Pediatric Acute Respiratory Distress Syndrome Research Articles

Pediatric COVID-19 extracorporeal membrane oxygenation transport during the pandemic.

ExtraCorporeal Membrane Oxygenation (ECMO) in pediatric patients with COVID-19 has a survival rate similar to adults. Occasionally, patients may need to be cannulated by an ECMO team in a referring hospital and transported to an ECMO center. The ECMO transport of a COVID-19 patient has additional risks than normal pediatric ECMO transport for the possible COVID-19 transmissibility to the ECMO team and the reduction of the ECMO team performance due to the need of wearing full personal protective equipment. Since pediatric data on ECMO transport of COVID-19 patients are lacking, we explored the outcomes of the pediatric COVID-19 ECMO transports collected in the EuroECMO COVID_Neo/Ped Survey. We reported five European consecutive ECMO transports of COVID-19 pediatric patients collected in the EuroECMO COVID_Neo/Ped Survey including 52 European neonatal and/or pediatric ECMO centers and endorsed by the EuroELSO from March 2020 till September 2021. The ECMO transports were performed for two indications, pediatric ARDS and myocarditis associated to the multisystem inflammatory syndrome related to COVID-19. Cannulation strategies differed among patients according to the age of the patients, transport distance varied between 8 and 390km with a total transport duration between 5 to 15h. In all five cases, the ECMO transports were successfully performed without major adverse events. One patient reported a harlequin syndrome and another patient a cannula displacement both without major clinical consequences. Hospital survival was 60% with one patient reporting neurological sequelae. No ECMO team member developed COVID-19 symptoms after the transport. Five transports of pediatric patients with COVID-19 supported with ECMO were reported in the EuroECMO COVID_Neo/Ped Survey. All transports were performed by an experienced multidisciplinary ECMO team and were feasible and safe for both the patient and the ECMO team. Further experiences are needed to better characterize these transports and draw insightful conclusions.

Evaluation of Patients with Acute Respiratory Distress Syndrome Followed on Mechanical Ventilator in a Tertiary Pediatric Intensive Care and the Factors That May Be Associated with Death in These Patients.

We aimed to evaluate the clinical, demographic, and laboratory characteristics of the patients followed up with pediatric acute respiratory distress syndrome in our pediatric intensive care unit and to determine the factors that have an effect on the outcomes. The medical records of 40 patients with acute respiratory distress syndrome who were followed up on mechanical ventilators in the pediatric intensive care unit of Adıyaman University were retrospectively scanned. From the medical records, the demographic data, clinical features, and laboratory characteristics were recorded. Eighteen of the patients were female and 22 were male. The mean age was 45.25 ± 56.63 months. A total of 27 (67.5%) of the patients were classified as pulmonary and 13 (32.5%) as extrapulmonary acute respiratory distress syndrome. Sixteen (40%) patients were followed in pressure-controlled mode only, 2 (5%) patients in volume-controlled mode only, and 22 (55%) patients in alternate modes. A total of 17 (42.5%) patients died. The median pediatric index of mortality, pediatric index of mortality-II, pediatric risk of mortality, and pediatric logistic organ dysfunction score values of the surviving patients were significantly lower than the dead patients. Median aspartate aminotransferase (P = .003) and lactate dehydrogenase (P = .008) values were found to be significantly higher in patients who died, while median pH values (P = .049) were found to be lower. The median length of stay in pediatric intensive care unit and duration of mechanical ventilators were significantly shorter in patients who died. Also, the median pediatric index of mortality, pediatric index of mortality-II, pediatric risk of mortality, and pediatric logistic organ dysfunction values of pulmonary acute respiratory distress syndrome patients were significantly lower than those of extrapulmonary acute respiratory distress syndrome patients. Despite advances in follow-up and management, mortality due to acute respiratory distress syndrome is still high. Mechanical ventilator duration, length of stay in pediatric intensive care unit, some mechanical ventilator parameters, mortality scores, and laboratory tests were associated with mortality. Alternatively, mechanical ventilator applications may reduce mortality rates.

A Case of Pneumocystis jirovecii Pneumonia in an Infant with Ataxia-Pancytopenia Syndrome

BackgroundAtaxia-pancytopenia syndrome (ATXPC), a rare autosomal dominant disorder caused by pathogenic variants in the SAMD9L gene, is characterized by variable onset and severity of cerebellar ataxia, hematologic cytopenias, and immunodeficiency of myeloid, B-, and NK-cells. ATXPC has been associated with viral and bacterial infections, but no cases of opportunistic PJP have been reported. CaseAt 6 weeks of age, the patient was admitted to the hospital for acute hypoxemic respiratory failure due to rhino/enterovirus bronchiolitis, requiring supplemental oxygen. The increased oxygen requirement later led to intubation. A chest x-ray showed diffuse bilateral opacities concerning for pediatric acute respiratory distress syndrome (PARDS). Bronchoalveolar lavage and silver stain revealed organisms morphologically suggestive of Pneumocystis jirovecii pneumonia (PJP), which was confirmed with a positive serum beta-glucan. Based on the diagnosis of PJP, the patient was started on steroids and Bactrim. Immunology was consulted for further evaluation for possible underlying immunodeficiency. The patient had a normal newborn screening. HIV PCR was negative. Repeated TRECs, CD3+, CD8+, CD19+, and immunoglobulin levels (IgG, IgE) were within normal limits, but modest reduction of CD45 RA/RO ratio and IgA were observed. Additionally, natural killer cell function was low. T-cell proliferation to mitogens were normal, but significantly decreased to candida and tetanus antigens. A significant reduction in the expression of HLA-ABC and HLA-DR was observed in the lymphocytes and monocytes of the patient compared to the control. Interestingly, HLA-DR expression on monocytes was particularly affected. A next-generation sequencing of primary immunodeficiency genes identified likely pathogenic, maternally inherited variants: a heterozygous SAMD9L variant (ataxia-pancytopenia syndrome) and NLRP12 variant (familial cold autoinflammatory syndrome 2). DiscussionATXPC has been associated with variable cellular immunodeficiencies. While prior studies have reported recurrent bacterial and viral infections in ATXPC patients, this case is the first to document a PJP opportunistic infection in an infant. It is possible that the NLRP12 variant found in this patient could have also contributed to this clinical presentation. Early diagnosis of ATXPC through clinical recognition and genetic testing may improve prognosis.

Prevalence and Incidence of Pediatric Acute Respiratory Distress Syndrome in a Tertiary Academic PICU in South Africa.

To determine the prevalence and incidence of pediatric acute respiratory distress syndrome (pARDS) among infants and children admitted to the PICU. A single-center descriptive point prevalence study with twice weekly data collection over a 6 months (August 2020 to February 12, 2021). Red Cross War Memorial Children's Hospital, Cape Town, South Africa. All infants and children admitted to the PICU on study days were included. Data were captured electronically on a standardized case record form using a Research Electronic Data Capture electronic database. The Pediatric Acute Lung Injury Consensus Conference criteria were used to define pARDS cases. Prevalence was calculated as the total number of pARDS cases/1,000 PICU bed days. The study included 354 patients (median [interquartile range]) 10.1 months old (1.5-61.3 mo old), with 204 males (57.6%), who occupied 879 bed days. Of these 879 bed days, 266 (30.3%; 95% CI, 27.2-33.3%) were occupied by pARDS cases, with a calculated prevalence and incidence of 302.6 of 1,000 bed days (30.3%) and 29.7% (95% CI, 26.7-32.7%), respectively. Three cases from the cohort were defined using the oxygen saturation index calculation. In cases receiving invasive ventilation ( n = 494; 56.2%), pARDS severity was classified as mild ( n = 143; 16.3%), moderate ( n = 44; 5.0%), and severe ( n = 29, 3.3%). A further 205 beds (23.3%) were occupied by patients classified as being at risk of pARDS. The prevalence and incidence of pARDS in a South African PICU appears substantially higher than findings described in international reports. Further investigation of risk factors and outcomes is warranted.

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.

Advances in Management of Respiratory Failure in Children.

Providing the right respiratory support is an essential skill, vital for anyone treating sick children. Recent advances in respiratory support include developments in both non-invasive and invasive ventilatory strategies. In non-invasive ventilation, newer modalities are being developed, in an attempt to decrease the need for invasive ventilation. This include newer techniques like Heated humidified high-flow nasal cannula (HHHFNC) and improvements in existing modes. The success of Continuous positive airway pressure (CPAP) and other non-invasive modes depend to a large extent on choosing and maintaining a suitable interface. When it comes to invasive ventilation, recent advances are focussing on increasing automation, improving patient comfort and minimising lung injury. Concepts like mechanical power are attempts at understanding the mechanisms of unintended injuries resulting from respiratory support and newer monitoring methods like transpulmonary pressure, thoracic impedance tomography are attempts at measuring potential markers of lung injury. Using the vast arrays of available ventilatory options judiciously, considering their advantages and drawbacks in every individual case will be the prime responsibility of clinicians in the future. Simultaneously, efforts have been made to identify potential drugs that can favourably modify the pathophysiology of acute respiratory distress syndrome (ARDS). Unfortunately, though eagerly awaited, most pharmaceutical agents tried in pediatric ARDS have not shown definite benefit. Pulmonary local drug and gene therapy using liquid ventilation strategies may revolutionize our future understanding and management of lung diseases.

Sepsis-related pediatric acute respiratory distress syndrome: A multicenter prospective cohort study.

This study aimed to compare the risk factors and outcomes for organ dysfunction between sepsis-related Pediatric acute respiratory distress syndrome (PARDS) and nonsepsis PARDS. We prospective cohort recruited intubated patients with PARDS at four tertiary care centers in Thailand. The baseline characteristics, mechanical ventilation, fluid balance, and clinical outcomes were collected. The primary outcome was organ dysfunction. One hundred and thirty-two mechanically ventilated children with PARDS were included in the study. The median age was 29 months and 53.8% were male. The mortality rate was 22.7% and organ dysfunction was 45.4%. There were 26 (19.7%) and 106 (80.3%) patients who were classified into sepsis-related PARDS and nonsepsis PARDS, respectively. Sepsis-related PARDS patients had a significantly higher incidence of acute kidney injury (30.8% vs. 13.2%, P = 0.041), septic shock (88.5% vs. 32.1%, P < 0.001), organ dysfunction (84.6% vs. 35.8%, P < 0.001), and death (42.3% vs. 17.9%, P = 0.016) than nonsepsis PARDS group. Multivariate analysis adjusted for clinical variables showed that sepsis-related PARDS and percentage of fluid overload were significantly associated with organ dysfunction (odds ratio [OR] 11.414; 95% confidence interval [CI] 1.40892.557, P = 0.023 and OR 1.169; 95% CI 1.0121.352, P = 0.034). Sepsis-related PARDS patients had more severe illness, organ dysfunction, and mortality than nonsepsis PARDS patients. The higher percentage of fluid overload and presentation of sepsis was the independent risk factor of organ dysfunction in PARDS patients.

Association between serum HMGB1 elevation and early pediatric acute respiratory distress syndrome: a retrospective study of pediatric living donor liver transplant recipients with biliary atresia in China

BackgroundHigh mobility group box 1 (HMGB1) protein is one of the main risk factors for pediatric acute respiratory distress syndrome (PARDS) after living donor liver transplantation (LDLT). However, studies of the relationship between HMGB1 and PARDS are lacking. We evaluated the link between anomalies of intraoperative serum HMGB1 and PARDS in pediatric LDLT recipients with biliary atresia during the first week after transplant.MethodsData for 210 pediatric patients with biliary atresia who underwent LDLT between January 2018 and December 2021 were reviewed retrospectively. The main measure was serum HMGB1 levels 30 min after reperfusion, while the outcome was early PARDS after LDLT. Data including pretransplant conditions, laboratory indexes, variables of intraoperation, clinical complications, and outcomes after LDLT were analyzed for each patient. Univariate analysis of PARDS and multivariate logistic regression analyses of serum HMGB1 levels at 30 min in the neohepatic phase in the presence of PARDS were conducted to examine the potential associations. Subgroup interaction analyses and linear relationships between intraoperative serum HMGB1 levels and PARDS were also performed.ResultsAmong the participants, 55 had PARDS during 7 days after LDLT, including four in the first HMGB1 tertile (4.3–8.1 pg/mL), 18 in the second tertile (8.2–10.6 pg/mL), and 33 in the third tertile (10.6–18.8 pg/mL). The nonadjusted association between intraoperative HMGB1 levels and PARDS was positive (odds ratio 1.41, 95% confidence intervals 1.24–1.61, P < 0.0001). The association remained unchanged after adjustment for age, weight, pretransplant total bilirubin, albumin, graft cold ischemia time, and intraoperative blood loss volume (odds ratio 1.28, 95% confidence interval 1.10–1.49, P = 0.0017). After controlling for potential confounders, the association between intraoperative HMGB1 levels and PARDS remained positive, as well as in the subgroup analyses.ConclusionsSerum HMGB1 levels at 30 min after reperfusion were positively associated with early PARDS among pediatric patients with biliary atresia who had undergone LDLT. Identifying such patients early may increase the efficacy of perioperative respiratory management.

Fluid Overload Precedes and Masks Cryptic Kidney Injury in Pediatric Acute Respiratory Distress Syndrome.

Given the complex interrelatedness of fluid overload (FO), creatinine, acute kidney injury (AKI), and clinical outcomes, the association of AKI with poor outcomes in critically ill children may be underestimated due to definitions used. We aimed to disentangle these temporal relationships in a large cohort of children with acute respiratory distress syndrome (ARDS). Retrospective cohort study. Quaternary care PICU. Seven hundred twenty intubated children with ARDS between 2011 and 2019. None. Daily fluid balance, urine output (UOP), and creatinine for days 1-7 of ARDS were retrospectively abstracted. A subset of patients had angiopoietin 2 (ANGPT2) quantified on days 1, 3, and 7. Patients were classified as AKI by Kidney Disease Improving Global Outcomes (KDIGO) stage 2/3 then grouped by timing of AKI onset (early if days 1-3 of ARDS, late if days 4-7 of ARDS, persistent if both) for comparison of PICU mortality and ventilator-free days (VFDs). A final category of "Cryptic AKI" was used to identify subjects who met KDIGO stage 2/3 criteria only when creatinine was adjusted for FO. Outcomes were compared between those who had Cryptic AKI identified by FO-adjusted creatinine versus those who had no AKI. Conventionally defined AKI occurred in 26% of patients (early 10%, late 3%, persistent 13%). AKI was associated with higher mortality and fewer VFDs, with no differences according to timing of onset. The Cryptic AKI group (6% of those labeled no AKI) had higher mortality and fewer VFDs than patients who did not meet AKI with FO-adjusted creatinine. FO, FO-adjusted creatinine, and ANGPT2 increased 1 day prior to meeting AKI criteria in the late AKI group. AKI was associated with higher mortality and fewer VFDs in pediatric ARDS, irrespective of timing. FO-adjusted creatinine captures a group of patients with Cryptic AKI with outcomes approaching those who meet AKI by traditional criteria. Increases in FO, FO-adjusted creatinine, and ANGPT2 occur prior to meeting conventional AKI criteria.

Identification of a pediatric acute hypoxemic respiratory failure signature in peripheral blood leukocytes at 24 hours post-ICU admission with machine learning.

There is no generalizable transcriptomics signature of pediatric acute respiratory distress syndrome. Our goal was to identify a whole blood differential gene expression signature for pediatric acute hypoxemic respiratory failure (AHRF) using transcriptomic microarrays within twenty-four hours of diagnosis. We used publicly available human whole-blood gene expression arrays of a Berlin-defined pediatric acute respiratory distress syndrome (GSE147902) cohort and a sepsis-triggered AHRF (GSE66099) cohort within twenty-four hours of diagnosis and compared those children with a PaO2/FiO2 < 200 to those with a PaO2/FiO2 ≥ 200. We used stability selection, a bootstrapping method of 100 simulations using logistic regression as a classifier, to select differentially expressed genes associated with a PaO2/FiO2 < 200 vs. PaO2/FiO2 ≥ 200. The top-ranked genes that contributed to the AHRF signature were selected in each dataset. Genes common to both of the top 1,500 ranked gene lists were selected for pathway analysis. Pathway and network analysis was performed using the Pathway Network Analysis Visualizer (PANEV) and Reactome was used to perform an over-representation gene network analysis of the top-ranked genes common to both cohorts. Changes in metabolic pathways involved in energy balance, fundamental cellular processes such as protein translation, mitochondrial function, oxidative stress, immune signaling, and inflammation are differentially regulated early in pediatric ARDS and sepsis-induced AHRF compared to both healthy controls and to milder acute hypoxemia. Specifically, fundamental pathways related to the severity of hypoxemia emerged and included (1) ribosomal and eukaryotic initiation of factor 2 (eIF2) regulation of protein translation and (2) the nutrient, oxygen, and energy sensing pathway, mTOR, activated via PI3K/AKT signaling. Cellular energetics and metabolic pathways are important mechanisms to consider to further our understanding of the heterogeneity and underlying pathobiology of moderate and severe pediatric acute respiratory distress syndrome. Our findings are hypothesis generating and support the study of metabolic pathways and cellular energetics to understand heterogeneity and underlying pathobiology of moderate and severe acute hypoxemic respiratory failure in children.

CLINICO-ETIOLOGICAL PROFILE AND OUTCOME OF ACUTE RESPIRATORY DISTRESS SYNDROME IN PAEDIATRIC INTENSIVE CARE UNIT (PICU) IN A TERTIARY CARE HOSPITAL IN BHUBANESWAR.

Objective:-To study the clinical profile of the patients of acute respiratory distress syndrome (ARDS) in terms of etiology and clinical course &amp; to evaluate the outcome of the patients with ARDS in term of mortality. :- Study design Prospective observational study. Study was conducted in PICU of HI-Tech medical college, Bhubaneswar. Study group:- All children aged between 3months to 12yrs admitted in PICU from 1st sep 2020 to 31 august 2022,with a diagnosis of pediatric acute respiratory distress syndrome as per pediatric acute lung injury consensus conference definition (PLICC). - Out of 130 patients having acute respiratory distress syndrome, 64.6% Measurements &amp; main results: expired in PICU during stay &amp; 35.3% were discharged. Out of admitted 60% were male &amp; 40 % were female. Most common primary etiology was Pneumonia followed by sepsis, other causes may be drowning, trauma, burns, transfusion related acute lung injury. Pediatric acute respiratory distress syndrome contributes to a significa Conclusion:- nt burden in the PICU of developing country and is associated with significant high mortality. Infection remains the most common etiology.

Analysis of risk factors of mortality in infants and toddlers with moderate to severe pediatric acute respiratory distress syndrome

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ2=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ2=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ2=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.

A Web-Based Platform for the Automatic Stratification of ARDS Severity

Acute respiratory distress syndrome (ARDS), including severe pulmonary COVID infection, is associated with a high mortality rate. It is crucial to detect ARDS early, as a late diagnosis may lead to serious complications in treatment. One of the challenges in ARDS diagnosis is chest X-ray (CXR) interpretation. ARDS causes diffuse infiltrates through the lungs that must be identified using chest radiography. In this paper, we present a web-based platform leveraging artificial intelligence (AI) to automatically assess pediatric ARDS (PARDS) using CXR images. Our system computes a severity score to identify and grade ARDS in CXR images. Moreover, the platform provides an image highlighting the lung fields, which can be utilized for prospective AI-based systems. A deep learning (DL) approach is employed to analyze the input data. A novel DL model, named Dense-Ynet, is trained using a CXR dataset in which clinical specialists previously labelled the two halves (upper and lower) of each lung. The assessment results show that our platform achieves a recall rate of 95.25% and a precision of 88.02%. The web platform, named PARDS-CxR, assigns severity scores to input CXR images that are compatible with current definitions of ARDS and PARDS. Once it has undergone external validation, PARDS-CxR will serve as an essential component in a clinical AI framework for diagnosing ARDS.

Association of Interventions With Outcomes in Children At-Risk for Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

Describe the frequency with which transfusion and medications that modulate lung injury are administered to children meeting at-risk for pediatric acute respiratory distress syndrome (ARF-PARDS) criteria and evaluate for associations of transfusion, fluid balance, nutrition, and medications with unfavorable clinical outcomes. Secondary analysis of the Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study, a prospective point prevalence study. All enrolled ARF-PARDS patients were included unless they developed subsequent pediatric acute respiratory distress syndrome (PARDS) within 24 hours of PICU admission or PICU length of stay was less than 24 hours. Univariate and multivariable analyses were used to identify associations between therapies given during the first 2 calendar days after ARF-PARDS diagnosis and subsequent PARDS diagnosis (primary outcome), 28-day PICU-free days (PFDs), and 28-day ventilator-free days (VFDs). Thirty-seven international PICUs. Two hundred sixty-seven children meeting Pediatric Acute Lung Injury Consensus Conference ARF-PARDS criteria. None. During the first 2 days after meeting ARF-PARDS criteria, 55% of subjects received beta-agonists, 42% received corticosteroids, 28% received diuretics, and 9% were transfused. Subsequent PARDS (15%) was associated with platelet transfusion (n = 11; adjusted odds ratio: 4.75 [95% CI 1.03-21.92]) and diuretics (n = 74; 2.55 [1.19-5.46]) in multivariable analyses that adjusted for comorbidities, PARDS risk factor, initial oxygen saturation by pulse oximetry:Fio2 ratio, and initial type of ventilation. Beta-agonists were associated with lower adjusted odds of subsequent PARDS (0.43 [0.19-0.98]). Platelets and diuretics were also associated with fewer PFDs and fewer VFDs in the multivariable models, and TPN was associated with fewer PFDs. Corticosteroids, net fluid balance, and volume of enteral feeding were not associated with the primary or secondary outcomes. There is an independent association between platelet transfusion, diuretic administration, and unfavorable outcomes in children at risk for PARDS, although this may be related to treatment bias and unmeasured confounders. Nevertheless, prospective evaluation of the role of these management strategies on outcomes in children with ARF-PARDS is needed.

The end-tidal alveolar dead space fraction for risk stratification during the first week of invasive mechanical ventilation: an observational cohort study

BackgroundThe end-tidal alveolar dead space fraction (AVDSf = [PaCO2−PETCO2]/PaCO2) is a metric used to estimate alveolar dead space. Higher AVDSf on the first day of mechanical ventilation is associated with mortality and fewer ventilator-free days. It is not clear if AVDSf is associated with length of ventilation in survivors, how AVDSf performs for risk stratification beyond the first day of ventilation, or whether AVDSf adds predictive value to oxygenation (oxygenation index [OI]) or severity of illness (Pediatric Risk of Mortality [PRISM III]) markers.MethodsRetrospective single-center observational cohort study of children and young adults receiving invasive mechanical ventilation. In those with arterial or capillary blood gases, AVDSf was calculated at the time of every blood gas for the first week of mechanical ventilation.ResultsThere were 2335 children and young adults (median age 5.8 years [IQR 1.2, 13.2]) enrolled with 8004 analyzed AVDSf values. Higher AVDSf was associated with mortality and longer length of ventilation in survivors throughout the first week of ventilation after controlling for OI and PRISM III. Higher OI was not associated with increased mortality until ≥ 48 h of ventilation after controlling for AVDSf and PRISM III. When using standardized variables, AVDSf effect estimates were generally higher than OI for mortality, whereas OI effect estimates were generally higher than AVDSf for the length of ventilation in survivors. An AVDSf > 0.3 was associated with a higher mortality than an AVDSf < 0.2 within each pediatric acute respiratory distress syndrome severity category.The maximum AVDSf within 12 h of intensive care unit admission demonstrated good risk stratification for mortality (AUC 0.768 [95% CI 0.732, 0.803]). AVDSf did not improve mortality risk stratification when added to PRISM III but did improve mortality risk stratification when added to the gas exchange components of PRISM III (minimum 12-h PaO2 and maximum 12-h PCO2) (p < 0.00001).ConclusionsAVDSf is associated with mortality and length of ventilation in survivors throughout the first week of invasive mechanical ventilation. Some analyses suggest AVDSf may better stratify mortality risk than OI, whereas OI may better stratify risk for prolonged ventilation in survivors than AVDSf.

Prone Positioning Improved Ventilation-Perfusion Matching in Severe Pediatric Acute Respiratory Distress Syndrome.

Prone Positioning Improved Ventilation-Perfusion Matching in Severe Pediatric Acute Respiratory Distress Syndrome.

Nutritional Support in Children Meeting the At-Risk for Pediatric Acute Respiratory Distress Syndrome Criteria.

To examine associations between early enteral nutrition (EN) and PICU outcomes in a cohort of children meeting the 2015 Pediatric Acute Lung Injury Consensus Conference "at-risk" for pediatric acute respiratory distress syndrome (ARF-PARDS) criteria. This was a single-center, electronic health record-based retrospective chart review. We included children less than or equal to 18 years-old admitted to our mixed medical-surgical PICU from January 2017 to December 2018 who met ARF-PARDS criteria within 48 hours of admission. Children were categorized as receiving "early" EN if feeds were initiated within 48 hours of admission. All others were categorized as "delayed" EN. Extracted data included demographics, illness characteristics including primary diagnosis and Pediatric Risk of Mortality (PRISM) III score, respiratory support and oxygenation indices, nutritional data, and PICU length of stay (LOS). The primary outcome of interest was subsequent diagnosis of PARDS. Of 201 included children, 152 (75.6%) received early EN. The most common admission diagnoses were pneumonia, bronchiolitis, and influenza. Overall, 21.4% (n = 43) of children developed PARDS. Children receiving early EN had a subsequent diagnosis of PARDS less often then children receiving delayed EN (15.1% vs 40.8%; p < 0.001), an association that persisted after adjusting for patient demographics and illness characteristics, including PRISM III and diagnosis (adjusted odds ratio, 0.24; 95% CI, 0.10-0.58; p = 0.002). Early EN was also associated with a shorter PICU LOS in univariate analysis (2.2 d [interquartile range, 1.5-3.4 d] vs 4.2 d [2.7-8.9 d]; p < 0.001). In this single-center, retrospective cohort study, compared with children with ARF-PARDS who received late EN, those who received early EN demonstrated a reduced odds of subsequent diagnosis of PARDS, and an unadjusted reduction in PICU LOS when compared with delayed EN. Prospective studies should be designed to confirm these findings.

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

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. 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. Not applicable. Patients with or at risk for PARDS. None. 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%. 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.

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.

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