학술논문
Inflammation, endothelial injury, and the acute respiratory distress syndrome after out-of-hospital cardiac arrest.
Document Type
Academic Journal
Author
Katsandres SC; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, United States.; Hall J; Department of Emergency Medicine, University of Washington, Seattle, WA, United States.; Danielson K; Airlift Northwest, University of Washington, Seattle, WA, United States.; Sakr S; Division of Pulmonary, Critical Care, and Sleep Medicine, Harborview Medical Center, University of Washington, Seattle, WA, United States.; Dean SG; Division of Pulmonary, Critical Care, and Sleep Medicine, Harborview Medical Center, University of Washington, Seattle, WA, United States.; Carlbom DJ; Division of Pulmonary, Critical Care, and Sleep Medicine, Harborview Medical Center, University of Washington, Seattle, WA, United States.; Wurfel MM; Division of Pulmonary, Critical Care, and Sleep Medicine, Harborview Medical Center, University of Washington, Seattle, WA, United States.; Bhatraju PK; Division of Pulmonary, Critical Care, and Sleep Medicine, Harborview Medical Center, University of Washington, Seattle, WA, United States.; Hippensteel JA; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado, Denver, CO, United States.; Schmidt EP; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, United States.; Oshima K; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, United States.; Counts CR; Department of Emergency Medicine, University of Washington, Seattle, WA, United States.; Seattle Fire Department, Seattle, WA, United States.; Sayre MR; Department of Emergency Medicine, University of Washington, Seattle, WA, United States.; Seattle Fire Department, Seattle, WA, United States.; Henning DJ; Providence Swedish Health Alliance, Seattle, WA, United States.; Johnson NJ; Department of Emergency Medicine, University of Washington, Seattle, WA, United States.; Division of Pulmonary, Critical Care, and Sleep Medicine, Harborview Medical Center, University of Washington, Seattle, WA, United States.
Source
Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101774410 Publication Model: eCollection Cited Medium: Internet ISSN: 2666-5204 (Electronic) Linking ISSN: 26665204 NLM ISO Abbreviation: Resusc Plus Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Background: Acute respiratory distress syndrome (ARDS) is often seen in patients resuscitated from out-of-hospital cardiac arrest (OHCA). We aim to test whether inflammatory or endothelial injury markers are associated with the development of ARDS in patients hospitalized after OHCA.
Methods: We conducted a prospective, cohort, pilot study at an urban academic medical center in 2019 that included a convenience sample of adults with non-traumatic OHCA. Blood and pulmonary edema fluid (PEF) were collected within 12 hours of hospital arrival. Samples were assayed for cytokines (interleukin [IL]-1, tumor necrosis factor-α [TNF-α], tumor necrosis factor receptor1 [TNFR1], IL-6), epithelial injury markers (pulmonary surfactant-associated protein D), endothelial injury markers (Angiopoietin-2 [Ang-2] and glycocalyx degradation products), and other proteins (matrix metallopeptidase-9 and myeloperoxidase). Patients were followed for 7 days for development of ARDS, as adjudicated by 3 blinded reviewers, and through hospital discharge for mortality and neurological outcome. We examined associations between biomarker concentrations and ARDS, hospital mortality, and neurological outcome using multivariable logistic regression. Latent phase analysis was used to identify distinct biological classes associated with outcomes.
Results: 41 patients were enrolled. Mean age was 58 years, 29% were female, and 22% had a respiratory etiology for cardiac arrest. Seven patients (17%) developed ARDS within 7 days. There were no significant associations between individual biomarkers and development of ARDS in adjusted analyses, nor survival or neurologic status after adjusting for use of targeted temperature management (TTM) and initial cardiac arrest rhythm. Elevated Ang-2 and TNFR-1 were associated with decreased survival (RR = 0.6, 95% CI = 0.3-1.0; RR = 0.5, 95% CI = 0.3-0.9; respectively), and poor neurologic status at discharge (RR = 0.4, 95% CI = 0.2-0.8; RR = 0.4, 95% CI = 0.2-0.9) in unadjusted associations.
Conclusion: OHCA patients have markedly elevated plasma and pulmonary edema fluid biomarker concentrations, indicating widespread inflammation, epithelial injury, and endothelial activation. Biomarker concentrations were not associated with ARDS development, though several distinct biological phenotypes warrant further exploration. Latent phase analysis demonstrated that patients with low biomarker levels aside from TNF-α and TNFR-1 (Class 2) fared worse than other patients. Future research may benefit from considering other tools to predict and prevent development of ARDS in this population.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2024 The Author(s).)
Methods: We conducted a prospective, cohort, pilot study at an urban academic medical center in 2019 that included a convenience sample of adults with non-traumatic OHCA. Blood and pulmonary edema fluid (PEF) were collected within 12 hours of hospital arrival. Samples were assayed for cytokines (interleukin [IL]-1, tumor necrosis factor-α [TNF-α], tumor necrosis factor receptor1 [TNFR1], IL-6), epithelial injury markers (pulmonary surfactant-associated protein D), endothelial injury markers (Angiopoietin-2 [Ang-2] and glycocalyx degradation products), and other proteins (matrix metallopeptidase-9 and myeloperoxidase). Patients were followed for 7 days for development of ARDS, as adjudicated by 3 blinded reviewers, and through hospital discharge for mortality and neurological outcome. We examined associations between biomarker concentrations and ARDS, hospital mortality, and neurological outcome using multivariable logistic regression. Latent phase analysis was used to identify distinct biological classes associated with outcomes.
Results: 41 patients were enrolled. Mean age was 58 years, 29% were female, and 22% had a respiratory etiology for cardiac arrest. Seven patients (17%) developed ARDS within 7 days. There were no significant associations between individual biomarkers and development of ARDS in adjusted analyses, nor survival or neurologic status after adjusting for use of targeted temperature management (TTM) and initial cardiac arrest rhythm. Elevated Ang-2 and TNFR-1 were associated with decreased survival (RR = 0.6, 95% CI = 0.3-1.0; RR = 0.5, 95% CI = 0.3-0.9; respectively), and poor neurologic status at discharge (RR = 0.4, 95% CI = 0.2-0.8; RR = 0.4, 95% CI = 0.2-0.9) in unadjusted associations.
Conclusion: OHCA patients have markedly elevated plasma and pulmonary edema fluid biomarker concentrations, indicating widespread inflammation, epithelial injury, and endothelial activation. Biomarker concentrations were not associated with ARDS development, though several distinct biological phenotypes warrant further exploration. Latent phase analysis demonstrated that patients with low biomarker levels aside from TNF-α and TNFR-1 (Class 2) fared worse than other patients. Future research may benefit from considering other tools to predict and prevent development of ARDS in this population.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2024 The Author(s).)