Pediatric Acute Lung Injury Consensus Conference Research Articles

Interrater Reliability of the 2015 Pediatric Acute Lung Injury Consensus Conference Criteria for Pediatric ARDS

Diagnostic guidelines for pediatric acute respiratory distress syndrome (PARDS) were developed at the 2015 Pediatric Acute Lung Injury Consensus Conference (PALICC). Although this was an improvement in creating pediatric-specific diagnostic criteria, there remains potential for variability in identification of PARDS. What is the inter-rater reliability of the 2015 PALICC criteria for diagnosing moderate-severe PARDS? What clinical criteria and patient factors are associated with diagnostic disagreements? Patients with acute hypoxic respiratory failure admitted from 2016-2021 who received invasive mechanical ventilation were retrospectively reviewed by two PICU physicians. Reviewers evaluated whether the patient met the 2015 PALICC definition of moderate-severe PARDS and rated their diagnostic confidence. Inter-rater reliability was measured using Gwet's Agreement Coefficient (AC1). 37 of 191 encounters had a diagnostic disagreement. Inter-rater reliability was "substantial" (AC1=0.74, 95% CI [0.65 - 0.83]). Disagreements were due to different interpretations of chest radiographs (56.8%), ambiguity in origin of pulmonary edema (37.8%), or lack of clarity if patient's current condition was significantly different from baseline (27.0%). Disagreement was more likely in patients who were chronically ventilated (OR 4.66, 95% CI [2.16-10.08], p<0.001), had a primary cardiac admission diagnosis (OR 3.36, 95% CI [1.18 - 9.53], p=0.02), or underwent cardiothoracic surgery during the admission (OR 4.90, 95% CI [1.60 - 15.00], p=0.005). Reviewers were at least moderately confident in their decision 73% of the time, however were less likely to be confident if the patient had cardiac disease or chronic respiratory failure. The inter-rater reliability of the 2015 PALICC criteria for diagnosing moderate-severe PARDS in this cohort was substantial, with diagnostic disagreements commonly due to differences in chest radiograph interpretations. Patients with cardiac disease or chronic respiratory failure were more vulnerable to diagnostic disagreements. More guidance is needed on interpreting chest radiographs and diagnosing PARDS in these subgroups.

Definition, Incidence, and Epidemiology of Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

In 2015, the Pediatric Acute Lung Injury Consensus Conference (PALICC) provided the first pediatric-specific definitions for acute respiratory distress syndrome (pediatric acute respiratory distress syndrome [PARDS]). These definitions have since been operationalized in cohort and interventional PARDS studies. As substantial data have accrued since 2015, we have an opportunity to assess the construct validity and utility of the initial PALICC definitions. Therefore, the Second PALICC (PALICC-2) brought together multiple PARDS experts and aimed to identify and summarize relevant evidence related to the definition and epidemiology of PARDS and create modifications to the definition of PARDS. MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). We included studies of subjects with PARDS, or at risk for PARDS, excluding studies pertaining primarily to adults except as specified for identifying age-specific cutoffs. Title/abstract review, full-text review, and data extraction using a standardized data collection form. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. A total of 97 studies were identified for full-text extraction addressing distinct aspects of the PARDS definition, including age, timing, imaging, oxygenation, modes of respiratory support, and specific coexisting conditions. Data were assessed in a Patient/Intervention/Comparator/Outcome format when possible, and formally summarized for effect size, risk, benefit, feasibility of implementation, and equity. A total of 17 consensus-based definition statements were made that update the definition of PARDS, as well as the related diagnoses of "Possible PARDS" and "At-Risk for PARDS." These statements are presented alongside a summary of the relevant epidemiology. We present updated, data-informed consensus statements on the definition for PARDS and the related diagnoses of "Possible PARDS" and "At-Risk for PARDS."

Noninvasive Respiratory Support for Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.

To develop evidence-based recommendations for the Second Pediatric Acute Lung Injury Consensus Conference (PALICC) regarding the effectiveness of noninvasive respiratory support for pediatric acute respiratory distress syndrome (PARDS). These include consideration of the timing and duration of noninvasive ventilation (NIV) and high-flow nasal cannula (HFNC), whether effectiveness varies by disease severity or by characteristics of treatment delivery, and best practices for the use of NIV. MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). Searches included all studies involving the use of NIV or HFNC in children with PARDS or hypoxemic respiratory failure. Title/abstract review, full-text review, and data extraction using a standardized data extraction form. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Out of 6,336 studies, we identified 187 for full-text review. Four clinical recommendations were generated, related to indications, timing and duration of NIV in patients with PARDS, predictors of NIV failure and need for intubation (signs and symptoms of worsening disease including pulse oximetry saturation/Fio2 ratio), and use of NIV in resource-limited settings. Six good practice statements were generated related to how and where to deliver NIV, the importance of trained experienced staff and monitoring, types of NIV interfaces, the use of sedation, and the potential complications of this therapy. One research statement was generated related to indications of HFNC in patients with PARDS. NIV is a widely used modality for the treatment of respiratory failure in children and may be beneficial in a subset of patients with PARDS. However, there needs to be close monitoring for worsening disease and NIV failure.

A single-center PICU present status survey of pediatric sepsis-related acute respiratory distress syndrome.

To describe the incidence, clinical features, outcomes, and mortality risk factors of sepsis associated with acute respiratory distress syndrome (ARDS) in pediatric patients. Patients were included in the study if they met the 2005 version of the International Pediatric Sepsis Consensus Conference and met the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition within 48 h of sepsis diagnosis. Patients were classified as mild, moderate, and severe by the worst oxygenation index (OI) within 72 h of sepsis-related ARDS diagnosis. Between January 1, 2015 and March 13, 2020, 9836 patients were admitted to the pediatric intensive care unit(PICU) of the Children's Hospital of Chongqing Medical University and 828 (8.4%) were identified with sepsis and 203 (24.5%) met the PALICC definition with a PICU mortality rate of 24.6% (50/203) and a 90-day mortality rate of 40.9% (83/203). After adjusting for septic shock, the pediatric logistic organ dysfunction 2 (PELOD-2), high-frequency oscillation ventilation (HFOV), and continuous renal replacement therapy (CRRT), the variables that retained an independent association with increased 90-day mortality in pediatric sepsis-related ARDS included ARDS severity, the pediatric risk of mortality III (PRISM III), number of organ dysfunctions and use of vasoactive drug types during PICU stay. PICU mortality in pediatric sepsis-related ARDS was high (24.6%) and severity of hypoxemia based on the worst OI value 72 h after meeting the PALICC definition accurately stratified the patient outcomes. ARDS severity, PRISM III score, comorbid multiorgan dysfunction, and use of multiple vasoactive drugs during PICU stay were independent risk factors for 90-day mortality in pediatric sepsis-related ARDS.

ONE LUNG LUCY: PEDIATRIC ARDS IN A CHILD WITH LUNG AGENESIS

TYPE: Case Report TOPIC: Critical Care INTRODUCTION: Pediatric acute respiratory distress syndrome (PARDS) is a relatively common clinical problem in the PICU. However, ARDS in a pediatric patient with one lung is unique and not well defined. We present such a case and highlight challenges in management. CASE PRESENTATION: Our patient is a 14month old girl who presented to the ER in acute hypoxemic respiratory failure secondary to RSV bronchiolitis. Her past medical history is significant for left lung agenesis and supracardiac total anomalous pulmonary venous return (surgically repaired). She was admitted to the PICU and subsequently developed severe ARDS, with peak OI of 28. Single lung protective strategy was initially applied with the use of lower tidal volumes of 5-6 ml/kg and a PEEP of 6. Inhaled NO was employed and she was subsequently placed on tidal volumes of 8ml/kg and PEEP of 8 with subsequent improved lung compliance. She was successfully extubated after 2 weeks of MV. DISCUSSION: The Pediatric Acute Lung Injury Consensus Conference (PALICC) developed pediatric-specific definitions for ARDS and recommendations regarding treatment. Recommendations regarding management of patients with one lung who develop ARDS are lacking. One lung ventilation is a standard approach to facilitate surgical exposure for pulmonary and other thoracic surgeries, however it is not known whether ventilation strategies suggested by the anesthesia literature is applicable to PARDS. CONCLUSIONS: Our case presented challenges in providing adequate ventilation and oxygenation while minimizing further lung injury in a patient with one lung PARDS. Further study is needed to elucidate the optimum mechanical ventilation strategy. DISCLOSURE: Nothing to declare. KEYWORD: One Lung ARDS

Clinical Outcome Discrimination in Pediatric ARDS by Chest Radiograph Severity Scoring.

Background There is no accurate radiological measurement to estimate the severity of pediatrics acute respiratory distress syndrome (PARDS). We validated the effectiveness of an adult radiographic assessment of lung edema (RALE) score in PARDS. Aim To assess the severity and prognosis of PARDS based on a chest radiograph (CXR) RALE scoring method. Methods Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria were used to diagnose PARDS. General demographics, pulmonary complications, and 28‐day mortality of the patients were recorded. Subgroups were compared by prognosis (survive and death) and etiology (infection and noninfection). Two observers calculated RALE independently. Each quadrant of CXR was scored by consolidation scores 0 (none alveolar opacity), 1 (extent <25%), 2 (extent 25%–50%), 3 (50%–75%), and 4 (>75%) and density scores 1 (hazy), 2 (moderate), and 3 (dense). Quadrant score equals consolidation score times density score. Total score equals to the sum of four quadrants scores. The ROC curve and survival curve were established, and the optimal cutoff score for discrimination prognosis was set. Results 116 PARDS (72 boys and 44 girls) and 463 CXRs were enrolled. The median age was 25 months (5 months, 60.8 months) and with a mortality of 37.9% (44/116). The agreement between two independent observers was excellent (ICC = 0.98, 95% CI: 0.97–0.99). Day 3 score was independently associated with better survival (p < 0.001). The area under the curve of ROC was 0.773 (95% CI: 0.709–0.838). The cutoff score was 21 (sensitivity 71.7%, specificity 76.5%), and the hazard ratio (HR) was 9.268 (95% CI: 1.257–68.320). The pulmonary complication showed an HR of 3.678 (95% CI: 1.174–11.521) for the discrimination. Conclusion CXR RALE score can be used in PARDS for discriminating the prognosis and has a better agreement among radiologist and pediatrician. PARDS with pulmonary complications, day 3 score whether greater than 21 points, have a better predictive effectiveness.

P0439 / #2139: INCIDENCE AND OUTCOME OF PEDIATRIC ARDS: RETROSPECTIVE COMPARAISON BETWEEN THE BERLIN DEFINITION AND THE PALICC CRITERIA

Aims & Objectives: Aim was to compare incidence and outcomes of pediatric acute respiratory distress syndrome (pARDS) according to Berlin definitions and Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria. Methods: Data of all admitted patients (1 month to 14 years) to our Pediatric Intensive Care Unit over a 30-months period (July 2017–Dec 2019) were reviewed for presence of any respiratory distress at admission or during PICU stay. Patients with significant cardiac L-R shunt were excluded. PALICC and Berlin criteria were retrospectively applied to these patients. Collected data including criteria, severity and outcom. Patients was classified in 2 groups: the “PALICC only group” and the “Berlin with or without PALICC”. Results: A total of 568 admissions was recorded during the study period: Among them, 359 (63%) were identified had respiratory distress at admission or during PICU stay. A total of 87 childrens (15,3%; 95%) fulfilled definition of pARDS with either of the two PALICC and BERLIN criteria. 81 children (93,1%) fulfilled PALICC criteria and only 47 childrens (54%) fulfilled BERLIN definition. Statistical Agreement between two definitions was moderate (Kappa: 0,59; 95%, observed agreement 88%). More patients had severe ARDS in the “Berlin with or without PALICC group” as compared to the “PALICC only” group (61,7% vs. 25,2%). There was no difference regarding the duration of mechanical ventilation (8 vs. 10 days) but there was a non trend to increased mortality in the BERLIN group [36,1% vs. 22,1%). Conclusions: Compared to the Berlin definition, PALICC criteria seems to identify more patients with pARDS with more severe severity in “Berlin with or without PALICC” group with no difference in outcome.

P0397 / #958: CONCORDANCE STUDY OF BERLIN AND PALICC DEFINITIONS FOR ACUTE RESPIRATORY DISTRESS SYNDROME WITH AUTOPSY FINDINGS IN PEDIATRIC PATIENTS.

Aims & Objectives: Acute respiratory distress syndrome (ARDS) is an important cause of mortality. In pediatrics, its diagnosis is based on the Berlin consensus definition (BERLIN) and more recently on the Pediatric Acute Lung Injury Consensus Conference (PALICC). We measure the concordance of ARDS by BERLIN and PALICC definitions with autopsy findings in deceased patients from a pediatric intensive care unit (PICU). Methods: A cross-sectional study of clinical and autopsy records of patients who died in a PICU from a Hospital in Bogotá between 2000 and 2018. Concordance was measured with a Cohen Kappa coefficient test and a comparative analysis between definition components and diffuse alveolar damage (DAD) was performed and expressed as median with interquartile percentiles or relative frequencies with a Chi2 o a K-Wallis test were appropriate. Results: In a total of 222 autopsies, 53 (23.9%) met BERLIN criteria, 56 (25.2%) PALICC and 45 (20.2%) had DAD. Agreement was 0.48 for BERLIN and PALICC in relation to DAD. DAD cases were only significantly associated with bilateral opacities on chest X ray (77.8% vs. 56.0%; p = 0.025) and the presence of severe values in oxygenation (p = 0.04) or saturation (p = 0.04) indices. Conclusions: The agreement between ARDS definitions and DAD is moderate and has not changed with the most recent adjustment in the definition. Bilateral opacities and high oxygenation or saturation index are related to DAD. Models seeking therapeutic strategies should limit cases to these two findings to improve their specificity.

Development of a Standardized Clinical Assessment and Management Plan for Pediatric Acute Respiratory Distress Syndrome.

Pediatric acute respiratory distress syndrome (PARDS) is one of the most challenging patient populations for a clinician to manage with mortality between 8 and 31%. The project was designed to identify patients with PARDS, implement management guidelines with the goal of standardizing practice. Our objectives were to describe the development and implementation of a protocolized approach to identify patients with PARDS and institute ventilator management guidelines. Patients who met criteria for moderate or severe PARDS as per the Pediatric Acute Lung Injury Consensus Conference (PALICC) definitions were identified using the best practice alert (BPA) in the electronic health record (EHR). Patients who did not meet exclusion criteria qualified for management using the Standardized Clinical Assessment and Management Plan (SCAMP), a quality improvement (QI) methodology with iterative cycles. The creation of a BPA enabled identification of patients with PARDS. With our second cycle, the number of false BPA alerts due to incorrect data decreased from 66.7 (68/102) to 29.2% (19/65; p < 0.001) and enrollment increased from 48.3 (14/29) to 73.2% (30/41; p = 0.03). Evaluation of our statistical process control chart (SPC) demonstrated a shift in the adherence with the tidal volume guideline. Overall, we found that SCAMP methodology, when used in the development of institutional PARDS management guidelines, allows for development of a process to aid identification of patients and monitor adherence to management guidelines. This should eventually allow assessment of impact of deviations from clinical practice guidelines.

Acute viral bronchiolitis as a cause of pediatric acute respiratory distress syndrome

The Pediatric Acute Lung Injury Consensus Conference (PALICC) published pediatric-specific guidelines for the definition, management, and research in pediatric acute respiratory distress syndrome (PARDS). Acute viral bronchiolitis (AVB) remains one of the leading causes of admission to PICU. Respiratory syncytial virus (RSV) is the most common cause of AVB. We aimed to evaluate the incidence of PARDS in AVB and identify the risk of RSV as a trigger pathogen for PARDS. This study is a retrospective single-center observational cohort study including children < 2 years of age admitted to the pediatric intensive care unit at St Mary’s Hospital, London, and presented with AVB in 3 years (2016–2018). Clinical and demographic data was collected; PALICC criteria were applied to define PARDS. Data was expressed as median (IQR range); non-parametric tests were used. In this study, 144 infants with acute viral bronchiolitis were admitted to PICU in the study period. Thirty-nine infants fulfilled criteria of PARDS with RSV as the most common virus identified. Bacterial infection was identified as a risk factor for development of PARDS in infants with AVB.Conclusion: AVB is an important cause of PARDS in infants. RSV is associated with a higher risk of PARDS in AVB. Bacterial co-infection is a significant risk factor for development of PARDS in AVB.What is Known:• Bronchiolitis is a common cause of respiratory failure in children under 2 years.• ARDS is a common cause of PICU admission.What is New:• Evaluation of bronchiolitis as a cause of PARDS according to the PALLIC criteria.• Evaluation of different viruses’ outcome in PARDS especially RSV as a commonest cause of AVB.

Prognostic relevance and inter-observer reliability of chest-imaging in pediatric ARDS: a pediatric acute respiratory distress incidence and epidemiology (PARDIE) study

PurposeDefinitions of acute respiratory distress syndrome (ARDS) include radiographic criteria, but there are concerns about reliability and prognostic relevance. This study aimed to evaluate the independent relationship between chest imaging and mortality and examine the inter-rater variability of interpretations of chest radiographs (CXR) in pediatric ARDS (PARDS).MethodsProspective, international observational study in children meeting Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria for PARDS, which requires new infiltrate(s) consistent with pulmonary parenchymal disease, without mandating bilateral infiltrates. Mortality analysis focused on the entire cohort, whereas inter-observer variability used a subset of patients with blinded, simultaneous interpretation of CXRs by intensivists and radiologists.ResultsBilateral infiltrates and four quadrants of alveolar consolidation were associated with mortality on a univariable basis, using CXRs from 708 patients with PARDS. For patients on either invasive (IMV) or non-invasive ventilation (NIV) with PaO2/FiO2 (PF) ratios (or SpO2/FiO2 (SF) ratio equivalent) > 100, neither bilateral infiltrates (OR 1.3 (95% CI 0.68, 2.5), p = 0.43), nor 4 quadrants of alveolar consolidation (OR 1.6 (0.85, 3), p = 0.14) were associated with mortality. For patients with PF ≤ 100, bilateral infiltrates (OR 3.6 (1.4, 9.4), p = 0.01) and four quadrants of consolidation (OR 2.0 (1.14, 3.5), p = 0.02) were associated with higher mortality. A subset of 702 CXRs from 233 patients had simultaneous interpretations. Interobserver agreement for bilateral infiltrates and quadrants was “slight” (kappa 0.31 and 0.33). Subgroup analysis showed agreement did not differ when stratified by PARDS severity but was slightly higher for children with chronic respiratory support (kappa 0.62), NIV at PARDS diagnosis (kappa 0.53), age > 10 years (kappa 0.43) and fluid balance > 40 ml/kg (kappa 0.48).ConclusionBilateral infiltrates and quadrants of alveolar consolidation are associated with mortality only for those with PF ratio ≤ 100, although there is high- inter-rater variability in these chest-x ray parameters.Electronic supplementary materialThe online version of this article (10.1007/s00134-020-06074-7) contains supplementary material, which is available to authorized users.

Characteristics and trajectory of patients with pediatric acute respiratory distress syndrome

This study delineates the disease trajectory of patients with pediatric acute respiratory distress syndrome (PARDS) defined by the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition, and evaluates the impact of comorbidities on outcomes. This prospective study over November 2017-October 2019 was conducted in a single-center multidisciplinary pediatric intensive care unit (PICU) and included patients <21years of age with PARDS. Clinical history of those requiring mechanical ventilation for <3 days was interrogated and cases in which the diagnosis of PARDS were unlikely, identified. The impact of chronic comorbidities on clinical outcomes, in particular, pulmonary disease and immunosuppression, were analyzed. Eighty-five of 1272 PICU admissions (6.7%) met the criteria for PARDS and were included. Median age and oxygenation indexes were 2.8 (0.6, 8.3) years and 10.6 (7.6, 15.4), respectively. Overall mortality was 12 out of 85 (14.1%). Despite fulfilling criteria in 6/85 (7.1%), hypoxemia contributed by bronchospasm, mucus plugging, fluid overload, and atelectasis was quickly reversible and PARDS was unlikely in these patients. Comorbidities (57/85 [67.1%]) were not associated with worsened outcomes. However, pre-existing pulmonary disease and immunosuppression were associated with severe PARDS (12/20 [60.0%] vs 19/65 [29.2%]; P = .017), extracorporeal membrane oxygenation use (5/20 [25.0%] vs 3/65 [4.6%]; P = .016) and reduced ventilator free days (VFD) (15 [0, 19] vs 21 [6, 23]; P = .039), compared with those without them. A small percentage of children fulfilling the PALICC definition had quickly reversible hypoxemia with likely alternate pathophysiology to PARDS. Patients with pulmonary comorbidities and immunosuppression had a more severe course of PARDS compared with others.

Outcome Comparison Between Pulmonary and Extrapulmonary Acute Respiratory Distress Syndrome in Pediatric Intensive Care Unit

Acute respiratory distress syndrome (ARDS) is a lung disease characterized by severe diffuse inflammation and hypoxemia. The cause of ARDS can be pulmonary or extrapulmonary originated. The outcome of pulmonary and extrapulmonary pediatric ARDS are poorly described. The objective of this study was to determine the outcome differences between pulmonary and extrapulmonary pediatric ARDS. A retrospective study was carried out in 60 patients who admitted to the Pediatric Intensive Care Unit (PICU), Sanglah Hospital, between January 2018 until December 2019. All children aged 0-18 years old diagnosed with ARDS according to Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria were included in this study. Length of ventilation, ventilator-free days, PICU length of stay, and PICU mortality as the outcome of this study were obtained from medical records. Statistical analysis was done using Chi-square and Mann-Whitney test. Most of the patients were supported by invasive ventilation with the severity of ARDS was mild to moderate. The underlying disease of pulmonary ARDS (ARDSp) was pneumonia (100%), whereas in extrapulmonary ARDS (ARDSexp) was sepsis (100%). Analysis of outcome showed significant difference in mortality (33.3% vs 73.3%, p=0.002). The mortality was higher among those in the moderate severity of oxygenation index (64.5%, p=0.001). No significant difference was found in length of ventilation and PICU length of stay. The ventilator-free days in ARDSp was higher (22 days vs 0 days, p=0.000) compared with the ARDSexp. This study concluded that patients with extrapulmonary ARDS had poorer outcomes (higher mortality and less ventilator-free day) compared with pulmonary ARDS. The severity of ARDS based on the oxygenation index measurement can be used to discriminate mortality.

Post-discharge respiratory outcomes of children with acute respiratory distress syndrome.

While long-term sequelae of acute respiratory distress syndrome (ARDS) are well-documented in adults, few studies reported post-discharge respiratory complications in pediatric ARDS (PARDS) and none used the recent Pediatric Acute Lung Injury Consensus Conference (PALICC) diagnostic criteria. This study describes the respiratory symptoms, pulmonary function, and health resource use of PARDS survivors at 3 months post-discharge. Retrospective study. Children less than18 years admitted to the intensive care unitof Sainte-Justine University Health Center from 1st September2015 to 1st July2017, and meeting PALICC diagnostic criteria for PARDS. We evaluated 38 of the 44 children with PARDS in the follow-up clinic at a mean (SD) of 3.4 (2.0) months post-discharge for respiratory symptoms, age-appropriate pulmonary function tests (spirometry or oscillometry, maximal respiratory pressures), and all-cause emergency department (ED) visits or rehospitalizations since discharge. Fourteen (36.8%) had abnormal respiratory symptoms (most commonly cough between respiratory infections and wheezing), 7 of whom (18.4%) presented new respiratory symptoms since PARDS diagnosis. A mild-to-moderate restrictive pattern was observed in 3 of 10 patients who performed spirometry and mildly decreased maximal inspiratory pressures were noted in 2 of 8 patients who performed these maneuvers. Nine (23.7%) patients consulted in the ED and 4 (10.5%) were rehospitalized post-discharge. Despite our cohort's limited sample size, our findings suggest that a significant proportion of PARDS survivors experience abnormal respiratory symptoms, pulmonary function deficits, and recurrent problems requiring medical attention. Larger, multicenter studies are required to identify risk factors associated with poor post-discharge outcomes among PARDS survivors.

Current Trends in Pediatric ARDS

Pediatric acute respiratory distress syndrome (PARDS) incidence is reported between 2.95 to 12.8 cases per 100,000 person years,1,2 which is lower than in adults but remains one of the most challenging form of lung diseases for a Pediatric Intensivist. Application of the adult ARDS definition is limited in pediatrics due to differences in risk factors, etiology, pathophysiology, hard to obtain PaO2 values, and lower levels and variation of PEEP utilization. To address these limitations, to promote early recognition and diagnosis of PARDS, and to improve prognostication and stratification of disease severity, the Pediatric Acute Lung Injury Consensus Conference (PALICC) published the first definition for PARDS in 2015.3 This definition (Table 1) kept the criteria of onset within seven days of a known clinical insult and the presence of respiratory failure not fully explained by cardiac failure or fluid overload. It eliminated the term acute lung injury, excluded bilateral infiltrate, and stratified severity of PARDS based on the oxygenation deficit as mild, moderate, and severe. Either oxygenation index or the oxygen saturation index (when arterial blood gas is not available) can be used to assess the degree of hypoxemia. Non-invasive ventilation is now included for continuous positive airway pressure of more than 5 cm H2O. Furthermore, PALICC included recommendations for defining PARDS in children with preexisting chronic lung disease, cyanotic congenital heart disease, and left ventricular dysfunction.The PARDS management guidelines are based on very limited pediatric data and are largely based on expert opinions.3 For ventilatory management, no mode of ventilation is found to be superior, patient-specific tidal volumes per ideal body weight according to disease severity are recommended (3–6 mL/kg for patients with reduced and 5–8 mL/kg for patients with better-preserved compliance). In the absence of transpulmonary pressure measurements, plateau pressure should be limited to 28 cm H2O and 29–32 cm H2O during increased chest wall elastance. Moderately elevated PEEP to 10–15 cm H2O should be titrated in severe PARDS to the observed oxygenation and hemodynamic response. The oxygenation goal for mild PARDS (PEEP < 10) is 92–97% and severe PARDS (PEEP >10) 88–92%, although in some patients, < 88% can be considered with oxygen delivery monitoring. Permissive hypercapnia with a pH of >7.15 is the goal except in severe pulmonary hypertension, intracranial hypertension, select congenital heart lesions, significant ventricular dysfunction with hemodynamic instability, and pregnancy. Recruitment maneuvers by slow incremental and decremental PEEP steps may be used for severe hypoxemia. High-frequency oscillatory ventilation remains as an alternative ventilatory mode for patients with moderate-to-severe PARDS. There is not enough evidence to support the routine use of inhaled nitric oxide, steroids, or prone positioning for PARDS at this time.3 Since the publication of the new definition, several studies comparing the previous definitions to PALICC suggest that the PALICC definition can not only identify more patients with PARDS but it is also better at risk stratification for mortality.4,5 Despite decades of research and experience of managing PARDS, there remains a lack of definitive clinical evidence in Pediatrics. Further pediatric research is needed to gain more insight and to improve outcome of PARDS.

Definition and global epidemiology of pediatric acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) has been known to occur in children since early descriptions of the disease, but pediatric specific diagnostic criteria were first established in 2015 with the Pediatric Acute Lung Injury Consensus Conference (PALICC) definition of pediatric ARDS (PARDS). There were substantial changes proposed with the PALICC definition, including simplification of radiographic criteria, use of pulse oximetry based metrics to define PARDS, specific criteria for non-invasive ventilation, and the use of oxygenation index (OI) instead of PaO2/FiO2 ratio for those on invasive ventilation. While these changes could potentially result in major changes in the reported incidence and outcome of PARDS, review of the recent literature since publication of the PALICC definitions highlight that major elements regarding the contemporary epidemiology of PARDS have remained stable over the past 20 years. This highlights that the PARDS definition is likely catching up to changes in clinical practice, and suggests that this new definition should be used moving forward as it is more reflective of current practice than historical definitions. However, it is also clear that PARDS severity alone (as measured by the PALICC) criteria insufficiently characterizes the risk for mortality or other important clinical outcomes amongst PARDS patients, although there appears to be some association between PARDS severity and outcome, particularly when hypoxemia is severe.

The Current State of Pediatric Acute Respiratory Distress Syndrome.

Pediatric acute respiratory distress syndrome (PARDS) is a significant cause of morbidity and mortality in children. Children with PARDS often require intensive care admission and mechanical ventilation. Unfortunately, beyond lung protective ventilation, there are limited data to support our management strategies in PARDS. The Pediatric Acute Lung Injury Consensus Conference (PALICC) offered a new definition of PARDS in 2015 that has improved our understanding of the true epidemiology and heterogeneity of the disease as well as risk stratification. Further studies will be crucial to determine optimal management for varying disease severity. This review will present the physiologic basis of PARDS, describe the unique pediatric definition and risk stratification, and summarize the current evidence for current standards of care as well as adjunctive therapies.

Clinical application of the Pediatric Acute Lung Injury Consensus Conference definition of acute respiratory distress syndrome

Purpose: Despite improved quality of intensive care, acute respiratory distress syndrome (ARDS) significantly contributes to mortal ity in critically ill children. As pre-existing definitions of ARDS were adult-oriented standards, the Pediatric Acute Lung Injury Consen sus Conference (PALICC) group released a new definition of pediatric ARDS. In this study, we aimed to assess the performance of PALICC definition for ARDS risk stratification. Methods: Total 332 patients who admitted to the intensive care unit at Severance Hospital from January 2009 to December 2016 and diagnosed as having ARDS by either the PALICC definition or the Berlin definition were retrospectively analyzed. Patient charac teristics and mortality rates were compared between the individual severity groups according to both definitions. Results: The overall mortality rate was 36.1%. The mortality rate increased across the severity classes according to both definitions (26% in mild, 37% in moderate and 68% in severe by the PALICC definition [P<0.001]; 20% in mild, 32% in moderate and 64% in se vere by the Berlin definition [P<0.001]). The mortality risk increased only for severe ARDS in both definitions (hazard ratio [95% con fidence interval]: 2.279 [1.414-3.672], P=0.001 by the PALICC definition; 2.674 [1.518-4.712], P=0.001 by the Berlin definition). There was no significant difference in mortality discrimination between the 2 definitions (difference in integrated area under the curve: 0.017 [-0.018 to 0.049]). Conclusion: The PALICC definition demonstrated similar discrimination power on PARDS’ severity and mortality as the Berlin defini tion. (Allergy Asthma Respir Dis 2019;7:44-50)

Personalising care of acute respiratory distress syndrome according to patients' age

Acute respiratory distress was described by Ashbaugh and colleagues 1 Ashbaugh DG Bigelow DB Petty TL Levine BE Acute respiratory distress in adults. Lancet. 1967; 2: 319-323 Summary PubMed Google Scholar in a pivotal paper in The Lancet in 1967. Soon after publication, it became clear that this acute, severe, and hypoxaemic respiratory failure was a syndrome and not a disease, with many possible triggers, epidemiological causes, and clinical courses. Modern definitions of acute respiratory distress syndrome (ARDS) have recognised the peculiarities of the syndrome, taking into account patients' age and the latest innovations in critical care (table). 2 The ARDS Definition Task ForceAcute respiratory distress syndrome: The Berlin Definition. JAMA. 2012; 307: 2526-2533 Crossref PubMed Scopus (6505) Google Scholar , 3 Khemani RG Smith LS Zimmerman JJ Erickson S Pediatric acute respiratory distress syndrome: definition, incidence, and epidemiology: proceedings from the Pediatric Acute Lung Injury Concensus Conference. Pediatr Crit Care Med. 2015; 16: S23-S40 Crossref PubMed Scopus (251) Google Scholar , 4 De Luca D van Kaam AH Tingay DG et al. The Montreux definition of neonatal ARDS: biological and clinical background behind the description of a new entity. Lancet Respir Med. 2017; 5: 657-666 Summary Full Text Full Text PDF PubMed Scopus (149) Google Scholar In paediatrics, the few children affected by paediatric ARDS (PARDS) and the lack of networks for clinical research have been the main barriers to the advancement of knowledge. In The Lancet Respiratory Medicine, Robinder G Khemani and colleagues 5 Khemani RG Smith L Lopez-Fernandez YM et al. Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study. Lancet Respir Med. 2018; (published online Oct 22.)http://dx.doi.org/10.1016/S2213-2600(18)30344-8 Summary Full Text Full Text PDF PubMed Scopus (168) Google Scholar report an international, multicentre, cross-sectional study that describes PARDS epidemiology according to the new Pediatric Acute Lung Injury Consensus Conference (PALICC) definition. 5 Khemani RG Smith L Lopez-Fernandez YM et al. Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study. Lancet Respir Med. 2018; (published online Oct 22.)http://dx.doi.org/10.1016/S2213-2600(18)30344-8 Summary Full Text Full Text PDF PubMed Scopus (168) Google Scholar TableThe three definitions of ARDS by age group Neonatal definition: Montreux Paediatric definition: PALICC Adult definition: Berlin Age From birth until 44 weeks, or until 4 weeks, postnatal age (for neonates born after 40 weeks, postmenstrual age) Beyond the period covered by Montreux definition and until adolescence * Both the PALICC and Berlin definitions can be used for adolescents or young adults, according to clinicians' experience. Adults Timing Acute onset (ie, within 1 week) from a known or suspected clinical insult Acute onset (ie, within 1 week) from a known or suspected clinical insult Acute onset (ie, within 1 week) from a known or suspected clinical insult Imaging Diffuse, bilateral, and irregular opacities or infiltrates, or complete opacification of the lungs, which are not fully explained by local effusions, atelectasis, infant respiratory disease, † Hyaline membrane disease or primary surfactant deficiency. transient tachypnoea of the neonate, or congenital lung anomalies New infiltrates consistent with acute parenchymal process; No need for bilaterality Bilateral opacities not fully explained by effusions, lobar or lung collapse, or nodules Origin of oedema Not fully explained by congenital heart disease (this includes ductus arteriosus with pulmonary overflow if no acute pulmonary haemorrhage exists) Not fully explained by cardiac failure or fluid overload Not fully explained by cardiac failure or fluid overload Severity classes According to oxygenation index classes (same classes as the PALICC definition) According to PaO2:FIO2 ratio or oxygenation or oxygen saturation index classes (depending on ventilation strategy, with preference for PaO2) According to PaO2:FIO2 ratio classes Similarities and differences are evident and based on the best knowledge of ARDS biology and physiopathology across patients' age. ARDS=acute respiratory distress syndrome. PALICC=Pediatric Acute Lung Injury Consensus Conference. PaO2:FIO2=partial pressure of oxygen to fractional concentration of oxygen inspired air. * Both the PALICC and Berlin definitions can be used for adolescents or young adults, according to clinicians' experience. † Hyaline membrane disease or primary surfactant deficiency. Open table in a new tab Similarities and differences are evident and based on the best knowledge of ARDS biology and physiopathology across patients' age. ARDS=acute respiratory distress syndrome. PALICC=Pediatric Acute Lung Injury Consensus Conference. PaO2:FIO2=partial pressure of oxygen to fractional concentration of oxygen inspired air. Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational studyThe PALICC definition identified more children as having PARDS than the Berlin definition, and PALICC PARDS severity groupings improved the stratification of mortality risk, particularly when applied 6 h after PARDS diagnosis. The PALICC PARDS framework should be considered for use in future epidemiological and therapeutic research among children with PARDS. Full-Text PDF

Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study

Paediatric acute respiratory distress syndrome (PARDS) is associated with high mortality in children, but until recently no paediatric-specific diagnostic criteria existed. The Pediatric Acute Lung Injury Consensus Conference (PALICC) definition was developed to overcome limitations of the Berlin definition, which was designed and validated for adults. We aimed to determine the incidence and outcomes of children who meet the PALICC definition of PARDS. In this international, prospective, cross-sectional, observational study, 145 paediatric intensive care units (PICUs) from 27 countries were recruited, and over a continuous 5 day period across 10 weeks all patients were screened for enrolment. Patients were included if they had a new diagnosis of PARDS that met PALICC criteria during the study week. Exclusion criteria included meeting PARDS criteria more than 24 h before screening, cyanotic heart disease, active perinatal lung disease, and preparation or recovery from a cardiac intervention. Data were collected on the PICU characteristics, patient demographics, and elements of PARDS (ie, PARDS risk factors, hypoxaemia severity metrics, type of ventilation), comorbidities, chest imaging, arterial blood gas measurements, and pulse oximetry. The primary outcome was PICU mortality. Secondary outcomes included 90 day mortality, duration of invasive mechanical and non-invasive ventilation, and cause of death. Between May 9, 2016, and June 16, 2017, during the 10 study weeks, 23 280 patients were admitted to participating PICUs, of whom 744 (3·2%) were identified as having PARDS. 95% (708 of 744) of patients had complete data for analysis, with 17% (121 of 708; 95% CI 14-20) mortality, whereas only 32% (230 of 708) of patients met Berlin criteria with 27% (61 of 230) mortality. Based on hypoxaemia severity at PARDS diagnosis, mortality was similar among those who were non-invasively ventilated and with mild or moderate PARDS (10-15%), but higher for those with severe PARDS (33% [54 of 165; 95% CI 26-41]). 50% (80 of 160) of non-invasively ventilated patients with PARDS were subsequently intubated, with 25% (20 of 80; 95% CI 16-36) mortality. By use of PALICC PARDS definition, severity of PARDS at 6 h after initial diagnosis (area under the curve [AUC] 0·69, 95% CI 0·62-0·76) discriminates PICU mortality better than severity at PARDS diagnosis (AUC 0·64, 0·58-0·71), and outperforms Berlin severity groups at 6 h (0·64, 0·58-0·70; p=0·01). The PALICC definition identified more children as having PARDS than the Berlin definition, and PALICC PARDS severity groupings improved the stratification of mortality risk, particularly when applied 6 h after PARDS diagnosis. The PALICC PARDS framework should be considered for use in future epidemiological and therapeutic research among children with PARDS. University of Southern California Clinical Translational Science Institute, Sainte Justine Children's Hospital, University of Montreal, Canada, Réseau en Santé Respiratoire du Fonds de Recherche Quebec-Santé, and Children's Hospital Los Angeles, Department of Anesthesiology and Critical Care Medicine.