key: cord-0077931-u7hs4e18
authors: Gragossian, Alin; Siuba, Matthew T.
title: Acute Respiratory Distress Syndrome
date: 2022-05-10
journal: Emerg Med Clin North Am
DOI: 10.1016/j.emc.2022.05.002
sha: ec1d81eefb97f564fc8690c9e4d94c42f3363d74
doc_id: 77931
cord_uid: u7hs4e18

nan

Acute respiratory distress syndrome (ARDS) is characterized by inflammatory lung injury and carries a global mortality rate near 40%. 1 It occurs in approximately 6-10% of patients with respiratory failure who are admitted through the emergency department. 2, 3 Even within the context of the intensive care unit, the diagnosis is missed in up to half of all patients meeting criteria for the disease. 1 Early recognition is critical to ensure that evidence-based therapies can be implemented without delay.

The most common underlying etiologies for ARDS, by frequency, are commonly encountered in the emergency department: sepsis, pneumonia, aspiration, pancreatitis, blood transfusions, trauma, and burns. 4 While treating the underlying etiology is a cornerstone of ARDS management, there are specific diagnostic and therapeutic considerations which must be pursued as early as possible. Not only are many interventions time sensitive, but the initial care choices in the emergency department often carry over to the intensive care unit upon admission. 5 J o u r n a l P r e -p r o o f Diagnosis Criteria ARDS is currently diagnosed using the Berlin Definition (Table 1) . 6 In brief, it is characterized by an acute onset of respiratory illness (within one week) with bilateral opacities which cannot completely be explained by hydrostatic pulmonary edema, with a partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2:FiO2 ratio) of 300 millimeters of mercury or less. The current definition requires the application of at least five centimeters of water of positive airway pressure, delivered either via non-invasive positive pressure ventilation (NIV) or via invasive mechanical ventilation (IMV). Given the rise in use of high flow nasal cannula (HFNC) over the past decade, it has been proposed to include patients on HFNC in the definition, 7 though currently the Berlin criteria remains as standard ( Table 1) .

Imaging X-ray is usually sufficient chest imaging to evaluate a patient for ARDS. While chest computed tomography (CT) is not necessarily required to diagnose ARDS, it may help better characterize the pulmonary parenchyma and possibly identify an underlying etiology. Furthermore, contrasted CT scan could identify comorbid pulmonary emboli which would likely alter therapy. Small series report concurrent pulmonary emboli 17-39% of the time in patients with COVID-19 ARDS). 8, 9 A more recent development in the diagnosis of ARDS includes the use of point-of-care ultrasound (POCUS) by the bedside clinician using a combination of both lung J o u r n a l P r e -p r o o f ultrasound and echocardiography. ARDS can be detected by lung ultrasonography through the recognition of a pulmonary interstitial pattern which includes the following: B-lines with inhomogeneous and gravity-independent distribution, spared areas, pleural line thickening with decreased lung sliding, and subpleural consolidations. 10 Lung ultrasound performs reasonably well in terms of sensitivity and specificity (82.7% to 92.3% and 90.2% to 98.6%, respectively) in ARDS when compared to chest CT. 11 It also provides the ability for real-time monitoring of changes to vent settings, such as positive end expiratory pressure (PEEP) titration, 12-14 though this is not commonly utilized. Importantly, lung ultrasound would not be able to differentiate between wellaerated lung and overdistended lung, as both would result in an A-line pattern.

Focused cardiac ultrasound can also be utilized to establish the diagnosis (i.e. rule out cardiogenic pulmonary edema), as well as monitor the effect of ARDS on the right ventricle. Right ventricular dysfunction can be seen in 22-27% of patients with ARDS 15, 16 . Right heart failure due to increased pulmonary vascular resistance (acute cor pulmonale) is characterized by right ventricle dilatation and septal dyskinesia on echocardiography. 17 Moreover, a coexisting patent foramen ovale with shunt can occur in nearly 20% of patients with ARDS may be responsible for a higher rate of refractory hypoxemia and an increased number of ventilator-dependent days. 18 Discovering a shunt in the patient with ARDS may also alter therapy, whereby the pulmonary vascular resistance should be lowered as much as possible to decrease shunt fraction. Table 2 . It is important to note that this scoring system does not take work of breathing into account, and clinical assessment is needed to determine whether or not ongoing HFNC therapy is appropriate.

Non-invasive ventilation is frequently utilized in patients with ARDS, though its use remains controversial. The potential benefits include avoidance of ventilator-associated events and need for deep sedation which often come with IMV. Additionally, appropriately titrated end expiratory pressure could decrease injury related to vigorous spontaneous breathing. 22 Potential harms include delayed (necessary) intubation, inability to control tidal volumes and monitor airway pressures, and inconsistent mask seal which could lead to cyclic recruitment-derecruitment of lung units causing atelectrauma. A small randomized trial in patients with moderate-to-severe ARDS using a full helmet interface showed reduction in rate of intubation as well as mortality when compared to standard facemask NIV. 23 A study in patients with COVID-19 ARDS using helmet interface (compared to HFNC) did not show a mortality benefit, but did demonstrate a reduction in intubation rate as well as ventilator days. 24 Patients in the helmet NIV group frequently required sedation to facilitate comfort. Helmet NIV must be used with a traditional ventilator, as it requires a dual limb circuit (inspiratory and expiratory limbs), and the settings must be adjusted carefully to avoid carbon dioxide rebreathing. Helmet NIV is not routinely available in most North American hospitals, requires familiarity with the technology, and would benefit from further study in pragmatic trials before widespread use.

Most patients receive NIV via facemask interface, with widespread use due to its strong evidence base for hypercapnic respiratory failure and cardiogenic pulmonary edema.

The data on its role in ARDS is conflicting. The RECOVERY-RS trial in patients with COVID ARDS demonstrated a decreased intubation rate, but no mortality benefit, in patients treated with NIV (continuous positive airway pressure, specifically) compared to standard oxygen therapy; the same benefit was not observed when comparing HFNC to standard oxygen therapy. 25 A propensity-matched analysis of the LUNG-SAFE study demonstrated an increased risk of mortality of patients with moderate-to-severe ARDS who received NIV compared to those who received IMV only. 26 High-quality, prospective randomized trials are needed to better define the role of NIV in ARDS.

Safety monitoring in NIV is essential, and we advocate for these patients to be admitted to intensive care units when possible. Tidal volume monitoring plays an important role.

Patients with moderate to severe hypoxemia and tidal volumes greater than 9.5 ml/kg of ideal body weight (IBW) despite attempts to lower the tidal volume by changing settings are expected to fail NIV (82% sensitivity, 87% specificity). 27 The HACOR score (Heart rate, Acidosis, Consciousness, Oxygenation, Respiratory rate) predicts failure of NIV in patients with hypoxemic respiratory failure. 28 A summary of the score and its value at different timepoints can be found at this referenced summary 29 ; the score itself is listed in Table 3 . Score at one hour may also help differentiate patients who may be less likely to die if intubated early (within 12 hours of NIV initiation). 28 HACOR scores will tend to improve in patients with NIV success, and remain unchanged in patients with NIV J o u r n a l P r e -p r o o f failure. The presence of other organ failures may also predict NIV failure. 30 In summary, if a patient with ARDS is placed on NIV doesn't markedly improve, ongoing use in the individual should be reconsidered.

Awake prone positioning became popular during the early portion of the COVID-19 pandemic, despite a lack of meaningful outcome data at that time. Subsequently, a multinational randomized "meta-trial" of 1121 patients compared HFNC and awake prone positioning to HFNC alone. 31 There was a 6% absolute reduction in treatment failure (defined as intubation or death) in the prone position group, with no signal of harm detected. Patients who were able to prone for more than 8 hours per day had a lower rate of treatment failure compared to those who were in prone position for less than 8 hours as well. While prone, patients had improvement in ROX score as well as its components (SpO2:FiO2 ratio and respiratory rate). This treatment is easy to implement and could be instituted while still in the emergency department, assuming the patient is an otherwise suitable candidate for HFNC and can self-prone without difficulty or excess discomfort. Less is known about the combination of NIV and awake prone positioning.

See Figure 1 for a comprehensive management algorithm. The supporting information for this algorithm is in the following sections.

Limiting harm from mechanical ventilation is the highest priority action. Details on tidal volume and PEEP selection will be detailed subsequently. In general, oxygenation goals include partial pressure of arterial oxygen (PaO2) target between 55-80 mmHg or pulse oximetry (SpO2) values from 88-95%. Permissive hypercapnia is generally well tolerated and may actually be protective. 32 Various lower limits for pH have been described (anywhere from 7.15 -7.25), though no specific threshold is supported by strong evidence. Plateau pressure, a surrogate for compliance of the respiratory system, should be kept below 30 cm H2O. 33 This value can be obtained by initiating a brief (0.5 second) inspiratory pause on the ventilator, during passive ventilation. Observational data also suggests decreased mortality with the driving pressure (the difference between plateau pressure and PEEP) is kept lower than 13-15 cm H2O. [34] [35] [36] Plateau pressure should be rechecked periodically and after each ventilator adjustment; changes to plateau and driving pressures can be observed in as short as 1-5 minutes after adjustments are made 37 , though longer time periods are required to see improvements from slow recruitment. More information on these targets and how to reach them is included in Figure 1 .

Despite over two decades of knowledge that lower tidal volumes are associated with lower mortality 33 , implementation of low tidal volume ventilation (LTVV) is inconsistent, 1 even in expert centers and with higher severity of disease. 38 Several studies have J o u r n a l P r e -p r o o f demonstrated that protocolized care in ARDS is associated with better adherence to LTVV, as well as improved outcomes. 39, 40 In fact, similar findings have been demonstrated for protocol-driven ventilator management in the emergency department.

LOV-ED, a before-after implementation study, showed a 48% increase in lungprotective ventilation after protocol implementation. 5 Importantly, this protocol also improved adherence to lung protective ventilation of the same patients in the intensive care unit, suggesting a "carry over" effect. Prompt initiation of low tidal volume ventilation is important, as observational data suggest even early application of higher tidal volumes is associated with higher mortality. 41 It must be emphasized that tidal volume targets should be set based on ideal rather than actual body weight, as patients with obesity are more likely to receive higher tidal volumes. 42 For patients with ARDS the goal tidal volume range falls between 4-8 ml/kg of ideal body weight (starting at 6 ml/kg for most patients). 43 

The goal of PEEP titration is to achieve alveolar recruitment without overdistention, thereby homogenizing the alveoli as much as possible. No approach to the titration of positive end expiratory pressure has proven superior to any other in terms of patientcentered outcomes. 44, 45 Patients with more severe hypoxemia may have lower mortality rates when a higher PEEP strategy is employed. 46 In practice, PEEP may be set lower than appropriate, as even patients with severe hypoxemia receive only 10 cm H2O PEEP on average. 1 Some clinicians may be hesitant to increase PEEP if hemodynamic instability is present, though it is reasonable to still perform a brief trial of PEEP increase J o u r n a l P r e -p r o o f to see if it is tolerable and safe by hemodynamics and plateau pressures. Often, changes in oxygenation are used to assess if PEEP titration was helpful, though a "positive" response may be better reflected by a decrease in driving pressure. 34, 47 More data is needed to assess strategies of PEEP titration. In general it is reasonable to use the ARDSnet low PEEP table as a starting point (Figure 1 ), but to consider the high PEEP table if hypoxemia is more severe. 48 It is essential to monitor plateau and driving pressures, as well as hemodynamics, while titrating PEEP.

The physiologic benefits of prone positioning have been discussed in detail elsewhere, 49 but can be summarized briefly as improving dorsal lung recruitment, overall ventilation/perfusion matching, and homogenizing stress and strain throughout the lung.

There may also be hemodynamic benefits as well, since prone positioning tends to offload the right ventricule through a combination of mechanisms. 50 Prone positioning is consistently associated with improved mortality in patients with moderate to severe ARDS, 51,52 especially when paired with LTVV. 53 The largest trial showing mortality benefit, PROSEVA, enrolled patients with moderate to severe ARDS after 12-24 hours of optimized mechanical ventilation, 52 which calls into question whether this strategy is needed in patients while still in the emergency department. It may become necessary if long delays in transfer to the ICU or another facility are anticipated, though familiarity with the process is important, as the mortality reduction in PROSEVA was approximately 16%. A process for performing prone positioning in the emergency department has been described elsewhere. 54 

The use of neuromuscular blockade (NMB) in patients with moderate to severe ARDS is associated with improved oxygenation, decreased ventilator associated lung injury, and improved mortality at 28 days, without increasing the incidence of neuromuscular weakness. 55 The most recent multicenter trial of NMB in ARDS (ROSE, data from which is included in reference 55), did not demonstrate a mortality benefit compared to a control group which only used light sedation, so routine use of NMB has been called into question. NMB use does require deep sedation, which is associated with increased mortality even after accounting for severity of illness, so this strategy must be employed cautiously. 56 Optimal usage would likely be in a patient with moderate to severe ARDS who is also having significant ventilator dyssynchrony not amenable to ventilator adjustments. Bolus and/or infusions of NMB agents should be used for the shortest duration possible. In the emergency department, it may be more practical to use intermittent boluses depending on length of stay. It is also important to note that depth of sedation does not correlate with respiratory drive, so deep sedation without NMB may not be a viable strategy to mitigate dyssynchrony. 57 will likely depend on local/institutional factors, and multidisciplinary collaboration is encouraged. It is reasonable to consider steroids earlier in patients with higher severity of illness.

Inhaled pulmonary vasodilators have been used in ARDS with the intent of reversing hypoxemic vasoconstriction in ventilated lung units. This effect could also lead to decreased pulmonary vascular resistance, and therefore right ventricular afterload.

Unfortunately, these medications have not been shown to have any patient-centered outcome benefit in trials or high-quality observational studies. Nitric oxide may improve oxygenation without any benefit on mortality, and potentially increases the risk of acute J o u r n a l P r e -p r o o f kidney injury. 63 Additionally, nitric oxide is very expensive in the United States. Inhaled prostaglandins such as epoprostenol similarly have been shown to improve oxygenation and lower pulmonary artery pressures, without mortality benefit. 64 As such, these medications should be used sparingly (if at all), and could be considered in the following situations: (1) rescue of refractory hypoxemia, (2) coexistent right ventricular dysfunction, and/or (3) coexistent intracardiac shunt.

Airway pressure release ventilation (APRV) is an alternative mode of ventilation which leverages inverse ratio ventilation (inspiratory time greater than expiratory time) and allows spontaneous breathing. Trial data on APRV is sparse, and its use is most supported by a single-center study which demonstrated improved compliance, oxygenation, decreased days of mechanical ventilation, and sedation. 65 The use of APRV cannot be routinely recommended over conventional modes, but could be considered in centers with sufficient expertise to manage the mode, as well in cases of refractory hypoxemiaespecially if the patient is not a candidate for extracorporeal life support.

Extracorporeal carbon dioxide removal (ECCO2R) is a low-flow form of veno-venous support that has been studied in ARDS. An advantage over veno-venous extracorporeal membrane oxygenation (VV-ECMO) is the smaller cannula size (15.5 French, slightly larger than a hemodialysis catheter), though it does not provide any oxygenation J o u r n a l P r e -p r o o f support. The most recent trial compared usual care to a strategy of using ECCO2R to achieve ultraprotective tidal volumes (as low as 3 ml/kg ideal body weight). No mortality benefit was seen, and patients in the intervention group required more sedation, NMB, and had longer duration of mechanical ventilation. 66 Currently, the use of ECCO2R is not approved by the Food and Drug Administration and can only be used in the context of a clinical trial or under Emergency Use Authorization.

VV-ECMO has been studied in two large multicenter trials, CESAR 67 and EOLIA, 68 with somewhat conflicting results. However, an individual patient data meta-analysis of the two trials concluded that VV-ECMO reduces 90 day mortality in patients with severe ARDS (relative risk 0.75, 95% confidence interval 0.60 -0.94). 69 Notably, the median PaO2:FiO2 of patients at enrollment in both treatment and control groups was just under 80. VV-ECMO carries significant cost, invasiveness, and is associated with increased risk of morbidity due to cannulation and anticoagulation. Both trials were done in expert centers, an important consideration with evaluating external validity.

No standard definition for refractory hypoxemia exists; some studies have used a PaO2:FiO2 ratio of less than 60 while FiO2 is set at 1.0. 70 Furthermore, refractory ARDS may be better captured by inclusion of other factors, such as severe respiratory acidemia, unsafe airway pressures (plateau and driving pressure), and right ventricular dysfunction, rather than solely hypoxemia.

Most concerning is the poor utilization of evidence-based therapies in patients with moderate to severe ARDS. A recent multicenter observational study demonstrated that less than one third of patients received lung protective ventilation (defined as tidal volume less than or equal to 6.5 ml/kg ideal body weight and plateau pressure less than 30 cm H2O). 38 PEEP is usually lower than recommended targets in these patients as well. Interventions with low quality of evidence, such as inhaled pulmonary vasodilators, are more frequently implemented than prone positioning. 38, 70 The primary considerations for treating a patient with refractory/severe ARDS is sequential implementation of evidence-based therapies as in Figure 1 . Patients who are referred to expert centers may have improved outcomes, 67 so early consultation is recommended. After optimization of tidal volume and PEEP, early prone positioning and neuromuscular blockade should be initiated. If these interventions do not achieve safe airway pressure and gas exchange parameters, consultation with a VV-ECMO center is advised. If the patient is deemed not a candidate for VV-ECMO, alternative modes of ventilation such as APRV can be considered, as well as inhaled pulmonary vasodilators. 

Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries

Mechanical ventilation and acute lung injury in emergency department patients with severe sepsis and septic shock: an observational study

Mechanical Ventilation and ARDS in the ED: A Multicenter, Observational, Prospective, Cross-sectional Study

Incidence and outcomes of acute lung injury

Lung-Protective Ventilation Initiated in the Emergency Department (LOV-ED): A Quasi-Experimental, Before-After Trial

Acute Respiratory Distress Syndrome

The Berlin definition of acute respiratory distress syndrome: should patients receiving high-flow nasal oxygen be included?

Pulmonary embolism among critically ill patients with ARDS due to COVID-19

Pulmonary embolism or thrombosis in ARDS COVID-19 patients: A French monocenter retrospective study

Chest sonography: a useful tool to differentiate acute cardiogenic pulmonary edema from acute respiratory distress syndrome

Global and Regional Diagnostic Accuracy of Lung Ultrasound Compared to CT in Patients With Acute Respiratory Distress Syndrome

Bedside selection of positive endexpiratory pressure in mild, moderate, and severe acute respiratory distress syndrome

CT scan and ultrasound comparative assessment of PEEP-induced lung aeration changes in ARDS

Bedside ultrasound assessment of positive end-expiratory pressure-induced lung recruitment

Incidence and prognostic value of right ventricular failure in acute respiratory distress syndrome

Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact

Prevalence and prognosis of cor pulmonale during protective ventilation for acute respiratory distress syndrome

Prevalence and prognosis of shunting across patent foramen ovale during acute respiratory distress syndrome

High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure

The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline

An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy

High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious

Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal

Intubation in Patients With Acute Respiratory Distress Syndrome

Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial | Critical Care Medicine | JAMA | JAMA Network

An adaptive randomized controlled trial of non-invasive respiratory strategies in acute respiratory failure patients with COVID-19 | medRxiv

Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome. Insights from the LUNG SAFE Study

Failure of Noninvasive Ventilation for De Novo Acute Hypoxemic Respiratory Failure: Role of Tidal Volume

Assessment of heart rate, acidosis, consciousness, oxygenation, and respiratory rate to predict noninvasive ventilation failure in hypoxemic patients

Predicting NIV failure in hypoxemic patients: the HACOR score

Risk Factors for Noninvasive Ventilation Failure in Critically Ill Subjects With Confirmed Influenza Infection

Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, openlabel meta-trial

Bench-to-bedside review: Permissive hypercapnia

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome

Driving Pressure and Survival in the Acute Respiratory Distress Syndrome

Effect of driving pressure on mortality in ARDS patients during lung protective mechanical ventilation in two randomized controlled trials

Effect of Lowering Tidal Volume on Mortality in ARDS Varies with Respiratory System Elastance

PEEP Titration to Minimize Driving Pressure in Subjects With ARDS: A Prospective Physiological Study

Variation in Early Management Practices in Moderate-to-Severe ARDS in the United States: The Severe ARDS: Generating Evidence Study

Implementation of Protocolized Care in ARDS Improves Outcomes. Respir Care

The Clinical Effect of an Early, Protocolized Approach to Mechanical Ventilation for Severe and Refractory Hypoxemia

Timing of Low Tidal Volume Ventilation and Intensive Care Unit Mortality in Acute Respiratory Distress Syndrome. A Prospective Cohort Study

Higher Class of Obesity Is Associated With Delivery of Higher Tidal Volumes in Subjects With ARDS

Higher PEEP versus lower PEEP strategies for patients in ICU without acute respiratory distress syndrome: A systematic review and metaanalysis

Higher PEEP versus Lower PEEP Strategies for Patients with Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis

Higher vs Lower Positive End-Expiratory Pressure in Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome

Response to Ventilator Adjustments for Predicting Acute Respiratory Distress Syndrome Mortality. Driving Pressure versus Oxygenation

An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome

Prone Position in Acute Respiratory Distress Syndrome. Rationale, Indications, and Limits

Rationale and Description of Right Ventricle-Protective Ventilation in ARDS

Prone Position for Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis

Prone Positioning in Severe Acute Respiratory Distress Syndrome

Comparative Effectiveness of Protective Ventilation Strategies for Moderate and Severe ARDS: Network Meta-Analysis

A primer on proning in the emergency department

Neuromuscular Blocking Agents for ARDS: A Systematic Review and Meta-Analysis

Practice Patterns and Outcomes Associated With Early Sedation Depth in Mechanically Ventilated Patients: A Systematic Review and Meta-Analysis

Discordance Between Respiratory Drive and Sedation Depth in Critically Ill Patients Receiving Mechanical Ventilation

Comparison of Two Fluid-Management Strategies in Acute Lung Injury

Dexamethasone in Hospitalized Patients with Covid-19

The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis

Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial

Use of glucocorticoids in patients with acute respiratory distress syndrome: a meta-analysis and trial sequential analysis

The effect of inhaled nitric oxide in acute respiratory distress syndrome in children and adults: a Cochrane Systematic Review with trial sequential analysis

The Use of Inhaled Prostaglandins in Patients With ARDS

Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome

Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial

Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for J o u r n a l P r e -p r o o f severe adult respiratory failure (CESAR): a multicentre randomised controlled trial

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome

ECMO for severe ARDS: systematic review and individual patient data meta-analysis

Management of Acute Respiratory Distress Syndrome and Refractory Hypoxemia. A Multicenter Observational Study