Atelectasis, Shunt, and Worsening Oxygenation Following Reduction of Respiratory Rate in Healthy Pigs Undergoing ECMO: An Experimental Lung Imaging Study

Elena Spinelli; Giulia Colussi; Gaia Dal Santo; Eleonora Scotti; Ines Marongiu; Erica Garbelli; Alessandra Mazzucco; Daniele Dondossola; Raquel Maia; Michele Battistin; Osvaldo Biancolilli; Lorenzo Rosso; Stefano Gatti; Tommaso Mauri

doi:10.3389/fphys.2021.663313

Atelectasis, Shunt, and Worsening Oxygenation Following Reduction of Respiratory Rate in Healthy Pigs Undergoing ECMO: An Experimental Lung Imaging Study

Front Physiol. 2021 Apr 9:12:663313. doi: 10.3389/fphys.2021.663313. eCollection 2021.

Authors

Elena Spinelli¹, Giulia Colussi¹, Gaia Dal Santo², Eleonora Scotti¹, Ines Marongiu², Erica Garbelli², Alessandra Mazzucco³, Daniele Dondossola^{2

4}, Raquel Maia^{1

5}, Michele Battistin¹, Osvaldo Biancolilli¹, Lorenzo Rosso^{2

3}, Stefano Gatti⁶, Tommaso Mauri^{1

2}

Affiliations

¹ Department of Anesthesia, Critical Care and Emergency, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
² Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
³ Thoracic Surgery and Lung Transplantation Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁴ General and Liver Transplant Surgery Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁵ Department of Intensive Care Medicine, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal.
⁶ Center for Preclinical Research, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Abstract

Rationale: Reducing the respiratory rate during extracorporeal membrane oxygenation (ECMO) decreases the mechanical power, but it might induce alveolar de-recruitment. Dissecting de-recruitment due to lung edema vs. the fraction due to hypoventilation may be challenging in injured lungs. Objectives: We characterized changes in lung physiology (primary endpoint: development of atelectasis) associated with progressive reduction of the respiratory rate in healthy animals on ECMO. Methods: Six female pigs underwent general anesthesia and volume control ventilation (Baseline: PEEP 5 cmH₂O, Vt 10 ml/kg, I:E = 1:2, FiO₂ 0.5, rate 24 bpm). Veno-venous ECMO was started and respiratory rate was progressively reduced to 18, 12, and 6 breaths per minute (6-h steps), while all other settings remained unchanged. ECMO blood flow was kept constant while gas flow was increased to maintain stable PaCO₂. Measurements and Main Results: At Baseline (without ECMO) and toward the end of each step, data from quantitative CT scan, electrical impedance tomography, and gas exchange were collected. Increasing ECMO gas flow while lowering the respiratory rate was associated with an increase in the fraction of non-aerated tissue (i.e., atelectasis) and with a decrease of tidal ventilation reaching the gravitationally dependent lung regions (p = 0.009 and p = 0.018). Intrapulmonary shunt increased (p < 0.001) and arterial PaO₂ decreased (p < 0.001) at lower rates. The fraction of non-aerated lung was correlated with longer expiratory time spent at zero flow (r = 0.555, p = 0.011). Conclusions: Progressive decrease of respiratory rate coupled with increasing CO₂ removal in mechanically ventilated healthy pigs is associated with development of lung atelectasis, higher shunt, and poorer oxygenation.

Keywords: atelectasis; expiratory time; extracorporeal membrane oxygenation; respiratory rate; shunt.