From Protecting the Lung to Protecting the Heart and the Lung in Acute Respiratory Distress Syndrome.

To the Editor Right ventricular (RV) injury is a frequent complication of acute respiratory distress syndrome (ARDS) that is associated with high morbidity and mortality.1, 2 Despite the implementation of RV-protective strategies, such as lung-protective ventilation and prone positioning, RV injury remains prevalent in patients with severe ARDS. 3 The European Society of Intensive Care Medicine (ESICM) Taskforce on ARDS eloquently highlighted the management of ARDS based on the best available evidence. 4 ARDS increases pulmonary vascular resistance and RV afterload as a result of hypoxemia, hypercapnia, and acidemia, injury to the pulmonary microcirculation and formation of microthrombi, a reduction in the functional residual capacity, and an increase in dead space.5 Invasive mechanical ventilation in ARDS can increase the transpulmonary and regional driving pressure in lung regions with reduced compliance, leading to increased lung stress and strain.6 The high transpulmonary and driving pressures also increase RV afterload. Since the adoption of protective lung ventilation, the incidence of ARDS-associated acute cor pulmonale has decreased by 20-30%. 1 Prone positioning can further mitigate RV injury by enhancing venous return and reducing pulmonary vascular resistance through lung recruitment, decreasing ventilation/perfusion mismatch, and improving gas exchange. Prone positioning also reduces ventilator-induced lung injury by decreasing tidal hyperinflation and cyclic recruitment and derecruitment.7 However, there remain uncertainties (including diagnostic criteria, timing of interventions to protect the RV, pharmacological or mechanical support of the failing RV) about RV injury in acute respiratory failure. There is a lack of a consistent definition of acute RV injury in ARDS managed with positive pressure invasive ventilation, which needs to be urgently addressed.8 Echocardiographic parameters such as RV to left ventricular end-diastolic area ratio, tricuspid annular plane systolic excursion, RV free wall strain, septal kinetics, and flow with stroke volume index, have been used in some studies. 9, 10 Pulmonary artery catheter variables including high central venous pressure, low pulmonary artery pulsatility index, low pulmonary artery occlusion pressure, and low cardiac output have been used by others.11, 12 Similarly, the mechanism of abnormal RV-pulmonary arterial coupling in evaluation of stages of RV injury remains poorly understood. Phenotypes of RV injury have been described (ranging from RV diastolic dysfunction to RV failure/shock) in patients with ARDS that reflect compensated or decompensated RV adaptation to increased loading conditions. These phenotypes mainly reflect the different phases of RV adaptation to increased loading conditions. 13 In our view, the natural history and progression of RV injury in ARDS requires further study. In-vitro assessment of RV autoregulatory mechanisms to varying loading conditions may help identify the RV injury phenotypes that could progress to clinically relevant RV dysfunction. 14, 15 We believe that it is crucial to recognize and adopt early interventions to prevent the progression of RV injury and to test their risk-to-benefit ratio. Diagnosis of RV injury requires a high index of suspicion, especially in patients at risk for this complication, including those with lower respiratory tract infection, moderate-severe ARDS (arterial partial pressure-to-inspired oxygen ratio < 150, arterial partial pressure of carbon dioxide ≥ 48 mmHg and driving pressure ≥ 18 cmH2O). 16 The current management of ARDS-induced RV injury varies substantially from implementing evidence-based optimization of volume status and reduction of RV afterload to pharmacological or mechanical RV support. Veno-venous (V-V) extracorporeal membrane oxygenation (ECMO), as a rescue intervention in ARDS is likely to affect the RV as well.17 V-V ECMO corrects hypoxemia and hypercarbia while allowing a beneficial reduction in mechanical ventilation, but it does not provide circulatory support when RV failure is present. Hence, a new configuration (veno-pulmonary ECMO) that bypasses the RV might be protective to the RV.18 We feel strongly that future large-scale prospective studies, well-designed retrospective analyses, and translational research should examine the effects of lung-specific interventions (e.g., lung-protective ventilation, prone positioning, ECMO and additional mechanical circulatory RV support such as veno-pulmonary arterial ECMO) on RV injury in patients with ARDS. Future ARDS management guidelines should also consider RV-lung interactions to improve the outcomes. 1. Mekontso Dessap A, Boissier F, Charron C, et al. Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact. Intensive care medicine 2016;42:862-870. 2. Bunge JJH, Caliskan K, Gommers D, et al. Right ventricular dysfunction during acute respiratory distress syndrome and veno-venous extracorporeal membrane oxygenation. Journal of thoracic disease 2018;10:S674-s682. 3. Vieillard-Baron A, Schmitt JM, Augarde R, et al. Acute cor pulmonale in acute respiratory distress syndrome submitted to protective ventilation: incidence, clinical implications, and prognosis. Critical care medicine 2001;29:1551-1555. 4. Grasselli G, Calfee CS, Camporota L, et al. ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies. Intensive Care Medicine 2023;49:727-759. 5. Guérin C, Matthay MA. Acute cor pulmonale and the acute respiratory distress syndrome. Intensive care medicine 2016;42:934-936. 6. Petit M, Jullien E, Vieillard-Baron A. Right Ventricular Function in Acute Respiratory Distress Syndrome: Impact on Outcome, Respiratory Strategy and Use of Veno-Venous Extracorporeal Membrane Oxygenation. Frontiers in physiology 2021;12:797252. 7. Zochios V, Parhar K, Vieillard-Baron A. Protecting the Right Ventricle in ARDS: The Role of Prone Ventilation. Journal of cardiothoracic and vascular anesthesia 2018;32:2248-2251. 8. Dugar S, Sato R, Zochios V, et al. Defining Right Ventricular Dysfunction in Acute Respiratory Distress Syndrome. Journal of cardiothoracic and vascular anesthesia 2022;36:632-634. 9. Bonizzoli M, Cipani S, Lazzeri C, et al. Speckle tracking echocardiography and right ventricle dysfunction in acute respiratory distress syndrome a pilot study. Echocardiography 2018;35:1982-1987. 10. See KC, Ng J, Siow WT, et al. Frequency and prognostic impact of basic critical care echocardiography abnormalities in patients with acute respiratory distress syndrome. Ann Intensive Care 2017;7:120. 11. Monchi M, Bellenfant F, Cariou A, et al. Early predictive factors of survival in the acute respiratory distress syndrome. A multivariate analysis. American journal of respiratory and critical care medicine 1998;158:1076-1081. 12. Bull TM, Clark B, McFann K, et al. Pulmonary vascular dysfunction is associated with poor outcomes in patients with acute lung injury. American journal of respiratory and critical care medicine 2010;182:1123-1128. 13. Zochios V, Yusuff H, Schmidt M. Acute right ventricular injury phenotyping in ARDS. Intensive care medicine 2023;49:99-102. 14. Zochios V, Shelley B, Antonini MV, et al. Mechanisms of Acute Right Ventricular Injury in Cardiothoracic Surgical and Critical Care Settings: Part 1. Journal of cardiothoracic and vascular anesthesia 2023;37:2073-2086. 15. Yusuff H, Chawla S, Sato R, et al. Mechanisms of Acute Right Ventricular Injury in Cardiothoracic Surgical and Critical Care Settings: Part 2. Journal of cardiothoracic and vascular anesthesia 2023;37:2318-2326. 16. Mekontso Dessap A, Boissier F, Charron C, et al. Acute cor pulmonale during protective ventilation for acute respiratory distress syndrome: prevalence, predictors, and clinical impact. Intensive care medicine 2016;42:862-870. 17. Abrams D, Ferguson ND, Brochard L, et al. ECMO for ARDS: from salvage to standard of care? Lancet Respir Med 2019;7:108-110. 18. Zochios V, Yusuff H, Antonini MV, et al. Veno-Pulmonary Arterial Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Distress Syndrome: Should We Consider Mechanical Support of the Pulmonary Circulation From the Outset? ASAIO Journal 2023;69:511-518. The authors did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.