Gas exchange calculation may estimate changes in pulmonary blood flow during veno-arterial extracorporeal membrane oxygenation in a porcine model

Abstract

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is used as rescue therapy for severe cardiopulmonary failure. We tested whether the ratio of CO₂ elimination at the lung and the V-A ECMO (V˙co_2ECMO/V˙co_2Lung) would reflect the ratio of respective blood flows and could be used to estimate changes in pulmonary blood flow (Q˙_Lung), i.e., native cardiac output. Four healthy pigs were centrally cannulated for V-A ECMO. We measured blood flows with an ultrasonic flow probe. V˙co_2ECMO and V˙co_2Lung were calculated from sidestream capnographs under constant pulmonary ventilation during V-A ECMO weaning with changing sweep gas and/or V-A ECMO blood flow. If ventilation-to-perfusion ratio (V˙/Q˙) of V-A ECMO was not 1, the V˙co_2ECMO was normalized to V˙/Q˙ = 1 (V˙co_2ECMONorm). Changes in pulmonary blood flow were calculated using the relationship between changes in CO₂ elimination and V-A ECMO blood flow (Q˙_ECMO). Q˙_ECMO correlated strongly with V˙co_2ECMONorm (r² 0.95-0.99). Q˙_Lung correlated well with V˙co_2Lung (r² 0.65-0.89, P < = 0.002). Absolute Q˙_Lung could not be calculated in a nonsteady state. Calculated pulmonary blood flow changes had a bias of 76 (-266 to 418) mL/min and correlated with measured Q˙_Lung (r² 0.974-1.000, P = 0.1 to 0.006) for cumulative ECMO flow reductions. In conclusion, V˙co₂ of the lung correlated strongly with pulmonary blood flow. Our model could predict pulmonary blood flow changes within clinically acceptable margins of error. The prediction is made possible with normalization to a V˙/Q˙ of 1 for ECMO. This approach depends on measurements readily available and may allow immediate assessment of the cardiac output response.

Keywords: ECMO; carbon dioxide; cardiac output; intensive care; weaning.

Fig. 1.

Experimental protocol with stepwise reduction of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) sweep gas flow (V̇_ECMO) and/or blood flow (Q̇_ECMO). Steps 1–4 of each phase [reduction of V̇(V), reduction of Q̇(Q), and reduction of both (VQ)] indicated at top.

Fig. 2.

Schematics for veno-arterial extracorporeal membrane oxygenation (V-A ECMO). Q̇_ECMO, V-A ECMO blood flow; Q̇_Lung, lung blood flow; RA, right atrium; V̇co_2ECMO, elimination of CO₂ (V̇co₂) at V-A ECMO; V̇co_2Lung, V̇co₂ at lung; V̇o₂, oxygen intake; c_vCO2, mixed venous CO₂ content; c_pmCO₂, post oxygenator CO₂ content; claCO₂, left atrial CO₂ content; c_aoCO₂, aortal CO₂ content.

Fig. 3.

Effect of the normalization of the sweep gas flow-to-blood flow ratio on the veno-arterial extracorporeal membrane oxygenation (V-A ECMO). A: scatterplot for V-A ECMO blood flow (Q̇_ECMO) vs. elimination of CO₂ at V-A ECMO (V̇co_2ECMO). Smallest points represent phase rV̇_ECMO; medium-sized points represent phase rQ̇_ECMO; large points represent phase rV̇&Q̇_ECMO. No correlations reached significant levels (P < 0.05). B: scatterplot for Q̇_ECMO vs. V̇co_2ECMO normalized to ventilation-to-perfusion ratio (V̇/Q̇) = 1 (V̇co_2ECMONorm), all data points considered. Smallest points represent phase rV̇_ECMO; medium-sized points represent phase rQ̇_ECMO; large points represent phase rV̇&Q̇_ECMO. In phase rQ̇_ECMO, animal 3 did not tolerate the last reduction in V-A ECMO flow.

Fig. 4.

Correlation between lung blood flow (Q̇_Lung) and CO₂ elimination at the lung (V̇co_2Lung) absolute values: scatterplot for Q̇_Lung vs. V̇co_2Lung, all data points considered. Smallest points represent phase rV̇_ECMO; medium-sized points represent phase rQ̇_ECMO; large points represent phase rV̇&Q̇_ECMO. Note that in animal 1 ventilation and thus V̇co_2Lung is high, because baseline settings at respirator were 5.6 L/min [tidal volume (Vt) 465 mL, 12 times/min]. This was the first animal, and the ventilator settings were not adjusted from previous settings. In phase rQ̇_ECMO, animal 3 did not tolerate the last reduction in veno-arterial extracorporeal membrane oxygenation (V-A ECMO) flow.

Fig. 5.

A: Bland–Altman plot for all data points during veno-arterial extracorporeal membrane oxygenation (V-A ECMO) weaning. Bias is positive but close to zero, with wide limits of agreement. Bias stayed constant over increasing changes in lung blood flow (Q̇_Lung) (R² = 0.014). LoA, limits of agreement. B: scatterplot for the real change in Q̇_Lung vs. the calculated change in Q̇_Lung during V-A ECMO weaning. Smallest points represent phase rV̇_ECMO; medium-sized points represent phase rQ̇_ECMO; large points represent phase rV̇&Q̇_ECMO. Linear regressions yield animal 1: y = 0.75 × x + 73.34; animal 2: y = 0.44 × x – 47.85; animal 3: y = 0.73 × x + 7.17; animal 4: y = 0.8 × x – 30.17. C: scatterplot for subsumed weaning steps for each animal. Linear regressions yield animal 1: y = 0.91 × x + 125.05; animal 2: y = 0.47 × x – 166.98; animal 3: y = 0.70 × x + 34.8; animal 4: y = 0.79 × x – 84.95.

Fig. A1.

Relationship between ventilation-to-perfusion ratio (V̇/Q̇) and postmembrane Pco₂ ($\text{P}\mathrm{P}{\mathrm{M}}_{\mathrm{C}{\mathrm{O}}_2}$). Colors refer to different V̇/Q̇ data points resulting from the chosen interval of 0.25.

Fig. A2.

Three-dimensional mesh plot showing postmembrane Pco₂ ($\text{P}\mathrm{P}{\mathrm{M}}_{\mathrm{C}{\mathrm{O}}_2}$, mmHg) as a function of ventilation (L/min) and blood flow (L/min).

Fig. A3.

Three-dimensional mesh plot showing elimination of CO₂ at veno-arterial extracorporeal membrane oxygenation (V̇co_2ECMO, mL/min) as a function of ventilation (L/min) and blood flow (L/min).

Fig. A4.

Correction factor f calculated as a function of ventilation-to-perfusion ratio (V̇/Q̇). Colors refer to different V̇/Q̇ data points resulting from the chosen interval of 0.25.

Fig. A5.

Three-dimensional mesh plot showing elimination of CO₂ at veno-arterial extracorporeal membrane oxygenation (V̇co_2ECMO, mL/min) normalized to ventilation-to-perfusion ratio = 1 as a function of ventilation (L/min) and blood flow (L/min). With normalization, the influence of ventilation on V̇co₂ is eliminated.

Fig. A6.

Curve fitting for correction factor f as a function of ventilation-to-perfusion ratio (V̇/Q̇).