Effort and work-of-breathing parameters strongly correlate with increased resistance in an animal model

Background: Effort of Breathing (EOB) calculations may be a reliable alternative to Work of Breathing (WOB) calculations in which Respiratory Inductance Plethysmography (RIP) replaces spirometry. We sought to compare EOB and WOB measurements in a nonhuman primate model of increasing extrathoracic inspiratory resistance simulating upper airway obstruction (UAO).Methods: RIP, spirometry, and esophageal manometry were measured in spontaneously breathing, intubated Rhesus monkeys utilizing 11 calibrated resistors randomly applied for 2-min. EOB was calculated breath-by-breath as Pressure Rate Product (PRP) and Pressure Time Product (PTP). WOB was calculated from the Pressure-Volume curve based on spirometry (WOBSPIR) or RIP flow (WOBRIP).Results: WOB, PRP and PTP showed similar linear increases when exposed to higher levels of resistive loads. When comparing WOBSPIR to WOBRIP, a similar strong correlation was seen for both signals as resistance increased and there were no statistically significant differences.Conclusion: EOB and WOB parameters utilizing esophageal manometry and RIP, independent of spirometry, showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates. This allows several potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available. Impact: EOB and WOB parameters showed a strong correlation as a function of increasing inspiratory resistance in nonhuman primates.There was a strong correlation between spirometry-based WOB versus RIP-based WOB.To date, it has remained untested as to whether EOB is a reliable alternative for WOB and if RIP can replace spirometry in these measurements.Our results enable additional potential monitoring possibilities for non-invasively ventilated patients or situations where spirometry is not available.Where spirometry is not available, there is no need to apply a facemask post extubation to a spontaneously breathing, non-intubated infant to make objective EOB measurements.</p

Minimal Change in Cardiac Index With Increasing PEEP in Pediatric Acute Respiratory Distress Syndrome

Objective: To determine if increasing positive end expiratory pressure (PEEP) leads to a change in cardiac index in children with Pediatric Acute Respiratory Distress Syndrome ranging from mild to severe.Design: Prospective interventional study.Setting: Multidisciplinary Pediatric Intensive Care Unit in a University teaching hospital.Patients: Fifteen intubated children (5 females, 10 males) with a median age of 72 months (IQR 11, 132) and a median weight of 19.3 kg (IQR 7.5, 53.6) with a severity of Pediatric Acute Respiratory Distress Syndrome that ranged from mild to severe with a median lung injury score of 2.3 (IQR 2.0, 2.7).Measurements: Cardiac index (CI) and stroke volume (SV) were measured on baseline ventilator settings and subsequently with a PEEP 4 cmH2O higher than baseline. Change in CI and SV from baseline values was evaluated using Wilcoxon signed rank test.Results: A total of 19 paired measurements obtained. The median baseline PEEP was 8 cmH2O (IQR 8, 10) Range 6–14 cmH2O. There was no significant change in cardiac index or stroke volume with change in PEEP. Baseline median CI 4.4 L/min/m2 (IQR 3.4, 4.8) and PEEP 4 higher median CI of 4.3 L/min/m2 (IQR 3.6, 4.8), p = 0.65. Baseline median SV 26 ml (IQR 13, 44) and at PEEP 4 higher median SV 34 ml (IQR 12, 44) p = 0.63.Conclusion: There is no significant change in cardiac index or stroke volume with increasing PEEP by 4 cmH2O in a population of children with mild to severe PARDS.Clinical Trial Registration: The study is registered on Clinical trails.gov under the Identifier: NCT02354365

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