivalent safety and improved efficacy; therefore, we conducted a retrospective analysis of bimonthly pentamidine PCP prophylaxis. METHODS: We retrospectively reviewed records of all pediatric HCT patients who received bimonthly IV pentamidine between December 2006 and June 2013, and collected data regarding demographics, clinical course, prophylaxis rationale, laboratory values and adverse events. RESULTS: Between December 2006 and June 2013, 111 pediatric HCT patients received bimonthly IV pentamidine (574 doses, 8758 patient-days); 31 patients were younger than 2 years at initiation. In the majority (53% of courses), pentamidine was initiated because of cytopenias. Fourteen patients (12.6% of patients, 2.4% of doses) experienced a side-effect prompting discontinuation, including 3 patients with infusion-related hypotension/anaphylaxis and 3 with acute pancreatic dysfunction. No patients [0% (95% confidence interval: 0-3.2)] developed PCP during or after bimonthly IV pentamidine prophylaxis. CONCLUSIONS: Bimonthly IV pentamidine for PCP prophylaxis in the HCT pediatric population has comparable safety to monthly IV pentamidine and was highly effective, including in the very young. Bimonthly IV pentamidine should be considered in pediatric patients as second-line PCP prophylaxis.