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Background: Thermodilution is unreliable in veno-venous extracorporeal membrane oxygenation (VV-ECMO). Systemic oxygenation depends on recirculation fractions and ratios of extracorporeal membrane oxygenation (ECMO) flow to cardiac output. In a prospective in vitro simulation, this study assessed the diagnostic accuracy of a modified thermodilution technique for recirculation and cardiac output. The hypothesis was that this method provided clinically acceptable precision and accuracy for cardiac output and recirculation., Methods: Two ECMO circuits ran in parallel: one representing a VV-ECMO and the second representing native heart, lung, and circulation. Both circuits shared the right atrium. Extra limbs for recirculation and pulmonary shunt were added. This study simulated ECMO flows from 1 to 2.5 l/min and cardiac outputs from 2.5 to 3.5 l/min with recirculation fractions (0 to 80%) and pulmonary shunts. Thermistors in both ECMO limbs and the pulmonary artery measured the temperature changes induced by cold bolus injections into the arterial ECMO limb. Recirculation fractions were calculated from the ratio of the areas under the temperature curve (AUCs) in the ECMO limbs and from partitioning of the bolus volume (flow based). With known partitioning of bolus volumes between ECMO and pulmonary artery, cardiac output was calculated. High-precision ultrasonic flow probes served as reference for Bland-Altman plots and linear mixed-effect models., Results: Accuracy and precision for both the recirculation fraction based on AUC (bias, -5.4%; limits of agreement, -18.6 to 7.9%) and flow based (bias, -5.9%; limits of agreement, -18.8 to 7.0%) are clinically acceptable. Calculated cardiac output for all recirculation fractions was accurate but imprecise (RecirculationAUC: bias 0.56 l/min; limits of agreement, -2.27 to 3.4 l/min; and RecirculationFLOW: bias 0.48 l/min; limits of agreement, -2.22 to 3.19 l/min). Recirculation fraction increased bias and decreased precision., Conclusions: Adapted thermodilution for VV-ECMO allows simultaneous measurement of recirculation fraction and cardiac output and may help optimize patient management with severe respiratory failure., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.)

Assessment of native cardiac output during extracorporeal circulation is challenging. We assessed a modified Fick principle under conditions such as dead space and shunt in 13 anesthetized swine undergoing centrally cannulated veno-arterial extracorporeal membrane oxygenation (V-A ECMO, 308 measurement periods) therapy. We assumed that the ratio of carbon dioxide elimination (V̇co 2 ) or oxygen uptake (V̇o 2 ) between the membrane and native lung corresponds to the ratio of respective blood flows. Unequal ventilation/perfusion (V̇/Q̇) ratios were corrected towards unity. Pulmonary blood flow was calculated and compared to an ultrasonic flow probe on the pulmonary artery with a bias of 99 mL/min (limits of agreement -542 to 741 mL/min) with blood content V̇o 2 and no-shunt, no-dead space conditions, which showed good trending ability (least significant change from 82 to 129 mL). Shunt conditions led to underestimation of native pulmonary blood flow (bias -395, limits of agreement -1,290 to 500 mL/min). Bias and trending further depended on the gas (O 2 , CO 2 ) and measurement approach (blood content vs. gas phase). Measurements in the gas phase increased the bias (253 [LoA -1,357 to 1,863 mL/min] for expired V̇o 2 bias 482 [LoA -760 to 1,724 mL/min] for expired V̇co 2 ) and could be improved by correction of V̇/Q̇ inequalities. Our results show that common assumptions of the Fick principle in two competing circulations give results with adequate accuracy and may offer a clinically applicable tool. Precision depends on specific conditions. This highlights the complexity of gas exchange in membrane lungs and may further deepen the understanding of V-A ECMO.

The mean systemic pressure analog (Pmsa), calculated from running hemodynamic data, estimates mean systemic filling pressure (MSFP). This post hoc study used data from a porcine veno-arterial extracorporeal membrane oxygenation (ECMO) model [ n = 9; Sus scrofa domesticus ; ES breed (Schweizer Edelschwein)] with eight experimental conditions; Euvolemia [a volume state where ECMO flow produced normal mixed venous saturation (S V O 2 ) without vascular collapse]; three levels of increasing norepinephrine infusion (Vasoconstriction 1-3); status after stopping norepinephrine (Post Vasoconstriction); and three steps of volume expansion (10 mL/kg crystalloid bolus) (Volume Expansion 1-3). In each condition, Pmsa and a "reduced-pump-speed-Pmsa" (Pmsa red ) were calculated from baseline and briefly reduced pump speeds, respectively. We calculated agreement for absolute values (per condition) and changes (between consecutive conditions) of Pmsa and Pmsa red , against MSFP at zero ECMO flow. Euvolemia venous return driving pressure was 5.1 ± 2.0 mmHg. Bland-Altman analysis for Pmsa vs. MSFP (all conditions; 72 data pairs) showed bias (confidence interval) 0.5 (0.1-0.9) mmHg; limits of agreement (LoA) -2.7 to 3.8 mmHg. Bias for ΔPmsa vs. ΔMSFP (63 data pairs): 0.2 (-0.2 to 0.6) mmHg, LoA -3.2 to 3.6 mmHg. Bias for Pmsa red vs. MSFP (72 data pairs): 0.0 (-0.3 to -0.3) mmHg; LoA -2.3 to 2.4 mmHg. Bias for ΔPmsa red vs. ΔMSFP (63 data pairs) was 0.2 (-0.1 to 0.4) mmHg; LoA -1.8 to 2.1 mmHg. In conclusion, during veno-arterial ECMO, under clinically relevant levels of vasoconstriction and volume expansion, Pmsa accurately estimated absolute and changing values of MSFP, with low between-method precision. The within-method precision of Pmsa was excellent, with a least significant change of 0.15 mmHg. NEW & NOTEWORTHY This is the first study ever to validate the mean systemic pressure analog (Pmsa) against the reference mean systemic filling pressure (MSFP) determined at full arterio-venous pressure equilibrium. Using a porcine ECMO model with clinically relevant levels of vasoconstriction and volume expansion, we showed that Pmsa accurately estimated absolute and changing values of MSFP, with a poor between-method precision. The within-method precision of Pmsa was excellent.

Background: Veno-arterial extracorporeal membrane oxygenation therapy is a growing treatment modality for acute cardiorespiratory failure. Cardiac output monitoring during veno-arterial extracorporeal membrane oxygenation therapy remains challenging. This study aims to validate a new thermodilution technique during veno-arterial extracorporeal membrane oxygenation therapy using a pig model., Methods: Sixteen healthy pigs were centrally cannulated for veno-arterial extracorporeal membrane oxygenation, and precision flow probes for blood flow assessment were placed on the pulmonary artery. After chest closure, cold boluses of 0.9% saline solution were injected into the extracorporeal membrane oxygenation circuit, right atrium, and right ventricle at different extracorporeal membrane oxygenation flows (4, 3, 2, 1 l/min). Rapid response thermistors in the extracorporeal membrane oxygenation circuit and pulmonary artery recorded the temperature change. After calculating catheter constants, the distributions of injection volumes passing each circuit were assessed and enabled calculation of pulmonary blood flow. Analysis of the exponential temperature decay allowed assessment of right ventricular function., Results: Calculated blood flow correlated well with measured blood flow (r2 = 0.74, P < 0.001). Bias was -6 ml/min [95% CI ± 48 ml/min] with clinically acceptable limits of agreement (668 ml/min [95% CI ± 166 ml/min]). Percentage error varied with extracorporeal membrane oxygenation blood flow reductions, yielding an overall percentage error of 32.1% and a percentage error of 24.3% at low extracorporeal membrane oxygenation blood flows. Right ventricular ejection fraction was 17 [14 to 20.0]%. Extracorporeal membrane oxygenation flow reductions increased end-diastolic and end-systolic volumes with reductions in pulmonary vascular resistance. Central venous pressure and right ventricular ejection fractions remained unchanged. End-diastolic and end-systolic volumes correlated highly (r2 = 0.98, P < 0.001)., Conclusions: Adapted thermodilution allows reliable assessment of cardiac output and right ventricular behavior. During veno-arterial extracorporeal membrane oxygenation weaning, the right ventricle dilates even with stable function, possibly because of increased venous return., (Copyright © 2020, the American Society of Anesthesiologists, Inc. All Rights Reserved.)

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is used as rescue therapy for severe cardiopulmonary failure. We tested whether the ratio of CO 2 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 CO 2 elimination and V-A ECMO blood flow (Q˙ ECMO ). Q˙ ECMO correlated strongly with V˙co 2ECMONorm ( r 2 0.95-0.99). Q˙ Lung correlated well with V˙co 2Lung ( r 2 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 ( r 2 0.974-1.000, P = 0.1 to 0.006) for cumulative ECMO flow reductions. In conclusion, V˙co 2 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.

Abstract Background To optimize right ventricular–pulmonary coupling during veno-arterial (VA) ECMO weaning, inotropes, vasopressors and/or vasodilators are used to change right ventricular (RV) function (contractility) and pulmonary artery (PA) elastance (afterload). RV–PA coupling is the ratio between right ventricular contractility and pulmonary vascular elastance and as such, is a measure of optimized crosstalk between ventricle and vasculature. Little is known about the physiology of RV–PA coupling during VA ECMO. This study describes adaptive mechanisms for maintaining RV–PA coupling resulting from changing pre- and afterload conditions in VA ECMO. Methods In 13 pigs, extracorporeal flow was reduced from 4 to 1 L/min at baseline and increased afterload (pulmonary embolism and hypoxic vasoconstriction). Pressure and flow signals estimated right ventricular end-systolic elastance and pulmonary arterial elastance. Linear mixed-effect models estimated the association between conditions and elastance. Results At no extracorporeal flow, end-systolic elastance increased from 0.83 [0.66 to 1.00] mmHg/mL at baseline by 0.44 [0.29 to 0.59] mmHg/mL with pulmonary embolism and by 1.36 [1.21 to 1.51] mmHg/mL with hypoxic pulmonary vasoconstriction (p 0.05). Extracorporeal flow did not change coupling (0.0 [− 0.0 to 0.1] per change of 1 L/min, p > 0.05). End-diastolic volume increased with decreasing extracorporeal flow (7.2 [6.6 to 7.8] ml change per 1 L/min, p

This review describes the intricate physiological interactions involved in the application of extracorporeal therapy, with specific focus on cardiopulmonary relationships. Extracorporeal therapy significantly influences cardiovascular and pulmonary physiology, highlighting the necessity for clinicians to understand these interactions for improved patient care. Veno-arterial extracorporeal membrane oxygenation (veno-arterial ECMO) unloads the right ventricle and increases left ventricular (LV) afterload, potentially exacerbating LV failure and pulmonary edema. Veno-venous (VV) ECMO presents different challenges, where optimal device and ventilator settings remain unknown. Influences on right heart function and native gas exchange as well as end-expiratory lung volumes are important concepts that should be incorporated into daily practice. Future studies should not be limited to large clinical trials focused on mortality but rather address physiological questions to advance the understanding of extracorporeal therapies. This includes exploring optimal device and ventilator settings in VV ECMO, standardizing cardiopulmonary function monitoring strategies, and developing better strategies for device management throughout their use. In this regard, small human or animal studies and computational physiological modeling may contribute valuable insights into optimizing the management of extracorporeal therapies. [ABSTRACT FROM AUTHOR]