Abstract 15010: Myocardial Injury in Sepsis With Acute Respiratory Distress Syndrome

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Eunice S Dugan ◽  
Robert S Stephens ◽  
Steven P Schulman ◽  
Thomas S Metkus

Introduction: Sepsis is common and associated with high morbidity and mortality; novel prognostic biomarkers are needed. The association of myocardial injury with mortality in sepsis has not been fully characterized. Hypothesis: We hypothesized that elevated plasma high-sensitivity troponin I (hs-TnI) would be associated with 60-day mortality in patients with sepsis and acute respiratory distress syndrome (ARDS). Methods: We conducted a retrospective multicenter cohort study of subjects from the MI-ARDS study with ARDS and sepsis. The exposure variable was plasma hs-TnI on intubation (Day 0) and Day 3. Hs-TnI was measured using Abbott Laboratories’ ARCHITECT STAT assay. Patients were divided into four hs-TnI (ng/L) groups (Grp): GrpA: <2 (undetectable), GrpB: ≥2-<26 (<99 th percentile of population), GrpC: ≥26-<130 (<5 times upper limit of normal [ULN]), GrpD: ≥130 (>5 times ULN). The primary outcome was 60-day mortality. We determined the association between hs-TnI and mortality using Cox proportional hazards models. Results: Of 320 subjects, there were 15 (4%) in GrpA, 97 (30%) in GrpB, 88 (28%) in GrpC, and 120 (38%) in GrpD. Mean age was 50 years and 172 subjects (54%) required vasopressors. Higher plasma levels of hs-TnI were associated with higher SOFA score and creatinine, and more vasopressor use. Overall mortality was 33%. There was no significant difference in 60-day survival between clinical categories of Day 0 hs-TnI (Fig 1-A). Rising troponin between Day 0 and Day 3 was associated with a higher risk of mortality after adjusting for age, sex, trial assignment, and SOFA score (HR: 1.75, CI: 1.11-2.77, p=0.02) (Fig 1-B), and additionally adjusting for Day 0 hs-TnI (HR: 1.72, CI: 1.03-2.85, p=0.04). Conclusions: Initial hs-TnI in patients with sepsis and ARDS was not associated with mortality. Increase in hs-TnI of at least 20% by Day 3 was associated with 60-day mortality. Future studies should assess mechanism and treatment of myocardial injury in sepsis.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yiyu He ◽  
Xiaoxin Zheng ◽  
Xiaoyan Li ◽  
Xuejun Jiang

AbstractCardiac injury among patients with COVID-19 has been reported and is associated with a high risk of mortality, but cardiac injury may not be the leading factor related to death. The factors related to poor prognosis among COVID-19 patients with myocardial injury are still unclear. This study aimed to explore the potential key factors leading to in-hospital death among COVID-19 patients with cardiac injury. This retrospective single-center study was conducted at Renmin Hospital of Wuhan University, from January 20, 2020 to April 10, 2020, in Wuhan, China. All inpatients with confirmed COVID-19 (≥ 18 years old) and cardiac injury who had died or were discharged by April 10, 2020 were included. Demographic data and clinical and laboratory findings were collected and compared between survivors and nonsurvivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with mortality in COVID-19 patients with cardiac injury. A total of 173 COVID-19 patients with cardiac injury were included in this study, 86 were discharged and 87 died in the hospital. Multivariable regression showed increased odds of in-hospital death were associated with advanced age (odds ratio 1.12, 95% CI 1.05–1.18, per year increase; p < 0.001), coagulopathy (2.54, 1.26–5.12; p = 0·009), acute respiratory distress syndrome (16.56, 6.66–41.2; p < 0.001), and elevated hypersensitive troponin I (4.54, 1.79–11.48; p = 0.001). A high risk of in-hospital death was observed among COVID-19 patients with cardiac injury in this study. The factors related to death include advanced age, coagulopathy, acute respiratory distress syndrome and elevated levels of hypersensitive troponin I.


2020 ◽  
pp. 088506662094404
Author(s):  
Shubhi Kaushik ◽  
Sindy Villacres ◽  
Ruth Eisenberg ◽  
Shivanand S. Medar

Objectives: To describe the incidence of and risk factors for acute kidney injury (AKI) in children with acute respiratory distress syndrome (ARDS) and study the effect of AKI on patient outcomes. Design: A single-center retrospective study. Setting: A tertiary care children’s hospital. Patients: All patients less than 18 years of age who received invasive mechanical ventilation (MV) and developed ARDS between July 2010 and July 2013 were included. Acute kidney injury was defined using p-RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria. Interventions: None. Measurements and Main Results: One hundred fifteen children met the criteria and were included in the study. Seventy-four children (74/115, 64%) developed AKI. The severity of AKI was risk in 34 (46%) of 74, injury in 19 (26%) of 74, and failure in 21 (28%) of 74. The presence of AKI was associated with lower Pao 2 to Fio 2 (P/F) ratio ( P = .007), need for inotropes ( P = .003), need for diuretics ( P = .004), higher oxygenation index ( P = .03), higher positive end-expiratory pressure (PEEP; P = .01), higher mean airway pressure ( P = .008), and higher Fio 2 requirement ( P = .03). Only PEEP and P/F ratios were significantly associated with AKI in the unadjusted logistic regression model. Patients with AKI had a significantly longer duration of hospital stay, although there was no significant difference in the intensive care unit stay, duration of MV, and mortality. Recovery of AKI occurred in 68% of the patients. A multivariable model including PEEP, P/F ratio, weight, need for inotropes, and need for diuretics had a better receiver operating characteristic (ROC) curve with an AUC of 0.75 compared to the ROC curves for PEEP only and P/F ratio only for the prediction of AKI. Conclusions: Patients with ARDS have high rates of AKI, and its presence is associated with increased morbidity and mortality.


Biomeditsina ◽  
2021 ◽  
Vol 17 (3E) ◽  
pp. 17-22
Author(s):  
O. V. Alimkina ◽  
A. E. Petrenko

The work is devoted to the study of changes in the cellular composition of bronchoalveolar lavage over time in the modeling of acute respiratory distress syndrome (ARDS) in mice. ARDS was modeled by administering α-galactosylceramide and a mixture of lipopolysaccharide with a complete Freud’s adjuvant. After euthanasia, bronchoalveolar lavage was taken for analysis. On this basis, changes in the total number of white blood cells, the percentage of neutrophils and macrophages were assessed. It was found that the percentage of neutrophils in the ARDS group shows a statistically significant difference from that in the intact group, starting from 3 hours after modeling ARDS. Further, a statistically significant decrease in macrophages was observed. 


2021 ◽  
pp. 2102078
Author(s):  
Jens Gottlieb ◽  
Philipp M. Lepper ◽  
Cristina Berastegui ◽  
Beatriz Montull ◽  
Alexandra Wald ◽  
...  

BackgroundThe published experience of lung transplantation (LTX) in acute respiratory distress syndrome (ARDS) is limited. The aim of this study was to investigate the contemporary results of LTX attempts in ARDS in major European centers.MethodsWe conducted a retrospective multicenter cohort study of all patients listed for LTX between 2011 and 2019. We surveyed 68 centers in 22 European countries. All patients admitted to the waitlist for lung transplantation with a diagnosis of “ARDS//pneumonia” were included. Patients without extracorporeal membrane oxygenation (ECMO) or mechanical ventilation were excluded. Patients were followed until October 1st 2020 or death. Multivariable analysis for 1-year survival after listing and lung transplantation were performed.ResultsForty-eight centers (74%) with a total transplant activity of 12 438 lung transplants during the 9-year period gave feedback. Forty patients with a median age of 35 years were identified. Patients were listed for LTX in 18 different centers in 10 countries. Thirty-one-patients underwent LTX (0·25% of all indications) and 9 patients died on the waitlist. Ninety percent of transplanted patients were on ECMO in combination with mechanical ventilation before LTX. On multivariable analysis, transplantation during 2015 until 2019 was independently associated with better 1-year survival after LTX (odds ratio 10.493, 95% CI 1.977, 55.705, p=0.006). Sixteen survivors out of 23 patients with known status (70%) returned to work after LTX.ConclusionLTX in highly selected ARDS patients is feasible and outcome has improved in the modern era. The selection process remains ethically and technically challenging.


2020 ◽  
Author(s):  
Sheng-Yuan Ruan ◽  
Chun-Ta Huang ◽  
Ying-Chun Chien ◽  
Chun-Kai Huang ◽  
Jung-Yien Chien ◽  
...  

Abstract Background: Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described.Methods: In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal-Wallis rank tests and Chi-squared tests were used to compare between-etiology differences. Results: From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia.Conclusion: This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2015 ◽  
Author(s):  
Isabel Tovar ◽  
Rosa Guerrero ◽  
Jesús J. López-Peñalver ◽  
José Expósito ◽  
José Mariano Ruiz de Almodóvar

We have previously shown that the combination of radiotherapy with human umbilical-cord-derived mesenchymal stromal/stem cells (MSCs) cell therapy significantly reduces the size of the xenotumors in mice, both in the directly irradiated tumor and in the distant nonirradiated tumor or its metastasis. We have also shown that exosomes secreted from MSCs preirradiated with 2 Gy are quantitatively, functionally and qualitatively different from the exosomes secreted from nonirradiated mesenchymal cells, and also that proteins, exosomes and microvesicles secreted by MSCs suffer a significant change when the cells are activated or nonactivated, with the amount of protein present in the exosomes of the preirradiated cells being 1.5 times greater compared to those from nonirradiated cells. This finding correlates with a dramatic increase in the antitumor activity of the radiotherapy when is combined with MSCs or with preirradiated mesenchymal stromal/stem cells (MSCs*). After the proteomic analysis of the load of the exosomes released from both irradiated and nonirradiated cells, we conclude that annexin A1 is the most important and significant difference between the exosomes released by the cells in either status. Knowing the role of annexin A1 in the control of hypoxia and inflammation that is characteristic of acute respiratory-distress syndrome (ARDS), we designed a hypothetical therapeutic strategy, based on the transplantation of mesenchymal stromal/stem cells stimulated with radiation, to alleviate the symptoms of patients who, due to pneumonia caused by SARS-CoV-2, require to be admitted to an intensive care unit for patients with life-threatening conditions. With this hypothesis, we seek to improve the patients’ respiratory capacity and increase the expectations of their cure.


Author(s):  
Declan Byrnes ◽  
Claire H. Masterson ◽  
Antonio Artigas ◽  
John G. Laffey

AbstractSepsis and acute respiratory distress syndrome (ARDS) constitute devastating conditions with high morbidity and mortality. Sepsis results from abnormal host immune response, with evidence for both pro- and anti-inflammatory activation present from the earliest phases. The “proinflammatory” response predominates initially causing host injury, with later-phase sepsis characterized by immune cell hypofunction and opportunistic superinfection. ARDS is characterized by inflammation and disruption of the alveolar-capillary membrane leading to injury and lung dysfunction. Sepsis is the most common cause of ARDS. Approximately 20% of deaths worldwide in 2017 were due to sepsis, while ARDS occurs in over 10% of all intensive care unit patients and results in a mortality of 30 to 45%. Given the fact that sepsis and ARDS share some—but not all—underlying pathophysiologic injury mechanisms, the lack of specific therapies, and their frequent coexistence in the critically ill, it makes sense to consider therapies for both conditions together. In this article, we will focus on the therapeutic potential of mesenchymal stem/stromal cells (MSCs). MSCs are available from several tissues, including bone marrow, umbilical cord, and adipose tissue. Allogeneic administration is feasible, an important advantage for acute conditions like sepsis or ARDS. They possess diverse mechanisms of action of relevance to sepsis and ARDS, including direct and indirect antibacterial actions, potent effects on the innate and adaptive response, and pro-reparative effects. MSCs can be preactivated thereby potentiating their effects, while the use of their extracellular vesicles can avoid whole cell administration. While early-phase clinical trials suggest safety, considerable challenges exist in moving forward to phase III efficacy studies, and to implementation as a therapy should they prove effective.


2016 ◽  
Vol 26 (6) ◽  
pp. 747-762 ◽  
Author(s):  
Summer Paolone

Despite advances in mechanical ventilation, severe acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality rates ranging from 26% to 58%. Extracorporeal membrane oxygenation (ECMO) is a modified cardiopulmonary bypass circuit that serves as an artificial membrane lung and blood pump to provide gas exchange and systemic perfusion for patients when their own heart and lungs are unable to function adequately. ECMO is a complex network that provides oxygenation and ventilation and allows the lungs to rest and recover from respiratory failure while minimizing iatrogenic ventilator-induced lung injury. In critical care settings, ECMO is proven to improve survival rates and outcomes in patients with severe ARDS. This review defines severe ARDS; describes the ECMO circuit; and discusses recent research, optimal use of the ECMO circuit, limitations of therapy including potential complications, economic impact, and logistical factors; and discusses future research considerations.


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