key: cord-0862327-kv99sevp
authors: Kharat, Aileen; Ribeiro, Carla; Er, Berrin; Fisser, Christoph; López-Padilla, Daniel; Chatzivasiloglou, Foteini; Heunks, Leo M.A.; Patout, Maxime; D'Cruz, Rebecca F.
title: ERS International Congress 2021: highlights from the Respiratory Intensive Care Assembly
date: 2022-05-23
journal: ERJ Open Res
DOI: 10.1183/23120541.00016-2022
sha: 072095f92d8adc54ad5ab7204bdffd44403180af
doc_id: 862327
cord_uid: kv99sevp

Early Career Members of Assembly 2 (Respiratory Intensive Care) attended the European Respiratory Society International Congress through a virtual platform in 2021. Sessions of interest to our assembly members included symposia on the implications of acute respiratory distress syndrome phenotyping on diagnosis and treatment, safe applications of noninvasive ventilation in hypoxaemic respiratory failure, and new developments in mechanical ventilation and weaning, and a guidelines session on applying high-flow therapy in acute respiratory failure. These sessions are summarised in this article.

Assembly 2 of the European Respiratory Society (ERS) encompasses the broad fields of respiratory critical care. Our assembly is divided into two groups, those of acute critical care and of noninvasive ventilatory support. Currently, our assembly is headed by Leo Heunks, João Winck has the role of secretary and Maxime Patout is our Early Career Representative. The acute critical care subgroup is chaired by Christian Karagiannidis, with Ignacio Martin-Loeches as secretary. The noninvasive ventilatory support group is chaired by Marieke Duiverman, and Claudia Crimi is secretary. At the time of publication, we have 1553 Assembly 2 members, 36% of whom are early career members. A recent highlight of Assembly 2 was our organisation of the inaugural Respiratory Failure and Mechanical Ventilation conference, which was held in Berlin in March 2020. This was a great success, with attendees arriving from around the world to enjoy engaging and educational seminars delivered by expert panels, workshops and lectures within the streams of adult acute respiratory failure, chronic respiratory failure and paediatric respiratory failure [1] . Early career members had the opportunity to present cases and posters and to chair sessions. We look forward to the second meeting, which will be held in Berlin between 9 and 11 June 2022. In this review, we present highlights from the ERS International Congress 2021 of interest to Assembly 2 members and those interested in critical care and mechanical ventilation. The sessions we have reported on include the symposia on acute respiratory distress syndrome (ARDS) phenotypes, noninvasive ventilation (NIV) in hypoxic respiratory failure, and new developments in mechanical ventilation and weaning, and the guidelines session on high-flow therapy (HFT) in adults with acute respiratory failure.

ARDS phenotypes: implications for diagnosis and treatment ARDS pathophysiology was presented by Nuala Meyer (Philadelphia, PA, USA). In the 1970s, ARDS pathophysiology was driven by oxygen toxicity. Since then, ventilator management and supportive care have changed. Epithelial cell death is characteristic but endothelial damage is more subtle [2] . However, lung autopsy studies from patients with coronavirus disease 2019 (COVID-19) showed endothelial damage, microthrombi and endothelial disruption. Classic cells driving ARDS are predominantly neutrophils and macrophages [3] . Neutrophil-derived chlorolipids, neutrophil extracellular traps, are excellent biomarkers for ARDS [4] . Moreover, new cell death mechanisms and pathways may represent novel therapeutic targets in ARDS [5] .

Jean-Michel Constantin (Paris, France) focused on personalised ventilator settings and implications of lung morphology in ARDS. He reported that the mortality was lower in the focal ARDS group than in the non-focal groups, despite similar ratio of arterial pressure of oxygen to fraction of inspired oxygen (P aO 2 /F IO 2 ), with different responses to lung recruitment [6] . In the non-focal group, the lungs can be ventilated homogeneously with higher positive end-expiratory pressure (PEEP), whereas higher pressure can cause overinflation in normal areas in the focal group. Therefore, the LIVE study was designed by CONSTANTIN et al. [7] . In the intervention arm of this study, the focal group was ventilated with low PEEP and high tidal volume (8 mL·kg −1 ) and the non-focal group with low tidal volume and high PEEP. 90-day mortality was similar between groups. However, mortality was higher in those who had been misclassified. In conclusion, dynamic parameters like ultrasound, electrical impedance tomography (EIT) and computed tomography (CT) scan can help in choosing the correct ventilator settings.

Charlotte Summers (Cambridge, UK) presented biological sub-phenotyping of ARDS. Previously, two sub-phenotypes were identified by retrospectively analysing the ARMA and the ALVEOLI trials [8] . The hyperinflammatory group were observed to have higher mortality, while response to higher PEEP and conservative fluid therapy was better [9] . Data from the UK Critical Care Genomics, the Northern Ireland Clinical Trials Unit and the MOSAIC Influenza Consortium were integrated to develop disease subtypes. Three types of influenza-associated ARDS were identified as adaptive, endothelial leak and neutrophil-driven (figure 1). Survival was poorer in the neutrophil-driven subtype.

Brijesh Patel (London, UK) talked on individual approaches to resolve lung injury. Pneumonia, lower P aO 2 /F IO 2 , higher pressures, higher tidal volume and higher non-respiratory sequential organ failure assessment (SOFA) score were risk factors for persisting ARDS [10] . PATEL et al. [11] used machine learning to report that patients who did not resolve hypoxaemia within the first week had higher intensive care unit (ICU) mortality. To understand resolution phenotypes, multimodal approaches should be developed combining physiology, radiology and bioinformatics.

Take-home messages • ARDS may be phenotyped using imaging and inflammatory markers. • A range of imaging modalities may be used, including ultrasound, EIT and CT.

• Hyperinflammatory ARDS has a poorer prognosis.

• Phenotyping is important to guide the ventilatory strategy and may impact upon clinical outcomes.

Noninvasive respiratory support in hypoxic respiratory failure: stay safe and know your limits Luigi Camporota (London, UK) opened the session conceptualising the assessment of severity of respiratory failure as a triangle: gas exchange, radiology and biomarkers and respiratory effort, all connected with a fourth dimension corresponding to the disease evolution in time. The gas exchange reflects two separate phenomena: the alveolar integrity and the functional abnormalities such as dysregulated pulmonary perfusion. The COVID-19 pandemic was used throughout the presentation as a model for the different assessment methods, both invasive and noninvasive. L. Camporota reflected on a commonly used tool, the P aO 2 /F IO 2 , and its limitation being dependent on the F IO 2 , making it difficult to assess its evolution in case of change in the denominator. In a recent study, the ROX index (ratio of oxygen saturation as measured by pulse oximetry/F IO 2 to respiratory rate) has greater predictive validity than NEWS2 for deterioration in COVID-19 [12] .

Stefano Nava (Bologna, Italy) reported pros and cons of noninvasive respiratory support (NRS) during the COVID-19 pandemic, since NRS was used outside the intensive care setting, where no previous recommendations existed. On the one hand, studies showed that HFT, continuous positive airway pressure (CPAP) and NIV had similar adjusted mortality rate. Helmet NIV and CPAP had a significantly reduced intubation rate compared to HFT [13] . S. Nava challenged the audience with a provocative question: did we kill HFT? The answer is probably not. HFT must be used in specific situations for its already known indications. On the other hand, NRS depends on the severity of hypoxaemia. P aO 2 /F IO 2 is dependent on work of breathing. Therefore, it does not predict alone lung recruitment and mechanics. Patient effort is important and can contribute to ventilator-induced lung injury. A last consideration is staff contamination due to aerosol generation by NRS (figure 2).

Marieke Duiverman (Groningen, the Netherlands) reflected on the role of NRS in refractory breathlessness. A limitation within this area is that most studies include small patient numbers and short-term end-points. A 2015 systematic review concluded that opioids improved breathlessness in patients with severe COPD [14] , although the benefit was lower than the later described minimal clinically important difference [15] . Another systematic review demonstrated a slight benefit of NIV in relieving dyspnoea in COPD stable patients [16] , but whether it is clinically relevant remains uncertain. In the acute setting, it is essential to define the goals of life support versus symptom relief, and the side-effects patients (and physicians) tolerate depend on these goals. A randomised crossover study showed that HFT was superior to conventional oxygen therapy in reducing the severity of dyspnoea in the first hour of treatment in patients with do-not-intubate status and hypoxaemic respiratory failure [17] .

In her presentation, Maria Vega (Bologna, Italy) illustrated the physiological background in NRS based on a recent review [18] , showing lower intubation rate and mortality with NRS compared to standard oxygenation in hypoxaemic respiratory failure. Patient self-inflicted lung injury and ventilator-induced lung injury are influenced by dynamic transpulmonary pressure (transpulmonary pressure (P L )=airway pressure (P aw )+pleural pressure (P pl )), which in turn depends on patient effort. NIV decreases work of breathing, thus personalised pressure titration reduces risk of lung injury. Effect of applied pressure support is determined by oesophageal swing ( figure 3) . A strategy of respiratory support should consider patient inspiratory effort to avoid increase in dynamic stress.

Take-home messages • The P aO 2 /F IO 2 and the ROX index may be used to classify severity of hypoxic respiratory failure.

• Aerosol generation and use of appropriate personal protective equipment must be considered when implementing NRS. • There are limited data on the use of NRS in breathlessness management, and the burdens of treatment must be weighed up against physiological benefits. • Patient effort must be considered when selecting an appropriate ventilatory strategy.

Patient's perspective Olivia Fulton, a former ICU asthma patient and a volunteer for a charity for post-intensive care patients and their family, discussed her experience in the ICU. She highlighted that patience, communication and awareness about the patients' ability to hear or feel are the key parameters that ICU personnel need to embrace in order to make the patient's stay in the ICU less traumatic.

John Laffey (Galway, Ireland) highlighted that prolonged invasive mechanical ventilation and extubation failure are associated with multiple complications and higher mortality [19] . Several types of spontaneous breathing trial have been described, but a T-piece trial seems to better reflect work of breathing after extubation compared to pressure support ventilation (PSV) [20] . In terms of the epidemiology of weaning, J. Laffey summarised some preliminary results of the WEAN SAFE Study (WorldwidE AssessmeNt of Separation of pAtients From ventilatory assistancE), which addresses key issues regarding weaning from mechanical ventilation (ClinicalTrials.gov ID NCT03255109). We eagerly await publication of the full results. The study by BURNS et al. [21] found significant differences between participating countries regarding the methods and personnel involved in weaning, highlighting the worldwide variation in practices.

Personalised mechanical ventilation and weaning in patients with COPD Lise Piquilloud (Lausanne, Switzerland) emphasised that the goal of mechanical ventilation in COPD patients is to reduce hyperinflation. Regarding controlled ventilation, the usual approach is controlled hypoventilation with permissive hypercapnia. During assisted ventilation, the presence of intrinsic PEEP (PEEPi) leads to increased work of breathing and asynchronies, which may be mitigated by carefully titrating PEEP. Neurally adjusted ventilatory assist (NAVA) ventilates the patient based on the electrical activity of the diaphragm and reduces asynchrony compared with PSV [22, 23] . Moreover, NAVA has been associated with reduced duration of mechanical ventilation compared with PSV in patients at risk for prolonged mechanical ventilation [24] . L. Piquilloud stressed the importance of daily screening for weaning readiness and early extubation. In COPD patients at risk for extubation failure, we must consider the early use of NIV or HFT. When high PEEPi persists despite appropriate ventilation, we may use extracorporeal carbon dioxide removal (ECCO 2 R), which allows us to further decrease minute ventilation with beneficial effects on hyperinflation and mitigation of the deleterious consequences of hypercapnia and acidosis [25] . Moreover, ECCO 2 R may be used to facilitate weaning, since it may improve work of breathing [26] . Nevertheless, more studies are needed to prove its efficacy and safety before it can be used as a general treatment strategy in routine clinical practice.

Lung and diaphragm protective ventilation Katerina Vaporidi (Heraklion, Greece) discussed lung injury and protective mechanical ventilation strategies that include optimisation of tidal volume (V T ) and PEEP, prone positioning and allowing diaphragmatic contraction with early spontaneous breathing. The measurement of transpulmonary end-expiratory pressure by an oesophageal catheter and EIT may aid in PEEP titration. Global tidal lung stress may be monitored by measuring airway driving pressure. However, regional lung stress can be more accurately estimated by the transpulmonary driving pressure. High tidal stress may be mitigated by improving lung homogeneity, avoiding high V T and decreasing ventilatory demands [27, 28] . Passive ventilation as well as assisted ventilation can induce diaphragm disuse atrophy. Protective ventilation involves avoiding prolonged diaphragmatic rest, over-or under-assistance and dysynchrony. Titration of inspiratory effort can be achieved with measurement of the pressure time product of oesophageal pressure (PTP oes ), while simpler bedside methods include measurement of airway occlusion pressure (P 0.1 ) and oesophageal pressure swing. Modulating the respiratory drive can help in manipulating the patient's effort [27] [28] [29] .

The impact of machine learning on mechanical ventilation in critically ill patients Lucas Fleuren (Amsterdam, the Netherlands) started his lecture by emphasising the need for processing information. This need may be met by machine learning, which includes supervised, unsupervised and reinforcement learning [30] . L. Fleuren focused on supervised learning, which enables the prediction of outcome based on the input data. Machine learning is increasingly reported in the intensive care literature. Nonetheless, the vast majority of studies involve model prototyping and development, while there is a paucity of data regarding their implementation into clinical practice [31] . An application of the use of machine learning is described in the study by FLEUREN et al. [32] . They used the Dutch Data Warehouse, a multicentre electronic health record database, to determine the most important predictors for extubation failure. L. Fleuren argues that the next step is the determination of the appropriate parameters that will be used in research so that machine learning can assist clinicians in their everyday practice.

Take-home messages • Measures should be taken to minimise the short-and long-term psychological impact of a critical care admission for patients, including clear and appropriate methods of communication. • Readiness to wean should be assessed daily and may involve spontaneous breathing trials, T-piece ventilation and PSV, and results from the WEAN SAFE study are awaited. • In COPD, hyperinflation may be managed with controlled hypoventilation and permissive hypercapnia, and patients may benefit from post-extubation NIV or HFT. • Protective ventilation strategies should be implemented to avoid lung injury and diaphragm atrophy.

• Advances in machine learning may be a valuable adjunct to clinical evaluation to support critical care management.

High-flow nasal cannula in adults with acute respiratory failure There is a strong physiological rationale for the use of HFT in hypoxaemic respiratory failure, and justification for its application in hypercapnic respiratory failure [33] [34] [35] [36] [37] (figure 4).

Recent meta-analyses have reported its superiority compared to conventional oxygen therapy (COT) in terms of endotracheal intubation and mortality reduction [18, [39] [40] [41] . Moreover, when compared with other therapies such as helmet NIV, the risk of patient self-inflicted lung injury is lower with HFT [42] .

Considering the beneficial effects of both HFT and NIV, it is plausible that the combination of therapies might achieve better outcomes than a single treatment approach [43] [44] [45] . Regarding the applicability of HFT for COVID-19 patients, it has been widely used throughout the pandemic, with observational data indicating favourable results [46, 47] , which also apply in the prone position [48] , and might be more useful than other noninvasive strategies in the early stages of the disease [49] . Given that it is possible that HFT failure could delay intubation and increase mortality [50] , it is mandatory for these patients to be monitored in specifically designed physical spaces such as Respiratory Intermediate Care Units or the ICU, where healthcare personnel safety can also be optimised. A practical tool is the ROX index, which has been validated in patients with ARDS on HFT, with an index >4.88 after initiation consistently associated with a lower risk for intubation [51] . This index may be useful for COVID-19 patients as well [52] .

After a thorough systematic review and consensus of experts, the summary of guideline recommendations is as follows. 1) For acute hypoxaemic respiratory failure, it is suggested to use HFT over COT and NIV. As well, guideline authors suggest using HFT over COT during breaks from NIV. 2) In a post-operative scenario, either COT or HFT may be used in patients with lower risk of respiratory complications, and either HFT or NIV should be applied for patients at higher risk of respiratory complications. 3) Following extubation from invasive mechanical ventilation in non-surgical patients, guideline authors recommend use of HFT in preference to COT in patients at low or moderate risk of extubation failure, and the use of NIV Take-home messages • HFT is an effective treatment in acute hypoxaemic respiratory failure.

• HFT is associated with better clinical outcomes when used post-extubation compared to conventional oxygen in those at low risk of post-extubation respiratory failure. • HFT is a safe intervention that is tolerated well by patients and is associated with a lower incidence of interface-related skin damage and lung injury compared to NIV. • NIV is first-line therapy in COPD patients with acute hypercapnic respiratory failure after a period of medical management. • HFT may be used effectively in COVID-19 pneumonitis; however, patients should be monitored closely for deterioration and invasive mechanical ventilation initiated early if necessary. 

Highlights from the Respiratory Failure and Mechanical Ventilation 2020 Conference

Acute respiratory distress syndrome

Genome-wide transcription profiling in neutrophils in acute respiratory distress syndrome

Maladaptive role of neutrophil extracellular traps in pathogen-induced lung injury

Collateral damage: necroptosis in the development of lung injury

Elevated plasma levels of sRAGE are associated with nonfocal CT-based lung imaging in patients with ARDS: a prospective multicenter study

Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial

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

Acute respiratory distress syndrome subphenotypes respond differently to randomized fluid management strategy

Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study

Natural history, trajectory, and management of mechanically ventilated COVID-19 patients in the United Kingdom

The ROX index has greater predictive validity than NEWS2 for deterioration in Covid-19

Quantitative detection of hepatitis B virus DNA in sera from patients with acute hepatitis B

Effects of opioids on breathlessness and exercise capacity in chronic obstructive pulmonary disease. A systematic review

Minimal clinically important differences in average, best, worst and current intensity and unpleasantness of chronic breathlessness

Chronic non-invasive ventilation for chronic obstructive pulmonary disease

High-flow nasal cannula versus conventional oxygen therapy in relieving dyspnea in emergency palliative patients with do-not-intubate status: a randomized crossover study

Association of noninvasive oxygenation strategies with all-cause mortality in adults with acute hypoxemic respiratory failure: a systematic review and meta-analysis

The decision to extubate in the intensive care unit

Effort to breathe with various spontaneous breathing trial techniques. A physiologic meta-analysis

Ventilator weaning and discontinuation practices for critically ill patients

Neurally adjusted ventilatory assist improves patient-ventilator interaction

Neurally adjusted ventilatory assist as an alternative to pressure support ventilation in adults: a French multicentre randomized trial

Neurally adjusted ventilatory assist versus pressure support ventilation: a randomized controlled feasibility trial performed in patients at risk of prolonged mechanical ventilation

The use of extracorporeal CO 2 removal in acute respiratory failure

Physiological effects of adding ECCO 2 R to invasive mechanical ventilation for COPD exacerbations

Lung-and diaphragm-protective ventilation

Clinical strategies for implementing lung and diaphragm-protective ventilation: avoiding insufficient and excessive effort

Respiratory drive in critically ill patients. Pathophysiology and clinical implications

Artificial intelligence in intensive care: are we there yet?

Moving from bytes to bedside: a systematic review on the use of artificial intelligence in the intensive care unit

The Dutch Data Warehouse, a multicenter and full-admission electronic health records database for critically ill COVID-19 patients

Heated humidified high-flow nasal oxygen in adults: mechanisms of action and clinical implications

Noninvasive ventilatory support for acute hypercapnic respiratory failure

High-flow nasal cannula oxygen in adults: an evidence-based assessment

Use of nasal high flow in stable COPD: rationale and physiology

High-flow nasal oxygen therapy and noninvasive ventilation in the management of acute hypoxemic respiratory failure

High-flow therapy: physiological effects and clinical applications

The effect of high-flow nasal cannula in reducing the mortality and the rate of endotracheal intubation when used before mechanical ventilation compared with conventional oxygen therapy and noninvasive positive pressure ventilation. A systematic review and meta-analysis

Can high-flow nasal cannula reduce the rate of endotracheal intubation in adult patients with acute respiratory failure compared with conventional oxygen therapy and noninvasive positive pressure ventilation? A systematic review and meta-analysis

High flow nasal cannula versus conventional oxygen therapy and non-invasive ventilation in adults with acute hypoxemic respiratory failure: a systematic review

Physiological comparison of high-flow nasal cannula and helmet noninvasive ventilation in acute hypoxemic respiratory failure

High-flow nasal cannula oxygen therapy and noninvasive ventilation for preventing extubation failure during weaning from mechanical ventilation assessed by lung ultrasound score: a single-center randomized study

Apnoeic oxygenation via high-flow nasal cannula oxygen combined with non-invasive ventilation preoxygenation for intubation in hypoxaemic patients in the intensive care unit: the single-centre, blinded, randomised controlled OPTINIV trial

Combined noninvasive respiratory support therapies to treat COVID-19

Non-invasive ventilatory support and high-flow nasal oxygen as first-line treatment of acute hypoxemic respiratory failure and ARDS

High-flow nasal cannula and COVID-19: a clinical review

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

Spontaneous breathing and evolving phenotypes of lung damage in patients with COVID-19: review of current evidence and forecast of a new scenario

Failure of high-flow nasal cannula therapy may delay intubation and increase mortality

An index combining respiratory rate and oxygenation to predict outcome of nasal high-flow therapy

ROX index as a good predictor of high flow nasal cannula failure in COVID-19 patients with acute hypoxemic respiratory failure: a systematic review and meta-analysis