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Letter to the Editor
Dangers in using beta-blockers in patients with venovenous extracorporeal membrane oxygenation
Diego Rodríguez Álvarezorcid, Elena Pérez-Costaorcid, Juan José Menéndez Susoorcid
Acute and Critical Care 2022;37(4):683-684.
Published online: July 18, 2022

Pediatric Intensive Care Department, La Paz University Hospital, Madrid, Spain

Corresponding author: Diego Rodríguez Álvarez Pediatric Intensive Care Department, La Paz University Hospital, Paseo de la Castellana, 261, Madrid 28046, Spain Tel: +34-60-549-5869 E-mail:
• Received: May 15, 2022   • Accepted: June 16, 2022

Copyright © 2022 The Korean Society of Critical Care Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Dear Editor:
We have read with interest the review “Awakening in extracorporeal membrane oxygenation as a bridge to lung transplantation” by Lee [1] published in your journal, explaining how the application of awake venovenous extracorporeal membrane oxygenation (VV-ECMO) performed by an appropriately trained ECMO multi-disciplinary team, can be useful as a bridging strategy, in patients waiting for lung transplantation.
We fully agree with the awake ECMO management proposed by Lee [1]. However, the section “Problems during Awake ECMO” discusses the problem of hypoxemia due to excessive patient cardiac output (CO). The proposed solution is to use beta-blockers to resolve hypoxemia in patients with high CO, as a result of increased heart rate. We would like to point out the possible inaccuracy of this recommendation for managing refractory hypoxemia in patients with VV-ECMO.
Since the work of Guarracino et al. [2], there have been numerous publications recommending the use of beta-blockers to increase oxygen saturation (SaO2) in situations of high CO [3]. The blood propelled by the heart is a mixture of the flow coming from the VV-ECMO, with an SaO2 in the blood exiting the oxygenator (membrane) (SmO2) of approximately 100%, and the desaturated venous flow, with a central venous oxygen saturation (ScvO2) of approximately 40%–70%, which returns to the heart through the vena cava. By using beta-blockers and slowing the heart rate, the total CO will be lowered. Whereas the ECMO flow will remain constant, the desaturated venous flow will decrease. Less venous flow will be needed to complete the total CO, and therefore the blood mixture will have a higher SaO2, as derived from the following formula described by Messaï et al. [4]:
SaO2SpaO2=EFCOSmO2+1EFCOScvO2+ΔSaO2, in which SpaO2 is SaO2 in the pulmonary artery, EF is the effective flow rate (EF=(1−recirculation)×pump flow) and ∆SaO2 is the increase in SaO2 due to dissolved oxygen (%).
The increase in oxygen consumption stimulates the general visceral afferent fibers (by mechanoreceptors, nociceptors, and chemoreceptors) that activate the autonomic nervous system, generating a response (in this case, tachycardia) to increase the supply of oxygen according to the formula: DO2=CO × CaO2, where CaO2 is the arterial oxygen content according to the formula CaO2=1.34×SaO2×Hb+pO2×0.0031, where pO2 is the partial pressure of oxygen and Hb is the hemoglobin content. SaO2 is only part of the equation in oxygen supply.
Following the mathematical model of Zanella et al. [5], we can confirm that increasing the CO while keeping the rest of the variables constant will lead to an increase in oxygen delivery (DO2) despite a decrease in SaO2. As the heart rate increases, the CO will increase. If CO is increased by a value of k, SaO2 can be calculated using the following formula:
SaO2=EFSmO2ScvO2+kCOScvO2+ΔSaO2 kCO obtaining a decrease in SaO2 for any value k increase in CO. Substituting SaO2 in the DO2 equation results in the following formula: DO2=EF×1.34×Hb(SmO2-ScvO2 )+kCO×1.34×Hb(ScvO2+∆SaO2 )+(kCO×pO2×0.0031)
where for any value k increase in CO, there will be an increase in DO2. These formulas show that by increasing the CO by a proportion k, the SaO2 will decrease, while the total DO2 will increase.
The study by Guarracino et al. [2 ], on which numerous review articles are based, corresponds only to a series of three patient cases that did not report their SaO2, did not indicate how CO was calculated, and observed that DO2 decreased when the heart rate decreased. The objective for patients with VV-ECMO assistance should be to prevent hypoxia rather than hypoxemia, and maintain adequate DO2. We believe that more studies are necessary along these lines to be able to make a strong recommendation against the use of beta-blockers in VV-ECMO patients with high CO.


No potential conflict of interest relevant to this article was reported.






Conceptualization: all authors. Data curation: all authors. Visualization: all authors. Writing–original draft: all authors. Writing–review & editing: all authors.

  • 1. Lee SH. Awakening in extracorporeal membrane oxygenation as a bridge to lung transplantation. Acute Crit Care 2022;37:26-34.ArticlePubMedPMCPDF
  • 2. Guarracino F, Zangrillo A, Ruggeri L, Pieri M, Calabrò MG, Landoni G, et al. β-Blockers to optimize peripheral oxygenation during extracorporeal membrane oxygenation: a case series. J Cardiothorac Vasc Anesth 2012;26:58-63.ArticlePubMed
  • 3. Pappalardo F, Zangrillo A, Pieri M, Landoni G, Morelli A, Stefani M, et al. Esmolol administration in patients with VV ECMO: why not? J Cardiothorac Vasc Anesth 2013;27:e40. Article
  • 4. Messaï E, Bouguerra A, Harmelin G, Di Lascio G, Cianchi G, Bonacchi M. A new formula for determining arterial oxygen saturation during venovenous extracorporeal oxygenation. Intensive Care Med 2013;39:327-34.ArticlePubMedPDF
  • 5. Zanella A, Salerno D, Scaravilli V, Giani M, Castagna L, Magni F, et al. A mathematical model of oxygenation during venovenous extracorporeal membrane oxygenation support. J Crit Care 2016;36:178-86.ArticlePubMed

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        Dangers in using beta-blockers in patients with venovenous extracorporeal membrane oxygenation
        Acute Crit Care. 2022;37(4):683-684.   Published online July 18, 2022
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