The Additional Prognostic Value of Serial Biomarker Measurements for Extubation Failure Among Patients With COVID-19 Acute Respiratory Distress Syndrome

Carline N.L. Groenland; Adinde H. Siemers; Eric A. Dubois; Diederik Gommers; Leo Heunks; Evert Jan Wils; Vivan J.M. Baggen; Henrik Endeman

doi:10.1177/11772719251385929

The Additional Prognostic Value of Serial Biomarker Measurements for Extubation Failure Among Patients With COVID-19 Acute Respiratory Distress Syndrome

Carline N.L. Groenland^*
, Adinde H. Siemers
, Eric A. Dubois
, Diederik Gommers
, Leo Heunks
, Evert Jan Wils
, Vivan J.M. Baggen
, Henrik Endeman

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background:

Extubation failure is associated with adverse outcomes in critically ill patients. While single biomarker measurements can aid prediction, repeated biomarker measurements can help to timely recognize underlying diseases.

Objectives:

The aim of this study was to investigate the temporal evolution of cardiac (N-terminal pro–B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [Hs-TnT]) and inflammatory biomarkers (interleukin-6 [IL-6] and procalcitonin [PCT]) prior to extubation and determine their additional prognostic value.

Design:

Retrospective cohort study.

Methods:

Patients with COVID-19 extubated after mechanical ventilation were included. Daily biomarker levels were collected up to 3 days before extubation. The primary endpoint was extubation failure, defined as reintubation or death within 7 days. Linear mixed-effect models were used to analyze biomarker trajectories in patients with extubation success and failure. Each day before extubation a logistic regression model (consisting of the 4 biomarkers) was constructed to determine the model with the best discriminative ability.

Results:

Among 297 patients, 21.5% experienced extubation failure. Log₂Hs-TnT, NT-proBNP and PCT were higher on all days in patients with extubation failure (P < .001, P = .01, P = .01, respectively), whereas log₂IL-6 was not (P = .54). There was no difference in the change of biomarkers over the days between patients with extubation success and failure (P-value for interaction = .11, P = .82, P = .31, P = .84, respectively). The performance of the logistic regression model including the 4 biomarkers on the day of extubation was significantly better than the model 3 days before extubation (AUC 0.71, 95% CI: 0.64-0.79 vs AUC 0.66, 95% CI: 0.58-0.73, P = .03).

Conclusion:

Hs-TnT, NT-proBNP and PCT measured on the days before extubation are consistently higher in patients with extubation failure. However, there was no relation between the change in biomarker levels over time and extubation outcome. The serial assessment of Hs-TnT, NT-proBNP, PCT, and IL-6 do not seem to add prognostic information to predict extubation failure.

Original language	English
Journal	Biomarker Insights
Volume	20
DOIs	https://doi.org/10.1177/11772719251385929
Publication status	E-pub ahead of print - 12 Nov 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

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The Additional Prognostic Value of Serial Biomarker Measurements for Extubation Failure Among Patients With COVID-19 Acute Respiratory Distress SyndromeFinal published version, 564 KBLicence: CC BY

Cite this

Groenland, C. N. L., Siemers, A. H., Dubois, E. A., Gommers, D., Heunks, L., Wils, E. J., Baggen, V. J. M., & Endeman, H. (2025). The Additional Prognostic Value of Serial Biomarker Measurements for Extubation Failure Among Patients With COVID-19 Acute Respiratory Distress Syndrome. Biomarker Insights, 20. Advance online publication. https://doi.org/10.1177/11772719251385929

@article{15e27e9271da46ae867c9521b9593a37,

title = "The Additional Prognostic Value of Serial Biomarker Measurements for Extubation Failure Among Patients With COVID-19 Acute Respiratory Distress Syndrome",

abstract = "Background: Extubation failure is associated with adverse outcomes in critically ill patients. While single biomarker measurements can aid prediction, repeated biomarker measurements can help to timely recognize underlying diseases. Objectives: The aim of this study was to investigate the temporal evolution of cardiac (N-terminal pro–B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [Hs-TnT]) and inflammatory biomarkers (interleukin-6 [IL-6] and procalcitonin [PCT]) prior to extubation and determine their additional prognostic value. Design: Retrospective cohort study. Methods: Patients with COVID-19 extubated after mechanical ventilation were included. Daily biomarker levels were collected up to 3 days before extubation. The primary endpoint was extubation failure, defined as reintubation or death within 7 days. Linear mixed-effect models were used to analyze biomarker trajectories in patients with extubation success and failure. Each day before extubation a logistic regression model (consisting of the 4 biomarkers) was constructed to determine the model with the best discriminative ability. Results: Among 297 patients, 21.5\% experienced extubation failure. Log2Hs-TnT, NT-proBNP and PCT were higher on all days in patients with extubation failure (P < .001, P = .01, P = .01, respectively), whereas log2IL-6 was not (P = .54). There was no difference in the change of biomarkers over the days between patients with extubation success and failure (P-value for interaction = .11, P = .82, P = .31, P = .84, respectively). The performance of the logistic regression model including the 4 biomarkers on the day of extubation was significantly better than the model 3 days before extubation (AUC 0.71, 95\% CI: 0.64-0.79 vs AUC 0.66, 95\% CI: 0.58-0.73, P = .03). Conclusion: Hs-TnT, NT-proBNP and PCT measured on the days before extubation are consistently higher in patients with extubation failure. However, there was no relation between the change in biomarker levels over time and extubation outcome. The serial assessment of Hs-TnT, NT-proBNP, PCT, and IL-6 do not seem to add prognostic information to predict extubation failure.",

author = "Groenland, \{Carline N.L.\} and Siemers, \{Adinde H.\} and Dubois, \{Eric A.\} and Diederik Gommers and Leo Heunks and Wils, \{Evert Jan\} and Baggen, \{Vivan J.M.\} and Henrik Endeman",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).",

year = "2025",

month = nov,

day = "12",

doi = "10.1177/11772719251385929",

language = "English",

volume = "20",

journal = "Biomarker Insights",

issn = "1177-2719",

publisher = "SAGE Publications Ltd",

}

TY - JOUR

T1 - The Additional Prognostic Value of Serial Biomarker Measurements for Extubation Failure Among Patients With COVID-19 Acute Respiratory Distress Syndrome

AU - Groenland, Carline N.L.

AU - Siemers, Adinde H.

AU - Dubois, Eric A.

AU - Gommers, Diederik

AU - Heunks, Leo

AU - Wils, Evert Jan

AU - Baggen, Vivan J.M.

AU - Endeman, Henrik

N1 - Publisher Copyright: © The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

PY - 2025/11/12

Y1 - 2025/11/12

N2 - Background: Extubation failure is associated with adverse outcomes in critically ill patients. While single biomarker measurements can aid prediction, repeated biomarker measurements can help to timely recognize underlying diseases. Objectives: The aim of this study was to investigate the temporal evolution of cardiac (N-terminal pro–B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [Hs-TnT]) and inflammatory biomarkers (interleukin-6 [IL-6] and procalcitonin [PCT]) prior to extubation and determine their additional prognostic value. Design: Retrospective cohort study. Methods: Patients with COVID-19 extubated after mechanical ventilation were included. Daily biomarker levels were collected up to 3 days before extubation. The primary endpoint was extubation failure, defined as reintubation or death within 7 days. Linear mixed-effect models were used to analyze biomarker trajectories in patients with extubation success and failure. Each day before extubation a logistic regression model (consisting of the 4 biomarkers) was constructed to determine the model with the best discriminative ability. Results: Among 297 patients, 21.5% experienced extubation failure. Log2Hs-TnT, NT-proBNP and PCT were higher on all days in patients with extubation failure (P < .001, P = .01, P = .01, respectively), whereas log2IL-6 was not (P = .54). There was no difference in the change of biomarkers over the days between patients with extubation success and failure (P-value for interaction = .11, P = .82, P = .31, P = .84, respectively). The performance of the logistic regression model including the 4 biomarkers on the day of extubation was significantly better than the model 3 days before extubation (AUC 0.71, 95% CI: 0.64-0.79 vs AUC 0.66, 95% CI: 0.58-0.73, P = .03). Conclusion: Hs-TnT, NT-proBNP and PCT measured on the days before extubation are consistently higher in patients with extubation failure. However, there was no relation between the change in biomarker levels over time and extubation outcome. The serial assessment of Hs-TnT, NT-proBNP, PCT, and IL-6 do not seem to add prognostic information to predict extubation failure.

AB - Background: Extubation failure is associated with adverse outcomes in critically ill patients. While single biomarker measurements can aid prediction, repeated biomarker measurements can help to timely recognize underlying diseases. Objectives: The aim of this study was to investigate the temporal evolution of cardiac (N-terminal pro–B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [Hs-TnT]) and inflammatory biomarkers (interleukin-6 [IL-6] and procalcitonin [PCT]) prior to extubation and determine their additional prognostic value. Design: Retrospective cohort study. Methods: Patients with COVID-19 extubated after mechanical ventilation were included. Daily biomarker levels were collected up to 3 days before extubation. The primary endpoint was extubation failure, defined as reintubation or death within 7 days. Linear mixed-effect models were used to analyze biomarker trajectories in patients with extubation success and failure. Each day before extubation a logistic regression model (consisting of the 4 biomarkers) was constructed to determine the model with the best discriminative ability. Results: Among 297 patients, 21.5% experienced extubation failure. Log2Hs-TnT, NT-proBNP and PCT were higher on all days in patients with extubation failure (P < .001, P = .01, P = .01, respectively), whereas log2IL-6 was not (P = .54). There was no difference in the change of biomarkers over the days between patients with extubation success and failure (P-value for interaction = .11, P = .82, P = .31, P = .84, respectively). The performance of the logistic regression model including the 4 biomarkers on the day of extubation was significantly better than the model 3 days before extubation (AUC 0.71, 95% CI: 0.64-0.79 vs AUC 0.66, 95% CI: 0.58-0.73, P = .03). Conclusion: Hs-TnT, NT-proBNP and PCT measured on the days before extubation are consistently higher in patients with extubation failure. However, there was no relation between the change in biomarker levels over time and extubation outcome. The serial assessment of Hs-TnT, NT-proBNP, PCT, and IL-6 do not seem to add prognostic information to predict extubation failure.

UR - https://www.scopus.com/pages/publications/105022160069

U2 - 10.1177/11772719251385929

DO - 10.1177/11772719251385929

M3 - Article

C2 - 41245882

AN - SCOPUS:105022160069

SN - 1177-2719

VL - 20

JO - Biomarker Insights

JF - Biomarker Insights

ER -

The Additional Prognostic Value of Serial Biomarker Measurements for Extubation Failure Among Patients With COVID-19 Acute Respiratory Distress Syndrome

Abstract

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