May 5, 2020

EJRC - Pulmonary characteristics in COVID-19 patients: article review of cohort study

Cohort Study showing low compliance of Mechanically Ventilated COVID-19 lungs

The mortality of ICU patients affected by SARS-CoV-2 remains very high. In many cases, this is due to respiratory failure. It is fundamental to understand the underlying pathophysiology in order to tailor the management accordingly.

Ziehr et al conducted a cohort study on 66 COVID-19 patients in two hospitals during March 2020. The authors aimed to determine the pulmonary characteristics in COVID-19 patients. The management was as per the hospitals’ established ARDS protocol.

The latter recommends against the use of NIV or HFNC, and recommends a tidal volume less than 6 ml/kg and a low PEEP/High FiO2 strategy.

All patients were intubated and only 85% met the Berlin definition of ARDS (vast majority were mild to moderate ARDS). Patients had been intubated after a median of 8 days from the onset of symptoms. Proning and neuromuscular blockade were used in 47 and 42% of patients respectively.

The results showed a median physiological dead space fraction of 45%. Respiratory system static compliance was available only in 48 patients with a median of 35 ml/cm H2O (IQR 30-43). The authors document a successful extubation rate of 62% and mortality of 16% after more than 30 days of follow-up.

The results contrast in part the concept of transition between two different phenotypes, as suggested earlier by Prof. Gattinoni and co-workers (2,3).   According to this concept, most patients have preserved compliance (50.2 ± 14.3 ml/cmH2O) associated with a high shunt fraction of 0.50 ± 0.11 (Phenotype L). A minority of 20-30% of patients have a low compliance (Phenotype H).

A transition between the two phenotypes is hypothesised to happen due to a combination of a self-inflicted lung injury (P-SILI) and disease progression. (3) P-SILI can be aggravated by Non-Invasive Ventilation (NIV).  However, in the Ziehr et al cohort, only one patient was treated by NIV and intubation was relatively early.

The data were also collected at an early point (on intubation). More interestingly, the lower compliance was associated with milder degree of hypoxia (median PaO2:FiO2: 182 (IQR 135-245)).

While the findings are interesting, it arises from a small cohort of patients. It raises the question if there are in fact more than two phenotypes in COVID-19 associated lung injury.  However, many factors may have affected the respiratory system compliance: Proning and muscle relaxant was used in less than half of the patients, as well as the low tidal volume (<6 ml/kg) (4).   It would have been of benefit to perform a sub-group analysis to describe any difference in compliance, but the small number of patients remain an obstacle.

The milder hypoxia and high extubation success rate raise the question if those patients would have profited from NIV. However, overcoming a less compliant respiratory system, a greater work of breathing is needed which can precipitate P-SILI.




  • New concept, theory-generating study.
  • Challenges a current concept.


  • Cohort study on small number of patients.
  • Lung mechanics were not available for all patients (48/66).
  • No subgroup analysis.
  • External validity is affected by the specificity of the hospital protocol.



A cohort study showed in a small number of patients, a low respiratory system compliance despite early intubation. Such findings need confirmation in a larger multi-centric study. There is also a need to study the factors which affect such compliance.


This article review was prepared and submitted by Dr Ashraf Roshdy, Locum Consultant, Critical Care, Whipps Cross University Hospital – Barts Health NHS Trust, London, United Kingdom, on behalf of the ESICM Journal Review Club.

1. Ziehr DR, Alladina J, Petri CR, et al.Respiratory Pathophysiology of Mechanically Ventilated Patients with COVID-19: A Cohort Study.  American Journal of Respiratory and Critical Care Medicine 2020.
2. Gattinoni L, Coppola S, Cressoni M, et al. Covid-19 Does Not Lead to a “Typical” Acute Respiratory Distress Syndrome.  Am J Respir Crit Care Med. 2020 Mar 30. doi: 10.1164/rccm.202003-0817LE
3. Gattinoni L, Chiumello D, Caironi P, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? [published online ahead of print, 2020 Apr 14]. Intensive Care Med. 2020;1‐4. doi:10.1007/s00134-020-06033-2
4. Suter PM, Fairley HB, Isenberg MD.  Effect of tidal volume and positive end-expiratory pressure on compliance during mechanical ventilation. Chest. 1978 Feb;73(2):158-62.


Comment on this news

1 reactions

  1. Is Prone Positioning (and high PEEP) a One-Size-Fits-All Strategy for Type 1 Patients With COVID-19 Pneumonia?
    Professor Gattinoni proposed an interesting mechanism by which prone positioning improves oxygenation in type 1 patients with COVID-19 pneumonia who have near-normal compliance with only minimal recruitability. According to Professor Gattinoni, prone positioning (and high PEEP) does not improve oxygenation by recruitment of collapsed areas, but through redistribution of pulmonary perfusion and improvement of V/Q matching. The physiologic mechanism underlying oxygenation improvement in prone-positioned patients who have non-recruitable lung is gravity-dependent reduction in perfusion of the basal (non-dependent) regions such that perfusion becomes more properly matched with ventilation. However, for this mechanism to act there must be a “baseline” increase in pulmonary perfusion relative to alveolar ventilation, such as might result from loss of hypoxic pulmonary vasoconstriction and/or AT2 receptor-mediated vasodilatation (dysregulated pulmonary perfusion). Obviously, when the “baseline” V/Q abnormality is increased shunt due to increased pulmonary blood flow, measures that reduce blood flow such as prone positioning (and high PEEP) would be expected to improve V/Q ratio and arterial oxygenation—regardless of alveolar recruitment. However, this is unlikely to occur if dead space ventilation resulting from pulmonary micro-thrombi, right heart failure or AT1 receptor-mediated pulmonary vasoconstriction is the main mechanism of hypoxemia. By further decreasing pulmonary perfusion, prone positioning (and high PEEP) may actually worsen dead space ventilation and pulmonary gas exchange. The effect of prone positioning (and high PEEP) on arterial oxygenation in type 1 patients is probably determined by which type of V/Q mismatch is present at baseline—shunt vs dead space ventilation. Thus, it is likely that prone positioning (and high PEEP) is not a “one-size-fits-all” strategy for patients with type 1 disease, and that careful evaluation of the underlying physiologic abnormality is mandatory before considering prone positioning (and high PEEP) in these patients.