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Endothelial Glycocalyx Degradation Patterns in Sepsis-Associated Pediatric Acute Respiratory Distress Syndrome: A Single Center Retrospective Observational Study.
Sallee, Colin J; Hippensteel, Joseph A; Miller, Kristen R; Oshima, Kaori; Pham, Andrew T; Richter, Robert P; Belperio, John; Sierra, Yamila L; Schwingshackl, Andreas; Mourani, Peter M; Schmidt, Eric P; Sapru, Anil; Maddux, Aline B.
Afiliação
  • Sallee CJ; Department of Pediatrics, Division of Pediatric Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles and Mattel Children's Hospital, Los Angeles, CA, USA.
  • Hippensteel JA; Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Miller KR; Department of Pediatrics, Section of Pediatric Critical Care, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
  • Oshima K; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
  • Pham AT; Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Richter RP; Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL, USA.
  • Belperio J; Department of Medicine, Division of Pulmonary Critical Care and Sleep Medicine, David Geffen School of Medicine at University of California Los Angeles and Ronald Reagan Medical Center, Los Angeles, CA, USA.
  • Sierra YL; Department of Pediatrics, Section of Pediatric Critical Care, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
  • Schwingshackl A; Department of Pediatrics, Division of Pediatric Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles and Mattel Children's Hospital, Los Angeles, CA, USA.
  • Mourani PM; Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA.
  • Schmidt EP; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA.
  • Sapru A; Department of Pediatrics, Division of Pediatric Critical Care Medicine, David Geffen School of Medicine at University of California Los Angeles and Mattel Children's Hospital, Los Angeles, CA, USA.
  • Maddux AB; Department of Pediatrics, Section of Pediatric Critical Care, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO, USA.
J Intensive Care Med ; 39(3): 277-287, 2024 Mar.
Article em En | MEDLINE | ID: mdl-37670670
BACKGROUND: Sepsis-associated destruction of the pulmonary microvascular endothelial glycocalyx (EGCX) creates a vulnerable endothelial surface, contributing to the development of acute respiratory distress syndrome (ARDS). Constituents of the EGCX shed into circulation, glycosaminoglycans and proteoglycans, may serve as biomarkers of endothelial dysfunction. We sought to define the patterns of plasma EGCX degradation products in children with sepsis-associated pediatric ARDS (PARDS), and test their association with clinical outcomes. METHODS: We retrospectively analyzed a prospective cohort (2018-2020) of children (≥1 month to <18 years of age) receiving invasive mechanical ventilation for acute respiratory failure for ≥72 h. Children with and without sepsis-associated PARDS were selected from the parent cohort and compared. Blood was collected at time of enrollment. Plasma glycosaminoglycan disaccharide class (heparan sulfate, chondroitin sulfate, and hyaluronan) and sulfation subtypes (heparan sulfate and chondroitin sulfate) were quantified using liquid chromatography tandem mass spectrometry. Plasma proteoglycans (syndecan-1) were measured through an immunoassay. RESULTS: Among the 39 mechanically ventilated children (29 with and 10 without sepsis-associated PARDS), sepsis-associated PARDS patients demonstrated higher levels of heparan sulfate (median 639 ng/mL [interquartile range, IQR 421-902] vs 311 [IQR 228-461]) and syndecan-1 (median 146 ng/mL [IQR 32-315] vs 8 [IQR 8-50]), both p = 0.01. Heparan sulfate subtype analysis demonstrated greater proportions of N-sulfated disaccharide levels among children with sepsis-associated PARDS (p = 0.01). Increasing N-sulfated disaccharide levels by quartile were associated with severe PARDS (n = 9/29) with the highest quartile including >60% of the severe PARDS patients (test for trend, p = 0.04). Higher total heparan sulfate and N-sulfated disaccharide levels were independently associated with fewer 28-day ventilator-free days in children with sepsis-associated PARDS (all p < 0.05). CONCLUSIONS: Children with sepsis-associated PARDS exhibited higher plasma levels of heparan sulfate disaccharides and syndecan-1, suggesting that EGCX degradation biomarkers may provide insights into endothelial dysfunction and PARDS pathobiology.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndrome do Desconforto Respiratório / Sepse Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Child / Humans Idioma: En Revista: J Intensive Care Med Assunto da revista: TERAPIA INTENSIVA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Síndrome do Desconforto Respiratório / Sepse Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Child / Humans Idioma: En Revista: J Intensive Care Med Assunto da revista: TERAPIA INTENSIVA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos