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P50 implies adverse clinical outcomes in pediatric acute respiratory distress syndrome by reflecting extrapulmonary organ dysfunction.

ABSTRACT: Hypoxemia and multiple organ dysfunction are significant contributors to mortality in patients with pediatric acute respiratory distress syndrome (PARDS). P50, the oxygen tension at which hemoglobin is 50% saturated, is a measure of hemoglobin-oxygen affinity, and its alteration might have implications for tissue hypoxia and organ dysfunction. The purpose of this single-center, retrospective study was to evaluate P50 levels in PARDS and to determine the association between P50 and clinical outcomes. The study included 212 children diagnosed with PARDS according to the Pediatric Acute Lung Injury Consensus Conference definition who required invasive mechanical ventilation and had arterial blood gas results of hemoglobin oxygen saturation < 97% at the time of diagnosis. P50 levels were calculated using Doyle's method, and organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 score. Most patients exhibited more than one dysfunctional extrapulmonary organ at PARDS onset. P50 increased with increasing PARDS severity (mild (26.6 [24.9-29.6]), moderate (26.8 [25.0-29.5]), and severe PARDS (29.1 [26.1-32.4] mmHg; P = 0.025). Moreover, P50 demonstrated a significant positive association with extrapulmonary organ dysfunction score (β = 0.158, P = 0.007) and risk of mortality (adjusted hazard ratio, 1.056; 95% confidence interval, 1.015-1.098; P = 0.007), irrespective of initial PARDS severity. The relationship between P50 and mortality was largely mediated by extrapulmonary organ dysfunction. A high P50 value at the time of PARDS diagnosis may be associated with mortality via dysfunctional extrapulmonary organs. Future studies should consider P50 as a potential candidate index for risk stratification of PARDS patients.

SUBMITTER: Kim Y

PROVIDER: S-EPMC9372160 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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P50 implies adverse clinical outcomes in pediatric acute respiratory distress syndrome by reflecting extrapulmonary organ dysfunction.

Kim Yura Y Jung Jae Hwa JH Kim Ga Eun GE Park Mireu M Lee Myeongjee M Kim Soo Yeon SY Kim Min Jung MJ Kim Yoon Hee YH Kim Kyung Won KW Sohn Myung Hyun MH

Scientific reports 20220811 1

Hypoxemia and multiple organ dysfunction are significant contributors to mortality in patients with pediatric acute respiratory distress syndrome (PARDS). P50, the oxygen tension at which hemoglobin is 50% saturated, is a measure of hemoglobin-oxygen affinity, and its alteration might have implications for tissue hypoxia and organ dysfunction. The purpose of this single-center, retrospective study was to evaluate P50 levels in PARDS and to determine the association between P50 and clinical outco ...[more]

PMID: 35953629

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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:OBJECTIVES:Limited data exist about the timing and significance of mitochondrial alterations in children with sepsis. We therefore sought to determine if alterations in mitochondrial respiration and content within circulating peripheral blood mononuclear cells were associated with organ dysfunction in pediatric sepsis. DESIGN:Prospective observational study SETTING:: Single academic PICU. PATIENTS:One-hundred sixty-seven children with sepsis/septic shock and 19 PICU controls without sepsis, infection, or organ dysfunction. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Mitochondrial respiration and content were measured in peripheral blood mononuclear cells on days 1-2, 3-5, and 8-14 after sepsis recognition or once for controls. Severity and duration of organ dysfunction were determined using the Pediatric Logistic Organ Dysfunction score and organ failure-free days through day 28. Day 1-2 maximal uncoupled respiration (9.7?±?7.7 vs 13.7?±?4.1 pmol O2/s/10 cells; p = 0.02) and spare respiratory capacity (an index of bioenergetic reserve: 6.2?±?4.3 vs 9.6?±?3.1; p = 0.005) were lower in sepsis than controls. Mitochondrial content, measured by mitochondrial DNA/nuclear DNA, was higher in sepsis on day 1-2 than controls (p = 0.04) and increased in sepsis patients who had improving spare respiratory capacity over time (p = 0.005). Mitochondrial respiration and content were not associated with day 1-2 Pediatric Logistic Organ Dysfunction score, but low spare respiratory capacity was associated with higher Pediatric Logistic Organ Dysfunction score on day 3-5. Persistently low spare respiratory capacity was predictive of residual organ dysfunction on day 14 (area under the receiver operating characteristic, 0.72; 95% CI, 0.61-0.84) and trended toward fewer organ failure-free days although day 28 (? coefficient, -0.64; 95% CI, -1.35 to 0.06; p = 0.08). CONCLUSIONS:Mitochondrial respiration was acutely decreased in peripheral blood mononuclear cells in pediatric sepsis despite an increase in mitochondrial content. Over time, a rise in mitochondrial DNA tracked with improved respiration. Although initial mitochondrial alterations in peripheral blood mononuclear cells were unrelated to organ dysfunction, persistently low respiration was associated with slower recovery from organ dysfunction.

Project description:ObjectivesSystemic endothelial activation may contribute to sepsis-associated organ injury, including acute respiratory distress syndrome. We hypothesized that children with extrapulmonary sepsis with versus without acute respiratory distress syndrome would have plasma biomarkers indicative of increased endothelial activation and that persistent biomarker changes would be associated with poor outcome.DesignObservational cohort.SettingAcademic PICU.PatientsPatients less than 18 years old with sepsis from extrapulmonary infection with (n = 46) or without (n = 54) acute respiratory distress syndrome and noninfected controls (n = 19).InterventionsNone.Measurements and main resultsEndothelial (angiopoietin-1, angiopoietin-2, tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2, vascular endothelial growth factor, soluble fms-like tyrosine kinase, von Willebrand factor, E-selectin, intercellular adhesion molecule, vascular cell adhesion molecule, thrombomodulin) and inflammatory biomarkers (C-reactive protein, interleukin-6, and interleukin-8) were measured from peripheral plasma collected within 3 days (time 1) of sepsis recognition and at 3-6 days (time 2) and 7-14 days (time 3). Time 1 biomarkers and longitudinal measurements were compared for sepsis patients with versus without acute respiratory distress syndrome and in relation to complicated course, defined as greater than or equal to two organ dysfunctions at day 7 or death by day 28. Angiopoietin-2, angiopoietin-2/angiopoietin-1 ratio, tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2, vascular endothelial growth factor, von Willebrand factor, E-selectin, intercellular adhesion molecule, vascular cell adhesion molecule, thrombomodulin, endocan, C-reactive protein, interleukin-6, and interleukin-8 were different between sepsis and noninfected control patients at time 1. Among patients with sepsis, those with acute respiratory distress syndrome had higher angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor, vascular cell adhesion molecule, thrombomodulin, endocan, interleukin-6, and interleukin-8 than those without acute respiratory distress syndrome (all p < 0.003). Angiopoietin-2 and angiopoietin-2/angiopoietin-1 ratio remained higher in sepsis with versus without acute respiratory distress syndrome after multivariable analyses. Time 1 measures of angiopoietin-2, angiopoietin-2/-1 ratio, von Willebrand factor, and endocan were indicative of complicated course in all sepsis patients (all area under the receiver operating curve ≥ 0.80). In sepsis without acute respiratory distress syndrome, soluble fms-like tyrosine kinase decreased more quickly and von Willebrand factor and thrombomodulin decreased more slowly in those with complicated course.ConclusionsChildren with extrapulmonary sepsis with acute respiratory distress syndrome had plasma biomarkers indicative of greater systemic endothelial activation than those without acute respiratory distress syndrome. Several endothelial biomarkers measured near sepsis recognition were associated with complicated course, whereas longitudinal biomarker changes yielded prognostic information only in those without sepsis-associated acute respiratory distress syndrome.

Project description:ObjectivesThe trajectory and importance of right ventricular systolic function and pulmonary hypertension during the course of pediatric acute respiratory distress syndrome are unknown. We hypothesized that new or persistent right ventricular systolic dysfunction and pulmonary hypertension would be associated with worse patient outcomes.DesignRetrospective, single-center cohort study.SettingTertiary care, university-affiliated PICU.PatientsChildren who had at least two echocardiograms less than 8 days following pediatric acute respiratory distress syndrome diagnosis.InterventionsNone.Measurements and main resultsBetween July 1, 2012, and April 30, 2018, 74 children met inclusion criteria. The first echocardiogram was performed a median of 0.61 days (interquartile range, 0.36-0.94 d) and the second echocardiogram was performed a median of 2.57 days (interquartile range, 1.67-3.63 d) after pediatric acute respiratory distress syndrome diagnosis. Univariate analyses showed that new or persistent right ventricular systolic dysfunction as defined by global longitudinal strain or free wall strain was associated with a greater number of ICU days in survivors (global longitudinal strain p = 0.04, free wall strain p = 0.04), lower ventilator-free days at 28 days (global longitudinal strain p = 0.03, free wall strain p = 0.01), and higher rate of PICU death (global longitudinal strain p = 0.046, free wall strain p = 0.01). Mixed-effects multivariate modeling showed that right ventricular global longitudinal strain and right ventricular fractional area change stayed relatively constant over the course of the first 8 days in nonsurvivors and that there was a linear improvement in global longitudinal strain (p = 0.037) and fractional area change (p = 0.05) in survivors. Worsening right ventricular dysfunction at the time of repeat echocardiogram as defined by global longitudinal strain and free wall strain were independently associated with decreased probability of extubation (subdistribution hazard ratio, 0.30 [0.14-0.67]; p = 0.003 and subdistribution hazard ratio, 0.47 [0.23-0.98]; p = 0.043, respectively). In univariate and multivariate analyses, pulmonary hypertension had no significant associations with outcomes in his cohort.ConclusionsNew or persistent right ventricular systolic dysfunction over the first week following pediatric acute respiratory distress syndrome onset is associated with worse patient outcomes, including decreased probability of extubation and higher PICU mortality.

Project description:ObjectivesTo describe mechanical ventilation management and factors associated with nonadherence to lung-protective ventilation principles in pediatric acute respiratory distress syndrome.DesignA planned ancillary study to a prospective international observational study. Mechanical ventilation management (every 6 hr measurements) during pediatric acute respiratory distress syndrome days 0-3 was described and compared with Pediatric Acute Lung Injury Consensus Conference tidal volume recommendations (< 7 mL/kg in children with impaired respiratory system compliance, < 9 mL/kg in all other children) and the Acute Respiratory Distress Syndrome Network lower positive end-expiratory pressure/higher Fio2 grid recommendations.SettingSeventy-one international PICUs.PatientsChildren with pediatric acute respiratory distress syndrome.InterventionsNone.Measurements and main resultsAnalyses included 422 children. On pediatric acute respiratory distress syndrome day 0, median tidal volume was 7.6 mL/kg (interquartile range, 6.3-8.9 mL/kg) and did not differ by pediatric acute respiratory distress syndrome severity. Plateau pressure was not recorded in 97% of measurements. Using delta pressure (peak inspiratory pressure - positive end-expiratory pressure), median tidal volume increased over quartiles of median delta pressure (p = 0.007). Median delta pressure was greater than or equal to 18 cm H2O for all pediatric acute respiratory distress syndrome severity levels. In severe pediatric acute respiratory distress syndrome, tidal volume was greater than or equal to 7 mL/kg 62% of the time, and positive end-expiratory pressure was lower than recommended by the positive end-expiratory pressure/Fio2 grid 70% of the time. In multivariable analysis, tidal volume nonadherence was more common with severe pediatric acute respiratory distress syndrome, fewer PICU admissions/yr, non-European PICUs, higher delta pressure, corticosteroid use, and pressure control mode. Adherence was associated with underweight stature and cuffed endotracheal tubes. In multivariable analysis, positive end-expiratory pressure/Fio2 grid nonadherence was more common with higher pediatric acute respiratory distress syndrome severity, ventilator decisions made primarily by the attending physician, pre-ICU cardiopulmonary resuscitation, underweight stature, and age less than 2 years. Adherence was associated with respiratory therapist involvement in ventilator management and longer time from pediatric acute respiratory distress syndrome diagnosis. Higher nonadherence to tidal volume and positive end-expiratory pressure recommendations were independently associated with higher mortality and longer duration of ventilation after adjustment for confounding variables. In stratified analyses, these associations were primarily influenced by children with severe pediatric acute respiratory distress syndrome.ConclusionsNonadherence to lung-protective ventilation principles is common in pediatric acute respiratory distress syndrome and may impact outcome. Modifiable factors exist that may improve adherence.

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P50 implies adverse clinical outcomes in pediatric acute respiratory distress syndrome by reflecting extrapulmonary organ dysfunction.

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P50 implies adverse clinical outcomes in pediatric acute respiratory distress syndrome by reflecting extrapulmonary organ dysfunction.

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