Personalizing Invasive Mechanical Ventilation Strategies in Coronavirus Disease 2019 (COVID-19)–Associated Lung Injury: The Utility of Lung Ultrasound

On March 11, 2020, the World Health Organization declared coronavirus disease 2019 (COVID-19), caused by severe respiratory syndrome coronavirus-2 (SARS-CoV-2), a worldwide pandemic. Severe acute respiratory failure due to SARS-CoV-2 requiring invasive mechanical ventilation in the intensive care unit is associated with high mortality.1Yang X Yu Y Xu J et al.Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-center retrospective observational study.Lancet Respir Med. 2020; 8 (Accessed April 25, 2020): 475-481Abstract Full Text Full Text PDF PubMed Scopus (6633) Google Scholar, 2Livingston E Bucher K. Coronavirus disease 2019 (COVID-19) in Italy [e-pub ahead of print].JAMA. 2020 Mar 17; (Accessed April 25, 2020)https://doi.org/10.1001/jama.2020.4344Crossref Scopus (741) Google Scholar, 3MunsWu Z McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention [e-pub ahead of print].JAMA. 2020 Feb 24; https://doi.org/10.1001/jama.2020.2648Crossref Scopus (11971) Google Scholar Patient self-inflicted lung injury and ventilator-associated lung injury potentially could exacerbate lung inflammation and biotrauma, increasing further the mortality of that very sick patient population.4Gattinoni L Chiumello D Caironi P et al.COVID-19 pneumonia: different respiratory treatments for different phenotypes? [e-pub ahead of print].Intensive Care Med. 2020 Apr 14; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06033-2Crossref Scopus (1171) Google Scholar More than 1 clinical phenotypes with different radiological and pulmonary mechanics profiles have been described recently.5Brochard L Slutsky A Pesenti A Mechanical ventilation to minimize progression of lung injury in acute respiratory failure.Am J Respir Crit Care Med. 2017; 195 (Accessed April 16 2020): 438-442Crossref PubMed Scopus (701) Google Scholar Identifying the clinical phenotype and applying principles of precision medicine to ventilatory management theoretically could be beneficial. Lung ultrasound (LUS) potentially could be an invaluable diagnostic tool in guiding therapy and assessing response to therapy, as SARS-CoV-2 pneumonitis demonstrates particular features on LUS at different stages of the disease, which may require individualized ventilatory management.6Smith MJ Hayward SA Innes SM et al.Point-of-care lung ultrasound in patients with COVID-19 - a narrative review [e-pub ahead of print].Anaesthesia. 2020 Apr 10; (Accessed April 16 2020)https://doi.org/10.1111/anae.15082Crossref Scopus (230) Google Scholar,7Pan C Chen L Lu C et al.Lung recruitability in COVID-19- associated acute respiratory distress syndrome: A single-center observational study [e-pub ahead of print].Am J Respir Crit Care Med. 2020 May 15; (Accessed April 18 2020)https://doi.org/10.1164/rccm.202003-0527LECrossref PubMed Scopus (225) Google Scholar Critically ill patients need rapid access to accurate and reproducible imaging techniques to diagnose pathology and implement and monitor treatment. Point-of-care ultrasound has been established firmly in the acute and critical care settings, with the development of the Intensive Care Society Focused Ultrasound Intensive Care accreditation process in the United Kingdom. The COVID-19 pandemic has pushed LUS to the forefront as an important tool in the assessment of patients with COVID-19. Lung ultrasound has a higher diagnostic accuracy than physical examination and chest radiography combined.8Lichtenstein DA Meziere GA. Relevance of lung ultrasound in the diagnosis of acute respiratory failure: The BLUE protocol.Chest. 2008; 134: 117-125Abstract Full Text Full Text PDF PubMed Scopus (1254) Google Scholar For many years, direct sonographic evaluation of lung parenchyma was considered inaccessible because of the presence of air. The high acoustic mismatch between the lung air and adjacent extrapulmonary tissue creates a complete reflection of the ultrasound beam, and creates an ultrasound image of air artifacts without any discernable imaging of the lung parenchyma.9Volpicelli G Lung sonography.J Ultrasound Med. 2013; 32: 165-171Crossref PubMed Scopus (128) Google Scholar However, it is now recognized that pathology of the lung creates distinct artifacts that can be used to diagnose pathology and guide therapy. Lung US has proved to be useful in the evaluation of many different acute conditions, namely cardiogenic pulmonary edema, acute lung injury, pneumothorax, pneumonia, and pleural effusions. With the appropriate training and supervision, the intensivist can use ultrasound to diagnose lung pathology rapidly, as well as plan and monitor therapy in real time. Reports from Italy and China highlighted variation in respiratory mechanics profiles among invasively ventilated patients with COVID-19 pneumonitis.4Gattinoni L Chiumello D Caironi P et al.COVID-19 pneumonia: different respiratory treatments for different phenotypes? [e-pub ahead of print].Intensive Care Med. 2020 Apr 14; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06033-2Crossref Scopus (1171) Google Scholar,7Pan C Chen L Lu C et al.Lung recruitability in COVID-19- associated acute respiratory distress syndrome: A single-center observational study [e-pub ahead of print].Am J Respir Crit Care Med. 2020 May 15; (Accessed April 18 2020)https://doi.org/10.1164/rccm.202003-0527LECrossref PubMed Scopus (225) Google Scholar,10Gattinoni L Coppola S Cressoni M et al.COVID-19 does not lead to a “typical” acute respiratory distress syndrome [e-pub ahead of print].Am J Respir Crit Care Med. 2020; 201: 1299-1300Crossref PubMed Scopus (920) Google Scholar Gattinoni et al recently have identified 2 clinical phenotypes: (1) type L, characterized by Low elastance (near-normal compliance), low ventilation- to- perfusion ratio, low lung weight (predominantly ground-glass changes on computed tomography [CT]), and low recruitability (due to minimal non-aerated lung)4Gattinoni L Chiumello D Caironi P et al.COVID-19 pneumonia: different respiratory treatments for different phenotypes? [e-pub ahead of print].Intensive Care Med. 2020 Apr 14; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06033-2Crossref Scopus (1171) Google Scholar,10Gattinoni L Coppola S Cressoni M et al.COVID-19 does not lead to a “typical” acute respiratory distress syndrome [e-pub ahead of print].Am J Respir Crit Care Med. 2020; 201: 1299-1300Crossref PubMed Scopus (920) Google Scholar; and (2) type H, characterized by high elastance (reduced compliance), high right- to- left shunt (caused by cardiac output perfusing non-aerated edematous lung), high lung weight (mimicking acute respiratory distress syndrome [ARDS)], and high recruitability (as in severe ARDS).4Gattinoni L Chiumello D Caironi P et al.COVID-19 pneumonia: different respiratory treatments for different phenotypes? [e-pub ahead of print].Intensive Care Med. 2020 Apr 14; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06033-2Crossref Scopus (1171) Google Scholar,10Gattinoni L Coppola S Cressoni M et al.COVID-19 does not lead to a “typical” acute respiratory distress syndrome [e-pub ahead of print].Am J Respir Crit Care Med. 2020; 201: 1299-1300Crossref PubMed Scopus (920) Google Scholar The aforementioned observations indicate that not all patients with COVID-19 and severe acute respiratory failure have Berlin ARDS, and therefore blind implementation of ARDS-oriented open lung ventilatory strategy potentially could be harmful.11A personalized lung-protective ventilatory approach tailored to lung mechanics therefore should be considered. Apart from pulmonary mechanics (elastance/compliance and recruitability), the 2 clinical phenotypes ideally should be confirmed radiologically on CT (L phenotype: subpleural ground glass with minimal non-aerated lung volume [Fig 1, A]; H phenotype: ARDS-type features [Fig 1, B]).4Gattinoni L Chiumello D Caironi P et al.COVID-19 pneumonia: different respiratory treatments for different phenotypes? [e-pub ahead of print].Intensive Care Med. 2020 Apr 14; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06033-2Crossref Scopus (1171) Google Scholar,10Gattinoni L Coppola S Cressoni M et al.COVID-19 does not lead to a “typical” acute respiratory distress syndrome [e-pub ahead of print].Am J Respir Crit Care Med. 2020; 201: 1299-1300Crossref PubMed Scopus (920) Google Scholar In a pandemic surge, however, transportation of critically ill invasively ventilated patients to radiology is challenging. This is in part due to the logistics of transferring the sheer volume of patients out of hot zones and the risk of exposure and transmission that this involves. Our colleagues in both China and Italy have found LUS to be a suitable alternative to CT in times when rapid diagnosis, triage, and evaluation of ventilation strategies are required, and when CT is not a feasible option.12Peng QY Wang XT Zhang LN et al.Findings of lung ultrasonography of novel corona virus pneumonia during the 2019-2020 epidemic [e-pub ahead of print].Intensive Care Med. 2020; 46 (Accessed April 26, 2020): 849-850Crossref PubMed Scopus (553) Google Scholar, 13Huang Y Wang S Liu Y et al.A preliminary study on the ultrasonic manifestations of peripulmonary lesions of non-critical novel coronavirus pneumonia (COVID-19) [e-pub ahead of print].SSRN. 2020 Feb 26; (Accessed April 26, 2020)https://doi.org/10.2139/ssrn.3544750Crossref Google Scholar, 14Volpicelli C Lamorte A Villén T What's new in lung ultrasound during the COVID-19 pandemic [e-pub ahead of print].Intensive Care Medicine. 2020; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06048-9Crossref Scopus (176) Google Scholar However, the main reason LUS has been the favored imaging modality is due to its ability to identify and evaluate serially progression or indeed resolution of superficial pathology; in particular, the lung signs and patterns we now know to be characteristic of SARS-CoV-2.12Peng QY Wang XT Zhang LN et al.Findings of lung ultrasonography of novel corona virus pneumonia during the 2019-2020 epidemic [e-pub ahead of print].Intensive Care Med. 2020; 46 (Accessed April 26, 2020): 849-850Crossref PubMed Scopus (553) Google Scholar Characteristic sonographic findings, first described by Chinese intensivists, with consensus from clinicians of other affected countries, include (1) thickened, irregular pleural line; (2) B-lines (focal, multifocal, and diffuse); (3) consolidation varying from focal, nontranslobar to translobar with or without air bronchograms; (4) A-lines, indicating air under the pleural line, during the recovery phase; and (5) pleural effusions (less common).8Lichtenstein DA Meziere GA. Relevance of lung ultrasound in the diagnosis of acute respiratory failure: The BLUE protocol.Chest. 2008; 134: 117-125Abstract Full Text Full Text PDF PubMed Scopus (1254) Google Scholar,12Peng QY Wang XT Zhang LN et al.Findings of lung ultrasonography of novel corona virus pneumonia during the 2019-2020 epidemic [e-pub ahead of print].Intensive Care Med. 2020; 46 (Accessed April 26, 2020): 849-850Crossref PubMed Scopus (553) Google Scholar, 13Huang Y Wang S Liu Y et al.A preliminary study on the ultrasonic manifestations of peripulmonary lesions of non-critical novel coronavirus pneumonia (COVID-19) [e-pub ahead of print].SSRN. 2020 Feb 26; (Accessed April 26, 2020)https://doi.org/10.2139/ssrn.3544750Crossref Google Scholar, 14Volpicelli C Lamorte A Villén T What's new in lung ultrasound during the COVID-19 pandemic [e-pub ahead of print].Intensive Care Medicine. 2020; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06048-9Crossref Scopus (176) Google Scholar, 15Intensive Care Society. FUSIC guidance for lung ultrasound during COVID-19. Available at: https://www.ics.ac.uk/ICS/ICS/FUSIC/FUSIC_COVID-19.aspx. Accessed April 22, 2020.Google Scholar, 16Fiala MJ. A brief review of lung ultrasound in COVID-19: Is it useful? [e-pub ahead of print].Ann Emerg Med. 2020 Apr 8; (Accessed April 19, 2020)https://doi.org/10.1016/j.annemergmed.2020.03.033Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar, 17Lichtenstein DA. Lung ultrasound in the critically ill.Ann Intensive Care. 2014; 4: 1Crossref PubMed Scopus (398) Google Scholar B-lines are a form of reverberation artifact, produced as a result of the interaction between ultrasound as it encounters a mix of fluid and air.8Lichtenstein DA Meziere GA. Relevance of lung ultrasound in the diagnosis of acute respiratory failure: The BLUE protocol.Chest. 2008; 134: 117-125Abstract Full Text Full Text PDF PubMed Scopus (1254) Google Scholar,17Lichtenstein DA. Lung ultrasound in the critically ill.Ann Intensive Care. 2014; 4: 1Crossref PubMed Scopus (398) Google Scholar Intensivists from Northern Italy described 2 distinctive sonographic LUS patterns.18Italian Group for the Evaluation of Interventions in Intensive Care Medicine (GIVITI) COVID-19 webinar. Available at:https://giviti.marionegri.it/covid-19-en/. Accessed March 10, 2020.Google Scholar These patterns potentially can be used to differentiate patients who respond to high positive end-expiratory pressure (PEEP) as an initial management strategy from patients who would benefit from moderate PEEP or mechanical ventilation in the prone position. Pattern 1 shows diffuse or coalescent B-line artifact descending from the pleural line to the bottom of the scan sector without fade, moving in concert with the sliding pleura.19Volpicelli G Elbarbary M Blaivas M et al.International evidence-based recommendations for point-of-care lung ultrasound.Intensive Care Med. 2012; 38: 577-579Crossref PubMed Scopus (1905) Google Scholar In COVID-19 pneumonitis, this pattern likely is caused by local subpleural inflammation/interstitial edema (“ground-glass” lesions) on CT (Fig 1, A).4Gattinoni L Chiumello D Caironi P et al.COVID-19 pneumonia: different respiratory treatments for different phenotypes? [e-pub ahead of print].Intensive Care Med. 2020 Apr 14; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06033-2Crossref Scopus (1171) Google Scholar,10Gattinoni L Coppola S Cressoni M et al.COVID-19 does not lead to a “typical” acute respiratory distress syndrome [e-pub ahead of print].Am J Respir Crit Care Med. 2020; 201: 1299-1300Crossref PubMed Scopus (920) Google Scholar,20Volpicelli G Mussa A Garofalo G et al.Bedside lung ultrasound in the assessment of alveolar-interstitial syndrome.Am J Emerg Med. 2006; 24: 689-696Abstract Full Text Full Text PDF PubMed Scopus (424) Google Scholar These sonographic features correlate with the “L phenotype” described by Gattinoni et al and do not fit ARDS criteria.4Gattinoni L Chiumello D Caironi P et al.COVID-19 pneumonia: different respiratory treatments for different phenotypes? [e-pub ahead of print].Intensive Care Med. 2020 Apr 14; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06033-2Crossref Scopus (1171) Google Scholar,11Ranieri VM Rubenfeld GD et al.ARDS Definition Task ForceAcute respiratory distress syndrome: The Berlin Definition.JAMA. 2012; 307: 2526-2533Crossref PubMed Scopus (7211) Google Scholar Moderate levels of PEEP (8-10 cmH2O) would be an appropriate initial strategy in this situation given that lung mechanics are preserved, there is limited recruitability, and hypoxemia is assumed to be caused mainly by deregulated pulmonary perfusion.4Gattinoni L Chiumello D Caironi P et al.COVID-19 pneumonia: different respiratory treatments for different phenotypes? [e-pub ahead of print].Intensive Care Med. 2020 Apr 14; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06033-2Crossref Scopus (1171) Google Scholar,10Gattinoni L Coppola S Cressoni M et al.COVID-19 does not lead to a “typical” acute respiratory distress syndrome [e-pub ahead of print].Am J Respir Crit Care Med. 2020; 201: 1299-1300Crossref PubMed Scopus (920) Google Scholar High PEEP (10-15 cmH2O) or alveolar recruitment maneuvers could lead to overdistention and cardiovascular instability and should not be used as a first-line measure. Prone ventilation should be considered in refractory cases. Response to proning and its physiological efficacy in this group of patients likely is related to redistribution of blood flow and offloading of the right ventricle rather than homogenous distribution of transpulmonary pressure and recruitment (Fig 2).4Gattinoni L Chiumello D Caironi P et al.COVID-19 pneumonia: different respiratory treatments for different phenotypes? [e-pub ahead of print].Intensive Care Med. 2020 Apr 14; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06033-2Crossref Scopus (1171) Google Scholar,10Gattinoni L Coppola S Cressoni M et al.COVID-19 does not lead to a “typical” acute respiratory distress syndrome [e-pub ahead of print].Am J Respir Crit Care Med. 2020; 201: 1299-1300Crossref PubMed Scopus (920) Google Scholar,21Guerin C Reignier J Richard JC et al.Prone positioning in severe acute respiratory distress syndrome.N Engl J Med. 2013; 368: 2159-2168Crossref PubMed Scopus (2536) Google Scholar,22Vieillard-Baron A Charron C Caille V et al.Prone positioning unloads the right ventricle in severe ARDS.Chest. 2007; 132: 1440-1446Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar Pattern 2 typically displays significant basal consolidation in the posterior lateral zone referred to as “"lung hepatization” due to its appearance of the liver. The lung tissue in this region is completely deaerated, either due to extensive atelectasis or a pneumonic process.23Parlamento S Copetti R Di Bartolomeo S Evaluation of lung ultrasound for the diagnosis of pneumonia in the ED.Am J Emerg Med. 2009; 27: 379-384Abstract Full Text Full Text PDF PubMed Scopus (148) Google Scholar The anterior zones tend to be spared and therefore signs of aeration may be present (Fig 1, B). This pattern of lung injury (H phenotype) resembles ARDS, and those patients may benefit from high levels of PEEP and prone positioning (Fig 2).4Gattinoni L Chiumello D Caironi P et al.COVID-19 pneumonia: different respiratory treatments for different phenotypes? [e-pub ahead of print].Intensive Care Med. 2020 Apr 14; (Accessed April 26, 2020)https://doi.org/10.1007/s00134-020-06033-2Crossref Scopus (1171) Google Scholar,16Fiala MJ. A brief review of lung ultrasound in COVID-19: Is it useful? [e-pub ahead of print].Ann Emerg Med. 2020 Apr 8; (Accessed April 19, 2020)https://doi.org/10.1016/j.annemergmed.2020.03.033Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar,21Guerin C Reignier J Richard JC et al.Prone positioning in severe acute respiratory distress syndrome.N Engl J Med. 2013; 368: 2159-2168Crossref PubMed Scopus (2536) Google Scholar In both patterns, use of low- tidal- volume ventilation (6 mL/kg predicted body weight) and low plateau and driving pressures (less than 30 and 15 cmH2O, respectively) to reduce the risk of ventilator-associated lung injury is paramount.24Brower RG Matthay MA et al.Acute Respiratory Distress Syndrome NetworkVentilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med. 2000; 342: 1301-1308Crossref PubMed Scopus (10490) Google Scholar It has been argued that patients with the L phenotype profile (pattern 1 on LUS) can be ventilated safely with higher tidal volumes (7-8 mL/kg predicted body weight) given the preserved respiratory system compliance (resulting in lower plateau and driving pressures).25Marini JJ Gattinoni L. Management of COVID-19 respiratory distress [e-pub ahead of print].JAMA. 2020 Apr 24; (Accessed April 26, 2020)https://doi.org/10.1001/jama.2020.6825Crossref PubMed Scopus (709) Google Scholar The Acute Respiratory Distress Syndrome Network trial, however, demonstrated that patients with ARDS can have preserved pulmonary compliance and that this subgroup of patients still would benefit from low volume/low pressure ventilation.24Brower RG Matthay MA et al.Acute Respiratory Distress Syndrome NetworkVentilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med. 2000; 342: 1301-1308Crossref PubMed Scopus (10490) Google Scholar It therefore would be prudent to avoid use of liberal tidal volumes in mechanically ventilated patients with COVID-19 and injured lungs. Daily LUS can be used to assess disease progression; transition between patterns and phenotypes; and aid prognostication, decision-making, and modification of ventilation strategies. In theory, LUS can be used to assess reaeration and tissue recruitment (A-lines/A-profile resolution) in response to high PEEP or proning where appropriate; however, this should be interpreted with caution, taking into account changes in pulmonary mechanics and oxygenation markers since subtle sonographic changes may not be clinically evident or significant. The pathophysiology of COVID-19–associated lung injury is not well understood. The concept of different phenotypes is hypothesis- generating and not based on rigorous data supporting differences in treatment. It is quite possible that there are more than 2 physiological models and patterns and that L and H represent the extremes of a very heterogenous disease spectrum. Lung ultrasound is an invaluable tool in the intensivist's armory that can be used to characterize COVID-19 lung disease and its natural history and individualize ventilation strategies. Prospective research comparing LUS-guided care versus standard ventilatory management of patients with COVID-19 lung injury is needed before any changes in practice are imposed.