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Invasive mechanical ventilation (MV) is one of the most practiced interventions in the intensive care unit (ICU) and is unmistakably lifesaving for children with acute respiratory failure (ARF). However, if delivered inappropriately (i.e. ignoring the respiratory system mechanics and not targeted to the need of the individual patient at a specific time point in the disease trajectory), the side effects will outweigh the benefits. Decades of experimental and clinical investigations have resulted in a better understanding of three important detrimental effects of MV. These are ventilation-induced lung injury (VILI), patient self-inflicted lung injury (P-SILI), and ventilation-induced diaphragmatic injury (VIDD). VILI, P-SILI, and VIDD have in common that they occur when there is either too much or too little ventilatory assistance.Conclusion: The purpose of this review is to give the paediatrician an overview of the challenges to prevent these detrimental effects and titrate MV to the individual patient needs., (© 2024. The Author(s).)

Background: The underlying pathophysiological pathways how reverse triggering is being caused are not fully understood. Respiratory entrainment may be one of these mechanisms, but both terms are used interchangeably. We sought to characterize reverse triggering and the relationship with respiratory entrainment among mechanically ventilated children with and without acute lung injury., Methods: We performed a secondary phyiology analysis of two previously published data sets of invasively mechanically ventilated children < 18 years with and without lung injury mechanically ventilated in a continuous or intermittent mandatory ventilation mode. Ventilator waveforms, electrical activity of the diaphragm measured with surface electromyography and oesophageal tracings were analyzed for entrained and non-entrained reverse triggered breaths., Results: In total 102 measurements (3110 min) from 67 patients (median age 4.9 [1.8 ; 19,1] months) were analyzed. Entrained RT was identified in 12 (12%) and non-entrained RT in 39 (38%) recordings. Breathing variability for entrained RT breaths was lower compared to non-entrained RT breaths. We did not observe breath stacking during entrained RT. Double triggering often occurred during non-entrained RT and led to an increased tidal volume. Patients with respiratory entrainment related RT had a shorter duration of MV and length of PICU stay., Conclusions: Reverse triggering is not one entity but a clinical spectrum with different mechanisms and consequences., Trial Registration: Not applicable., (© 2024. The Author(s).)

Background: Accuracy of esophageal pressure measured by an air-filled esophageal balloon catheter is dependent on balloon filling volume. However, this has been understudied in mechanically ventilated children. We sought to study the optimal filling volume in children receiving ventilation by using previously reported calibration methods. Secondary objectives included to examine the difference in pressure measurements at individualized optimal filling volume versus a standardized inflation volume and to study if a static hold during calibration is required to identify the optimal filling volume., Methods: An incremental inflation calibration procedure was performed in children receiving ventilation, <18 y, instrumented with commercially available catheters (6 or 8 French) who were not breathing spontaneously. The balloon was manually inflated by 0.2 to 1.6 mL (6 French) or 2.6 mL (8 French). Esophageal pressure (P es ) and airway pressure tracings were recorded during the procedure. Data were analyzed offline by using 2 methods: visual determination of filling range with the calculation of the highest difference between expiratory and inspiratory P es and determination of a correctly filled balloon by calculating the esophageal elastance., Results: We enrolled 40 subjects with median (interquartile range [IQR]) age 6.8 (2-25) months. The optimal filling volume ranged from 0.2 to 1.2 mL (median [IQR] 0.6 [0.2-1.0] mL) in the subjects with a 6 French catheter and 0.2-2.0 mL (median [IQR] 0.7 [0.5-1.2] mL) for 8 French catheters. Inflating the balloon with 0.6 mL (median computed from the whole cohort) gave an absolute difference in transpulmonary pressure that ranged from -4 to 7 cm H 2 O compared with the personalized volume. P es calculated over 5 consecutives breaths differed with a maximum of 1 cm H 2 O compared to P es calculated during a single inspiratory hold. The esophageal elastance was correlated with weight, age, and sex., Conclusions: The optimal balloon inflation volume was highly variable, which indicated the need for an individual calibration procedure. P es was not overestimated when an inspiratory hold was not applied., (Copyright © 2024 by Daedalus Enterprises.)

Background: Common, operational definitions are crucial to assess interventions and outcomes related to pediatric mechanical ventilation. These definitions can reduce unnecessary variability among 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 that 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 noninvasive respiratory support), liberation and failed attempts to liberate from invasive mechanical ventilation, liberation from respiratory support, duration of noninvasive 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 noninvasive respiratory support., Interpretation: We propose that 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., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The patient's neuro-respiratory drive, measured as electrical activity of the diaphragm (EAdi), quantifies the mechanical load on the respiratory muscles. It correlates with respiratory effort but requires a dedicated esophageal catheter. Transcutaneous (surface) monitoring of respiratory muscle electromyographic (sEMG) signals may be considered a suitable alternative to EAdi because of its non-invasive character, with the additional benefit that it allows for simultaneously monitoring of other respiratory muscles. We therefore sought to study the neuro-respiratory drive and timing of inspiratory muscles using sEMG in a cohort of children enrolled in a pediatric ventilation liberation trial. The neuro-mechanical coupling, relating the pressure generated by the inspiratory muscles to the sEMG signals of these muscles, was also calculated., Methods: This is a secondary analysis of data from a randomized cross-over trial in ventilated patients aged < 5 years. sEMG recordings of the diaphragm and parasternal intercostal muscles (ICM), esophageal pressure tracings and ventilator scalars were simultaneously recorded during continuous spontaneous ventilation and pressure controlled-intermittent mandatory ventilation, and at three levels of pressure support. Neuro-respiratory drive, timing of diaphragm and ICM relative to the mechanical ventilator's inspiration and neuro-mechanical coupling were quantified., Results: Twenty-nine patients were included (median age: 5.9 months). In response to decreasing pressure support, both amplitude of sEMG (diaphragm: p = 0.001 and ICM: p = 0.002) and neuro-mechanical efficiency indices increased (diaphragm: p = 0.05 and ICM: p < 0.001). Poor correlations between neuro-respiratory drive and respiratory effort were found, with R 2 : 0.088 [0.021-0.152]., Conclusions: sEMG allows for the quantification of the electrical activity of the diaphragm and ICM in mechanically ventilated children. Both neuro-respiratory drive and neuro-mechanical efficiency increased in response to lower inspiratory assistance. There was poor correlation between neuro-respiratory drive and respiratory effort., Trial Registration: ClinicalTrials.gov ID NCT05254691. Registered 24 February 2022, registered retrospectively., (© 2023. The Author(s).)

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 ⩾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 ⩾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.

Objectives: To explore the level and time course of patient-ventilator asynchrony in mechanically ventilated children and the effects on duration of mechanical ventilation, PICU stay, and Comfort Behavior Score as indicator for patient comfort., Design: Secondary analysis of physiology data from mechanically ventilated children., Setting: Mixed medical-surgical tertiary PICU in a university hospital., Patients: Mechanically ventilated children 0-18 years old were eligible for inclusion. Excluded were patients who were unable to initiate and maintain spontaneous breathing from any cause., Measurements and Main Results: Twenty-nine patients were studied with a total duration of 109 days. Twenty-two study days (20%) were excluded because patients were on neuromuscular blockade or high-frequency oscillatory ventilation, yielding 87 days (80%) for analysis. Patient-ventilator asynchrony was detected through analysis of daily recorded ventilator airway pressure, flow, and volume versus time scalars. Approximately one of every three breaths was asynchronous. The percentage of asynchronous breaths significantly increased over time, with the highest prevalence on the day of extubation. There was no correlation with the Comfort Behavior score. The percentage of asynchronous breaths during the first 24 hours was inversely correlated with the duration of mechanical ventilation. Patients with severe patient-ventilator asynchrony (asynchrony index > 10% or > 75th percentile of the calculated asynchrony index) did not have a prolonged duration of ventilation., Conclusions: The level of patient-ventilator asynchrony increased over time was not related to patient discomfort and inversely related to the duration of mechanical ventilation., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Patient-ventilator asynchrony is associated with increased morbidity and mortality. A direct causative relationship between Patient-ventilator asynchrony and adverse clinical outcome have yet to be demonstrated. It is hypothesized that during trigger errors excessive pleural pressure swings are generated, contributing to increased work-of-breathing and self-inflicted lung injury. The objective of this study was to determine the additional work-of-breathing and pleural pressure swings caused by trigger errors in mechanically ventilated children., Methods: Prospective observational study in a tertiary paediatric intensive care unit in an university hospital. Patients ventilated > 24 h and < 18 years old were studied. Patients underwent a 5-min recording of the ventilator flow-time, pressure-time and oesophageal pressure-time scalar. Pressure-time-product calculations were made as a proxy for work-of-breathing. Oesophageal pressure swings, as a surrogate for pleural pressure swings, during trigger errors were determined., Results: Nine-hundred-and-fifty-nine trigger errors in 28 patients were identified. The additional work-of-breathing caused by trigger errors showed great variability among patients. The more asynchronous breaths were present the higher the work-of-breathing of these breaths. A higher spontaneous breath rate led to a lower amount of trigger errors. Patient-ventilator asynchrony was not associated with prolonged duration of mechanical ventilation or paediatric intensive care stay., Conclusions: The additional work-of-breathing caused by trigger errors in ventilated children can take up to 30-40% of the total work-of-breathing. Trigger errors were less common in patients breathing spontaneously and those able to generate higher pressure-time-product and pressure swings., Trial Registration: Not applicable.

Background: Recurrent delivery of tidal mechanical energy (ME) inflicts ventilator-induced lung injury (VILI) when stress and strain exceed the limits of tissue tolerance. Mechanical power (MP) is the mathematical description of the ME delivered to the respiratory system over time. It is unknown how ME relates to underlying lung pathology and outcome in mechanically ventilated children. We therefore tested the hypothesis that ME per breath with tidal volume (Vt) normalized to bodyweight correlates with underlying lung pathology and to study the effect of resistance on the ME dissipated to the lung., Methods: We analyzed routinely collected demographic, physiological, and laboratory data from deeply sedated and/or paralyzed children < 18 years with and without lung injury. Patients were stratified into respiratory system mechanic subgroups according to the Pediatric Mechanical Ventilation Consensus Conference (PEMVECC) definition. The association between MP, ME, lung pathology, and duration of mechanical ventilation as a primary outcome measure was analyzed adjusting for confounding variables and effect modifiers. The effect of endotracheal tube diameter (ETT) and airway resistance on energy dissipation to the lung was analyzed in a bench model with different lung compliance settings., Results: Data of 312 patients with a median age of 7.8 (1.7-44.2) months was analyzed. Age (p <  0.001), RR p <  0.001), and Vt <  0.001) were independently associated with MPrs. ME but not MP correlated significantly (p <  0.001) better with lung pathology. Competing risk regression analysis adjusting for PRISM III 24 h score and PEMVECC stratification showed that ME on day 1 or day 2 of MV but not MP was independently associated with the duration of mechanical ventilation. About 33% of all energy generated by the ventilator was transferred to the lung and highly dependent on lung compliance and airway resistance but not on endotracheal tube size (ETT) during pressure control (PC) ventilation., Conclusions: ME better related to underlying lung pathology and patient outcome than MP. The delivery of generated energy to the lung was not dependent on ETT size during PC ventilation. Further studies are needed to identify injurious MErs thresholds in ventilated children.

Objectives: To calculate imposed work of breathing during simulated spontaneous breathing at a given tidal volume across the range of normal length or shortened pediatric endotracheal tube sizes and endotracheal tubes with an intraluminal catheter in situ., Design: In vitro study., Setting: Research laboratory., Interventions: A bench model (normal compliance, no airway resistance) simulating sinusoid flow spontaneous breathing used to calculate imposed work of breathing for various endotracheal tube sizes (3.0-7.5 mm). Imposed work of breathing was calculated by integrating inspiratory tidal volume over the end-expiratory difference between the positive end-expiratory pressure and the tracheal pressure. Measurements were taken at different combinations of set spontaneous tidal volume (2.5, 5.0, 7.5, and 10 mL/kg), age-appropriate inspiratory times, length of endotracheal tube, and presence of intraluminal catheter., Measurements and Main Results: Overall median imposed work of breathing (Joules/L) was not significantly different between the four age groups: 0.047 Joules/L (interquartile range, 0.020-0.074 Joules/L) for newborns, 0.077 Joules/L (interquartile range, 0.032-0.127 Joules/L) for infants, 0.109 Joules/L (interquartile range, 0.0399-0.193 Joules/L) for small children, and 0.077 Joules/L (interquartile range, 0.032-0.132 Joules/L) for adolescents. Shortening the endotracheal tubes resulted in a significant difference in reduction in overall imposed work of breathing, but the absolute reduction was most notable in small children (0.030 Joules/L) and the least effect in neonates (0.016 Joules/L). Overall imposed work of breathing increased in each age group when an intraluminal catheter was in situ: 91.09% increase in imposed work of breathing in neonates to 0.168 Joules/L, 84.98% in infants to 0.142 Joules/L, 81.98% in small children to 0.219 Joules/L, and 55.45% in adolescents to 0.140 Joules/L., Conclusions: Calculated imposed work of breathing were not different across the range of endotracheal tube sizes. The low imposed work of breathing values found in this study might be appreciated as clinically irrelevant. Our findings add to the change in reasoning that it is appropriate to perform spontaneous breathing trials without pressure support. Nonetheless, our findings on the measured imposed work of breathing values need to be confirmed in a clinical study.

Objectives: We sought to investigate factors that affect the difference between the peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions (resistive pressure) during pressure controlled ventilation across a range of endotracheal tube sizes, respiratory mechanics, and ventilator settings., Design: In vitro study., Setting: Research laboratory., Patients: None., Interventions: An in vitro bench model of the intubated respiratory system during pressure controlled ventilation was used to obtain the difference between peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions across a range of endotracheal tubes sizes (3.0-8.0 mm). Measurements were taken at combinations of pressure above positive end-expiratory pressure (10, 15, and 20 cm H2O), airway resistance (no, low, high), respiratory system compliance (ranging from normal to extremely severe), and inspiratory time at constant positive end-expiratory pressure (5 cm H2O). Multiple regression analysis was used to construct models predicting resistive pressure stratified by endotracheal tube size., Measurements and Main Results: On univariate regression analysis, respiratory system compliance (β -1.5; 95% CI, -1.7 to -1.4; p < 0.001), respiratory system resistance (β 1.7; 95% CI, 1.5-2.0; p < 0.001), pressure above positive end-expiratory pressure (β 1.7; 95% CI, 1.4-2.0; p < 0.001), and inspiratory time (β -0.7; 95% CI, -1.0 to -0.4; p < 0.001) were associated with resistive pressure. Multiple linear regression analysis showed the independent association between increasing respiratory system compliance, increasing airway resistance, increasing pressure above positive end-expiratory pressure, and decreasing inspiratory time and resistive pressure across all endotracheal tube sizes. Inspiratory time was the strongest variable associated with a proportional increase in resistive pressure. The contribution of airway resistance became more prominent with increasing endotracheal tube size., Conclusions: Peak inspiratory pressures measured during pressure controlled ventilation overestimated plateau pressure irrespective of endotracheal tube size, especially with decreased inspiratory time or increased airway resistance.

Purpose: Much of the common practice in paediatric mechanical ventilation is based on personal experiences and what paediatric critical care practitioners have adopted from adult and neonatal experience. This presents a barrier to planning and interpretation of clinical trials on the use of specific and targeted interventions. We aim to establish a European consensus guideline on mechanical ventilation of critically children., Methods: The European Society for Paediatric and Neonatal Intensive Care initiated a consensus conference of international European experts in paediatric mechanical ventilation to provide recommendations using the Research and Development/University of California, Los Angeles, appropriateness method. An electronic literature search in PubMed and EMBASE was performed using a combination of medical subject heading terms and text words related to mechanical ventilation and disease-specific terms., Results: The Paediatric Mechanical Ventilation Consensus Conference (PEMVECC) consisted of a panel of 15 experts who developed and voted on 152 recommendations related to the following topics: (1) general recommendations, (2) monitoring, (3) targets of oxygenation and ventilation, (4) supportive measures, (5) weaning and extubation readiness, (6) normal lungs, (7) obstructive diseases, (8) restrictive diseases, (9) mixed diseases, (10) chronically ventilated patients, (11) cardiac patients and (12) lung hypoplasia syndromes. There were 142 (93.4%) recommendations with "strong agreement". The final iteration of the recommendations had none with equipoise or disagreement., Conclusions: These recommendations should help to harmonise the approach to paediatric mechanical ventilation and can be proposed as a standard-of-care applicable in daily clinical practice and clinical research.