Invasive Ventilatory Support in Patients With Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVE: To provide evidence for the Second Pediatric Acute Lung Injury Consensus Conference updated recommendations and consensus statements for clinical practice and future research on invasive mechanical ventilation support of patients with pediatric acute respiratory distress syndrome (PARDS). DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included clinical studies of critically ill patients undergoing invasive mechanical ventilation for PARDS, January 2013 to April 2022. In addition, meta-analyses and systematic reviews focused on the adult acute respiratory distress syndrome population were included to explore new relevant concepts (e.g., mechanical power, driving pressure, etc.) still underrepresented in the contemporary pediatric literature. 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, good practice statements and research statements. We identified 26 pediatric studies for inclusion and 36 meta-analyses or systematic reviews in adults. We generated 12 recommendations, two research statements, and five good practice statements related to modes of ventilation, tidal volume, ventilation pressures, lung-protective ventilation bundles, driving pressure, mechanical power, recruitment maneuvers, prone positioning, and high-frequency ventilation. Only one recommendation, related to use of positive end-expiratory pressure, is classified as strong, with moderate certainty of evidence. CONCLUSIONS: Limited pediatric data exist to make definitive recommendations for the management of invasive mechanical ventilation for patients with PARDS. Ongoing research is needed to better understand how to guide best practices and improve outcomes for patients with PARDS requiring invasive mechanical ventilation.

The effects of adding quinolones to beta-lactam antibiotics for sepsis.

BACKGROUND: Sepsis is common, deadly, and a major challenge to treat. Quinolones added to beta-lactam antibiotics are currently recommended as a second-line empiric regimen in sepsis, but the evidence regarding their benefits and harms is unclear. OBJECTIVE: To assess the benefits and harms of adding quinolones to standard care for sepsis. DATA SOURCES: We conducted a systematic review of randomized clinical trials with meta-analysis and Trial Sequential Analysis. We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, and BIOSIS. STUDY SELECTION: Randomized clinical trials assessing the effects of adding any quinolone to standard care for children and adults with sepsis. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers screened studies and extracted data. The certainty of the evidence was assessed by GRADE. RESULTS: We included three trials randomizing 995 adults. All trials were at overall "high risk of bias." All trials compared a quinolone (moxifloxacin, levofloxacin, or ciprofloxacin) and a beta-lactam antibiotic versus the same beta-lactam antibiotic. We found no evidence of an effect of adding quinolones to beta-lactam antibiotics when assessing all-cause mortality (RR 1.07, 95% CI 0.86 to 1.33; 2 trials; 915 participants; very low certainty of evidence) and serious adverse events (RR 1.00, 95% CI 0.67 to 1.50; 977 participants; two trials; very low certainty of evidence). No trials reported on quality of life. CONCLUSIONS: The effects of adding quinolones to beta-lactam antibiotics for the treatment of sepsis were unclear for all outcomes. Additional trial data are warranted to support the recommendation of empirical use of quinolones for sepsis.

A new tool to assess Clinical Diversity In Meta-analyses (CDIM) of interventions.

OBJECTIVE: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. STUDY DESIGN AND SETTING: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. RESULTS: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. CONCLUSION: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.