key: cord-1034882-8kfj6lam
authors: Perier, François; Tuffet, Samuel; Maraffi, Tommaso; Alcala, Glasiele; Victor, Marcus; Haudebourg, Anne-Fleur; De Prost, Nicolas; Amato, Marcelo; Carteaux, Guillaume; Mekontso Dessap, Armand
title: Effect of Positive End-Expiratory Pressure and Proning on Ventilation and Perfusion in COVID-19 Acute Respiratory Distress Syndrome
date: 2020-12-15
journal: Am J Respir Crit Care Med
DOI: 10.1164/rccm.202008-3058le
sha: 49b1113780f5406f469ea4932968f6430d24b8ea
doc_id: 1034882
cord_uid: 8kfj6lam

nan

To the Editor:

Assessment of lung ventilation and perfusion of coronavirus disease (COVID-19) with acute respiratory distress syndrome (C-ARDS) is still scarce, especially in response to positive end-expiratory pressure (PEEP) and prone positioning. The objective of this study was to describe the physiological effects of PEEP and prone position on respiratory mechanics, ventilation, and pulmonary perfusion in patients with C-ARDS. to exploration, prior to prone positioning, and at the end of proning.

The following parameters were collected in each phase: expiratory VT, peak pressure, plateau pressure, total PEEP, end-inspiratory and end-expiratory esophageal pressure (Nutrivent; Sidam), pulse oximetry, end-tidal expired carbon dioxide pressure, respiratory rate, heart rate, blood pressure, and cardiac output (CO, FloTrac system; Edwards Lifesciences). EIT data analysis. We separated the lung into a dependent area corresponding to the posterior half (dorsal) and a nondependent area corresponding to the anterior half (ventral) of the lung EIT image taken in supine position. We measured the following parameters in dependent and nondependent lung regions: impedance variation during ventilation (ΔZ _ V) and perfusion (ΔZ _ Q) and relative distribution of ventilation and perfusion, VT distending lung regions, regional respiratory system compliance (2), and _ VA/ _ Q ratio for each pixel derived from the formula, assuming a 30% fixed anatomical dead space:

The _ VA/ _ Q ratio of each pixel was used to define shunt (severe if ,0.1 and moderate if between 0.1 and 0.5) or a dead space (severe if .10 and moderate if between 2 and 10). The shunt fraction was the fraction of CO perfusing the shunt pixels. The dead space fraction was the fraction of alveolar ventilation supplying the dead space pixels. This is an ancillary report of two ongoing prospective observational studies on ARDS (CPP-66/17 and IRB-2018-A00867-48).

Statistics. Quantitative data are expressed as median (first to third quartile). Effects of PEEP were analyzed by Friedman test followed by Wilcoxon paired test with Benjamini-Hochberg correction for multiple testing. Effects of prone positioning were studied using Wilcoxon paired test.

Among 41 patients with C-ARDS admitted during the study period, 9 completed full explorations and could be analyzed ( Table 1 and Figure 1 (including an illustrative typical response).

PEEP. Ventilation was predominantly ventral at low PEEP and dorsal at high PEEP, and the anteroposterior gradient got inversed with the increase in PEEP. This inversion was mainly driven by ventral hyperdistention (as suggested by the decrease in ventral compliance and the increase in driving pressure, end-inspiratory transpulmonary pressure, and stress index at higher PEEP). Lung perfusion was predominant in the dorsal areas regardless of the PEEP level, but the increase in PEEP reduced CO and further decreased absolute ventral perfusion. Increased PEEP also reduced the proportion of ventral severe dead space and dorsal severe shunt.

Prone position. Turning the patient from supine to prone position increased Pa O 2 /FI O 2 ratio by 64 mm Hg (41-90) and induced recruitment in dorsal regions (i.e., increase in dorsal regional compliance) and collapse in ventral regions (i.e., decrease in ventral regional compliance), but it did not change the dorsal predominance of pulmonary perfusion. Proning decreased ventral dead space and dorsal shunt. The decrease in chest wall compliance was not significant, and lung compliance was not affected.

The effects of PEEP in C-ARDS were close to those reported in classical ARDS. The increase in PEEP resulted in alveolar recruitment associated with a significant decrease in severe shunt, mainly in the dorsal regions, driven by the increase in dorsal ventilation. Additionally, increasing PEEP resulted in less severe alveolar dead space in the ventral regions because ventilation decreased more than perfusion. However, the better _ VA/ _ Q matching at high PEEP was at the price of a clear hyperdistention as suggested by the respiratory mechanics data and, in particular, by the decrease in ventral compliance and ventilation. The effect of prone position was also comparable to that previously observed in classical ARDS. Typically, proning provokes recruitment of dorsal areas and collapse of ventral areas (3), does not change predominantly dorsal pulmonary perfusion in experimental studies (4), and eventually improves _ VA/ _ Q ratios (4) and, consequently, oxygenation, all of which we proved for the first time in our human study. On the one hand, prone position decreases the dorsal shunt because it increases ventilation in this zone and maintains its rich perfusion. On the other hand, proning decreases the ventral dead space because it decreases ventilation in a zone that is poorly perfused. Overall, there was no improvement in lung compliance, which is variable in prone position (5, 6) and depends on the ratio between dorsal recruitment and ventral collapse. The decrease in chest wall compliance did not reach significance, probably because of the small sample size.

The dead space fraction seemed to exceed the shunt fraction in the various tested situations. On the same line, previous work suggested that _ VA/ _ Q mismatch resulted from having ventilated but nonperfused areas in C-ARDS (7). Many reports have highlighted severe pulmonary vascular dysfunction in C-ARDS with high rates of pulmonary embolism and in situ thrombosis (8) . 

The main limitations include the small sample size, highly selected cohort, single PEEP level in prone position, lack of repeated blood gases with PEEP titration (because of specific safety measures at the beginning of the COVID-19 pandemic), and estimation of a fixed anatomical dead space. These preliminary results should be confirmed in a larger population.

Conclusions. Prone positioning and, to a lesser extent, increased PEEP shifted ventilation from ventral to dorsal regions in patients with C-ARDS but did not change perfusion, which remained predominantly dorsal, resulting in better _ VA/ _ Q matching. n Author disclosures are available with the text of this letter at www.atsjournals.org. 

ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition

Bedside assessment of the effects of positive end-expiratory pressure on lung inflation and recruitment by the helium dilution technique and electrical impedance tomography

Body position changes redistribute lung computed-tomographic density in patients with acute respiratory failure

Effect of prone position on regional shunt, aeration, and perfusion in experimental acute lung injury

Effects of the prone position on respiratory mechanics and gas exchange during acute lung injury

Short-term effects of the prone positioning Maneuver on lung and chest wall mechanics in patients with acute respiratory distress syndrome

Potential for lung recruitment and ventilation-perfusion mismatch in patients with the acute respiratory distress syndrome from coronavirus disease 2019

Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19

To the Editor:Spontaneous breathing during mechanical ventilation may lead to worsening lung injury in acute respiratory distress syndrome (ARDS), particularly when high inspiratory efforts that limit the application of lung-protective ventilation are present (1). This hypothesized mechanism of lung injury has been referred to as patient self-inflicted lung injury (P-SILI). High regional transpulmonary pressures secondary to vigorous inspiratory efforts can increase regional lung stress and strain, resulting in local volutrauma (2) . Because the intensity of these inspiratory efforts will depend, at least in part, on the force-generating capacity of the diaphragm, patients with greater diaphragm muscle mass and strength may be at higher risk. This hypothesis is indirectly supported by the recent description of asymmetrically distributed fibrosis in two patients with idiopathic pulmonary fibrosis and hemidiaphragm weakness and atrophy: computed tomography scanning revealed that lesions were restricted to the hemithorax