Pathophysiology and Clinical Meaning of Ventilation-Perfusion Mismatch in the Acute Respiratory Distress Syndrome

Douglas Slobod, Anna Damia, Marco Leali, Elena Spinelli, Tommaso Mauri, Douglas Slobod, Anna Damia, Marco Leali, Elena Spinelli, Tommaso Mauri

Abstract

Acute respiratory distress syndrome (ARDS) remains an important clinical challenge with a mortality rate of 35-45%. It is being increasingly demonstrated that the improvement of outcomes requires a tailored, individualized approach to therapy, guided by a detailed understanding of each patient's pathophysiology. In patients with ARDS, disturbances in the physiological matching of alveolar ventilation (V) and pulmonary perfusion (Q) (V/Q mismatch) are a hallmark derangement. The perfusion of collapsed or consolidated lung units gives rise to intrapulmonary shunting and arterial hypoxemia, whereas the ventilation of non-perfused lung zones increases physiological dead-space, which potentially necessitates increased ventilation to avoid hypercapnia. Beyond its impact on gas exchange, V/Q mismatch is a predictor of adverse outcomes in patients with ARDS; more recently, its role in ventilation-induced lung injury and worsening lung edema has been described. Innovations in bedside imaging technologies such as electrical impedance tomography readily allow clinicians to determine the regional distributions of V and Q, as well as the adequacy of their matching, providing new insights into the phenotyping, prognostication, and clinical management of patients with ARDS. The purpose of this review is to discuss the pathophysiology, identification, consequences, and treatment of V/Q mismatch in the setting of ARDS, employing experimental data from clinical and preclinical studies as support.

Keywords: acute respiratory distress syndrome; electrical impedance tomography; perfusion; ventilation; ventilation-induced lung injury.

Conflict of interest statement

TM reports receiving personal fees from Fisher and Paykel, Dräger, Mindray and B. Braun. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanisms of V/Q mismatch and their interaction.
Figure 2
Figure 2
Ventilation, perfusion, and ventilation-perfusion matching via electrical impedance tomography in 4 experimental swine study groups. Images on the left display regional ventilation, middle images depict regional perfusion and were obtained by administering a hypertonic saline bolus under apneic conditions (see text), and images on the right depict ventilation-perfusion matching, which is expressed as the superposition of the ventilation and perfusion maps. The percentages of ventilation and perfusion to each of the four quadrants are annotated as blue and red numbers, respectively, on the right-side panels. The letters R and L indicate the right and left lung, respectively. (Panels A and B) were obtained during one-lung ventilation (OLV) with exclusion of the left lung and a tidal volume of 15 mL/kg (panel A) and 7.5 mL/kg (panel B) [83]. At both tidal volumes, there is no ventilation of the left lung and perfusion appears to be redistributed to the ventilated lung. OLV at higher tidal volume (panel A) caused bilateral lung injury (lung histological score 5 ± 2 in the right lung and 10 ± 2 in the left lung); this was compared to two-lung-ventilated controls (lung histological score 3 ± 1 in right lung and 3 ± 1 in left lung). Interestingly, lowering tidal volume to 7.5 mL/kg (panel B) attenuated inflammation and lung injury (lung histological score 3 ± 1 in the right lung and 7 ± 1 in the left lung) despite an absence of change in the overall distributions of ventilation and perfusion (ANOVA p ≤ 0.01 for the right lung and p ≤ 0.001 for the left lung). (Panels C and D) were obtained from a study of selective left pulmonary artery ligation [84]. (Panel C) represents ligation alone whereas (panel D) represents ligation + 5% inhaled CO2. The two groups differ significantly both for ventilation and perfusion distributions: In the ligation group, perfusion is only present in the right lung, ventilation is also diverted to the right lung, and total lung histological score was 11 ± 3. In the ligation + inhaled CO2 group, there is a more homogeneous distribution of ventilation and perfusion in both lungs and total lung histological score decreased to 4 ± 2 (ANOVA p ≤ 0.0001). The occurrence of perfusion to the ligated lung with inhaled CO2 is thought to transpire due to increased flow through bronchial circulation.
Figure 3
Figure 3
Evaluation of ventilation and perfusion maps at the bedside using electrical impedance tomography. Left-side blue panels display the regional distribution of ventilation. The red-colored middle panels display the regional distribution of perfusion (see text for details). Right-sided panels show the superposition of the contours of the ventilation and perfusion maps. The percentages of ventilation and perfusion for each of the four quadrants are annotated as blue and red numbers, respectively. (Row A) was obtained from a patient with COVID-19-associated acute respiratory distress syndrome (ARDS) ventilated in the supine position. The maps displayed in (row B) were obtained from the same patient during ventilation in the prone position, resulting in a reduction in ventilation-perfusion mismatch [60]. (Row C) illustrates an ARDS patient in the supine position with a set PEEP of 5 cmH2O. (Row D) was obtained from the same patient in the supine position after PEEP was increased to 15 cmH2O, resulting in an increase in the size of the ventilated area and improved superposition of the ventilation and perfusion maps [63].

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