Changes in shunt, ventilation/perfusion mismatch, and lung aeration with PEEP in patients with ARDS: a prospective single-arm interventional study

Dan Stieper Karbing, Mauro Panigada, Nicola Bottino, Elena Spinelli, Alessandro Protti, Stephen Edward Rees, Luciano Gattinoni, Dan Stieper Karbing, Mauro Panigada, Nicola Bottino, Elena Spinelli, Alessandro Protti, Stephen Edward Rees, Luciano Gattinoni

Abstract

Background: Several studies have found only a weak to moderate correlation between oxygenation and lung aeration in response to changes in PEEP. This study aimed to investigate the association between changes in shunt, low and high ventilation/perfusion (V/Q) mismatch, and computed tomography-measured lung aeration following an increase in PEEP in patients with ARDS.

Methods: In this preliminary study, 12 ARDS patients were subjected to recruitment maneuvers followed by setting PEEP at 5 and then either 15 or 20 cmH2O. Lung aeration was measured by computed tomography. Values of pulmonary shunt and low and high V/Q mismatch were calculated by a model-based method from measurements of oxygenation, ventilation, and metabolism taken at different inspired oxygen levels and an arterial blood gas sample.

Results: Increasing PEEP resulted in reduced values of pulmonary shunt and the percentage of non-aerated tissue, and an increased percentage of normally aerated tissue (p < 0.05). Changes in shunt and normally aerated tissue were significantly correlated (r = - 0.665, p = 0.018). Three distinct responses to increase in PEEP were observed in values of shunt and V/Q mismatch: a beneficial response in seven patients, where shunt decreased without increasing high V/Q; a detrimental response in four patients where both shunt and high V/Q increased; and a detrimental response in a patient with reduced shunt but increased high V/Q mismatch. Non-aerated tissue decreased with increased PEEP in all patients, and hyperinflated tissue increased only in patients with a detrimental response in shunt and V/Q mismatch.

Conclusions: The results show that improved lung aeration following an increase in PEEP is not always consistent with reduced shunt and V/Q mismatch. Poorly matched redistribution of ventilation and perfusion, between dependent and non-dependent regions of the lung, may explain why patients showed detrimental changes in shunt and V/Q mismatch on increase in PEEP, despite improved aeration.

Trial registration: ClinicalTrails.gov, NCT04067154. Retrospectively registered on August 26, 2019.

Keywords: ARDS; CT; Lung aeration; PEEP; Shunt; Ventilation/perfusion mismatch.

Conflict of interest statement

DSK and SER’s institution has received funding from Mermaid Care A/S. DSK and SER have performed consultancy work for Mermaid Care A/S. DSK and SER are minor shareholders in Mermaid Care A/S, and SER is an unpaid board member of the company. MP, NB, ES, AP, and LG have no further potential conflicts of interest.

Figures

Fig. 1
Fig. 1
Study protocol. Protocol steps and measurements performed in the protocol. Separation of protocol steps between different locations is indicated (dashed lines). Measurements of shunt and V/Q mismatch were performed in the intensive care unit (ICU). Lung aeration measurements were performed in the CT lab
Fig. 2
Fig. 2
Data analysis example. Patient example of measured data and results of data analysis describing gas exchange and lung aeration. a Input data for calculating shunt and V/Q mismatch parameters. Left subplot shows measured FETO2 versus SpO2 (+) and SaO2 at low (▽) and high (△) PEEP along with curves illustrating model-fitted simulations at low (solid curve) and high (dashed curve) PEEP. Right subplot shows measured FETCO2 versus simulated PaCO2 (○) and measured PaCO2 at low (▽) and high (△) PEEP. b CT scans taken at 5, 20, and 45 cmH2O. c Resulting gas exchange model parameters from the model fit to the measured data illustrated in a. d Resulting CT HU frequency distributions from CT scans illustrated in b for PEEP 5 (solid line), 20 (dashed line), and 45 (dotted line) cmH2O
Fig. 3
Fig. 3
Correlation of lung aeration and shunt and V/Q mismatch. Scatterplots of changes in gas exchange parameters and CT scan lung aeration with increases in PEEP (values at high minus low PEEP) and linear regression lines (solid lines). a Changes in ΔA-cPCO2 versus changes in hyperinflated lung regions. b Changes in ΔA-cPO2 versus changes in poorly aerated lung regions. c Changes in shunt versus changes in non-aerated lung regions. d Changes in shunt versus changes in normally aerated lung regions
Fig. 4
Fig. 4
Individual patient changes in shunt, V/Q mismatch, and lung aeration. Changes from low to high PEEP in shunt and V/Q mismatch (top row) and lung aeration (bottom row). Beneficial and detrimental responses in shunt and V/Q mismatch to an increase in PEEP are marked by line styles, with solid and dashed lines signifying beneficial and detrimental responses, respectively. The combinations of symbols and line styles are unique per patient so that individual patients can be identified across all subplots

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