Lung response to prone positioning in mechanically-ventilated patients with COVID-19

Abstract

Background: Prone positioning improves survival in moderate-to-severe acute respiratory distress syndrome (ARDS) unrelated to the novel coronavirus disease (COVID-19). This benefit is probably mediated by a decrease in alveolar collapse and hyperinflation and a more homogeneous distribution of lung aeration, with fewer harms from mechanical ventilation. In this preliminary physiological study we aimed to verify whether prone positioning causes analogue changes in lung aeration in COVID-19. A positive result would support prone positioning even in this other population.

Methods: Fifteen mechanically-ventilated patients with COVID-19 underwent a lung computed tomography in the supine and prone position with a constant positive end-expiratory pressure (PEEP) within three days of endotracheal intubation. Using quantitative analysis, we measured the volume of the non-aerated, poorly-aerated, well-aerated, and over-aerated compartments and the gas-to-tissue ratio of the ten vertical levels of the lung. In addition, we expressed the heterogeneity of lung aeration with the standardized median absolute deviation of the ten vertical gas-to-tissue ratios, with lower values indicating less heterogeneity.

Results: By the time of the study, PEEP was 12 (10-14) cmH₂O and the PaO₂:FiO₂ 107 (84-173) mmHg in the supine position. With prone positioning, the volume of the non-aerated compartment decreased by 82 (26-147) ml, of the poorly-aerated compartment increased by 82 (53-174) ml, of the normally-aerated compartment did not significantly change, and of the over-aerated compartment decreased by 28 (11-186) ml. In eight (53%) patients, the volume of the over-aerated compartment decreased more than the volume of the non-aerated compartment. The gas-to-tissue ratio of the ten vertical levels of the lung decreased by 0.34 (0.25-0.49) ml/g per level in the supine position and by 0.03 (- 0.11 to 0.14) ml/g in the prone position (p < 0.001). The standardized median absolute deviation of the gas-to-tissue ratios of those ten levels decreased in all patients, from 0.55 (0.50-0.71) to 0.20 (0.14-0.27) (p < 0.001).

Conclusions: In fifteen patients with COVID-19, prone positioning decreased alveolar collapse, hyperinflation, and homogenized lung aeration. A similar response has been observed in other ARDS, where prone positioning improves outcome. Therefore, our data provide a pathophysiological rationale to support prone positioning even in COVID-19.

Keywords: Acute respiratory distress syndrome; Coronavirus disease 2019; Hypoxia; Mechanical ventilation; Pneumonia; Prone positioning.

Fig. 1

Individual morphological response to prone positioning. Fifteen mechanically-ventilated patients with COVID-19 underwent a lung computed tomography in the supine and prone position. A–D we describe the individual changes in the total (tissue and gas) volume of the non-aerated (density above − 100 HU), poorly-aerated (from − 100 to − 500 HU), normally-aerated (from − 500 to − 900 HU), and over-aerated (below − 900 HU) compartments with prone positioning, in descending order. E, F each CT slice was divided into ten equal vertical levels, from the sternum (vertical level 1) to the vertebra (vertical level 10), and in ten equal horizontal levels, from the apex (horizontal level 1) to the base (horizontal level 10) of the lung. Herein we describe the individual change in the degree of heterogeneous aeration along the vertical and horizontal axis, expressed with the standardized median absolute deviation of regional gas-to-tissue ratios, and presented in descending order. Negative values indicate that the volume of a given compartment or the degree of heterogeneity decreased with prone positioning. Each bar refers to one patient. The same letter in the six panels refers to the same patient. Patient N had a baseline PaO₂:FiO₂ of 273 mmHg; the decision to prone him was based on the detection of large ventral lung hyperinflation at the CT taken in the supine position (please refer to the main text for other details)

Fig. 2

Colour-coded analysis of lung computed tomography (CT) data. Representative CT images taken at the level of carina from three patients with COVID-19 in the supine and prone position, with a very large decrease in the volume of the over-aerated compartment in response to prone positioning. Upper panels: original lung CT images, with aeration shown on a continuous grayscale. Lower panels: using an automated encoding system, we attributed a specific colour to the non-aerated, poorly-aerated, normally-aerated, and over-aerated compartments. The three patients are identified with the same letters as in other figures. With prone positioning, the volume of the over-aerated lung decreased from 318 to 121 ml in patient J; from 738 to 148 ml in patient C; from 503 to 230 ml in patient F

Fig. 3

Regional lung gas-to-tissue ratio in the supine and prone position. Fifteen mechanically-ventilated patients with COVID-19 underwent a lung computed tomography (CT) in supine and prone positions. Each CT slice was divided into ten equal vertical levels, from the sternum (vertical level 1) to the vertebra (vertical level 10), and in ten equal horizontal levels, from the apex (horizontal level 1) to the base (horizontal level 10) of the lung. Herein we describe the ratio of the gas volume (ml) to the tissue weight (g) in each of those levels, in the supine and prone positions. Data are reported as median (Q1–Q3). A vertical gradient of lung inflation. On average, the gas-to-tissue ratio decreased by 0.34 (0.25–0.49) ml/g per level in the supine position and by 0.03 (− 0.11 to 0.14) ml/g in the prone position (p < 0.001). B horizontal gradient of lung inflation. On average, the gas-to-tissue ratio decreased by 0.14 (0.04–0.27) ml/g per level in the supine position and by 0.11 (− 0.05 to 0.21) ml/g in the prone position (p = 0.003)

Fig. 4

Individual functional response to prone positioning. Fourteen mechanically-ventilated patients with COVID-19 were evaluated in the supine and prone positions. Herein we describe the response to prone positioning in terms of change in arterial oxygenation (expressed as the ratio of the arterial tension to the inspiratory fraction of oxygen [PaO₂:FiO₂]) (n = 14) (A), respiratory system compliance (n = 14) (B), and carbon dioxide tension (PaCO₂) for the same minute ventilation (n = 13) (C), in descending order. Each bar refers to one patient. The same letter in the three panels refers to the same patient. Please note that patient D, present in other figures, did not undergo prone positioning and is absent from this figure. FiO₂ was decreased in the prone position in patient K and patient F, and increased in patient G. The impact of prone positioning on PaCO₂ could not be assessed in patient L because his minute ventilation was increased during prone positioning. Finally, patient N had a baseline PaO₂:FiO₂ of 273 mmHg; the decision to prone him was based on the detection of large ventral lung hyperinflation at the CT taken in the supine position (please refer to the main text for other details)