We have read with interest the case report by Lim and his recent review of the Fick principle on veno-arterial extracorporeal membrane oxygenation (VA ECMO).^{1, 2} We are delighted that the measurement of native cardiac output during extracorporeal support found its successful way to the bedside. Still, we wonder how our work on the subject has gone unnoticed.^3-6 We therefore take the liberty to offer some comments. Lim's method to create a right-to-left shunt by turning off sweep gas flow on the ECMO is not novel. Instead, it represents a special case of our modified Fick principle during VA ECMO. This concept, published in 2020, provides a general solution to the problem.⁴

Our approach represents a generalized solution to the problem without the restriction of turning off sweep gas flow. Our method was theoretically derived, tested in a small pilot study,⁴ and further elucidated in a bench study.⁵ Then, we assessed the method on 16 animals with varying conditions, such as high dead space and shunt fractions.⁶ This integral assessment, which has meticulously documented gas exchange during VA ECMO in the blood and gas phases of the native and artificial lungs, incorporating over 1500 blood gas analyses, has proven that a modified Fick principle is feasible. Monitoring of gas exchange estimates native cardiac output with acceptable precision and accuracy.⁶ Based on our work, we conclude the following and would like to highlight certain limitations regarding Lim's method.¹

First, our method does not limit itself to states of no sweep gas flow (i.e. building an artificial right–left shunt). It also estimates cardiac output with clinically adequate bias and accuracy when extracorporeal gas exchange is present. This may allow continuous monitoring of native cardiac output at all stages of ECMO therapy.^4-6 The concept proposed by Lim maximizes the content differences between the extracorporeal circuit and the native cardiopulmonary unit and may therefore improve accuracy.

Second, our previous experimental data demonstrate that both venous and arterial differential hypoxia are present during VA ECMO.⁶ While differential hypoxia on the arterial side is a known phenomenon (e.g. Harlequin or North–South), venous differential hypoxia is as common and important to managing patients on VA ECMO, albeit less often recognized.^{3, 7} The method is only accurate if and only if the inlet and outlet conditions of both the ECMO and the native lung are perfectly mixed; that is, there is no venous and arterial differential hypoxia.^{5, 6} Lim acknowledges the limitations of venous oxygen differences but suggests assuming a pulmonary vein (or left atrial) saturation of 100% to obviate the need for direct blood sampling and advises caution for critically ill patients with his assumption. Our data confirm that left atrial saturation cannot be assumed to be 100% in healthy lungs, let alone in states of shunt.⁶

In conclusion, Lim's approach is a modification of our method and therefore shares the limitations we have assessed extensively. Alternative approaches to the assessment of native cardiac output during VA ECMO may include modified thermodilution, which would also allow the evaluation of right ventricular performance.⁸ We highly welcome further studies within the field of gas exchange and extracorporeal support and commend Lim for his work.

我们饶有兴趣地阅读了 Lim 的病例报告以及他最近对静脉-动脉体外膜氧合 (VA ECMO) 菲克原理的回顾。^{1, 2}我们很高兴体外支持期间的自然心输出量测量成功应用于床边。尽管如此，我们还是想知道我们在这个主题上的工作为何没有被注意到。^3-6因此，我们冒昧提出一些意见。 Lim 通过关闭 ECMO 上的吹扫气流来创建从右到左分流的方法并不新颖。相反，它代表了我们在 VA ECMO 期间修改的菲克原理的一个特例。这个概念于 2020 年发布，为该问题提供了通用解决方案。⁴

我们的方法代表了该问题的通用解决方案，不受关闭吹扫气流的限制。我们的方法是从理论上推导出来的，在小型试点研究中进行了测试⁴ ，并在实验室研究中得到了进一步阐明。⁵然后，我们在 16 只具有不同条件（例如高死腔和分流分数）的动物上评估了该方法。⁶这项综合评估详细记录了 VA ECMO 期间自体肺和人工肺的血液和气相中的气体交换，结合了 1500 多次血气分析，证明修改后的菲克原理是可行的。气体交换监测以可接受的精度和准确度估计自然心输出量。⁶根据我们的工作，我们得出以下结论，并想强调 Lim 方法的某些局限性。¹

首先，我们的方法并不局限于无吹扫气流的状态（即建立人工右-左分流器）。当存在体外气体交换时，它还能以临床上足够的偏差和准确性来估计心输出量。这可以允许在 ECMO 治疗的所有阶段连续监测自然心输出量。^4-6 Lim 提出的概念最大化了体外回路和本地心肺单元之间的内容差异，因此可以提高准确性。

其次，我们之前的实验数据表明，VA ECMO 期间存在静脉和动脉差异性缺氧。⁶虽然动脉侧差异性缺氧是一种已知现象（例如 Harlequin 或南北），但静脉差异性缺氧对于管理 VA ECMO 患者同样常见且重要，尽管很少被认识到。^{3, 7}仅当且仅当 ECMO 和自体肺的入口和出口条件完美混合时，该方法才是准确的；即不存在静脉和动脉差别性缺氧。^{5, 6} Lim 承认静脉氧差异的局限性，但建议假设肺静脉（或左心房）饱和度为 100%，以避免直接采血的需要，并建议危重患者谨慎对待他的假设。我们的数据证实，健康肺部的左心房饱和度不能假设为 100%，更不用说在分流状态下。⁶

总之，Lim 的方法是对我们方法的修改，因此具有我们广泛评估的局限性。 VA ECMO 期间评估自然心输出量的替代方法可能包括改进的热稀释法，这也可以评估右心室性能。⁸我们高度欢迎在气体交换和体外支持领域进行进一步研究，并赞扬 Lim 的工作。