Framework for Research Gaps in Pediatric Ventilator Liberation.

BACKGROUND: The 2023 international pediatric ventilator liberation clinical practice guidelines provided evidence-based recommendations to guide pediatric critical care providers on how to perform daily aspects of ventilator liberation. However, due to the lack of high-quality pediatric studies, most recommendations were conditional based on very low to low certainty of evidence. RESEARCH QUESTION: What are the research gaps related to pediatric ventilator liberation that can be studied to strengthen the evidence for future updates of the guidelines? STUDY DESIGN: and Methods: We conducted systematic reviews of the literature in 8 pre-defined PICO areas related to pediatric ventilator liberation to generate recommendations. Subgroups responsible for each PICO question subsequently identified major research gaps by synthesizing the literature. These gaps were presented at an international symposium at the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) meeting in Spring 2022 for open discussion, feedback was incorporated, and final evaluation of research gaps are summarized in this document. While randomized trials trials (RCTs) represent the highest level of evidence, the panel sought to highlight areas where alternative study designs may also be appropriate, given challenges with conducting large multi-center RCTs in children. RESULTS: Significant research gaps were identified in six broad areas related to pediatric ventilator liberation. Several of these areas necessitate multi-center RCTs to provide definitive results, while other gaps can be addressed with multi-center observational studies or quality improvement initiatives. Furthermore, there remains a need for some physiologic studies in several areas, particularly regarding newer diagnostic methods to improve identification of patients at high-risk of extubation failure. INTERPRETATION: While pediatric ventilator liberation guidelines have been created, the certainty of evidence remains low and there are multiple research gaps which should be filled through high quality RCTs, and multi-center observational studies and quality improvement initiatives.

Safety of primary nasotracheal intubation in the pediatric intensive care unit (PICU).

Background: Nasal tracheal intubation (TI) represents a minority of all TI in the pediatric intensive care unit (PICU). The risks and benefits of nasal TI are not well quantified. As such, safety and descriptive data regarding this practice are warranted. Methods: We evaluated the association between TI route and safety outcomes in a prospectively collected quality improvement database (National Emergency Airway Registry for Children: NEAR4KIDS) from 2013 to 2020. The primary outcome was severe desaturation (SpO2 > 20% from baseline) and/or severe adverse TI-associated events (TIAEs), using NEAR4KIDS definitions. To balance patient, provider, and practice covariates, we utilized propensity score (PS) matching to compare the outcomes of nasal vs. oral TI. Results: A total of 22,741 TIs [nasal 870 (3.8%), oral 21,871 (96.2%)] were reported from 60 PICUs. Infants were represented in higher proportion in the nasal TI than the oral TI (75.9%, vs 46.2%), as well as children with cardiac conditions (46.9% vs. 14.4%), both p < 0.001. Severe desaturation or severe TIAE occurred in 23.7% of nasal and 22.5% of oral TI (non-adjusted p = 0.408). With PS matching, the prevalence of severe desaturation and or severe adverse TIAEs was 23.6% of nasal vs. 19.8% of oral TI (absolute difference 3.8%, 95% confidence interval (CI): - 0.07, 7.7%), p = 0.055. First attempt success rate was 72.1% of nasal TI versus 69.2% of oral TI, p = 0.072. With PS matching, the success rate was not different between two groups (nasal 72.2% vs. oral 71.5%, p = 0.759). Conclusion: In this large international prospective cohort study, the risk of severe peri-intubation complications was not significantly higher. Nasal TI is used in a minority of TI in PICUs, with substantial differences in patient, provider, and practice compared to oral TI.A prospective multicenter trial may be warranted to address the potential selection bias and to confirm the safety of nasal TI.

Immunocompromised-Associated Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study.

OBJECTIVES: To characterize immunocompromised-associated pediatric acute respiratory distress syndrome (I-PARDS) and contrast it to PARDS. DESIGN: This is a secondary analysis of the 2016-2017 PARDS incidence and epidemiology (PARDIE) study, a prospective observational, cross-sectional study of children with PARDS. SETTING: Dataset of 145 PICUs across 27 countries. PATIENTS: During 10 nonconsecutive weeks (from May 2016 to June 2017), data about immunocompromising conditions (ICCs, defined as malignancy, congenital/acquired immunodeficiency, posttransplantation, or diseases requiring immunosuppression) were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 708 subjects, 105 (14.8%) had ICC. Before the development of I-PARDS, those with ICC were more likely to be hospitalized (70% vs. 35%, p < 0.001), have more at-risk for PARDS ( p = 0.046), and spent more hours at-risk (20 [interquartile range, IQR: 8-46] vs. 11 [IQR: 4-33], [ p = 0.002]). Noninvasive ventilation (NIV) use was more common in those with ICC ( p < 0.001). Of those diagnosed with PARDS on NIV ( n = 161), children with ICC were more likely to be subsequently intubated ( n = 28/40 [70%] vs n = 53/121 [44%], p = 0.004). Severe PARDS was more common (32% vs 23%, p < 0.001) in I-PARDS. Oxygenation indices were higher at diagnosis and had less improvement over the first 3 days of PARDS ( p < 0.001). Children with I-PARDS had greater nonpulmonary organ dysfunction. Adjusting for Pediatric Risk of Mortality IV and oxygenation index, children with I-PARDS had a higher severity of illness-adjusted PICU mortality (adjusted hazard ratio: 3.0 [95% CI, 1.9-4.7] p < 0.001) and were less likely to be extubated alive within 28 days (subdistribution hazard ratio: 0.47 [95% CI, 0.31-0.71] p < 0.001). CONCLUSIONS: I-PARDS is a unique subtype of PARDS associated with hospitalization before diagnosis and increased: time at-risk for PARDS, NIV use, hypoxia, nonpulmonary organ dysfunction, and mortality. The opportunity for early detection and intervention seems to exist. Dedicated study in these patients is imperative to determine if targeted interventions will benefit these unique patients with the ultimate goal of improving outcomes.

Determining Optimal Mean Arterial Blood Pressure Based on Cerebral Autoregulation in Children after Cardiac Surgery.

To evaluate the feasibility of continuous determination of the optimal mean arterial blood pressure (opt-MAP) according to cerebral autoregulation and to describe the opt-MAP, the autoregulation limits, and the time spent outside these limits in children within 48 h of cardiac surgery. Cerebral autoregulation was assessed using the correlation coefficient (COx) between cerebral oxygenation and MAP in children following cardiac surgery. Plots depicting the COx according to the MAP were used to determine the opt-MAP using weighted multiple time windows. For each patient, we estimated (1) the time spent with MAP outside the autoregulation limits and (2) the burden of deviation, defined as the area between the MAP curve and the autoregulation limits when the MAP was outside these limits. Fifty-one patients with a median age of 7.1 (IQR 0.7-52.0) months old were included. The opt-MAP was calculated for 94% (IQR 90-96) of the monitored time. The opt-MAP was significantly lower in neonates < 1 month old. The patients spent 24% (18-31) of the time outside of the autoregulation limits, with no significant differences between age groups. Continuous determination of the opt-MAP is feasible in children within the first 48 h following cardiac surgery.

Noninvasive Neurally Adjusted Ventilatory Assist in Infants With Bronchiolitis: Respiratory Outcomes in a Single-Center, Retrospective Cohort, 2016-2018.

OBJECTIVES: To describe our experience of using noninvasive neurally adjusted ventilatory assist (NIV-NAVA) in infants with bronchiolitis, its association with the evolution of respiratory effort, and PICU outcomes. DESIGN: Retrospective analysis of a prospectively curated, high-frequency electronic database. SETTING: A PICU in a university-affiliated maternal-child health center in Canada. PATIENTS: Patients younger than 2 years old who were admitted with a diagnosis of acute bronchiolitis and treated with NIV-NAVA from October 2016 to June 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, as well as respiratory and physiologic parameters, including electrical diaphragmatic activity (Edi), were extracted from the electronic database. Respiratory effort was estimated using the modified Wood Clinical Asthma Score (mWCAS) and the inspiratory Edi. A comparison in the respiratory effort data was made between the 2 hours before and 2 hours after starting NIV-NAVA. In the two seasons, 64 of 205 bronchiolitis patients were supported with NIV-NAVA. These 64 patients had a median (interquartile range [IQR]) age of 52 days (32-92 d), and there were 36 of 64 males. Treatment with NIV-NAVA was used after failure of first-tier noninvasive respiratory support; 25 of 64 patients (39%) had at least one medical comorbidity. NIV-NAVA initiation was associated with a moderate decrease in mWCAS from 3.0 (IQR, 2.5-3.5) to 2.5 (IQR, 2.0-3.0; p < 0.001). NIV-NAVA initiation was also associated with a statistically significant decrease in Edi ( p < 0.01). However, this decrease was only clinically relevant in infants with a 2-hour baseline Edi greater than 20 µV; here, the before and after Edi was 44 µV (IQR, 33-54 µV) compared with 27 µV (IQR, 21-36 µV), respectively ( p < 0.001). Overall, six of 64 patients (9%) required endotracheal intubation. CONCLUSIONS: In this single-center retrospective cohort, in infants with bronchiolitis who were considered to have failed first-tier noninvasive respiratory support, the use of NIV-NAVA was associated with a rapid decrease in respiratory effort and a 9% intubation rate.

Evaluation of the SIMULRESP: A simulation software of child and teenager cardiorespiratory physiology.

BACKGROUND: Mathematical models based on the physiology when programmed as a software can be used to teach cardiorespiratory physiology and to forecast the effect of various ventilatory support strategies. We developed a cardiorespiratory simulator for children called "SimulResp." The purpose of this study was to evaluate the quality of SimulResp. METHODS: SimulResp quality was evaluated on accuracy, robustness, repeatability, and reproducibility. Blood gas values (pH, PaCO2 , PaO2,  and SaO2 ) were simulated for several subjects with different characteristics and in different situations and compared to expected values available as reference. The correlation between reference and simulated data was evaluated by the coefficient of determination and Intraclass correlation coefficient. The agreement was evaluated with the Bland & Altman analysis. RESULTS: SimulResp produced healthy child physiological values within normal range (pH 7.40 ± 0.5; PaCO2 40 ± 5 mmHg; PaO2 90 ± 10 mmHg; SaO2 97 ± 3%) starting from a weight of 25-35 kg, regardless of ventilator support. SimulResp failed to simulate accurate values for subjects under 25 kg and/or affected with pulmonary disease and mechanically ventilated. Based on the repeatability was considered as excellent and the reproducibility as mild to good. SimulResp's prediction remains stable within time. CONCLUSIONS: The cardiorespiratory simulator SimulResp requires further development before future integration into a clinical decision support system.

Associations With Severe Desaturation Events Among Children Receiving Noninvasive Respiratory Support at Time of Intubation.

BACKGROUND: Endotracheal intubation is a common procedure associated with adverse events, including severe desaturation. Many patients receive noninvasive respiratory support to reduce the need for intubation. There are minimal data about the association between noninvasive respiratory support and the risk of a severe desaturation event during intubation. We aim to differentiate patients based on the level of noninvasive respiratory support, analyze the severe desaturation event by groups, and identify modifiable risk factors. METHODS: Oral intubations, excluding tube exchanges or re-intubation after unplanned extubation, from October 2018 through July 2020, at the study site were reviewed. A severe desaturation event was defined as [Formula: see text] < 70% or a >15% decrease from baseline in cyanotic heart disease. We analyzed outcomes by 4 groups: room air/nasal cannula (≤0.5 L/kg/min), high-flow nasal cannula (HFNC) (0.5-2 L/kg/min), high HFNC (≥2 L/kg/min), and noninvasive ventilation (NIV). RESULTS: Of 243 subjects who were intubated, 31% were receiving room air/nasal cannula, 25% were receiving HFNC, 18% were receiving high HFNC, and 26% were receiving NIV. Twelve percent of all the subjects had a severe desaturation event. In a univariate analysis, the incidence of a severe desaturation event was similar among all levels of respiratory support (P = .14). A severe desaturation event was more likely in those subjects who were receiving [Formula: see text] ≥ 0.6 at the time of the decision to intubate (19.6%) versus [Formula: see text] < 0.6 (8.1%) (P = .02). The duration of noninvasive respiratory support was longer (5 vs 1 h; P = .02) among those with a severe desaturation event. In a regression analysis, when adjusting for ≥2 intubation attempts pre-intubation, NIV use was independently associated with increased odds of severe desaturation events (odds ratio 3.14, CI 1.08-10.5). CONCLUSIONS: Results of our study suggest that [Formula: see text] > 0.60, the duration of noninvasive respiratory support, and exposure to NIV before an intubation are risk factors of severe desaturation events during intubation.

Noninvasive Ventilation for Pediatric Acute Respiratory Distress Syndrome: Experience From the 2016/2017 Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Prospective Cohort Study.

OBJECTIVES: The worldwide practice and impact of noninvasive ventilation (NIV) in pediatric acute respiratory distress syndrome (PARDS) is unknown. We sought to describe NIV use and associated clinical outcomes in PARDS. DESIGN: Planned ancillary study to the 2016/2017 prospective Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study. SETTING: One hundred five international PICUs. PATIENTS: Patients with newly diagnosed PARDS admitted during 10 study weeks. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children were categorized by their respiratory support at PARDS diagnosis into NIV or invasive mechanical ventilation (IMV) groups. Of 708 subjects with PARDS, 160 patients (23%) received NIV at PARDS diagnosis (NIV group). NIV failure rate (defined as tracheal intubation or death) was 84 of 160 patients (53%). Higher nonrespiratory pediatric logistic organ dysfunction (PELOD-2) score, Pa o2 /F io2 was less than 100 at PARDS diagnosis, immunosuppression, and male sex were independently associated with NIV failure. NIV failure was 100% among patients with nonrespiratory PELOD-2 score greater than 2, Pa o2 /F io2 less than 100, and immunosuppression all present. Among patients with Pa o2 /F io2 greater than 100, children in the NIV group had shorter total duration of NIV and IMV, than the IMV at initial diagnosis group. We failed to identify associations between NIV use and PICU survival in a multivariable Cox regression analysis (hazard ratio 1.04 [95% CI, 0.61-1.80]) or mortality in a propensity score matched analysis ( p = 0.369). CONCLUSIONS: Use of NIV at PARDS diagnosis was associated with shorter exposure to IMV in children with mild to moderate hypoxemia. Even though risk of NIV failure was high in some children, we failed to identify greater hazard of mortality in these patients.

Elevated Diaphragmatic Tonic Activity in PICU Patients: Age-Specific Definitions, Prevalence, and Associations.

OBJECTIVES: Tonic diaphragmatic activity (tonic Edi, i.e., sustained diaphragm activation throughout expiration) reflects diaphragmatic effort to defend end-expiratory lung volumes. Detection of such elevated tonic Edi may be useful in identifying patients who need increased positive end-expiratory pressure. We aimed to: 1) identify age-specific definitions for elevated tonic Edi in ventilated PICU patients and 2) describe the prevalence and factors associated with sustained episodes of high tonic Edi. DESIGN: Retrospective study using a high-resolution database. SETTING: Single-center tertiary PICU. PATIENTS: Four hundred thirty-one children admitted between 2015 and 2020 with continuous Edi monitoring. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We characterized our definition of tonic Edi using data from the recovery phase of respiratory illness (i.e., final 3 hr of Edi monitoring, excluding patients with significant persistent disease or with diaphragm pathology). High tonic Edi was defined as population data exceeding the 97.5th percentile, which for infants younger than 1 year was greater than 3.2 µV and for older children as greater than 1.9 µV. These thresholds were then used to identify patients with episodes of sustained elevated tonic Edi in the first 48 hours of ventilation (acute phase). Overall, 62 of 200 (31%) of intubated patients and 138 of 222 (62%) of patients on noninvasive ventilation (NIV) had at least one episode of high tonic Edi. These episodes were independently associated with the diagnosis of bronchiolitis (intubated patients: adjusted odds [aOR], 2.79 [95% CI, 1.12-7.11]); NIV patients: aOR, 2.71 [1.24-6.0]). There was also an association with tachypnea and, in NIV patients, more severe hypoxemia. CONCLUSIONS: Our proposed definition of elevated tonic Edi quantifies abnormal diaphragmatic activity during expiration. Such a definition may help clinicians to identify those patients using abnormal effort to defend end-expiratory lung volume. In our experience, high tonic Edi episodes are frequent, especially during NIV and in patients with bronchiolitis.

Clinical practice guidelines: management of severe bronchiolitis in infants under 12 months old admitted to a pediatric critical care unit.

PURPOSE: We present guidelines for the management of infants under 12 months of age with severe bronchiolitis with the aim of creating a series of pragmatic recommendations for a patient subgroup that is poorly individualized in national and international guidelines. METHODS: Twenty-five French-speaking experts, all members of the Groupe Francophone de Réanimation et Urgence Pédiatriques (French-speaking group of paediatric intensive and emergency care; GFRUP) (Algeria, Belgium, Canada, France, Switzerland), collaborated from 2021 to 2022 through teleconferences and face-to-face meetings. The guidelines cover five areas: (1) criteria for admission to a pediatric critical care unit, (2) environment and monitoring, (3) feeding and hydration, (4) ventilatory support and (5) adjuvant therapies. The questions were written in the Patient-Intervention-Comparison-Outcome (PICO) format. An extensive Anglophone and Francophone literature search indexed in the MEDLINE database via PubMed, Web of Science, Cochrane and Embase was performed using pre-established keywords. The texts were analyzed and classified according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. When this method did not apply, an expert opinion was given. Each of these recommendations was voted on by all the experts according to the Delphi methodology. RESULTS: This group proposes 40 recommendations. The GRADE methodology could be applied for 17 of them (3 strong, 14 conditional) and an expert opinion was given for the remaining 23. All received strong approval during the first round of voting. CONCLUSION: These guidelines cover the different aspects in the management of severe bronchiolitis in infants admitted to pediatric critical care units. Compared to the different ways to manage patients with severe bronchiolitis described in the literature, our original work proposes an overall less invasive approach in terms of monitoring and treatment.

Executive Summary of the Second International Guidelines for the Diagnosis and Management of Pediatric Acute Respiratory Distress Syndrome (PALICC-2).

OBJECTIVES: We sought to update our 2015 work in the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2) guidelines for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS), considering new evidence and topic areas that were not previously addressed. DESIGN: International consensus conference series involving 52 multidisciplinary international content experts in PARDS and four methodology experts from 15 countries, using consensus conference methodology, and implementation science. SETTING: Not applicable. PATIENTS: Patients with or at risk for PARDS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eleven subgroups conducted systematic or scoping reviews addressing 11 topic areas: 1) definition, incidence, and epidemiology; 2) pathobiology, severity, and risk stratification; 3) ventilatory support; 4) pulmonary-specific ancillary treatment; 5) nonpulmonary treatment; 6) monitoring; 7) noninvasive respiratory support; 8) extracorporeal support; 9) morbidity and long-term outcomes; 10) clinical informatics and data science; and 11) resource-limited settings. The search included MEDLINE, EMBASE, and CINAHL Complete (EBSCOhost) and was updated in March 2022. Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to summarize evidence and develop the recommendations, which were discussed and voted on by all PALICC-2 experts. There were 146 recommendations and statements, including: 34 recommendations for clinical practice; 112 consensus-based statements with 18 on PARDS definition, 55 on good practice, seven on policy, and 32 on research. All recommendations and statements had agreement greater than 80%. CONCLUSIONS: PALICC-2 recommendations and consensus-based statements should facilitate the implementation and adherence to the best clinical practice in patients with PARDS. These results will also inform the development of future programs of research that are crucially needed to provide stronger evidence to guide the pediatric critical care teams managing these patients.

Methodology of the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: This article describes the methodology used for The Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2). The PALLIC-2 sought to develop evidence-based clinical recommendations and when evidence was lacking, expert-based consensus statements and research priorities for the diagnosis and management of pediatric acute respiratory distress syndrome (PARDS). DATA SOURCES: Electronic searches were conducted using PubMed, Embase, and Cochrane Library (CENTRAL) databases from 2012 to March 2022. STUDY SELECTION: Content was divided into 11 sections related to PARDS, with abstract and full text screening followed by data extraction for studies which met inclusion with no exclusion criteria. DATA EXTRACTION: We used a standardized data extraction form to construct evidence tables, grade the evidence, and formulate recommendations or statements using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. DATA SYNTHESIS: This consensus conference was comprised of a multidisciplinary group of international experts in pediatric critical care, pulmonology, respiratory care, and implementation science which followed standards set by the Institute of Medicine, using the GRADE system and Research And Development/University of California, Los Angeles appropriateness method, modeled after PALICC 2015. The panel of 52 content and four methodology experts had several web-based meetings over the course of 2 years. We conducted seven systematic reviews and four scoping reviews to cover the 11 topic areas. Dissemination was via primary publication listing all statements and separate supplemental publications for each subtopic that include supporting arguments for each recommendation and statement. CONCLUSIONS: A consensus conference of experts from around the world developed recommendations and consensus statements for the definition and management of PARDS and identified evidence gaps which need further research.

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 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.

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 ⩾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.

Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome.

Paediatric acute respiratory distress syndrome (PARDS) is a heterogeneous clinical syndrome that is associated with high rates of mortality and long-term morbidity. Factors that distinguish PARDS from adult acute respiratory distress syndrome (ARDS) include changes in developmental stage and lung maturation with age, precipitating factors, and comorbidities. No specific treatment is available for PARDS and management is largely supportive, but methods to identify patients who would benefit from specific ventilation strategies or ancillary treatments, such as prone positioning, are needed. Understanding of the clinical and biological heterogeneity of PARDS, and of differences in clinical features and clinical course, pathobiology, response to treatment, and outcomes between PARDS and adult ARDS, will be key to the development of novel preventive and therapeutic strategies and a precision medicine approach to care. Studies in which clinical, biomarker, and transcriptomic data, as well as informatics, are used to unpack the biological and phenotypic heterogeneity of PARDS, and implementation of methods to better identify patients with PARDS, including methods to rapidly identify subphenotypes and endotypes at the point of care, will drive progress on the path to precision medicine.

University of Montreal's Clinician-Investigator Program: A 10-Year Descriptive Evaluation.

PURPOSE: Clinician-investigators have an important role in the development and implantation of new therapies and treatment modalities; however, there have been several reports highlighting a pending shortage in the clinician-investigators' workforce. In Canada, the Royal College has promoted the development of clinician-investigators programs (CIP) to facilitate the training of these individuals. There is currently a paucity of data regarding the outcomes of such programs. This study aims to identify the strengths and areas of improvement of the Montreal University CIP.  Methods: An internet-based 51-question survey was distributed to all the alumni from the University of Montreal CIP. Participation was voluntary and no incentives were provided. The response rate was 64%.  Results: Among respondents, 50% (n=16) had completed their clinical residency and all CIP requirements. The majority of these individuals (63%) had become independent investigators and had secured provincial and national funding. Satisfaction of the respondents was high regarding the overall program (85%), the research skills developed during the CIP (84%) and the financial support obtained during the program (72%). The satisfaction rate regarding career planning was lower (63%).  Conclusion: This survey demonstrates that, while indicators are favorable, some areas still require improvement. Several steps to improve the CIP have been identified; notably, the transition from the CIP to early independent career has been identified as critical in the development of clinician-investigators and steps have been taken to improve this progression.

The Use and Duration of Preintubation Respiratory Support Is Associated With Increased Mortality in Immunocompromised Children With Acute Respiratory Failure.

OBJECTIVES: To determine the association between preintubation respiratory support and outcomes in patients with acute respiratory failure and to determine the impact of immunocompromised (IC) diagnoses on outcomes after adjustment for illness severity. DESIGN: Retrospective multicenter cohort study. SETTING: Eighty-two centers in the Virtual Pediatric Systems database. PATIENTS: Children 1 month to 17 years old intubated in the PICU who received invasive mechanical ventilation (IMV) for greater than or equal to 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: High-flow nasal cannula (HFNC) or noninvasive positive-pressure ventilation (NIPPV) or both were used prior to intubation in 1,825 (34%) of 5,348 PICU intubations across 82 centers. When stratified by IC status, 50% of patients had no IC diagnosis, whereas 41% were IC without prior hematopoietic cell transplant (HCT) and 9% had prior HCT. Compared with patients intubated without prior support, preintubation exposure to HFNC (adjusted odds ratio [aOR], 1.33; 95% CI, 1.10-1.62) or NIPPV (aOR, 1.44; 95% CI, 1.20-1.74) was associated with increased odds of PICU mortality. Within subgroups of IC status, preintubation respiratory support was associated with increased odds of PICU mortality in IC patients (HFNC: aOR, 1.50; 95% CI, 1.11-2.03; NIPPV: aOR, 1.76; 95% CI, 1.31-2.35) and HCT patients (HFNC: aOR, 1.75; 95% CI, 1.07-2.86; NIPPV: aOR, 1.85; 95% CI, 1.12-3.02) compared with IC/HCT patients intubated without prior respiratory support. Preintubation exposure to HFNC/NIPPV was not associated with mortality in patients without an IC diagnosis. Duration of HFNC/NIPPV greater than 6 hours was associated with increased mortality in IC HCT patients (HFNC: aOR, 2.41; 95% CI, 1.05-5.55; NIPPV: aOR, 2.53; 95% CI, 1.04-6.15) and patients compared HCT patients with less than 6-hour HFNC/NIPPV exposure. After adjustment for patient and center characteristics, both preintubation HFNC/NIPPV use (median, 15%; range, 0-63%) and PICU mortality varied by center. CONCLUSIONS: In IC pediatric patients, preintubation exposure to HFNC and/or NIPPV is associated with increased odds of PICU mortality, independent of illness severity. Longer duration of exposure to HFNC/NIPPV prior to IMV is associated with increased mortality in HCT patients.