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Acute Respiratory Distress Syndrome (ARDS)

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 30041

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Prof. Dr. Christian Putensen

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Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany
Interests: positive-pressure respiration; Sepsis (Diptera); septic shock; ventilator-induced lung injury; adult respiratory distress syndrome; artificial ventilation; critical illness; cardiovascular collapse; intracerebral hemorrhage; stroke; extracorporeal membrane oxygenation; cardiopulmonary resuscitation (CPR); pulmonary inflammation

Prof. Dr. Paolo Pelosi

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Guest Editor

1. Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy
2. Anesthesia and Critical Care, San Martino Policlinico Hospital, IRCCS for Oncology and Neurosciences, 16132 Genoa, Italy
Interests: intensive care medicine; perioperative care; anesthesiology; critical care medicine; mechanical ventilation; ARDS; personalized medicine
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Dear Colleagues,

The acute respiratory distress syndrome (ARDS) is a syndrome characterized by severe inflammatory damage to the alveolar–capillary membrane, which leads to high-permeability edema, resulting in a substantial loss of aerated lung tissue which is clinically characterized by bilateral radiographic opacities and severe hypoxemia. Despite progress in understanding the pathophysiologic mechanisms, there are no pharmacological treatments proven to improve outcome other than supportive care with lung-protective mechanical ventilatory strategies. Recent research demonstrates the heterogeneity of ARDS in respect to etiology, timing, lung function and morphology, and pathophysiological mechanisms. Better understanding of these heterogeneities and taking into consideration the different ARDS phenotypes and/or genotypes, allied to recent advances in technology, may allow for improved characterization of individual pathophysiology and targeted more individualized treatment. The aim of this Special Issue is to present clinical and experimental scientific reports that improve our understanding of ARDS and provide information to improve “personalized” or “individualized” pharmacological and ventilator therapies in ARDS patients.

Prof. Dr. Christian Putensen
Dr. Paolo Pelosi
Guest Editors

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Keywords

acute respiratory distress syndrome
mechanical ventilation
lung physiology
lung imaging
pharmacological therapies
long-term outcome

Published Papers (10 papers)

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Research

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14 pages, 2197 KiB

Open AccessArticle

Study to Explore the Association of the Renin-Angiotensin System and Right Ventricular Function in Mechanically Ventilated Patients

by Armand Mekontso Dessap, Kate Hanrott, William M. Powley, Andrew Fowler, Andrew Bayliffe, François Bagate, David A. Hall, Aili L. Lazaar, David C. Budd and Antoine Vieillard-Baron

J. Clin. Med. 2022, 11(15), 4362; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm11154362 - 27 Jul 2022

Viewed by 1091

Abstract

Background: Right ventricular (RV) dysfunction is associated with pulmonary vasoconstriction in mechanically ventilated patients. Enhancing the activity of angiotensin-converting enzyme 2 (ACE2), a key enzyme of the renin-angiotensin system (RAS), using recombinant human ACE2 (rhACE2) could alleviate RAS-mediated vasoconstriction and vascular remodeling. Methods: This prospective observational study investigated the association between concentrations of RAS peptides (Ang II or Ang(1–7)) and markers of RV function, as assessed by echocardiography (ratio of RV to left ventricular end-diastolic area, interventricular septal motion, and pulmonary arterial systolic pressure (PASP)). Results: Fifty-seven mechanically ventilated patients were enrolled. Incidence rates of acute cor pulmonale (ACP) and pulmonary circulatory dysfunction (PCD) were consistent with previous studies. In the 45 evaluable participants, no notable or consistent changes in RAS peptides concentration were observed over the observation period, and there was no correlation between Ang II concentration and either PASP or RV size. The model of the predicted posterior distributions for the pre- and post-dose values of Ang II demonstrated no change in the likelihood of PCD after hypothetical dosing with rhACE2, thus meeting the futility criteria. Similar results were observed with the other RAS peptides evaluated. Conclusions: Pre-defined success criteria for an association between PCD and the plasma RAS peptides were not met in the mechanically ventilated unselected patients. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS))

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11 pages, 1043 KiB

Open AccessArticle

Outcomes of Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome in COVID-19 Patients: A Propensity-Matched Analysis

by Teresa Autschbach, Nima Hatam, Koray Durak, Oliver Grottke, Michael Dreher, Katharina Nubbemeyer, Rolf Rossaint, Gernot Marx, Nikolaus Marx, Jan Spillner, Rashad Zayat, Sebastian Kalverkamp and Alex Kersten

J. Clin. Med. 2021, 10(12), 2547; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10122547 - 09 Jun 2021

Cited by 8 | Viewed by 2801

Abstract

It remains unclear to what extent the outcomes and complications of extracorporeal membrane oxygenation (ECMO) therapy in COVID-19 patients with acute respiratory distress syndrome (ARDS) differ from non-COVID-19 ARDS patients. In an observational, propensity-matched study, outcomes after ECMO support were compared between 19 COVID-19 patients suffering from ARDS (COVID group) and 34 matched non-COVID-19 ARDS patients (NCOVID group) from our historical cohort. A 1:2 propensity matching was performed based on respiratory ECMO survival prediction (RESP) score, age, gender, bilirubin, and creatinine levels. Patients’ characteristics, laboratory parameters, adverse events, and 90-day survival were analyzed. Patients’ characteristics in COVID and NCOVID groups were similar. Before ECMO initiation, fibrinogen levels were significantly higher in the COVID group (median: 493 vs. 364 mg/dL, p < 0.001). Median ECMO support duration was similar (16 vs. 13 days, p = 0.714, respectively). During ECMO therapy, patients in the COVID group developed significantly more thromboembolic events (TEE) than did those in the NCOVID group (42% vs. 12%, p = 0.031), which were mainly pulmonary artery embolism (PAE) (26% vs. 0%, p = 0.008). The rate of major bleeding events (42% vs. 62%, p = 0.263) was similar. Fibrinogen decreased significantly more in the COVID group than in the NCOVID group (p < 0.001), whereas D-dimer increased in the COVID group (p = 0.011). Additionally, 90-day mortality did not differ (47% vs. 74%; p = 0.064) between COVID and NCOVID groups. Compared with that in non-COVID-19 ARDS patients, ECMO support in COVID-19 patients was associated with comparable in-hospital mortality and similar bleeding rates but a higher incidence of TEE, especially PAE. In contrast, coagulation parameters differed between COVID and NCOVID patients. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS))

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11 pages, 817 KiB

Open AccessArticle

Prognostic Factors to Predict ICU Mortality in Patients with Severe ARDS Who Received Early and Prolonged Prone Positioning Therapy

by Po-Hsin Lee, Chen-Tsung Kuo, Chiann-Yi Hsu, Shih-Pin Lin and Pin-Kuei Fu

J. Clin. Med. 2021, 10(11), 2323; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10112323 - 26 May 2021

Cited by 3 | Viewed by 2256

Abstract

Early and prolonged prone positioning (PP) therapy improve survival in advanced ARDS; however, the predictors of mortality remain unclear. The study aims to identify predictive factors correlated with mortality and build-up the prognostic score in patients with severe ARDS who received early and prolonged PP therapy. A total of 116 patients were enrolled in this retrospective cohort study. Univariate and multivariate regression models were used to estimate the odds ratio (OR) of mortality. Factors associated with mortality were assessed by Cox regression analysis and presented as the hazard ratio (HR) and 95% CI. In the multivariate regression model, renal replacement therapy (RRT; OR: 4.05, 1.54–10.67), malignant comorbidity (OR: 8.86, 2.22–35.41), and non-influenza-related ARDS (OR: 5.17, 1.16–23.16) were significantly associated with ICU mortality. Age, RRT, non-influenza-related ARDS, malignant comorbidity, and APACHE II score were included in a composite prone score, which demonstrated an area under the curve of 0.816 for predicting mortality risk. In multivariable Cox proportional hazard model, prone score more than 3 points was significantly associated with ICU mortality (HR: 2.13, 1.12–4.07, p = 0.021). We suggest prone score ≥3 points could be a good predictor for mortality in severe ARDS received PP therapy. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS))

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12 pages, 858 KiB

Open AccessArticle

Renal Replacement Therapy in Patients with Influenza Pneumonia Related Acute Respiratory Distress Syndrome

by Ko-Wei Chang, Shaw-Woei Leu, Shih-Wei Lin, Shinn-Jye Liang, Kuang-Yao Yang, Ming-Cheng Chan, Wei-Chih Chen, Han-Chung Hu, Wen-Feng Fang, Yu-Mu Chen, Chau-Chyun Sheu, Ming-Ju Tsai, Hao-Chien Wang, Ying-Chun Chien, Chung-Kan Peng, Chieh-Liang Wu, Kuo-Chin Kao and TSIRC (Taiwan Severe Influenza Research Consortium)

J. Clin. Med. 2021, 10(9), 1837; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10091837 - 23 Apr 2021

Cited by 1 | Viewed by 1853

Abstract

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) increases the mortality of acute respiratory distress syndrome (ARDS) patients. The aim of this study was to investigate the outcomes and predictors of RRT in patients with influenza pneumonia-related ARDS. This retrospective cohort study includes patients from eight tertiary referral centers in Taiwan between January and March 2016, and all 282 patients with influenza pneumonia-related ARDS were enrolled. Thirty-four patients suffered from AKI requiring RRT, while 16 patients had underlying end stage renal disease (ESRD). The 30- and 60-day mortality rates were significantly higher in patients with AKI requiring RRT compared with those not requiring RRT (50.0% vs. 19.8%, p value < 0.001; 58.8% vs. 27.2%, p value = 0.001, respectively), but the patients with ESRD had no significant difference in mortality (12.5% vs. 19.8%, p value = 0.744; 31.3% vs. 27.2%, p value = 0.773, respectively). The predictors for AKI requiring RRT included underlying chronic liver disease and C-reactive protein. The mortality predictors for patients with AKI requiring RRT included the pneumonia severity index, tidal volume, and continuous renal replacement therapy. In this study, patients with influenza pneumonia-related ARDS with AKI requiring RRT had significantly higher mortality compared with other patients. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS))

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8 pages, 847 KiB

Open AccessArticle

SP-D Serum Levels Reveal Distinct Epithelial Damage in Direct Human ARDS

by Konrad Peukert, Benjamin Seeliger, Mario Fox, Caroline Feuerborn, Andrea Sauer, Patrick Schuss, Matthias Schneider, Sascha David, Tobias Welte, Christian Putensen, Christoph Wilhelm, Folkert Steinhagen and Christian Bode

J. Clin. Med. 2021, 10(4), 737; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10040737 - 12 Feb 2021

Cited by 9 | Viewed by 2179

Abstract

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome with multiple underlying diseases. Particularly epithelial damage results from direct (e.g., pneumonia) rather than indirect lung injury (e.g., nonpulmonary sepsis), which is more likely associated with endothelial damage. Hence, targeting ARDS patients based on their molecular phenotypes is a promising approach to improve outcome. With regard to distinct inflammatory responses and subsequent lung damage in direct ARDS due to the causing pathogen, we quantified markers of epithelial and endothelial damage and pro-inflammatory cytokines in patients with ARDS triggered by bacterial, viral, and atypical pathogen pneumonia or indirect ARDS. The serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8), lung epithelial injury markers surfactant protein D (SP-D), and soluble receptor for advanced glycation end-products (sRAGE) as well as endothelial injury marker angiopoietin-2 (Ang-2) from 49 patients with distinct types of ARDS were analyzed by multiplex immunoassay. Epithelial damage marker SP-D was significantly higher in direct ARDS caused by viral and atypical pathogens in contrast to ARDS caused by typical bacterial pneumonia and nonpulmonary sepsis. In contrast, sRAGE levels did not differ due to the causing pathogen. Patients with atypical pathogen pneumonia related ARDS showed significantly lower Ang-2 levels compared to patients with viral and indirect ARDS. Patients with viral and atypical pneumonia related ARDS possessed significantly lower serum IL-6 levels compared to bacterial pneumonia related ARDS and IL-6 levels in atypical pneumonia related ARDS were significantly lower than in indirect ARDS. Current findings report a potential difference in ARDS biomarkers due to the underlying disease and pathogen. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS))

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13 pages, 861 KiB

Open AccessArticle

Impact of Different Positive End-Expiratory Pressures on Lung Mechanics in the Setting of Moderately Elevated Intra-Abdominal Pressure and Acute Lung Injury in a Porcine Model

by Mascha O. Fiedler, Emilis Simeliunas, B. Luise Deutsch, Dovile Diktanaite, Alexander Harms, Maik Brune, Maximilian Dietrich, Florian Uhle, Markus A. Weigand and Armin Kalenka

J. Clin. Med. 2021, 10(2), 306; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10020306 - 15 Jan 2021

Cited by 2 | Viewed by 1717

Abstract

The effects of a moderately elevated intra-abdominal pressure (IAP) on lung mechanics in acute respiratory distress syndrome (ARDS) have still not been fully analyzed. Moreover, the optimal positive end-expiratory pressure (PEEP) in elevated IAP and ARDS is unclear. In this paper, 18 pigs under general anesthesia received a double hit lung injury. After saline lung lavage and 2 h of injurious mechanical ventilation to induce an acute lung injury (ALI), an intra-abdominal balloon was filled until an IAP of 10 mmHg was generated. Animals were randomly assigned to one of three groups (group A = PEEP 5, B = PEEP 10 and C = PEEP 15 cmH₂O) and ventilated for 6 h. We measured end-expiratory lung volume (EELV) per kg bodyweight, driving pressure (ΔP), transpulmonary pressure (ΔP_L), static lung compliance (C_stat), oxygenation (P/F ratio) and cardiac index (CI). In group A, we found increases in ΔP (22 ± 1 vs. 28 ± 2 cmH₂O; p = 0.006) and ΔP_L (16 ± 1 vs. 22 ± 2 cmH₂O; p = 0.007), with no change in EELV/kg (15 ± 1 vs. 14 ± 1 mL/kg) when comparing hours 0 and 6. In group B, there was no change in ΔP (26 ± 2 vs. 25 ± 2 cmH₂O), ΔP_L (19 ± 2 vs. 18 ± 2 cmH₂O), C_stat (21 ± 3 vs. 21 ± 2 cmH₂O/mL) or EELV/kg (12 ± 2 vs. 13 ± 3 mL/kg). ΔP and ΔP_L were significantly lower after 6 h when comparing between group C and A (21 ± 1 vs. 28 ± 2 cmH₂O; p = 0.020) and (14 ± 1 vs. 22 ± 2 cmH₂O; p = 0.013)). The EELV/kg increased over time in group C (13 ± 1 vs. 19 ± 2 mL/kg; p = 0.034). The P/F ratio increased in all groups over time. CI decreased in groups B and C. The global lung injury score did not significantly differ between groups (A: 0.25 ± 0.05, B: 0.21 ± 0.02, C: 0.22 ± 0.03). In this model of ALI, elevated IAP, ΔP and ΔP_L increased further over time in the group with a PEEP of 5 cmH₂O applied over 6 h. This was not the case in the groups with a PEEP of 10 and 15 cmH₂O. Although ΔP and ΔP_L were significantly lower after 6 hours in group C compared to group A, we could not show significant differences in histological lung injury score. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS))

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11 pages, 635 KiB

Open AccessArticle

Characteristics and Outcomes in Patients with Ventilator-Associated Pneumonia Who Do or Do Not Develop Acute Respiratory Distress Syndrome. An Observational Study

by Enric Barbeta, Adrian Ceccato, Antoni Artigas, Miquel Ferrer, Laia Fernández, Rubén López, Leticia Bueno, Anna Motos, Gianluigi Li Bassi, Ricard Mellado, Carlos Ferrando, Andrea Catalina Palomeque, Mauro Panigada, Albert Gabarrús, Diego de Mendoza and Antoni Torres

J. Clin. Med. 2020, 9(11), 3508; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9113508 - 29 Oct 2020

Cited by 2 | Viewed by 2051

Abstract

Ventilator-associated pneumonia (VAP) is a well-known complication of patients on invasive mechanical ventilation. The main cause of acute respiratory distress syndrome (ARDS) is pneumonia. ARDS can occur in patients with community-acquired or nosocomial pneumonia. Data regarding ARDS incidence, related pathogens, and specific outcomes in patients with VAP is limited. This is a cohort study in which patients with VAP were evaluated in an 800-bed tertiary teaching hospital between 2004 and 2016. Clinical outcomes, microbiological and epidemiological data were assessed among those who developed ARDS and those who did not. Forty-one (13.6%) out of 301 VAP patients developed ARDS. Patients who developed ARDS were younger and presented with higher prevalence of chronic liver disease. Pseudomonas aeruginosa was the most frequently isolated pathogen, but without any difference between groups. Appropriate empirical antibiotic treatment was prescribed to ARDS patients as frequently as to those without ARDS. Ninety-day mortality did not significantly vary among patients with or without ARDS. Additionally, patients with ARDS did not have significantly higher intensive care unit (ICU) and 28-day mortality, ICU, and hospital length of stay, ventilation-free days, and duration of mechanical ventilation. In summary, ARDS deriving from VAP occurs in 13.6% of patients. Although significant differences in clinical outcomes were not observed between both groups, further studies with a higher number of patients are needed due to the possibility of the study being underpowered. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS))

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13 pages, 1505 KiB

Open AccessArticle

Prospective Observational Study to Evaluate the Effect of Different Levels of Positive End-Expiratory Pressure on Lung Mechanics in Patients with and without Acute Respiratory Distress Syndrome

by Mascha O. Fiedler, Dovile Diktanaite, Emilis Simeliunas, Maximilian Pilz and Armin Kalenka

J. Clin. Med. 2020, 9(8), 2446; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm9082446 - 31 Jul 2020

Cited by 3 | Viewed by 2187

Abstract

Background: The optimal level of positive end-expiratory pressure is still under debate. There are scare data examining the association of PEEP with transpulmonary pressure (TPP), end-expiratory lung volume (EELV) and intraabdominal pressure in ventilated patients with and without ARDS. Methods: We analyzed lung mechanics in 3 patient groups: group A, patients with ARDS; group B, obese patients (body mass index (BMI) > 30 kg/m²) and group C, a control group. Three levels of PEEP (5, 10, 15 cm H₂O) were used to investigate the consequences for lung mechanics. Results: Fifty patients were included, 22 in group A, 18 in group B (BMI 38 ± 2 kg/m²) and 10 in group C. At baseline, oxygenation showed no differences between the groups. Driving pressure (ΔP) and transpulmonary pressure (ΔP_L) was higher in group B than in groups A and C at a PEEP of 5 cm H₂O (ΔP A: 15 ± 1, B: 18 ± 1, C: 14 ± 1 cm H₂O; ΔP_L A: 10 ± 1, B: 13 ± 1, C: 9 ± 0 cm H₂O). Peak inspiratory pressure (P_insp) rose in all groups as PEEP increased, but the resulting driving pressure and transpulmonary pressure were reduced, whereas EELV increased. Conclusion: Measuring EELV or TPP allows a personalized approach to lung-protective ventilation. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS))

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Review

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16 pages, 1057 KiB

Open AccessReview

Mechanical Ventilation during Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome: A Narrative Review

by Li-Chung Chiu and Kuo-Chin Kao

J. Clin. Med. 2021, 10(21), 4953; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10214953 - 26 Oct 2021

Cited by 8 | Viewed by 5592

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening condition involving acute hypoxemic respiratory failure. Mechanical ventilation remains the cornerstone of management for ARDS; however, potentially injurious mechanical forces introduce the risk of ventilator-induced lung injury, multiple organ failure, and death. Extracorporeal membrane oxygenation (ECMO) is a salvage therapy aimed at ensuring adequate gas exchange for patients suffering from severe ARDS with profound hypoxemia where conventional mechanical ventilation has failed. ECMO allows for lower tidal volumes and airway pressures, which can reduce the risk of further lung injury, and allow the lungs to rest. However, the collateral effect of ECMO should be considered. Recent studies have reported correlations between mechanical ventilator settings during ECMO and mortality. In many cases, mechanical ventilation settings should be tailored to the individual; however, researchers have yet to establish optimal ventilator settings or determine the degree to which ventilation load can be decreased. This paper presents an overview of previous studies and clinical trials pertaining to the management of mechanical ventilation during ECMO for patients with severe ARDS, with a focus on clinical findings, suggestions, protocols, guidelines, and expert opinions. We also identified a number of issues that have yet to be adequately addressed. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS))

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13 pages, 1855 KiB

Open AccessReview

Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review

by Chiara Robba, Denise Battaglini, Lorenzo Ball, Alberto Valbusa, Italo Porto, Roberta Della Bona, Giovanni La Malfa, Nicolò Patroniti, Iole Brunetti, Maurizio Loconte, Matteo Bassetti, Daniele R. Giacobbe, Antonio Vena, Claudia Lucia M. Silva, Patricia R. M. Rocco and Paolo Pelosi

J. Clin. Med. 2021, 10(1), 140; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10010140 - 03 Jan 2021

Cited by 25 | Viewed by 6526

Abstract

In critically ill patients with acute respiratory distress syndrome (ARDS) coronavirus disease 2019 (COVID-19), a high incidence of thromboembolic and hemorrhagic events is reported. COVID-19 may lead to impairment of the coagulation cascade, with an imbalance in platelet function and the regulatory mechanisms of coagulation and fibrinolysis. Clinical manifestations vary from a rise in laboratory markers and subclinical microthrombi to thromboembolic events, bleeding, and disseminated intravascular coagulation. After an inflammatory trigger, the mechanism for activation of the coagulation cascade in COVID-19 is the tissue factor pathway, which causes endotoxin and tumor necrosis factor-mediated production of interleukins and platelet activation. The consequent massive infiltration of activated platelets may be responsible for inflammatory infiltrates in the endothelial space, as well as thrombocytopenia. The variety of clinical presentations of the coagulopathy confronts the clinician with the difficult questions of whether and how to provide optimal supportive care. In addition to coagulation tests, advanced laboratory tests such as protein C, protein S, antithrombin, tissue factor pathway inhibitors, D-dimers, activated factor Xa, and quantification of specific coagulation factors can be useful, as can thromboelastography or thromboelastometry. Treatment should be tailored, focusing on the estimated risk of bleeding and thrombosis. The aim of this review is to explore the pathophysiology and clinical evidence of coagulation disorders in severe ARDS-related COVID-19 patients. Full article

(This article belongs to the Special Issue Acute Respiratory Distress Syndrome (ARDS))

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