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Thrombomodulin is Associated with Increased Mortality and Organ Failure in Mechanically Ventilated Children with Acute Respiratory Failure: A Prospective Observational Study.
Ana C Monteiro
Ronald Reagan UCLA Medical Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1501-4435
License:
This work is licensed under a CC BY 4.0 License. Read Full License
BACKGROUND
Acute respiratory failure (ARF) can progress to acute respiratory distress syndrome (ARDS) and death. Biomarkers such as soluble thrombomodulin (sTM), implicated in pulmonary vascular injury, may allow for risk stratification and prognostic enrichment in ARF.
METHODS
This 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-hour intervals within 5 days after intubation. sTM was assayed by ELISA. 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.
RESULTS
sTM 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).
CONCLUSIONS
Plasma sTM are associated with mortality, severity of ARDS extrapulmonary MOF in children with ARF. This suggests a role of vascular injury in pathogenesis of ARF and provide potential application for targeted therapies.
TRIAL REGISTRATION
NCT00814099
Keywords
Acute Respiratory Distress Syndrome, Acute Respiratory Failure, Dead Space Ventilation, Thrombomodulin, coagulation, vascular injury
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CURRENT STATUS: Under Revision
Version 1
Posted 21 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 16 Feb, 2021
Review #3 received
Received 15 Feb, 2021
Review #2 received
Received 07 Feb, 2021
Reviewer #3 agreed
On 05 Feb, 2021
Review #1 received
Received 28 Jan, 2021
Reviewer #2 agreed
On 21 Jan, 2021
Reviewer #1 agreed
On 20 Jan, 2021
Editor assigned
On 19 Jan, 2021
Reviewers invited
Invitations sent on 19 Jan, 2021
Editor invited
On 19 Jan, 2021
Submission checks complete
On 19 Jan, 2021
First submitted
On 14 Jan, 2021
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Subject Areas
Critical Care & Emergency Medicine
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This preprint is under consideration at Critical Care. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Thrombomodulin is Associated with Increased Mortality and Organ Failure in Mechanically Ventilated Children with Acute Respiratory Failure: A Prospective Observational Study.
Ana C Monteiro
Ronald Reagan UCLA Medical Center
Corresponding Author
ORCiD: https://orcid.org/0000-0002-1501-4435
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 1
Posted 21 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 16 Feb, 2021
Review #3 received
Received 15 Feb, 2021
Review #2 received
Received 07 Feb, 2021
Reviewer #3 agreed
On 05 Feb, 2021
Review #1 received
Received 28 Jan, 2021
Reviewer #2 agreed
On 21 Jan, 2021
Reviewer #1 agreed
On 20 Jan, 2021
Editor assigned
On 19 Jan, 2021
Reviewers invited
Invitations sent on 19 Jan, 2021
Editor invited
On 19 Jan, 2021
Submission checks complete
On 19 Jan, 2021
First submitted
On 14 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Critical Care & Emergency Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
BACKGROUND
Acute respiratory failure (ARF) can progress to acute respiratory distress syndrome (ARDS) and death. Biomarkers such as soluble thrombomodulin (sTM), implicated in pulmonary vascular injury, may allow for risk stratification and prognostic enrichment in ARF.
METHODS
This 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-hour intervals within 5 days after intubation. sTM was assayed by ELISA. 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.
RESULTS
sTM 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).
CONCLUSIONS
Plasma sTM are associated with mortality, severity of ARDS extrapulmonary MOF in children with ARF. This suggests a role of vascular injury in pathogenesis of ARF and provide potential application for targeted therapies.
TRIAL REGISTRATION
NCT00814099
Figure 1
Figure 2