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Treating ARDS in the Era of COVID: A Refined Approach

Amesh A. Adalja, MD, FACP, FACEP, FIDSA | April 30, 2020

We are quickly learning that our standard approach to treating acute respiratory distress syndrome (ARDS) needs to change for many COVID-19 patients. One of the biggest advances in the treatment of ARDS was the realization that lung protective ventilation was lifesaving. This is a strategy developed to protect the already damaged lungs from ventilator-induced lung injury (VILI) by using low tidal volumes, carefully monitoring pressures, and being permissive with hypercapnia. The rationale was that any remaining lung that was not severely damaged could not handle the barotrauma from high pressures and needed more gentle ventilation, because it was, in essence, a “baby lung.” This protocol eventually spread throughout the world and became the standard of care for all forms of ARDS; it was even extended to non-ARDS-related mechanical ventilation.

The advent of SARS-CoV-2 and COVID-19 added to the myriad causes of ARDS, and, not surprisingly, ARDS-based protocols were employed in those who required mechanical ventilation. It was quickly determined, however, that the usual ARDS protocols were not ideally suited to the ventilation of individuals with COVID-19 who suffered respiratory failure.


2 Phenotypes: L and H

A pioneer in the treatment of ARDS, Luciano Gattinoni, described 2 separate phenotypes with COVID-19 respiratory failure based on lung compliance. Compliance in the lung is calculated as the ratio of the change in volume of the lung for a given pressure change.

One phenotype (L) was characterized by high compliance in the lungs (or low elastance, hence L). This scenario exists at a time when, although oxygenation may be poor, radiographic infiltrates are minimal (“ground glass”) and lung weight is not markedly elevated. A patient in this situation can accept higher tidal volumes (7-8 mL per kilogram of ideal body weight), as the insult is primary endothelial damage that has restricted the ability of the pulmonary vasculature to vasoconstrict in response to hypoxia, causing a ventilation-perfusion (VQ) mismatch wherein poorly ventilated areas are perfused. In these individuals, high-flow oxygen and noninvasive ventilation (CPAP or BiPAP) may be useful so long as a patient does not have a persistently high respiratory drive, which causes increased stress forces in the lung, leading to injury. In those with high respiratory drive, intubation and mechanical ventilation with higher tidal volumes and lower positive end expiratory pressures (PEEP) are preferred.

The H phenotype is characterized by low compliance (high elastance) and can be the result of lung injury induced during the L phase. Lungs in this state are heavy, and infiltrates may be extensive. In this situation, traditional ARDS-type management is recommended. Various modes can be used, but there is increased interest in using airway pressure release ventilation (APRV), which is a special mode characterized by 2 levels of pressure that invert (by increasing) inspiratory time. Prone position ventilation improves the function of the dependent areas of the lungs, which have been compressed in a sponge-like fashion (“sponge lung”), and has also been used in cases of severe ARDS.

COVID-19 also induces a hypercoagulable state that is evidenced by elevated d-dimer levels. This can further compromise respiratory function by creating microthrombi in the lungs.



To recognize the idiosyncrasies of managing ARDS in a COVID-19 patient, Gattinoni and Marini coined the acronym CARDS. Distinguishing between different variants of ARDS and their unique ventilator needs will be increasingly important for clinicians around the world. It will be fascinating to determine if other infectious causes of ARDS have this pattern or another pattern as well. Dissemination of this research is crucial, as improved ventilator management may substantially decrease mortality, duration of mechanical ventilation, ICU length of stay, and hospital length of stay – all crucial parameters to minimize, as we will face severe COVID-19 for the foreseeable future.



Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation 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(18):1301-1308.

Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA 2020. doi: 10.1001/jama.2020.6825. Accessed April 30, 2020.

Gattinoni L, Chiumello D, Caironi P, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med 2020; doi: 10.1007/s00134-020-06033-2. Accessed April 30, 2020.

Farkas J. Guide to APRV for COVID. The Internet Book of Critical Care. April 8, 2020.