key: cord-1036537-50hcisj9 authors: Kopanczyk, Rafal; Bhatt, Amar; Kumar, Nicolas; Henson, Christopher Patrick title: Persistent Hypoxemia in COVID-19 Patients on ECMO: Keep Your Eyes on the Prize date: 2022-04-14 journal: J Cardiothorac Vasc Anesth DOI: 10.1053/j.jvca.2022.04.011 sha: 5c0abd828d2dc6461168b4999d7473fa2e4ceb21 doc_id: 1036537 cord_uid: 50hcisj9 nan Funding statement: Support was provided solely from institutional and/or departmental sources. The authors declare no competing interests. Dear Editor, Venovenous extracorporeal membrane oxygenation (VV-ECMO) has been utilized during the coronavirus disease 2019 (COVID-19) pandemic to support patients with the most severe cases of COVID-19 acute respiratory distress syndrome (ARDS). The earliest investigations of VV-ECMO use in COVID-19 ARDS reported outcomes similar to prepandemic ARDS cohorts, with mortality <40%. 1 However, studies conducted during subsequent waves of the pandemic painted a worse picture, with mortality between 50%-73%. 2, 3 While variant-specific pathology and increased severity of disease have been suggested as culprits, other potential contributors include higher incidences of delirium, right ventricular (RV) failure, and persistent hypoxemia while on VV-ECMO than previously encountered. 4, 5 Persistent hypoxemia is particularly problematic, as routine measurements of oxygenation are frequently misunderstood and may lead to inappropriate treatment changes and complications. In fact, many centers around the country now set oxygenation goals incongruent with Extracorporeal Life Support Organization (ELSO) guidelines. Therefore, it is important to revisit the physiology of VV-ECMO oxygenation, clarify the clinical relevance of apparent persistent hypoxemia in this patient population, and illustrate how its misunderstanding may lead to initiation of therapies associated with harm. Assessment of adequate oxygenation is unique in patients supported with VV-ECMO. While in typical clinical practice oxygenation can be evaluated by patient appearance, pulse oximetry, or blood gas analysis with partial pressure of arterial oxygen (PaO 2 ) and its saturation (SaO 2 ), these data may be insufficient in patients on extracorporeal support. In the latter, oxygenation goals incorporate arterial oxygen content (CaO 2 ), oxygen delivery (DO 2 ), and oxygen consumption (VO 2 ), described by well-known formulas. It is essential that clinicians consider CaO 2 and DO 2 when managing gas exchange on VV-ECMO, as PaO 2 and SaO 2 are incapable of estimating the amount of oxygen present in a mixture of two separate blood flows with different oxygen content. Oxygen concentration of a blood mixture can only be described mathematically by averaging oxygen content of each blood flow, not PaO 2 values. This is indeed the case in VV-ECMO, in which blood from the circuit mixes with venous return within the right atrium. In effect, a labor-intensive process is needed, requiring bedside calculations and cardiac output measurements. Cardiac output can be obtained by means of point-of-care ultrasonography, proprietary arterial waveform analysis, or mathematical calculation as described by Bartlett. 6 Cardiac output can be deduced by calculating the oxygen content at Conversely, use of absolute PaO 2 and SaO 2 values can lead to misinterpretation of a clinical condition resulting in therapeutic actions that may worsen patient outcomes. In situations when PaO 2 and SaO 2 are below normal limits and the VV-ECMO circuit is functioning properly, practitioners should avoid instinctively adjusting ventilator settings, and continue lowvolume/low-pressure lung-protective ventilation to avoid further lung injury and allow the VV-ECMO circuit to shoulder the full burden of gas exchange. 9 Additionally, clinicians should be cautious when attempting to manipulate the shunt fraction between native and VV-ECMO flows by decreasing cardiac output with beta-blockade. Any potential improvement in CaO 2 would be exclusively due to a small increase in SaO 2 , although the amount of oxygen supplied by the circuit stays the same (assuming no recirculation). Moreover, recalling the DO 2 formula, lowering cardiac output may actually decrease DO 2 , since the reduction in cardiac output with beta-blockade will likely offset any improvement in SaO 2 , a result inconsistent with therapeutic goals of VV-ECMO. 6, 8 Beta-blockade can have additional detrimental effects on RV performance in patients with existing RV dysfunction, as is often the case in COVID-19 ARDS. Attempts to decrease metabolic demand and VO 2 with sedation and neuromuscular blockade must be weighed carefully as their detrimental effects in critically ill have been well described. 10 Many sedatives also have negative inotropic effects, further harming the RV. Finally, the use of hybrid and parallel circuits with supplemental cannulas and/or oxygenators should only be considered when inadequate oxygenation is certain in order avoid unnecessary medical procedures. The COVID-19 pandemic continues to challenge the medical community, and the recent upward trend in mortality seen in patients with COVID-19 ARDS despite support from VV-ECMO is sending critical care physicians back to the drawing board. In the meantime, it is important to remember the basic tenants of VV-ECMO physiology and management. Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry High In-Hospital Mortality Rate in Patients with COVID-19 Receiving Extracorporeal Membrane Oxygenation in Germany: A Critical Analysis Extracorporeal membrane oxygenation for COVID-19: evolving outcomes from the international Extracorporeal Life Support Organization Registry Treating the Most Critically Ill Patients With COVID-19: The Evolving Role of Extracorporeal Membrane Oxygenation Extracorporeal Membrane Oxygenation and Coronavirus Disease Physiology of gas exchange during ECMO for respiratory failure ELSO Guidelines for Cardiopulmonary extracorporeal life support Extracorporeal life support: the ELSO red book Extracorporeal Membrane Oxygenation for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization Sedation in the intensive care setting