Patients with coronavirus disease 2019 (COVID-19) pneumonia are most often hospitalized with hypoxemic respiratory failure (1). A substantial number of these individuals present with bilateral infiltrates and Pao2/Fio2 ratios less than 300 mm Hg/cm H2O even when receiving positive end-expiratory pressure (PEEP)/continuous positive airway pressure greater than or equal to 5 cm H2O (2). These patients, therefore, meet consensus criteria for acute respiratory distress syndrome (ARDS) (3). Nonetheless, preliminary reports suggested that patients with COVID-19 pneumonia presented or developed peculiar characteristics that set them apart from those with “typical” ARDS (4). Indeed, some suggest refining the ARDS nomenclature so that COVID-19 may be identified as distinct from “classical” ARDS (4,5). The particular differences noted in COVID patients by multiple clinicians in different countries include unusually high levels of respiratory compliance and dramatic increases in dead space (6,7). This pliability starkly contrasts with both the severity of hypoxemia and the characteristics of ARDS, where compliance and oxygenation are both indicators of severity (8). Conversely, two recent reports on 66 COVID-19 patients requiring mechanical ventilation indicated that median static compliance was comparable with the values observed in ARDS (9,10). The authors in one posited that “Patients with COVID-19 respiratory failure exhibit similar gas exchange, respiratory system mechanics and response to prone ventilation as prior large cohorts of patients with ARDS.” However, Haudebourg et al (10) noted that both COVID and non-COVID groups had large dispersion of compliance, with greater than 25% of values above 50 mL/cm H2O, a range overlapping with those observed during abdominal surgery (11). An additional discrepancy is apparent on CT scans. Edema, vertical distribution of pulmonary gas and tissue, and substantial areas of collapse in dependent lung segments are the characteristics of ARDS (12). In contrast, many COVID-19 patients display sparse opacities with relatively preserved overall aeration, a lack of collapse in dependent lung regions, and limited evidence of increased lung water (13). Furthermore, a recent report using perfusional CT scans showed mosaic disturbances of blood distribution, with hyperemia and oligemia interspersed in the areas of opacified tissue (14). In contrast to classical ARDS, these findings suggest that ventilation/perfusion maldistribution in some COVID-19 patients reflects a vascular, rather than alveolar, problem. Thus, it appears that pulmonary abnormalities in patients with COVID-19 pneumonia may take several different forms, one of which resembles classical ARDS. Alternatively, it has been proposed that ARDS presents with a number of pathobiological phenotypes (15–17). The “hypercompliance” present in some patients with COVID-19 pneumonia may represent a phenotype that has not previously been described.
Adjudication on this controversy may directly affect treatment. While there are evidence-based standards of care for ARDS (low stretch ventilation, prone positioning, and conservative fluid management), the data regarding management of COVID-19 respiratory failure are at best incomplete. Furthermore, our ability to determine where on the spectrum of disease a given case of COVID-19 lies is problematic. Patients who closely resemble individuals with classical ARDS—hypoxemia accompanied by impaired compliance and difficult to recruit respiratory units in dependent lung regions—may be appropriately managed with the tools that have been effective in the treatment of that disorder, tidal volumes (TVs) limited to 4–6 cc/kg, titrated levels of PEEP, prone positioning, etc. However, in a patient whose compliance is high, these approaches may lead to overly restrictive limitations on TVs, unnecessary high levels of PEEP, and, for the patient to tolerate these measures, a potentially problematic need for sedation. Prone positioning may not provide benefit unless used to improve the misdistribution of tidal inflation or to reverse severe hypoxemia (18), and the effort involved may increase the risk to medical personnel. There are additional concerns regarding the application of “standard” ARDS care to the treatment of COVID-19. First, studies suggest that COVID-19 patients are prone to pulmonary blood clots and microangiopathy (19). Additionally, autopsy results reveal renal (and perhaps cardiac) pathology consistent with ischemia-reperfusion injury (20,21). Both abnormalities are potential consequences of hypovolemia. Although confirmation in larger studies is required, the implications of this constellation of findings are striking. Overly small TVs can increase dead space. High levels of PEEP might enhance hyperinflation and alveolar dead space (7). Additionally, fluid restriction may lead to excessive coagulation and hypoperfusion. Overall, the factors that identify distinct differences between the COVID-19 patients and other forms of acute respiratory failure should raise concern about the application of one-size-fits-all therapy.
Thus, while we await in-depth studies (as opposed to opinion papers and descriptive case series), it seems appropriate to apply “standard” ARDS care to those COVID-19 patients whose pulmonary pathophysiology is consistent with that disorder. However, reliance on thoughtful bedside observation and physiologic understanding, the elements that identify the essence of intensive care practice, is essential. An example of such individualized approach is a rescue strategy optimizing lung mechanics, ventilation distribution, and right ventricular function to improve the survival of obese ARDS patients (22). We should also consider a larger question: has critical care medicine evolved to the point where we are able to titrate care to the complexity of the disorder and the characteristics of individual patients? In this regard, COVID-19 may serve as an important test. Consensus criteria identify and grade ARDS severity based on the degree of oxygenation impairment (3). Clinical criteria have been applied to other disorders in the critically ill, most notably sepsis (Sepsis-3) (23). However, specific patterns of respiratory mechanics (20), the response to alveolar recruitment (24), and biomarker profiles (25) are predictive of differences in outcomes and treatment efficacy in ARDS. These findings suggest that “ARDS” is not a single entity but rather an umbrella term for a number of distinct syndromes. Investigators at the University of California, San Francisco have used biomarker profiles to identify subsets of patients with ARDS who have unique responses to PEEP/TV (16), fluid administration (15), and certain drugs (17). Key differences between COVID-19 pneumonia and ARDS suggest that COVID-19 patients may occupy their own unique space under the “ARDS umbrella.”
In conclusion, standards of care should not suffocate the ability of an observant and well-trained practitioner to modify and refine management. However, the emergence of COVID-19 highlights the dilemma that may present when provision of individualized care is attempted in poorly understood disorders in complex patients. Finding a balance is essential to combat COVID-19 pneumonia and to advance the discipline of critical care medicine.
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