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Am J Respir Crit Care Med
Am J Respir Crit Care Med
ajrccm
American Journal of Respiratory and Critical Care Medicine
1073-449X
1535-4970
American Thoracic Society

38747640
202403-0654ED
10.1164/rccm.202403-0654ED
Editorials
Extracorporeal Blood Flow Rate: Target the Right Thing!
Douflé Ghislaine 1 2
https://orcid.org/0000-0002-4504-7094
Katira Bhushan H. 3
1 Interdepartmental Division of Critical Care Medicine
University of Toronto
Toronto, Ontario, Canada
2 Department of Anesthesia and Pain Management
Toronto General Hospital
Toronto, Ontario, Canada
3 Department of Pediatrics
Washington University in St. Louis
St. Louis, Missouri
15 5 2024
1 9 2024
15 5 2024
210 5 539541
Copyright © 2024 by the American Thoracic Society
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0. For commercial usage and reprints, please e-mail Diane Gern (dgern@thoracic.org).
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pmcAlthough venovenous (VV) extracorporeal membrane oxygenation (ECMO) is used in refractory respiratory failure, its role goes beyond maintaining oxygenation. More important, the overarching goal of ECMO support is to optimize oxygen delivery (Do2) in relationship to oxygen consumption (V˙o2) while maintaining lung-protective ventilation. To achieve these physiological goals, the Extracorporeal Life Support Organization guidelines recommend titrating the ECMO blood flow rate (EBFR) and Hb to maintain a Do2:V˙o2 ratio of at least the critical threshold of 2:1, at which point V˙o2 becomes dependent on delivery; preferably, Do2 should be close to or above half the normal Do2 (namely, 300 ml/m2/min) (1). Importantly, on VV ECMO, in the complete absence of native lung function with patients entirely dependent on ECMO, a ratio of EBFR to Q˙ ratio of approximately 60% is needed to maintain an SaO2 of about 90% (2). Higher EBFRs may, however, lead to more negative pressures on the ECMO circuit, shear stress, and associated blood trauma (3). Beyond these considerations, there is little guidance on how to titrate blood flow on ECMO in daily clinical practice. To address this gap, Spinelli and colleagues (pp. 629–638) investigated, in a study reported in this issue of the Journal, the effects of modulating ECMO blood flow to a target mixed venous oxygen saturation (SvO2) on several physiological parameters, such as pulmonary circulation, right ventricular (RV) workload, and V˙/Q˙ matching (4).

Although VV ECMO does not directly affect cardiac function, improving gas exchange and acidosis, as well as concomitantly reducing the intensity of mechanical ventilation upon ECMO initiation, has been shown to improve RV function (5). However, as these phenomena occur simultaneously, it may be challenging to identify the exact mechanism responsible for the improvement. One of the strengths of Spinelli and colleagues’ (4) experiments was the isolated modification of ECMO blood flow and SvO2, while all other parameters were kept constant. Moreover, they altered SvO2 in the range of 70–90%, which is achievable and meaningful at the bedside. Targeting SvO2 below 70% could have led to significant changes in pulmonary vascular resistance (PVR), while achieving SvO2 above 90% would not be practical. Increasing the SvO2 led to increased pulmonary artery (PA) compliance and decreased PVR by inhibiting hypoxic pulmonary vasoconstriction. Both PA compliance and PVR affect RV afterload. PA compliance and PVR are inversely related by resistance × compliance time, considered constant over a wide range of clinical conditions (6). One would therefore assume that an increase in compliance would be accompanied by a reduction in resistance, thus favorably affecting RV function, which should in turn lead to an increase in RV output. Instead, the authors observed a decrease in RV output. Although this seems counterintuitive at first, it can be explained by an increase in Do2, leading to a higher Do2:V˙o2 ratio at high ECMO flows, reducing the dependence on high native Q˙ to meet V˙o2 requirements. This indicates that a significant contributor to the hemodynamic finding, namely, a decrease in systolic PA pressure, was likely from lower Q˙ and less likely from the increase in SvO2 itself. In fact, increased PA compliance and decreased PVR could be explained by the reduction in Q˙ itself.

Despite its investigation of complex physiology, this study adds to our understanding of manipulating ECMO blood flow and provides opportunity to target higher SvO2 with the aim of lowering RV workload. It is important to note that most benefits occurred between the low and intermediate groups and in patients with high baseline PA pressure or Q˙, suggesting that patients with low Do2:V˙o2 ratios benefited most from higher SvO2. Therefore, titrating blood flow during VV ECMO to reduce RV workload may be a strategy independent of mechanical ventilation or vasopressor support to prevent significant RV strain. Moreover, lowered PA pressure and flow help reduce the vascular side of forces contributing to increased lung permeability (7). This could be an additional strategy for heart and lung protection during VV ECMO.

Despite the study’s astute design, several limitations preclude the generalization of its findings. First, the use of thermodilution to estimate Q˙ on VV ECMO can be problematic. Indeed, as the blood is drained and reinfused in the right atrium, significant alterations in blood flow, especially with higher ECMO flows, may modify the temperature around the PA catheter (8). In addition, the degree of recirculation was not estimated and may have influenced temperature changes and Q˙ measurements (9, 10). Changes in RV stroke volume and pulmonary pressures may have been accompanied by changes in RV size and in tricuspid regurgitation severity, which may also confound RV output estimation (11). Both limitations (Q˙ estimation and assessment of tricuspid regurgitation severity) could have been circumvented by performing echocardiography at different ECMO flows. Even though echocardiography-derived Q˙ estimation comes with its own caveats, changes in left ventricular outflow tract velocity–time integral could have been used as a surrogate if all other parameters were kept equal (12, 13).

Another important point worth mentioning is the low ratio of EBFR to Q˙ observed in this study. Indeed, the mean EBFR:Q˙ ratio ranged from 20% to 44% for low and high SvO2, respectively. Thus, even at higher ECMO flows, the EBFR:Q˙ ratio remained less than 50%, which suggests that these patients’ lung function was still sufficient to maintain adequate oxygenation. The patient population, therefore, may not be representative of the most severe forms of ARDS, in which patients are fully ECMO dependent for oxygenation.

Last, the experiment did not include patients with significant hemodynamic instability (more than 0.1 μg/kg/min norepinephrine equivalent), irrespective of the underlying cause. It would have been of great interest to see the effect of SvO2 modulation on patients with RV dysfunction. Indeed, RV failure frequently emerges as a risk factor for mortality in patients with ARDS, but it remains unclear whether the link between RV failure and mortality is a causal effect or represents disease severity and whether therapies targeted at improving RV function may increase survival (14).

In conclusion, this study demonstrates the potential advantage of modulating ECMO blood flow to achieve higher SvO2, resulting in improved Do2:V˙o2 ratio and lowered RV workload. However, the exclusion of patients with significant hemodynamic instability and the greater impact observed mainly in undersupported patients limit the broader application of this strategy. Further studies are needed to investigate if the titration of blood flow on VV ECMO would benefit patients with RV failure and whether this would improve outcomes.

Originally Published in Press as DOI: 10.1164/rccm.202403-0654ED on May 15, 2024

Author disclosures are available with the text of this article at www.atsjournals.org.
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