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Impact of Weight Extremes on Clinical Outcomes in Pediatric Acute Respiratory Distress Syndrome.

ABSTRACT: OBJECTIVES:To determine whether weight extremes impact clinical outcomes in pediatric acute respiratory distress syndrome. DESIGN:Post hoc analysis of a cohort created by combining five multicenter pediatric acute respiratory distress syndrome studies. SETTING:Forty-three academic PICUs worldwide. PATIENTS:A total of 711 subjects prospectively diagnosed with pediatric acute respiratory distress syndrome. INTERVENTION:Subjects more than 2 years were included and categorized by Center for Disease Control and Prevention body mass index z score criteria: underweight (< -1.89), normal weight (-1.89 to +1.04), overweight (+1.05 to +1.64), and obese (? +1.65). Subjects were stratified by direct versus indirect lung injury leading to pediatric acute respiratory distress syndrome. The primary outcome was in-hospital mortality. In survivors, secondary analyses included duration of mechanical ventilation and ICU length of stay. MEASUREMENTS AND MAIN RESULTS:A total of 331 patients met inclusion criteria; 12% were underweight, 50% normal weight, 11% overweight, and 27% obese. Overall mortality was 20%. By multivariate analysis, body mass index category was independently associated with mortality (p = 0.004). When stratified by lung injury type, there was no mortality difference between body mass index groups with direct lung injury; however, in the indirect lung injury group, the odds of mortality in the obese were significantly lower than normal weight subjects (odds ratio, 0.11; 95% CI, 0.02-0.84). Survivors with direct lung injury had no difference in the duration of mechanical ventilation or ICU length of stay; however, those with indirect lung injury, the overweight required longer duration of mechanical ventilation than other groups (p < 0.001). CONCLUSIONS:These data support the obesity paradox in pediatric acute respiratory distress syndrome. Obese children with indirect lung injury pediatric acute respiratory distress syndrome have a lower risk of mortality. Importantly, among survivors, the overweight with indirect lung injury requires longer duration of mechanical ventilation. Our data require prospective validation to further elucidate the pathobiology of this phenomenon.

SUBMITTER: Ward SL

PROVIDER: S-EPMC5199718 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Impact of Weight Extremes on Clinical Outcomes in Pediatric Acute Respiratory Distress Syndrome.

Ward Shan L SL Gildengorin Virginia V Valentine Stacey L SL Sapru Anil A Curley Martha A Q MA Thomas Neal N Willson Douglas F DF Flori Heidi R HR

Critical care medicine 20161101 11

<h4>Objectives</h4>To determine whether weight extremes impact clinical outcomes in pediatric acute respiratory distress syndrome.<h4>Design</h4>Post hoc analysis of a cohort created by combining five multicenter pediatric acute respiratory distress syndrome studies.<h4>Setting</h4>Forty-three academic PICUs worldwide.<h4>Patients</h4>A total of 711 subjects prospectively diagnosed with pediatric acute respiratory distress syndrome.<h4>Intervention</h4>Subjects more than 2 years were included an ...[more]

PMID: 27355525

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Project description:OBJECTIVES:The impact of tidal volume on outcomes in mechanically ventilated children with pediatric acute respiratory distress syndrome remains unclear. To date, observational investigations have failed to calculate tidal volume based on standardized corrections of weight. We investigated the impact of tidal volume on mortality and probability of extubation in pediatric acute respiratory distress syndrome using ideal body weight-adjusted tidal volume. DESIGN:Retrospective analysis of an ongoing prospective cohort of pediatric acute respiratory distress syndrome patients. Tidal volume was calculated based on actual body weight and two different formulations of ideal body weight. SETTING:PICU at a large, tertiary care children's hospital. PATIENTS:Pediatric acute respiratory distress syndrome patients on conventional ventilation with a documented height or length. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:There were 483 patients with a measured height or length at pediatric acute respiratory distress syndrome onset included in the final analysis, with 73 nonsurvivors (15%). At 24 hours, there remained 400 patients on conventional ventilation. When calculating tidal volume based on ideal body weight by either method, volumes were larger both at onset and at 24 hours compared with tidal volume based on actual body weight (all p < 0.001), and the proportion of patients being ventilated with tidal volumes greater than 10?mL/kg based on ideal body weight was larger both at onset (12.4% and 15.5%) and 24 hours (10.3% and 11.5%) compared with actual body weight at onset (3.5%) and 24 hours (4.0%) (all p < 0.001). Tidal volume, based on both actual body weight and ideal body weight, was not associated with either increased mortality or decreased probability of extubation after adjusting for oxygenation index in the whole cohort, whereas associations between higher tidal volume and poor outcomes were seen in subgroup analyses in overweight children and in severe pediatric acute respiratory distress syndrome. CONCLUSIONS:Our retrospective analysis of a cohort of pediatric acute respiratory distress syndrome patients did not find a consistent association between tidal volume adjusted for ideal body weight and outcomes, although an association may exist in certain subgroups. Although it remains to be shown in a prospective trial whether high volumes or pressures are injurious in pediatric acute respiratory distress syndrome, tidal volume is likely an imprecise parameter for titrating lung-protective ventilation.

Project description:Acute Respiratory Distress Syndrome (ARDS) severity may be influenced by heterogeneity of neutrophil activation. Interferon-stimulated genes (ISG) are a broad gene family induced by Type I interferons, often as a response to viral infections, which evokes extensive immunomodulation. We tested the hypothesis that over- or under-expression of immunomodulatory ISG by neutrophils is associated with worse clinical outcomes in patients with ARDS. Genome-wide transcriptional profiles of circulating neutrophils isolated from patients with sepsis-induced ARDS (n = 31) and healthy controls (n = 19) were used to characterize ISG expression. Hierarchical clustering of expression identified 3 distinct subject groups with Low, Mid and High ISG expression. ISG accounting for the greatest variability in expression were identified (MX1, IFIT1, and ISG15) and used to analyze a prospective cohort at the Colorado ARDS Network site. One hundred twenty ARDS patients from four urban hospitals were enrolled within 72 hours of initiation of mechanical ventilation. Circulating neutrophils were isolated from patients and expression of ISG determined by PCR. Samples were stratified by standard deviation from the mean into High (n = 21), Mid, (n = 82) or Low (n = 17) ISG expression. Clinical outcomes were compared between patients with High or Low ISG expression to those with Mid-range expression. At enrollment, there were no differences in age, gender, co-existing medical conditions, or type of physiologic injury between cohorts. After adjusting for age, race, gender and BMI, patients with either High or Low ISG expression had significantly worse clinical outcomes than those in the Mid for number of 28-day ventilator- and ICU-free days (P = 0.0006 and 0.0004), as well as 90-day mortality and 90-day home with unassisted breathing (P = 0.02 and 0.004). These findings suggest extremes of ISG expression by circulating neutrophils from ARDS patients recovered early in the syndrome are associated with poorer clinical outcomes.

Project description:ObjectivesPediatric acute respiratory distress syndrome is heterogeneous, with a paucity of risk stratification tools to assist with trial design. We aimed to develop and validate mortality prediction models for patients with pediatric acute respiratory distress syndrome.DesignLeveraging additional data collection from a preplanned ancillary study (Version 1) of the multinational Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology study, we identified predictors of mortality. Separate models were built for the entire Version 1 cohort, for the cohort excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths. Models were externally validated in a cohort of intubated pediatric acute respiratory distress syndrome patients from the Children's Hospital of Philadelphia.SettingThe derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia.PatientsThere were 624 and 640 subjects in the derivation and validation cohorts, respectively.InterventionsNone.Measurements and main resultsThe model for the full cohort included immunocompromised status, Pediatric Logistic Organ Dysfunction 2 score, day 0 vasopressor-inotrope score and fluid balance, and PaO2/FIO2 6 hours after pediatric acute respiratory distress syndrome onset. This model had good discrimination (area under the receiver operating characteristic curve 0.82), calibration, and internal validation. Models excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths also demonstrated good discrimination (all area under the receiver operating characteristic curve ≥ 0.84) and calibration. In the validation cohort, models for intubated pediatric acute respiratory distress syndrome (including and excluding neurologic deaths) had excellent discrimination (both area under the receiver operating characteristic curve ≥ 0.85), but poor calibration. After revision, the model for all intubated subjects remained miscalibrated, whereas the model excluding neurologic deaths showed perfect calibration. Mortality models also stratified ventilator-free days at 28 days in both derivation and validation cohorts.ConclusionsWe describe predictive models for mortality in pediatric acute respiratory distress syndrome using readily available variables from day 0 of pediatric acute respiratory distress syndrome which outperform severity of illness scores and which demonstrate utility for composite outcomes such as ventilator-free days. Models can assist with risk stratification for clinical trials.

Project description:ObjectivesInfectious pneumonia is the most common cause of acute respiratory distress syndrome, with viruses frequently implicated as causative. However, the significance of viruses in pediatric acute respiratory distress syndrome is unknown. We aimed to characterize the epidemiology of viral pneumonia in pediatric acute respiratory distress syndrome and compare characteristics and outcomes between pneumonia subjects with and without viruses. Secondarily, we examined the association between specific viruses and outcomes.DesignWe performed a secondary analysis of a prospectively enrolled pediatric acute respiratory distress syndrome cohort. Subjects with pneumonia acute respiratory distress syndrome underwent testing of respiratory secretions for viruses and culture for bacteria and fungi and were stratified according to presence or absence of a virus.SettingTertiary care children's hospital.PatientsChildren with acute respiratory distress syndrome.InterventionsNone.Measurements and main resultsOf 544 children with acute respiratory distress syndrome, 282 (52%) had pneumonia as their inciting etiology, of whom 212 were virus-positive. In 141 of 282 (50%) pneumonia acute respiratory distress syndrome cases, a virus was the sole pathogen identified. Virus-positive pneumonia had fewer organ failures but worse oxygenation, relative to virus-negative pneumonia, with no differences in antibiotic use, ventilator duration, or mortality. Subjects with respiratory syncytial virus-associated acute respiratory distress syndrome had lower mortality (0%), and subjects with influenza-associated acute respiratory distress syndrome had shorter ventilator duration, relative to other viral acute respiratory distress syndrome. Nonadeno herpesviruses, tested for exclusively in immunocompromised subjects, had greater than 80% mortality.ConclusionsPneumonia was the most common cause of pediatric acute respiratory distress syndrome, and viruses were commonly isolated as the sole pathogen. Respiratory syncytial virus and influenza were associated with better outcomes relative to other viral etiologies. Viral pneumonias in immunocompromised subjects, particularly nonadeno herpesviruses, drove the mortality rate for pneumonia acute respiratory distress syndrome. Specific viral etiologies are associated with differential outcomes in pediatric acute respiratory distress syndrome and should be accounted for in future studies.

Project description:ObjectivesTo summarize the evidence for the Second Pediatric Acute Lung Injury Consensus Conference-2 (PALICC-2) recommendations for assessment of outcomes among patients surviving pediatric acute respiratory distress syndrome (PARDS).Data sourcesMEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).Study selectionWe conducted a scoping review to identify studies evaluating outcomes following PARDS. We included studies of survivors of PARDS, acute respiratory failure with a high proportion of PARDS patients, or other critical illnesses if PARDS-specific outcomes could be extracted.Data extractionTitle/abstract review, full-text review, and data extraction using a standardized data collection form.Data synthesisThe Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. Of 8,037 abstracts screened, we identified 20 articles for inclusion. Morbidity following PARDS was common and affected multiple domains of pulmonary and nonpulmonary function. There was insufficient evidence to generate any evidence-based recommendations. We generated eight good practice statements and five research statements. A panel of 52 experts discussed each proposed good practice statement and research statement, and the agreement rate was measured with an online voting process. Good practice statements describe the approach to clinical outcome assessment, assessment of pulmonary outcomes of children surviving PARDS, and assessment of nonpulmonary outcomes of children surviving PARDS including health-related quality of life and physical, neurocognitive, emotional, family, and social functioning. The five research statements relate to assessment of patient preillness status, use of postdischarge endpoints for clinical trials, the association between short-term and longer term outcomes, the trajectory of recovery following PARDS, and practices to optimize follow-up.ConclusionsThere is increasing evidence that children are at risk for impairments across a range of pulmonary and nonpulmonary health domains following hospitalization for PARDS. The results of this extensive scoping review and consensus conference involving experts in PARDS research, clinical care, and outcomes assessment provide guidance to clinicians and researchers on postdischarge follow-up to optimize the long-term health of patients surviving PARDS.

Project description:ObjectivesFluid overload is associated with worse outcomes in adult and pediatric acute respiratory distress syndrome. However, the time-course of fluid overload and its relationship to outcome has not been described. We aimed to determine the relationship between the timing of fluid overload and outcomes over the first 7 days after acute respiratory distress syndrome onset in children.DesignRetrospective cohort study.SettingSingle tertiary care PICU.PatientsIntubated children with acute respiratory distress syndrome between 2011 and 2019.InterventionsNone.Measurements and main resultsDaily and cumulative total fluid intake, total output, urine output, and fluid balance were collected for each 24-hour period from days 1 to 7 after acute respiratory distress syndrome onset. We tested the association between daily cumulative fluid metrics with PICU mortality and probability of extubation by 28 days using multivariable logistic and competing risk regression, respectively. In a subset of children, plasma was collected on day 1 and day 3 of acute respiratory distress syndrome and angiopoietin-2 quantified. Of 723 children with acute respiratory distress syndrome, 132 died (18%). In unadjusted analysis, nonsurvivors had higher cumulative fluid balance starting on day 3. In multivariable analysis, a positive cumulative fluid balance on days 5 through 7 was associated with increased mortality. Higher cumulative fluid balance on days 4 to 7 was associated with lower probability of extubation. Elevated angiopoietin-2 on day 1 predicted early (within 3 d) fluid overload greater than or equal to 10%, and elevated angiopoietin-2 on day 3 predicted late (between days 4 and 7) fluid overload.ConclusionsFluid overload after day 4 of acute respiratory distress syndrome, but not before, was associated with worse outcomes. Higher angiopoietin-2 predicted subsequent fluid overload. Our results suggest that future interventions aimed at managing fluid overload may have differential efficacy depending on when in the time-course of acute respiratory distress syndrome they are initiated.

Project description:The prevalence, clinical characteristics, and outcomes of critically ill, nonintubated patients with evidence of the acute respiratory distress syndrome remain inadequately characterized.Secondary analysis of a prospective observational cohort study.Vanderbilt University Medical Center.Among adult patients enrolled in a large, multi-ICU prospective cohort study between the years of 2006 and 2011, we studied intubated and nonintubated patients with acute respiratory distress syndrome as defined by acute hypoxemia (PaO2/FIO2 ? 300 or SpO2/FIO2 ? 315) and bilateral radiographic opacities not explained by cardiac failure. We excluded patients not committed to full respiratory support.None.Of 457 patients with acute respiratory distress syndrome, 106 (23%) were not intubated at the time of meeting all other acute respiratory distress syndrome criteria. Nonintubated patients had lower morbidity and severity of illness than intubated patients; however, mortality at 60 days was the same (36%) in both groups (p = 0.91). Of the 106 nonintubated patients, 36 (34%) required intubation within the subsequent 3 days of follow-up; this late-intubation subgroup had significantly higher 60-day mortality (56%) when compared with the both early intubation group (36%, P<0.03) and patients never requiring intubation (26%; p = 0.002). Increased mortality in the late intubation group persisted at 2-year follow-up. Adjustment for baseline clinical and demographic differences did not change the results.A substantial proportion of critically ill adults with acute respiratory distress syndrome were not intubated in their initial days of intensive care, and many were never intubated. Late intubation was associated with increased mortality. Criteria defining the acute respiratory distress syndrome prior to need for positive pressure ventilation are required so that these patients can be enrolled in clinical studies and to facilitate early recognition and treatment of acute respiratory distress syndrome.

Project description:ObjectiveAdiponectin (APN) is an anti-inflammatory hormone derived from adipose tissue that attenuates acute lung injury in rodents. In this study, we investigated the association between circulating APN and outcomes among patients with acute respiratory distress syndrome (ARDS).MethodsWe performed a retrospective cohort study using data and plasma samples from participants in the multicenter ARDS Network Fluid and Catheter Treatment Trial.ResultsPlasma APN concentrations were measured in 816 (81.6%) trial participants at baseline and in 568 (56.8%) subjects at both baseline and day 7 after enrollment. Clinical factors associated with baseline APN levels in multivariable-adjusted models included sex, body mass index, past medical history of cirrhosis, and central venous pressure (model R2 = 9.7%). We did not observe an association between baseline APN and either severity of illness (APACHE III) or extent of lung injury (Lung Injury Score). Among patients who received right heart catheterization (n = 384), baseline APN was inversely related to mean pulmonary artery pressure (β = -0.015, R2 1.5%, p = 0.02); however, this association did not persist in multivariable models (β = -0.009, R2 0.5%, p = 0.20). Neither baseline APN levels [HR per quartile1.04 (95% CI 0.91-1.18), p = 0.61], nor change in APN level from baseline to day 7 [HR 1.04 (95% CI 0.89-1.23), p = 0.62)] were associated with 60 day mortality in Cox proportional hazards regression models. However, subgroup analysis identified an association between APN and mortality among patients who developed ARDS from extra-pulmonary etiologies [HR per quartile 1.31 (95% CI 1.08-1.57)]. APN levels did not correlate with mortality among patients developing ARDS in association with direct pulmonary injury [HR 0.96 (95% CI 0.83-1.13)], pinteraction = 0.016.ConclusionsPlasma APN levels did not correlate with disease severity or mortality in a large cohort of patients with ARDS. However, higher APN levels were associated with increased mortality among patients developing ARDS from extra-pulmonary etiologies.

Dataset Information

Impact of Weight Extremes on Clinical Outcomes in Pediatric Acute Respiratory Distress Syndrome.

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Impact of Weight Extremes on Clinical Outcomes in Pediatric Acute Respiratory Distress Syndrome.

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