TY - JOUR

T1 - Novel subgroups in acute respiratory failure based on the trajectories of three endotheliopathy biomarkers

T2 - A cohort study

AU - Schønemann-Lund, Martin

AU - Itenov, Theis S.

AU - Larsson, Johan E.

AU - Lindegaard, Birgitte

AU - Johansson, Pär I.

AU - Bestle, Morten H.

N1 - Funding Information: The authors wish to thank study nurses Lone Valbjørn and Sanne Lauritzen, research assistants Saif Adel Hamid Al‐Haidar and Frederik H. Bestle as well as biomedical laboratory scientists Cecilie Nguyen Brøns, Rola Zohair Ghadban and Doris Schnülle Nellemann for their invaluable contribution to the study. The study received grants from Danmarks Frie Forskningsfond, Hindsgavl Symposium, The Research Foundation at North Zealand's Hospital, and AP Møller Foundation. Martin Schønemann‐Lund takes responsibility for the content of the manuscript including all data and statistical analysis. The authors declare no conflict of interest. Publisher Copyright: © 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

PY - 2023

Y1 - 2023

N2 - Baseline levels of endotheliopathy are associated with worse respiratory outcomes and mortality in undifferentiated acute respiratory failure (ARF), but knowledge is lacking on the development of endotheliopathy over time in ARF. We, therefore, aimed to evaluate the prognostic significance of trajectories of endotheliopathy during the first days of ARF. We performed a secondary, exploratory analysis of a single-center prospective cohort including 459 patients requiring mechanical ventilation. Based on Days 1–3 Syndecan-1, soluble Thrombomodulin (sTM), and Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), we divided patients into subgroups using latent class mixed modeling and correlated subgroups with clinical outcomes using Cox regression. Based on Syndecan-1 and sTM, respectively, we identified two subgroups. Based on PECAM-1, we identified three subgroups. Subgroups based on Syndecan-1 and sTM were identifiable from the baseline levels, but subgroups based on PECAM-1 were not. Patients with persistently high levels of both sTM and PECAM-1 were liberated from mechanical ventilation more slowly (Group high vs. Group low, sTM: hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.50–0.88, p =.01, PECAM-1: HR: 0.59, 95% CI: 0.37–0.93, p =.02) and had higher 30-day mortality (sTM: HR: 1.90, 95% CI: 1.20–3.01, p =.01, PECAM-1: HR: 4.25, 95% CI: 1.99–9.07, p <.01). In ARF requiring mechanical ventilation, patients in subgroups with persistently high levels of sTM and PECAM-1 had lower rates of liberation from mechanical ventilation and higher 30-day mortality. However, patients with persistently high levels of sTM were identifiable based on the baseline level, and only the trajectory of PECAM-1 added information to that of the baseline level.

AB - Baseline levels of endotheliopathy are associated with worse respiratory outcomes and mortality in undifferentiated acute respiratory failure (ARF), but knowledge is lacking on the development of endotheliopathy over time in ARF. We, therefore, aimed to evaluate the prognostic significance of trajectories of endotheliopathy during the first days of ARF. We performed a secondary, exploratory analysis of a single-center prospective cohort including 459 patients requiring mechanical ventilation. Based on Days 1–3 Syndecan-1, soluble Thrombomodulin (sTM), and Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1), we divided patients into subgroups using latent class mixed modeling and correlated subgroups with clinical outcomes using Cox regression. Based on Syndecan-1 and sTM, respectively, we identified two subgroups. Based on PECAM-1, we identified three subgroups. Subgroups based on Syndecan-1 and sTM were identifiable from the baseline levels, but subgroups based on PECAM-1 were not. Patients with persistently high levels of both sTM and PECAM-1 were liberated from mechanical ventilation more slowly (Group high vs. Group low, sTM: hazard ratio [HR]: 0.66, 95% confidence interval [CI]: 0.50–0.88, p =.01, PECAM-1: HR: 0.59, 95% CI: 0.37–0.93, p =.02) and had higher 30-day mortality (sTM: HR: 1.90, 95% CI: 1.20–3.01, p =.01, PECAM-1: HR: 4.25, 95% CI: 1.99–9.07, p <.01). In ARF requiring mechanical ventilation, patients in subgroups with persistently high levels of sTM and PECAM-1 had lower rates of liberation from mechanical ventilation and higher 30-day mortality. However, patients with persistently high levels of sTM were identifiable based on the baseline level, and only the trajectory of PECAM-1 added information to that of the baseline level.

KW - endothelium

KW - observational study

KW - Platelet Endothelial Cell Adhesion Molecule-1

KW - respiratory insufficiency/physiopathology

KW - Syndecan-1

KW - Thrombomodulin

KW - vascular

U2 - 10.1111/aas.14246

DO - 10.1111/aas.14246

M3 - Journal article

C2 - 37042167

AN - SCOPUS:85152803169

VL - 67

SP - 896

EP - 908

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

SN - 0001-5172

IS - 7

ER -