Rationale: Subglottic edema is the most common cause of pediatric extubation failure, but few studies have confirmed risk factors or prevention strategies. This may be due to subjective assessment of stridor or inability to differentiate supraglottic from subglottic disease.Objectives: Objective 1 was to assess the utility of calibrated respiratory inductance plethysmography (RIP) and esophageal manometry to identify clinically significant post-extubation upper airway obstruction (UAO) and differentiate subglottic from supraglottic UAO. Objective 2 was to identify risk factors for subglottic UAO, stratified by cuffed versus uncuffed endotracheal tubes (ETTs).Methods: We conducted a single-center prospective study of children receiving mechanical ventilation. UAO was defined by inspiratory flow limitation (measured by RIP and esophageal manometry) and classified as subglottic or supraglottic based on airway maneuver response. Clinicians performed simultaneous blinded clinical UAO assessment at the bedside. Measurements and Main Results:A total of 409 children were included, 98 of whom had post-extubation UAO and 49 (12%) of whom were subglottic. The reintubation rate was 34 (8.3%) of 409, with 14 (41%) of these 34 attributable to subglottic UAO. Five minutes after extubation, RIP and esophageal manometry better identified patients who subsequently received UAO treatment than clinical UAO assessment (P , 0.006). Risk factors independently associated with subglottic UAO included low cuff leak volume or high preextubation leak pressure, poor sedation, and preexisting UAO (P , 0.04) for cuffed ETTs; and age (range, 1 mo to 5 yr) for uncuffed ETTs (P , 0.04). For uncuffed ETTs, the presence or absence of preextubation leak was not associated with subglottic UAO.Conclusions: RIP and esophageal manometry can objectively identify subglottic UAO after extubation. Using this technique, preextubation leak pressures or cuff leak volumes predict subglottic UAO in children, but only if the ETT is cuffed.

Key Points: By performing direct measures of patient effort of breathing before and after extubation on over 400 mechanically ventilated children, we have found that patient effort of breathing on CPAP of 5cmH20 alone provides a good estimate of post-extubation effort. Regardless of the endotracheal tube size, pressure support should not be added to CPAP for extubation readiness testing because it results in significant under-estimation of postextubation effort of breathing.Social Network: Regardless of endotracheal tube size, PS during ERTs significantly underestimates post-extubation effort of breathing. ManuscriptClick here to download Manuscript BreathingThroughStraw_ICM_NoFigs.doc Click here to view linked References 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64

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Objective Respiratory muscle weakness frequently develops during mechanical ventilation, although in children there are limited data about its prevalence and whether it is associated with extubation outcomes. We sought to identify risk factors for pediatric extubation failure, with specific attention to respiratory muscle strength. Design Secondary analysis of prospectively collected data Setting Tertiary care pediatric ICU Patients 409 mechanically ventilated children Interventions Respiratory measurements using esophageal manometry and respiratory inductance plethysmography were made pre-extubation during airway occlusion and on CPAP of 5 and PS of 10/ above PEEP 5 cmH20, as well as 5 and 60 minutes post-extubation. Measurements and Main Results Thirty-four patients (8.3%) were re-intubated within 48 hours of extubation. Re-intubation risk factors included lower maximum airway pressure during airway occlusion (aPiMax), longer length of ventilation, post-extubation upper airway obstruction (UAO), high respiratory effort post-extubation (Pressure Rate Product (PRP), Pressure Time Product, Tension Time Index) and high post-extubation Phase Angle. Nearly 35% of children had diminished respiratory muscle strength (aPiMax ≤ 30 cmH20) at the time of extubation, and were nearly three times more likely to be re-intubated than those with preserved strength (aPiMax >30 cmH20; 14% vs. 5.5%, p=0.006). Re-intubation rates exceeded 20% when children with low aPiMax had moderately elevated effort after extubation (PRP > 500), while children with preserved aPiMax had re-intubation rates > 20% only when post-extubation effort was very high (PRP > 1000). When children developed post-extubation UAO, re-intubation rates were 47.4% for those with low aPiMax compared to 15.4% for those with preserved aPiMax (p=0.02). Multivariable risk factors for re-intubation included acute neurologic disease, lower aPiMax, post-extubation UAO, higher pre-extubation PEEP, higher post-extubation PRP, and lower height. Conclusions Neuromuscular weakness at the time of extubation was common in children and was independently associated with re-intubation, particularly when post-extubation effort was high.

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Manufacturer-recommended esophageal balloon inflation ranges do not assure accuracy. Individual titration of esophageal balloon volume may improve accuracy. Better esophageal catheters are needed to provide reliable esophageal pressure measurements in children.

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Lung Protective Mechanical Ventilation (MV) of critically ill adults and children is lifesaving but it may decrease diaphragm contraction and promote Ventilator Induced Diaphragm Dysfunction (VIDD). An ideal MV strategy would balance lung and diaphragm protection. Building off a Phase I pilot study, we are conducting a Phase II controlled clinical trial that seeks to understand the evolution of VIDD in critically ill children and test whether a novel computer-based approach (Real-time Effort Driven ventilator management (REDvent)) can balance lung and diaphragm protective ventilation to reduce time on MV. REDvent systematically adjusts PEEP, FiO 2 , inspiratory pressure, tidal volume and rate, and uses real-time measures from esophageal manometry to target normal levels of patient effort of breathing. This trial targets 276 children with pulmonary parenchymal disease. Patients are randomized to REDvent vs. usual care for the acute phase of MV (intubation to first Spontaneous Breathing Trial (SBT)). Patients in either group who fail their first SBT will be randomized to REDvent vs usual care for weaning phase management (interval from first SBT to passing SBT). The primary clinical outcome is length of weaning, with several mechanistic outcomes. Upon completion, this study will provide important information on the pathogenesis and timing of VIDD during MV in children and whether this computerized protocol targeting lung and diaphragm protection can lead to improvement in intermediate clinical outcomes. This will form the basis for a larger, Phase III multi-center study, powered for key clinical outcomes such as 28day ventilator free days. Clinical Trials Registration: NCT03266016