key: cord-0934086-mkcc48a7
authors: Battaglini, Denise; Sottano, Marco; Ball, Lorenzo; Robba, Chiara; Rocco, Patricia R.M.; Pelosi, Paolo
title: Ten golden rules to individualize mechanical ventilation in acute respiratory distress syndrome
date: 2021-03-01
journal: nan
DOI: 10.1016/j.jointm.2021.01.003
sha: 58c0a5ee766580cbcfd3d6b157f5827e7c6c1e81
doc_id: 934086
cord_uid: mkcc48a7

Over the last decades, great strides have been made in the management of acute respiratory distress syndrome (ARDS). Mechanical ventilation remains the cornerstone of supportive therapy for ARDS. Lung-protective mechanical ventilation minimizes the risk of ventilator-induced lung injury (VILI) and improves survival. Several parameters are determinants of VILI and require careful setting, such as tidal volume (VT), plateau pressure (Pplat), driving pressure (DP), positive end-expiratory pressure (PEEP), and respiratory rate. Furthermore, measurement of energy and mechanical power may enable quantification of the relative contribution of its different components (VT, Pplat, ΔP, PEEP, respiratory rate, and airflow) and better individualize mechanical ventilation settings. The use of neuromuscular blocking agents is of interest, mainly in cases of severe ARDS, to improve oxygenation and reduce asynchrony; however, no significant changes in survival have been observed. Rescue respiratory therapies, such as prone positioning, inhaled nitric oxide, and extracorporeal support techniques may also be used in specific situations. Furthermore, respiratory weaning protocols should be discussed. After reviewing all recent clinical trials, we now present 10 golden rules to individualize mechanical ventilation in ARDS management.

Acute respiratory distress syndrome (ARDS) was first described more than 50 years ago [1] . Since then, despite the huge effort put into research for efficient causal/supportive therapies, ARDS remains hard to treat; 33.2 deaths in every 100,000 ARDS-related cases in the USA and between 2.6 and 7.2 in every 100,000 people in Europe, with a declining annual rate [2] .

It is estimated that more than 3 million people/year are affected by this syndrome [3] .

ARDS accounts for up to 10% of intensive care unit (ICU) admissions every year globally, requiring mechanical ventilation (MV), which can itself damage the already injured ARDS lung [4] . Ventilator-induced lung injury (VILI) is the main consequence of injurious MV [5] . Great effort has been made to identify possible ventilatory strategies to mitigate VILI in critically ill patients with ARDS [6] . Several randomized controlled trials (RCTs) and observational studies have investigated the role of lung-protective MV on ARDS outcome, thus revolutionizing conventional ventilatory management [7] [8] [9] [10] [11] . Moreover, the use of extracorporeal carbon dioxide removal (ECCO 2 R) [12] , extracorporeal membrane oxygenation (ECMO) [13] , inhaled vasodilators [14] , neuromuscular blocking agents (NMBAs) [15] , and prone positioning [16] [17] have been discussed by multidisciplinary writing groups in recent guidelines as possible rescue strategies for more severe cases [18] [19] .

The aim of this review is to provide practitioners with an updated, state of the art list of "tricks of the trade" for diagnosing, classifying and, above all, treating ARDS according to the new findings in this area of research, which still have to be completely clarified.

ARDS is a syndrome, not a disease [20] ,characterized by an inflammatory lung injury, resulting in parenchymal stiffening and consolidation, alveolar closure, alterations of vascular permeability, increase in lung water content and, eventually, severe gas exchange failure with an acute onset of hypoxemia. The most recent definition of ARDS is the Berlin Definition, stated in 2012 by a consensus panel of experts [21] . According to this, 4 criteria must be met simultaneously to diagnose ARDS: (1) 100 and 200) with a predicted mortality of 32%, and severe ARDS (PaO 2 /FiO 2 ratio <100) with a predicted mortality of 45% [21] . In 2013, Villar [23] , which seems to be similar to one of the phenotypes of COVID-19 [24] . The Berlin Definition, classification of severity, and prognostic accuracy of ARDS remain unclear and deserve further research to complete this puzzle.

The initial conventional approach to MV in ARDS included a tidal volume (V T ) of 10-15 ml/kg of predicted body weight (PBW) [8] .Over the past decades, much has been learned concerning the detrimental sequelae of MV. Mechanical ventilation can induce lung overdistention (as in case of higher V T ) with subsequent volutrauma, which along with atelectrauma and biotrauma form the basis for VILI [25] [26] Even though hypercapnia can lead to catecholamine release and increase pulmonary vascular resistance, there is a reduction of inflammatory processes and production of free radicals [27] . Current guidelines suggest the adoption of a heated humidifier to control hypercapnia; however, V T can be increased over 6 ml/kg (PBW) in the case of marked and persistent hypercapnia with already increased respiratory rate and reduced dead space [19] . A recent study comparing V T of 6.5 ml/kg or less with V T higher than 6.5 ml/kg observed that an increase of 1 ml/kg of PBW was associated with increased risk of death (hazard ratio, 1 [33] . P could be defined as V T /Crs (respiratory system compliance).

In this formula, V T is normalized to Crs of the damaged respiratory system and may be a better predictor of survival than V T scaled to normal lung volume using PBW determined by height and sex [34] . In other words, P represent the distending volume on the respiratory system when the V T is delivered by the ventilator. As previously reported, different factors, such as V T , PEEP, and Pplat can lead to VILI but can also interact with each other in a complex fashion. Therefore, the contribution of each single parameter to reduce mortality is not clear [35] . Because Crs is directly associated with normal aerated lung volume, some authors suggested using P as the best parameter to predict mortality in ARDS patients [36] . In a post-hoc analysis of previous clinical trials, Amato et al. demonstrated that P is well correlated with mortality [34] . PEEP and V T settings could have protective effects only when associated with a decrease in P. Another study [37] suggested targeting P below 13-15 cmH 2 O. Nevertheless, it is still under debate whether PEEP should be set to obtain minimal values of P. In a recent trial [38] , such a strategy resulted in increased mortality.

In short, a promising approach to set parameters based on a reduction of P is not recommended, and Pplat remains the optimal parameter to protect from lung damage [33] .Finally, the best P should not be used to optimize MV in ARDS.

PEEP is an essential component of ARDS management [21] . Beneficial effects of using PEEP include alveolar recruitment, reduction of intrapulmonary shunt, and arterial oxygenation [39] ; on the other hand, detrimental effects include an increased endinspiratory lung volume with raised risk of volutrauma and VILI [40] . Current guidelines recommend reserving high PEEP for patients with moderate or severe ARDS, and avoiding it in cases of mild ARDS [41] . In [38] . Thus, we do not recommend using an average PEEP level higher than 15; the use of extremely high PEEP levels is likely associated with major hemodynamic compromise and increased need for fluids.

or severe ARDS, PEEP set using either transpulmonary pressure (P L ) or PEEP/FiO 2 did not influence mortality [38] . Thus, the best method to individualize PEEP is the adoption of a low PEEP/PaO 2 [55] [56] [57] [58] [59] [60] [61] [62] [63] [64] [65] [66] [67] [68] [69] [70] [52] . PaO 2 and oxygen delivery can be optimized by increasing blood pHa and reducing PaCO 2 , increasing the hemoglobin concentration, cardiac output, and arterial content of oxygen. Close attention should be paid when adopting lung-protective strategies, particularly with low oxygen targets and permissive hypercapnia [53] . PEEP should also be set to protect the right ventricle, because the recruitment of lung units leads to derecruitment of the capillaries. At high PEEP, more fluids are needed to yield capillary recruitment and improve the function of the right ventricle. In addition, higher PEEP reduces lymphatic flow drainage from the lungs [54] .

Constantin et al. [55] reported that individualized ventilatory treatment optimized based on chest X-rays and computed tomography scans was not associated with a better outcome and even with a worse outcome, suggesting that chest imaging is not the best approach to optimize mechanical ventilation in ARDS patients.

Obese patients are at particular risk of developing ARDS due to their anatomic and physiological alterations, affecting the chest wall, lungs, pharynx, face and neck [56] . These patients present with reduced functional residual capacity (FRC) and lung compliance, hypoxia, and ventilation/perfusion mismatch. The application of PEEP in this population is important to mitigate atelectasis and distal airway closure. In this line, occlusion of the airway at end-inspiration is an important method to individualize PEEP according to a specific patient's physiology [57] [58] [59] .

Hence, we do not recommend using a PEEP level higher than 15 cmH 2 O. Lower V T combined with minimal PEEP levels to achieve saturation/PaO 2 targets (88-92%/55-70 mmHg) [52] should be the best option to avoid repetitive collapse and reopening of alveoli.

In short, close down the lungs and keep them resting to minimize VILI [60] . In other words, high or low PEEP does not exist, but it should be individualized based on the functional characteristics of each ARDS patient.

As previously mentioned, in ARDS, the total weight of the lungs is increased due to interstitial and alveolar edema. As a result, atelectasis of dependent areas of the lungs is common; the collapse of alveoli not only reduces the total lung surface available for gas exchange but also promotes lung injury by increasing the shear stress of the areas located at the interface between aerated and collapsed alveoli, which undergo cyclic recruitment and derecruitment [61] . Recruitment maneuvers (RMs) decrease the intrapulmonary shunt and improve oxygenation and compliance. With this in mind, RMs could be considered part of protective MV "open lung approach"; however, this can lead to hemodynamic impairment and overdistension. Overdistension seems to be more harmful than atelectrauma [62] [63] .

A recent meta-analysis by Goligher et al. [64] [65] [66] [67] [68] , and this heterogeneity may limit the accuracy of meta-analysis.

Further studies are needed to evaluate the beneficial effects of RMs. At this time, guidelines do not suggest routine use of RMs in patients with severe ARDS [19] .

NMBAs act by inhibiting patients' active breathing. Patients with severe ARDS may require the use of NMBAs, especially those with higher APACHE-II score, alveolar-arterial oxygen gradients, and plateau pressure, who may require rescue therapies such as prone position and ECMO . NMBAs reduce patient-ventilator asynchronies and oxygen consumption, increase compliance and functional residual capacity, and regional distribution of the V T , and lead to anti-inflammatory effects . NMBAs also play a pivotal role in limiting decruitment and maintaining PEEP, allowing the reduction of swings of P L due to strong inspiratory effort and expiratory alveolar collapse [71] . One In conclusion, NMBAs do not reduce the mortality risk at 28 and 90 days, ventilatorfree days, and duration of mechanical ventilation, but NMBAs improve oxygenation and reduce barotrauma without affecting ICU weakness. Figure 1 shows a possible management algorithm for the use of NMBAs in patients with moderate to severe ARDS.

NMBAs and in a protective, controlled ventilation mode, for the reasons explained above.

After this acute phase, when some clinical improvement is obtained, withdrawal from MV should be kept in mind. Spontaneous breathing is known to be related to desirable effects, such as reduction of wasting of respiratory muscles and improved of oxygenation and compliance [74] . It all starts with withdrawal of NMBAs and sedatives until a spontaneous breathing effort appears. At some point, return to spontaneous ventilation is as inevitable as it is challenging. There are several problems in relation to so-called pressure-support ventilation (PSV) modes. It has been shown that spontaneous breathing could increase inflammatory response and VILI [75] . In addition, an intense breathing effort due to exaggerated respiratory drive can worsen the situation in patient self-inflicted lung injury caused by hyperinflation of aerated lung areas with increased strain. As a rule of thumb, criteria on protectiveness must be ensured for assisted spontaneous ventilation too. These criteria are similar to those discussed for controlled ventilation in ARDS [36] . Concerning the ventilator mode before weaning and extubation, a recent non-inferiority RCT comparing assisted ventilation and assisted ventilation plus sigh maneuver in acute hypoxemic patients concluded that in the sigh group, 23% of patients failed to remain on pressure-control ventilation, whereas 30% of patients in the assisted ventilation group (absolute difference, −7%; 95% CI, −18% to 4%; p = 0.015), demonstrating feasibility in using a sigh maneuver during assisted ventilation [76] .

In ARDS patients in a supine position, the ventilation of dependent areas is severely impaired compared with non-ARDS patients [77] . Because of gravity, dependent areas are also more perfused, resulting in hypoxemia due to ventilation/perfusion mismatch. Dramatic increases in oxygenation are observed frequently in ARDS patients in the prone position, when a more homogeneous ventilation/perfusion ratio is achieved, and, subsequently, intrapulmonary shunt is diminished [78] . The prone position not only improves oxygenation but also VILI [79] . The improvement in oxygenation with no changes in PaCO 2 results in redistribution of perfusion instead of recruitment because regional ventilation does not improve. On the other hand, the improvement in oxygenation is associated with a reduction in PaCO 2 , leading to recruitment, improvement of regional ventilation, and higher survival rate [80] . Munshi et al. [82] including 8 RCTs again showed no statistically differences in mortality among the groups, but in a subgroup analysis, the mortality was lower in patients pronated for at least 12 h or more. In addition, the PaO 2 /FiO 2 ratio was significantly higher in the prone position group. Complications were more frequent in the prone position group and consisted of pressure sores and endotracheal tube obstruction [82] .The PROSEVA trial [83] 

Rescue therapies in ARDS is indicated when other less invasive strategies are unsuccessful. ECCO 2 R with a blood flow up to 1.500 ml/min is an effective therapy for ARDS patients who show both hypoxemic and hypercapnic respiratory. New lungs are commercially available, and this device might be used within a conventional system of centrifugal pumps separated or within a continuous renal replacement therapy circuit [84] .

It is our belief that further improvement in the circuits and pumps should be targeted in the near future. This system is attractive because it allows low-flow CO 2 removal in severe ARDS, reducing the invasiveness of high-flow ECMO. Low-flow CO 2 removal is able to decrease the mechanical power and to maintain oxygenation, and it is relatively easy and safe to apply at the bedside [84] [85] . The use of ECCO 2 R is VILI-saving by reducing V T and Pplat while also controlling respiratory acidosis [86] [87] .

Whereas low-flow systems such as ECCO 2 R (0.5-1.5 L/min) provide adequate flow both for oxygenation and CO 2 removal, high-flow systems such as ECMO (2-4 l/min) provide too much flow for targeting minimal oxygenation and CO 2 removal (low blood flow is needed) [86] [87] [88] . Criteria for using ECMO in the EOLIA trial included patients already pronated who did not improve enough. The EOLIA RCT did not show a significant difference in 60-day mortality between ECMO and control groups [69] . A recent meta-analysis of 2 RCTs with a total population of 429 patients reported lower 60- [90] [91] [92] . ECMO should also be used to reduce the risk of VILI by adopting an ultra-protective ventilator strategy [93] . Absolute contraindications are not available, albeit relative contraindications should be considered, including >7 days of maximal settings of MV; immunosuppression; central nervous system hemorrhage, damage or terminal malignancy; and increased age [88] .

A possible strategy to select patients who can benefit from rescue strategies is presented in Figure 2 .

conducted. Post-extubation respiratory failure is associated with higher mortality [94] [95] [96] .

Since 2000, a daily interruption of sedation to assess the levels of agitation and pain has been adopted. This strategy may reduce days on MV days and length of stay in the ICU [97] .

According to classification, weaning from MV can be categorized into 3 classes: simple, difficult, and prolonged [98] . Several methods have been proposed to predict successful weaning from MV, with pros and cons. The most common approach at the bedside to assess weaning failure is the use of the frequency/V T ratio [99] .

although the decision to connect to a high-flow nasal cannula or non-invasive ventilation (NIV) after extubation or to reconnect the patient 1 h before extubation was made during the randomization phase, the PSV arm received more high-flow nasal cannula or NIV than the T-piece arm (25% versus 19%; p = 0.01), potentially conflicting with the final results [100] . Moreover, in some trials, the patients were reconnected to the ventilator for a certain interval before extubation, whereas in others they were directly extubated after passing an SBT. In 2017, another RCT confirmed that a 1-h rest period after passing an SBT may reduce the rate of reintubation within 48 h after extubation [101] . A practical guideline for weaning is SBT with inspiratory pressure augmentation and a PEEP level between 0 and 5 cmH 2 O followed by extubation and NIV in patients at high risk of extubation failure (hypercapnia, chronic obstructive pulmonary disease, congestive heart failure, or other serious comorbidities) [102] . Personalized approaches for weaning of general ICU patients need to be safer and faster. Since specific studies of weaning in ARDS are still not available, we recommend following local protocols based on current evidence drawn from the general ICU population. In addition, the role of respiratory physiotherapy becomes crucial in this setting. Chest physiotherapy should be initiated as soon as possible, even during controlled MV, to improve outcome and reduce complications. In particular, assisted mobilization, postural therapy, neuromuscular electrical stimulation, and respiratory muscle training may reduce the rate of muscle weakness among ICU patients, and manual or ventilator hyperinflation [103] , positioning [104] , active cycle of breathing, and subglottic secretion drainage may help in the reduction of respiratory complications such as atelectasis, ventilator-associated pneumonia, and tracheobronchitis [105] .

Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first identified in Wuhan, China, in late 2019. It subsequently spread worldwide and rapidly became pandemic. Most cases are limited to a mild febrile illness, but some develop ARDS, requiring ICU admission and critical care [106] [107] . The respiratory management of COVID-19 ARDS is based on distinct phenotypes according to chest computed tomography (CT) findings [24-108-110] ] and lung physiology. COVID-19 ARDS phenotypes include: 1) phenotype 1, with preserved lung compliance, but few alveolar areas to recruit, and highperfusion areas; 2) phenotype 2, with inhomogeneously distributed atelectasis; and 3) phenotype 3, featuring low compliance and inhomogeneous distribution of atelectasis, i.e., very similar to traditional ARDS [108] .

In addition to protective mechanical ventilation strategy suggested in general ARDS patients, for phenotype 1 COVID-19 ARDS, we suggest using moderate PEEP levels to redistribute pulmonary blood flow from non-ventilated to more ventilated areas. In phenotype 2, we suggest using moderate-to-high PEEP levels to improve lung recruitment; rescue therapies can be considered. In phenotype 3, we suggest using current recommendations for typical (non-COVID) ARDS [24-105-111] .

Recent studies have reported that not only static parameters (PEEP, Pplat, and P) but also dynamic parameters (airflow, inspiratory time, and respiratory rate) may result in lung damage [112] . Mechanical power (MP), the product of mechanical energy and respiratory rate, represents a measure of the amount of energy imparted to the patient by the mechanical ventilator. A related parameter, intensity, represents the normalization of MP to the lung surface area [5-113-114] . Considering the same mechanical power, intensity is higher in reduced surface areas [5] . Three or more equations have been proposed for calculating MP, depending on the ventilatory setting. We propose the simplest equations be adopted at bedside in the case of pressure-and volume-control ventilation [115] [116] [117] [118] (Figure   3 ). MP should be maintained below 12 J/min in ARDS, and below 17 J/min in non-ARDS.

Moreover, during ECMO, MP levels higher than 27 J/min should be considered [119] 

All authors declare they have no conflicts of interest. 

Acute respiratory distress in adults

Mortality Trends of Acute Respiratory Distress Syndrome in the United States from

Incidence and outcomes of acute lung injury

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

Power to mechanical power to minimize ventilator-induced lung injury?

Perioperative anaesthetic management of patients with or at risk of acute distress respiratory syndrome undergoing emergency surgery

Extracorporeal life support for adults with acute respiratory distress syndrome

Current and evolving standards of care for patients with ARDS

Myorelaxants in ARDS patients

Prone position in ARDS patients: why, when, how and for whom

Prone positioning and neuromuscular blocking agents are part of standard care in severe ARDS patients: yes

Guidelines on the management of acute respiratory distress syndrome

Formal guidelines: management of acute respiratory distress syndrome

We've never seen a patient with ARDS! Intensive Care Med

Acute respiratory distress syndrome: the Berlin Definition

A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting--a prospective, multicenter validation study

Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials

Distinct phenotypes require distinct respiratory management strategies in severe COVID-19

High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure

volumes on oxygenation and respiratory system mechanics during the early stage of adult respiratory distress syndrome

A Quantile Analysis of Plateau and Driving Pressures: Effects on Mortality in Patients With Acute Respiratory Distress Syndrome Receiving Lung-Protective Ventilation

Should we titrate ventilation based on driving pressure? Maybe not in the way we would expect

Effects of high versus low positive end-expiratory pressures in acute respiratory distress syndrome

Driving pressure and survival in the acute respiratory distress syndrome

Association of Driving Pressure With Mortality Among Ventilated Patients With Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis

Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial

Fifty Years of Research in ARDS. Setting Positive End-Expiratory Pressure in Acute Respiratory Distress Syndrome

Ventilator-induced lung injury

Hemodynamic impact of a positive end-expiratory pressure setting in acute respiratory distress syndrome: importance of the volume status

Oxygenation response to positive end-expiratory pressure predicts mortality in acute respiratory distress syndrome. A secondary analysis of the LOVS and ExPress trials

Low Tidal Volume versus Non-Volume-Limited Strategies for Patients with Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis

Biological Impact of Transpulmonary Driving Pressure in Experimental Acute Respiratory Distress Syndrome

Comparative Effects of Volutrauma and Atelectrauma on Lung Inflammation in Experimental Acute Respiratory Distress Syndrome

Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome

Neurological Manifestations of Severe SARS-CoV-2 Infection: Potential Mechanisms and Implications of Individualized Mechanical Ventilation Settings

Acute respiratory distress syndrome, mechanical ventilation, and right ventricular function

Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in

LIVE study): a multicentre, single-blind, randomised controlled trial

ARDS in Obese Patients: Specificities and Management

How to ventilate obese patients in the ICU

How I ventilate an obese patient

Obesity in the critically ill: a narrative review

Close down the lungs and keep them resting to minimize ventilator-induced lung injury

Tidal ventilation at low airway pressures can augment lung injury

Complications from recruitment maneuvers in patients with acute lung injury: secondary analysis from the lung open ventilation study

Atelectrauma or volutrauma: the dilemma

Lung Recruitment Maneuvers for Adult Patients with Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis

Recruitment maneuvers for acute respiratory distress syndrome: the panorama in 2016. Rev Bras Ter Intensiva

Recruitment maneuvers in acute respiratory distress syndrome: The safe way is the best way

Recruitment maneuvers in acute respiratory distress syndrome and during general anesthesia

Pros and cons of recruitment maneuvers in acute lung injury and acute respiratory distress syndrome

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome

Volume-controlled Ventilation Does Not Prevent Injurious Inflation during Spontaneous Effort

Effects of neuromuscular blockers on transpulmonary pressures in moderate to severe acute respiratory distress syndrome

Neuromuscular blockade in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials

Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome

Higher levels of spontaneous breathing reduce lung injury in experimental moderate acute respiratory distress syndrome

Fifty Years of Research in ARDS. Spontaneous Breathing during Mechanical Ventilation. Risks, Mechanisms, and Management

Sigh in Patients With Acute Hypoxemic Respiratory Failure and ARDS: The PROTECTION Pilot Randomized Clinical Trial

Pleural pressure distribution and its relationship to lung volume and interstitial pressure

Influence of positioning on ventilation-perfusion relationships in severe adult respiratory distress syndrome

Prone position prevents regional alveolar hyperinflation and mechanical stress and strain in mild experimental acute lung injury

Decrease in PaCO2 with prone position is predictive of improved outcome in acute respiratory distress syndrome

Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial

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

Prone positioning in severe acute respiratory distress syndrome

Extracorporeal CO2 removal by hemodialysis: in vitro model and feasibility

Extracorporeal life support for adults with severe acute respiratory failure

ECCO(2)R therapy in the ICU: consensus of a European round table meeting

Inhaled nitric oxide therapy and risk of renal dysfunction: a systematic review and meta-analysis of randomized trials

Extracorporeal Life Support Organization Coronavirus Disease 2019 Interim Guidelines: A Consensus Document from an International Group of Interdisciplinary Extracorporeal Membrane Oxygenation Providers

Venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis

An expanded definition of the adult respiratory distress syndrome

Evaluation of the oxygenation index in adult respiratory failure

Age, PaO2/FIO2, and Plateau Pressure Score: A Proposal for a Simple Outcome Score in Patients With the Acute Respiratory Distress Syndrome

Mechanical Ventilation for Acute Respiratory Distress Syndrome during Extracorporeal Life Support. Research and Practice

Discontinuing mechanical ventilatory support

Outcome of reintubated patients after scheduled extubation

Effect of spontaneous breathing trial duration on outcome of attempts to discontinue mechanical ventilation. Spanish Lung Failure Collaborative Group

Spontaneous Breathing Trials and Conservative Sedation Practices Reduce Mechanical Ventilation Duration in Subjects With ARDS

Weaning from mechanical ventilation

The airway occlusion pressure (P(0.1)) to monitor respiratory drive during mechanical ventilation: increasing awareness of a not-so-new problem

Effect of Pressure Support vs T-Piece Ventilation Strategies During Spontaneous Breathing Trials on Successful Extubation Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial

Reconnection to mechanical ventilation for 1 h after a successful spontaneous breathing trial reduces reintubation in critically ill patients: a multicenter randomized controlled trial

Liberation From Mechanical Ventilation in Critically Ill Adults: An Official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline: Inspiratory Pressure Augmentation During Spontaneous Breathing Trials, Protocols Minimizing Sedation, and Noninvasive Ventilation Immediately After Extubation

Short-Term Appraisal of the Effects and Safety of Manual Versus Ventilator Hyperinflation in an Animal Model of Severe Pneumonia

Lateral position during severe mono-lateral pneumonia: an experimental study

Chest physiotherapy: An important adjuvant in critically ill mechanically ventilated patients with COVID-19

Multiple organ dysfunction in SARS-CoV-2: MODS-CoV-2

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

COVID-19 pneumonia: different respiratory treatments for different phenotypes?

COVID-19 phenotypes: leading or misleading?

Clinical phenotypes of critically ill COVID-19 patients

COVID-19-associated acute respiratory distress syndrome: is a different approach to management warranted?

What have we learned from animal models of ventilatorinduced lung injury?

Ventilator-related causes of lung injury: the mechanical power

Effect of mechanical power on intensive care mortality in ARDS patients

Calculation of mechanical power for pressure-controlled ventilation

Calculating mechanical power for pressure-controlled ventilation

Bedside calculation of mechanical power during volume-and pressure-controlled mechanical ventilation

Mechanical power at a glance: a simple surrogate for volume-controlled ventilation

Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts

None.