Pathobiology, Severity, and Risk Stratification of Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference

Abstract

To review the literature for studies published in children on the pathobiology, severity, and risk stratification of pediatric acute respiratory distress syndrome (PARDS) with the intent of guiding current medical practice and identifying important areas for future research related to severity and risk stratification.DATA SOURCES: Electronic searches of PubMed and Embase were conducted from 2013 to March 2022 by using a combination of medical subject heading terms and text words to capture the pathobiology, severity, and comorbidities of PARDS. STUDY SELECTION:We included studies of critically ill patients with PARDS that related to the severity and risk stratification of PARDS using characteristics other than the oxygenation defect. Studies using animal models, adult only, and studies with 10 or fewer children were excluded from our review.DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS:The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize relevant evidence and develop recommendations for clinical practice. There were 192 studies identified for full-text extraction to address the relevant Patient/ Intervention/Comparator/Outcome questions. One clinical recommendation was generated related to the use of dead space fraction for risk stratification. In addition, six research statements were generated about the impact of age on acute respiratory distress syndrome pathobiology and outcomes, addressing PARDS heterogeneity using biomarkers to identify subphenotypes and endotypes, and use of standardized ventilator, physiologic, and nonpulmonary organ failure measurements for future research. CONCLUSIONS:Based on an extensive literature review, we propose clinical management and research recommendations related to characterization and risk stratification of PARDS severity.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2)

“…There were another 112 statements: 18 related to the definition of PARDS and patients at risk for PARDS, 55 GPS, seven PS, and 32 RS. The evidence tables and rationale supporting CR are presented in the corresponding subgroup manuscripts (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

“…New concepts are addressed in ventilatory management and monitoring related to mechanical power, driving pressure, and patient-self-inflicted lung injury ( 16 ). Heterogeneity of treatment effect and the importance of precision medicine approaches, which embrace biological phenotypes has also been an area of focus, with growing pediatric data that are described in section 2 ( 15 ).…”

“…New concepts are addressed in ventilatory management and monitoring related to mechanical power, driving pressure, and patient-self-inflicted lung injury (16). Heterogeneity of treatment effect and the importance of precision medicine approaches, which embrace biological phenotypes has also been an area of focus, with growing pediatric data that are described in section 2 (15). In summary, the development of PALICC-2 recommendations was based on a rigorous and systematic assessment of available evidence, supported by transparent methodology using GRADE and the EtD framework.…”

“…Nevertheless, we believe these clinical practice guidelines will be valuable at the bedside, as we took into consideration feasibility, safety, equity, and implementation for all recommendations. Detailed considerations for all of these recommendations can be found in the supplemental articles (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). These guidelines have also identified many gaps that offer opportunities for the future PARDS research agenda.…”

“…We used a combination of medical subject heading terms and text words for concepts related to PARDS and each of the 11 sections. Search strategies are detailed in the methods article and supplemental digital files for each of the individual articles (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). References included in previous PALICC reviews were systematically added to the extracted evidence.…”