By Vibhu Sharma, MD, MS

Assistant Professor of Medicine, University of Colorado, Denver

SYNOPSIS: This retrospective analysis compared historical cohorts with COVID-19-related acute respiratory distress syndrome (ARDS) with respect to compliance and arterial partial pressure of oxygen/fraction of inspired oxygen (P/F) ratios. For comparable P/F ratios, patients with ARDS caused by COVID-19 had higher lung compliance and more lung gas volume.

SOURCE: Chiumello D, Busana M, Coppola S, et al. Physiological and quantitative CT-scan characterization of COVID-19 and typical ARDS: A matched cohort study. Intensive Care Med 2020;46:2187-2196.

This was a small, retrospective cohort study wherein 32 consecutive patients with COVID-19-related acute respiratory distress syndrome (ARDS) were matched with two historical ARDS cohorts, one matched for compliance (Crs) and the other matched for arterial partial pressure of oxygen/fraction of inspired oxygen (P/F) ratio. Historical cohorts also were matched for age, sex, ideal body weight, and body mass index (BMI). The study cohorts were comprised of patients cared for in Milan, Italy, by Luciano Gattinoni’s group.

Crs and P/F ratios for the matching non-COVID-19 cohorts were obtained at a positive end-expiratory pressure (PEEP) of 5 cm H2O during mechanical ventilation immediately before computed tomography (CT) imaging. CT imaging was available for all patients, and all patients underwent standardized physiologic testing and management as per the institution-specific protocol and ARDSNet criteria, respectively.

Whole lung imaging was performed under static conditions (all patients received muscle relaxation) with an end-expiratory breath hold at 5 cm H2O PEEP. Lung weight, gas volume, and amount of overinflated, well-aerated, poorly aerated, and non-aerated tissue were estimated using CT criteria. The radiodensity of various tissues is estimated by linear transformation of attenuation coefficients and expressed in Hounsfield units (HU). Overinflated tissue was estimated by assessing overall estimates of tissue with radiodensity of -1,000 HU to -900 HU, well-aerated tissue at -899 HU to -500 HU, poorly aerated tissue at -499 HU to -100 HU, and non-aerated tissue at -100 HU to + 100 HU. All analyses were performed using proprietary software on each whole slice as well as on 10 equally spaced slices on each lung.

Both COVID-19 ARDS and matched non-COVID-19 ARDS cohorts had similar baseline characteristics. At similar P/F ratios, COVID-19-ARDS lungs had higher compliance (49.9 ± 15 vs. 39.9 ± 11 mL/cm H2O; P = 0.003) as well as lower plateau pressures (Pplat) and driving pressures. At similar compliance levels, COVID-19-ARDS P/F ratios were significantly lower than matched non-COVID-19-ARDS P/F ratios (106.5 ± 59 vs. 160 ± 62 mmHg; P < 0.001). Alveolar to arterial oxygen concentration (A-a) gradients were higher in both compliance-matched and P/F-matched non-COVID-19 ARDS. Interestingly, although P/F ratios decreased as Crs dropped in non-COVID-19 ARDS, this was not true in the group of patients with COVID-19 ARDS. Indeed, there was no association between Crs and P/F ratios in COVID-19-ARDS lungs.

With respect to CT criteria, when matched for P/F ratio, COVID-19-ARDS lungs had more aerated lung tissue, less non-aerated lung tissue, and more normally aerated lung tissue. When matched for Crs, COVID-19-ARDS lungs had higher lung gas volumes. When measured by lung segment, COVID-19-ARDS lungs had the highest gas volumes, followed by Crs-matched non-COVID-19-ARDS lungs, and then P/F-matched non-COVID-19-ARDS lungs. The authors also assessed response to a PEEP trial, wherein PEEP was increased from 5 cm H2O to 15 cm H2O. Oxygenation improved in all three cohorts. However, dead space and respiratory system mechanics improved in the P/F-matched non-COVID-19-ARDS cohort, but remained unchanged or worsened in the Crs-matched non-COVID-19-ARDS cohort and the COVID-19-ARDS cohort.

COMMENTARY

The results of this interesting study contrast with some large studies that have shown that COVID-19 ARDS is similar to non-COVID-19 ARDS with respect to lung compliance and P/F ratios. The authors surmised that this may be related to the timing/condition of measurements. In this study, all measurements were made at a PEEP of 5 cm H2O and at 9.6 ± 4 days after the onset of COVID symptoms and were compared to non-COVID-19-ARDS patients early in their disease course (< 7 days from admission). As the disease course progresses, the imaging findings of COVID-19 ARDS progressively change from bilateral diffuse ground glass opacities to consolidations seen in the more typical non-COVID-19-ARDS population caused by sepsis and trauma, for example.

One reason for the higher lung gas seen in COVID-19-ARDS lungs may be the unique endothelialitis that accompanies COVID-19 ARDS. Although the histologic pattern of lung injury in both COVID-19 ARDS and influenza-related ARDS is diffuse alveolar damage, lungs from patients with COVID-19 ARDS show unique pathology. A histologic analysis found a nine-fold higher prevalence of alveolar capillary microthrombi compared with influenza.1 Neovascular angiogenesis also was seen more frequently. Both of these processes likely lead to a larger dead space fraction. Therefore, ventilation-perfusion (V/Q) mismatching seen in these patients may be related to the abnormalities in the capillary bed and not the result of alveolar filling or shunt physiology that is seen in more typical ARDS. However, this remains speculative, and more studies are needed to better define the endothelialitis that accompanies COVID-19 ARDS.

Case series of COVID-19 ARDS have demonstrated low lung compliance similar to patients with non-COVID-19 ARDS and the need for high levels of PEEP to maintain oxygenation.2-4 Although there may be a subset of patients with COVID-19 ARDS that has higher lung gas volumes when studied early in their disease onset, the preponderance of the evidence suggests that, on average, COVID-19 ARDS and non-COVID-19 ARDS have similar physiology, and the overall differences are not significant enough to merit a change in ventilator management. Until a large, multicenter, randomized study is able to demonstrate conclusively that a different approach to ventilator management of early COVID-19 ARDS (or the subset with higher lung gas) leads to improved outcomes, it is prudent to continue to rigorously adhere to the well-established ARDSNet criteria. 

REFERENCES

  1. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med 2020;383:120-128.
  2. Schenck EJ, Hoffman K, Goyal P, et al. Respiratory mechanics and gas exchange in COVID-19-associated respiratory failure. Ann Am Thorac Soc 2020;17:1158-1161.
  3. Grasselli G, Tonetti T, Protti A, et al. Pathophysiology of COVID-19-associated acute respiratory distress syndrome: A multicentre prospective observational study. Lancet Respir Med 2020;8:1201-1208.
  4. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy region, Italy. JAMA 2020;323:1574-1581.