Evidence map›Paper›PMID 34344416›Full record

Trial reportCritical care (London, England)2021

Thrombomodulin is associated with increased mortality and organ failure in mechanically ventilated children with acute respiratory failure: biomarker analysis from a multicenter randomized controlled trial.

Ana Carolina Costa Monteiro, Heidi Flori, Mary K Dahmer, Myung Shin Sim, Michael W Quasney, Martha A Q Curley, Michael A Matthay, Anil Sapru, BALI Study Investigators of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network

Registry-linked trialOpen access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Critical care (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00814099 (Sedation Management in Pediatric Patients With Acute Respiratory Failure), which is not on this map. Cited by 20 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00814099 nacompletednot on this map

Sedation Management in Pediatric Patients With Acute Respiratory Failure

TypeinterventionalSponsorUniversity of PennsylvaniaRan2009 to 2013Enrolled2,449ConditionsRespiratory Insufficiency, Respiratory Distress Syndrome, Newborn, Lung DiseasesArmsTeam approach to sedation management, Usual approach to sedation management
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Distinct Blood and Lung Proteins Drive Pulmonary Capillary Leak in Children With Severe Hypoxemic Respiratory Failure.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2026
    Observational
  6. Review
  7. Article
  8. Review
  9. Review
  10. Observational
  11. Article
  12. Review
  13. Article
  14. Advances in Biomarkers for Diagnosis and Treatment of ARDS.Diagnostics (Basel, Switzerland) · 2023
    Review
  15. [Application Value of Novel Coagulation Markers in Predicting Postoperarative Complications in the Early Stage After Liver Transplantation].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023
    Article
  16. Are circulating endothelial cells the next target for transcriptome-level pathway analysis in ARDS?American journal of physiology. Lung cellular and molecular physiology · 2023
    Article
  17. Article
  18. Pathobiology, Severity, and Risk Stratification of Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2023
    Review
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 20 institutions in 2 countries.

Ana Carolina Costa MonteiroDivision of Pulmonary and Critical Care Medicine, Department of Medicine, UCLA Ronald Reagan Hospital, University of California, Los Angeles, 757 Westwood Plaza, Los Angeles, CA, 90095, USA. acostamonteiro@mednet.ucla.edu.ORCID 0000-0002-1501-4435
Heidi FloriDivision of Pediatric Critical Care Medicine, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
Mary K DahmerDivision of Pediatric Critical Care Medicine, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
Myung Shin SimDivision of General Internal Medicine and Health Services Research, University of California, Los Angeles, Los Angeles, CA, USA.
Michael W QuasneyDivision of Pediatric Critical Care Medicine, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
Martha A Q CurleyDivision of Anesthesia and Critical Care Medicine (Perelman School of Medicine), Department of Family and Community Health (School of Nursing), University of Pennsylvania, Philadelphia, PA, USA.
Michael A MatthayDepartments of Medicine and Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA.
Anil SapruDivision of Pediatric Critical Care, Department of Pediatrics, University of California, Los Angeles, Los Angeles, CA, USA.
BALI Study Investigators of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
University of California, Los Angeles · USUniversity of Michigan · USChildren's Medical Center · USBoston Children's Hospital · USChildren's Hospital of Orange County · USChildren's of Alabama · USJackson Health System · USPrimary Children's Hospital · USSt. Louis Children's Hospital · USUniversity of California, San Francisco · USAdventHealth for Children · USChildren's Hospital at Dartmouth Hitchcock · USChildren's Hospital of Philadelphia · USConnecticut Children's Medical Center · USDartmouth Hospital · GBLurie Children's Hospital · USLurie Children's Hospital · USMemorial Medical Center · USUniversity of Pennsylvania · USYale New Haven Hospital · US

Funding

Sedation Management in Pediatric Patients with Acute Respiratory FailureU01HL086622 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI CURLEY, MARTHA AQ · 2008 to 2013
$10.0M
UCLA Pulmonary and Critical Care Medicine Training ProgramT32HL072752 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JOHN A BELPERIO, TOMAS GANZ · 2003 to 2026
$8.3M
Precision Medicine in the Acute Respiratory Distress SyndromeR35HL140026 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CALFEE, CAROLYN · 2018 to 2024
$6.8M
Prevention and Early Treatment of Acute Lung InjuryU01HL123004 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MATTHAY, MICHAEL A. · 2014 to 2020
$2.6M
Sedation Management in Pediatric Patients with Acute Respiratory Failure (DCC)U01HL086649 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI WYPIJ, DAVID · 2008 to 2012
$2.0M
Genetic variation and biomarkers in children with acute lung injuryR01HL095410 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAHMER, MARY K, FLORI, HEIDI R · 2009 to 2012
$1.8M
Coagulation and Fibrinolysis in Pediatric Insulin Titration TrialR01HL114484 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SAPRU, ANIL · 2012 to 2015
$1.6M
NHLBI NIH HHS 2T32HL072752-16NHLBI NIH HHS HL0114484NHLBI NIH HHS HL123004NHLBI NIH HHS HL140026NHLBI NIH HHS R01 HL095410NHLBI NIH HHS R01HL095410NHLBI NIH HHS R01 HL114484NHLBI NIH HHS R35 HL140026NHLBI NIH HHS T32 HL072752NHLBI NIH HHS U01 HL086622NHLBI NIH HHS U01HL086622NHLBI NIH HHS U01 HL086649NHLBI NIH HHS U01 HL123004
6 · The paper itself

Abstract

backgroundAcute respiratory failure (ARF) can progress to acute respiratory distress syndrome and death. Biomarkers may allow for risk stratification and prognostic enrichment in ARF. Thrombomodulin (TM) is a transmembrane antithrombotic mediator expressed in endothelial cells. It is cleaved into its soluble form (sTM) during inflammation and vascular injury. Levels of sTM correlate with inflammation and end organ dysfunction.

methodsThis was a prospective observational study of 432 patients aged 2 weeks-17 years requiring invasive mechanical ventilation. It was ancillary to the multicenter clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). After consent, patients had up to 3 plasma samples collected at 24-h intervals within 5 days after intubation. sTM was assayed by ELISA. The Hazard ratio (HR) for 90-day mortality was determined by Cox regression. Mixed effect models (MEM) were used to test for association with extrapulmonary multiorgan failure (MOF) and oxygenation index (OI). Age, race, sex and PRISM-III scores were used as confounding variables for multivariable analyses.

resultssTM values ranged from 16.6 to 670.9 ng/ml within 5 days after intubation. Higher sTM was associated with increased 90-day mortality (n = 432, adjusted HR = 1.003, p = 0.02) and worse OI in the first 5 days after intubation (n = 252, Estimate = 0.02, p < 0.01). Both initial and slope of sTM were associated with increased extrapulmonary MOF in unadjusted and adjusted analyses (Intercept, Estimate = 0.003, p < 0.0001; and slope, Estimate = 0.01, p = 0.0009, n = 386).

conclusionsPlasma sTM is associated with mortality, severity of hypoxic respiratory failure and worsening extrapulmonary MOF in children with ARF. This suggests a role of vascular injury in the pathogenesis of ARF and provides potential applicability towards targeted therapies.

trial registrationhttps://clinicaltrials.gov/ct2/show/NCT00814099 . In healthy lung endothelium, thrombomodulin (TM) recruits thrombin to activate Protein-C (PC/APC), that inhibits plasminogen activator-1 (PAI-1) and thrombosis. In inflamed and damaged endothelium, TM is cleaved into its soluble form (sTM), precluding its usual regulation of thrombosis. In this study, we measured plasma sTM levels in pediatric patients with respiratory failure and found that sTM correlated with mortality and other clinical markers of poor outcomes.

Indexed as

BiomarkersFemaleHumansMaleMiddle AgedMortalityMultiple Organ FailurePrognosisRespiration, ArtificialRespiratory InsufficiencyThrombomodulinBiomarkersTHBD protein, humanThrombomodulinAcute respiratory distress syndromeAcute respiratory failureCoagulationDead space ventilationThrombomodulinVascular injury

Identifiers

PMID34344416
PMCPMC8330123
OpenAlexW3189657508

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.