A Network Meta-analysis of Dexamethasone for Preventing Post-Extubation Upper Airway Obstruction in Children

RATIONALE: Peri-extubation corticosteroids are commonly used in children to prevent upper airway obstruction (UAO). However, the best timing and dose combination of corticosteroids is unknown. OBJECTIVES: To compare effectiveness of different corticosteroid regimens in preventing UAO and reintubation. METHODS: MEDLINE, CINAHL and Embase search identified randomized trials in children using corticosteroids to prevent UAO. All studies used dexamethasone. The studies were categorized based on timing of initiation of dexamethasone (early use: >12 hours prior to extubation) and the dose (high dose: (>/= 0.5mg/kg/dose). We performed Bayesian network meta-analysis (NMA) with studies grouped into four regimens- High dose, Early use (HE); Low dose, Early use (LE); High dose, Late use (HL) and Low dose, Late use (LL). RESULTS: 8 trials (n=903) were included in the analysis. For preventing UAO, (odds ratio, 95% credible interval), HE (0.13; 0.04, 0.36), HL (0.39; 0.19, 0.74) and LE (0.15; 0.04, 0.58) regimens appear to be more effective compared to no dexamethasone (low certainty). HE and LE had the highest probability of being the top ranked regimens for preventing UAO [surface under the cumulative ranking (SUCRA) 0.901 and 0.808 respectively]. For preventing reintubation, the effect estimate was imprecise for all four dexamethasone regimens compared to no dexamethasone (very low certainty). HE and LE were the top ranked regimens (SUCRA 0.803 and 0.720 respectively) for preventing reintubation. Sensitivity analysis showed that regimens which started >12 hours prior to extubation were likely more effective than regimens started >6 hours prior to extubation. CONCLUSIONS: Peri-extubation dexamethasone can prevent post-extubation UAO in children but effectiveness is highly dependent on timing and dosing regimen. Early initiation (ideally >12 hours prior to extubation) appears to be more important than the dose of dexamethasone. Ultimately the specific steroid strategy should be personalized considering the potential for adverse events associated with dexamethasone and the individual risk of UAO and reintubation.Eunice Kennedy Shriver National Institute of Child Health & Human Development. Grant number: R13HD10213

Executive Summary:International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients’ readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of &gt;80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of &gt;80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.</p

Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A PALISI Network Document

RATIONALE: Pediatric specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation. METHODS: Twenty-six international experts comprised a multi-professional panel to establish pediatric specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. Systematic review was conducted for questions which did not meet an a-priori threshold of ≥80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence, drafted, and voted on the recommendations. MEASUREMENTS AND MAIN RESULTS: Three questions related to systematic screening, using an extubation readiness testing bundle and use of a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ≥80% agreement. For the remaining 8 questions, 5 systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials; measures of respiratory muscle strength; assessment of risk of post-extubation upper airway obstruction and its prevention; use of post-extubation non-invasive respiratory support; and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. CONCLUSION: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.The project was funded by Eunice Kennedy Shriver National Institute of Child Health (NICHD) and Human Development National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (R13HD102137), in addition to funds from department of pediatrics at Indiana University School of Medicine, Indianapolis, Indiana

Operational Definitions related to Pediatric Ventilator Liberation

BACKGROUND: Common, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability amongst research and quality improvement efforts, to ensure findings are generalizable and can be pooled to establish best practices. RESEARCH QUESTION: Can we establish operational definitions for key elements related to pediatric ventilator liberation using a combination of detailed literature review and consensus-based approaches? STUDY DESIGN AND METHODS: A panel of 26 international experts in pediatric ventilator liberation, two methodologists and two librarians conducted systematic reviews on eight topic areas related to pediatric ventilator liberation. Through a series of virtual meetings, we established draft definitions which were voted upon using an anonymous web-based process. Definitions were revised by incorporating extracted data gathered during the systematic review and discussed in another consensus meeting. A second round of voting was conducted to confirm the final definitions. RESULTS: In eight topic areas identified by the experts, 16 preliminary definitions were established. Based on initial discussion and the first round of voting, modifications were suggested for 11 of the 16 definitions. There was significant variability in how these items were defined in the literature reviewed. The final round of voting achieved ≥80% agreement for all 16 definitions in the following areas: what constitutes respiratory support (invasive mechanical ventilation and non-invasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of non-invasive respiratory support, total duration of invasive mechanical ventilation, spontaneous breathing trials, extubation readiness testing, 28-ventilator free days, and planned vs rescue use of post-extubation non-invasive respiratory support. INTERPRETATION: We propose these consensus-based definitions for elements of pediatric ventilator liberation, informed by evidence, be used for future quality improvement initiatives and research studies to improve generalizability, and facilitate comparison.The project was funded by Eunice Kennedy Shriver National Institute of Child Health (NICHD) and Human Development National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (R13HD102137), in addition to funds from the Department of Pediatrics at Indiana University School of Medicine, Indianapolis, Indiana