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.
Highlights
Veno-venous extracorporeal membrane oxygenation (ECMO) is a rescue strategy for patients with severe acute respiratory distress syndrome (ARDS) not responsive to conventional positive pressure ventilation (Combes et al, 2020)
ECMO provided around 40% of total VO2, with minimal differences between study steps, while the ECMO VCO2 increased progressively with the reduction of the respiratory rate, up to around 60% of total VCO2 at 6 breaths per minute (Table 1)
The percentage of collapsed non-aerated lung tissue in the whole lungs measured by CT scan significantly increased at lower respiratory rate and higher ECMO CO2 extraction (Figure 1A and Table 1)
Summary
Veno-venous extracorporeal membrane oxygenation (ECMO) is a rescue strategy for patients with severe acute respiratory distress syndrome (ARDS) not responsive to conventional positive pressure ventilation (Combes et al, 2020). In usual clinical management of severe ARDS patients, respiratory rate is gradually reduced after start of ECMO but with highly variable targets (Spinelli et al, 2020); large clinical trials used rates ranging between 24 and 5 breaths per minute (Pesenti et al, 1982; Gattinoni et al, 1986; Peek et al, 2009; Terragni et al, 2009; Bein et al, 2013; Combes et al, 2018, 2019), and only two animal studies reported some physiological benefits of reduced respiratory rate during extracorporeal support, but rates differed widely, averaging 14 vs 5 breaths per minute (Grasso et al, 2014; Araos et al, 2019). The physiological targets to guide the reduction of respiratory rate during ECMO are still unclear
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