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Choosing the right reference cohort for assessing outcome of venovenous ECMO
Critical Care ( IF 8.8 ) Pub Date : 2022-01-10 , DOI: 10.1186/s13054-021-03880-3
Alexander Supady _{1,

2,

3} , Paul M Biever _{1,

2} , Dawid L Staudacher _{1,

2} , Tobias Wengenmayer _{1,

2}

Affiliation

We thank Karagiannidis et al. for reporting important mortality data of COVID-19 patients supported with extracorporeal membrane oxygenation (ECMO) in Germany [1]. The mortality they reported was notably higher than in other large cohorts [2]. The data come from nationwide billing data of all hospitals in Germany; therefore, the risk of selection bias or underreporting of negative results is lower than in previous cohorts.

The authors argue against the unselective use of ECMO in patients who have a high risk of dying during the course of treatment. We agree that ECMO is an expensive and resource-intensive support option. Therefore, it should be used only in selected patients after careful risk–benefit evaluation. This assessment should take into account all available and relevant prognostic information and the (presumed) patient will. During the COVID-19 pandemic, the availability of trained medical staff and the utilization of available intensive care resources must also be taken into consideration [3].

Yet, one of the major difficulties in patient selection is to predict with sufficient accuracy the prognosis of individual patients. This is true for both patients with ECMO support and without. A more liberal use of ECMO in healthier patients who might have had a favorable outcome even without ECMO improves the survival probability attributed to the procedure, as does a restrained use in very sick and older patients who have a rather poor prognosis with or without ECMO (Fig. 1) [2, 4]. However, in our view, the expansion of the scope of indications may nevertheless be justified or even warranted. This may be the case when experienced physicians base their decisions on a responsible bedside assessment of the individual patient and expect poorer outcome without the use of ECMO. This approach was recently described as “salvage ECMO” [5].

For a comprehensive appraisal of the role of ECMO for the treatment of severe respiratory failure, we believe that it is not sufficient to look at the survival rates of patients who eventually received ECMO. Instead, the entire cohort of invasively ventilated patients with defined severity criteria must be considered, including patients in whom ECMO was not chosen, both due to futility and based on the assessment that they will recover even without ECMO. Consequently, the approach that achieves the best overall outcome should be considered superior. This way may help us to offer each patient the optimal therapy and improve our algorithms for making decisions for or against the use of ECMO.

Thomas Bein,
Christian Karagiannidis,
Steffen Weber-Carstens,
Arthur Slutsky,
Wolfram Windisch &
Daniel Brodie

Faculty of Medicine, University of Regensburg, Regensburg, Germany
Thomas Bein
Department of Pneumology and Critical Care Medicine, ARDS and ECMO Centre, Cologne-Merheim Hospital, Kliniken Der Stadt Köln gGmbH, Witten, Germany
Christian Karagiannidis & Wolfram Windisch
Herdecke University Hospital, Ostmerheimer Strasse 200, 51109, Cologne, Germany
Christian Karagiannidis & Wolfram Windisch
Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité - Universitätsmedizin Berlin, Berlin, Germany
Steffen Weber-Carstens
Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute, St Michael’s Hospital, University of Toronto, Toronto, Canada
Arthur Slutsky
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA
Daniel Brodie
Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, USA
Daniel Brodie

We thank Dr. Supady and colleagues for their thoughtful letter regarding the difficulty with divining who should be placed on ECMO based on our data demonstrating high mortality with the use of ECMO for COVID-19 in Germany [1]. Implicit in their argument is that declaring a mortality rate to be high or low requires that we know what mortality rate should actually be expected without the use of ECMO in COVID-19, an information that uncontrolled observational data cannot provide [6] . This is an important argument for conducting well-designed randomized clinical trials. However, absent such evidence, how should we proceed? Nonetheless, we believe that the overall mortality rate should be seen as high relative to the investment of resources, suggesting that the use of ECMO in this population may indeed be too liberal.

One further point that merits discussion is that, while Supady et al. use the term “selection” regarding the decision to implement ECMO, we prefer the term “indication.” Indication is based on the careful assessment of the realistic rehabilitation potential of the patient in association with a given intervention (e.g., ECMO) to allow the patient to resume a reasonable quality of life and to achieve a well-defined therapeutic goal in concert with the goals and values of the individual patient [7]. This concept also aims to balance benefit (survival) against harm (invasive treatment, pain, sedation, immobilization and the psychological burden on surrogates). Therefore, the indication for ECMO should be based on several anamnestic, demographic, medical and prognostic parameters in each individual patient to avoid futile treatments as well as high in-hospital mortality. We agree with Dr. Supady’s framing of the balanced and rational use of ECMO; however, the reality in Germany—as expressed in our letter—shows that we are far from the rational use of ECMO. This has also been clearly emphasized by a recent paper showing that 40% of ECMO cases in Germany are performed in hospitals with 2 or fewer cases per year [8] with no assurances regarding the quality of ECMO delivery, which may reasonably be expected to contribute to high mortality.

For these reasons, we are confident that the high mortality rate in German ECMO patients reflects an opportunity to insist on a more rational ECMO application, to reflect both on the organizational approach to its use and on the indications that should be broadly acceptable.

Not applicable.

1.
Karagiannidis C, Slutsky AS, Bein T, Windisch W, Weber-Carstens S, Brodie D. Complete countrywide mortality in COVID patients receiving ECMO in Germany throughout the first three waves of the pandemic. Crit Care. 2021;25(1):413.
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Supady A, Taccone FS, Lepper PM, Ziegeler S, Staudacher DL. Group CO-S: survival after extracorporeal membrane oxygenation in severe COVID-19 ARDS: results from an international multicenter registry. Crit Care. 2021;25(1):90.
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8.
Bercker S, Petroff D, Polze N, Karagianidis C, Bein T, Laudi S, Stehr SN, Voelker MT. ECMO use in Germany: an analysis of 29,929 ECMO runs. PLoS ONE. 2021;16(12):e0260324.
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Affiliations

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany
Alexander Supady, Paul M. Biever, Dawid L. Staudacher & Tobias Wengenmayer
Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany
Alexander Supady, Paul M. Biever, Dawid L. Staudacher & Tobias Wengenmayer
Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, Germany
Alexander Supady

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Tobias WengenmayerView author publications
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AS designed the paper and prepared the first draft based on preceding discussions with all co-authors. All authors reviewed the draft and approved the final version of the manuscript.

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Correspondence to Alexander Supady.

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The authors declare that they have no competing interest.

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Supady, A., Biever, P.M., Staudacher, D.L. et al. Choosing the right reference cohort for assessing outcome of venovenous ECMO. Crit Care 26, 17 (2022). https://doi.org/10.1186/s13054-021-03880-3

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Received: 07 December 2021
Accepted: 14 December 2021
Published: 10 January 2022
DOI: https://doi.org/10.1186/s13054-021-03880-3

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Keywords

COVID-19
Extracorporeal membrane oxygenation
Patient selection

中文翻译：

选择正确的参考队列来评估静脉 ECMO 的结果

我们感谢 Karagiannidis 等人。用于报告德国体外膜肺氧合 (ECMO) 支持的 COVID-19 患者的重要死亡率数据 [1]。他们报告的死亡率明显高于其他大型队列[2]。数据来自德国所有医院的全国计费数据；因此，选择偏倚或漏报阴性结果的风险低于之前的队列。

作者反对在治疗过程中死亡风险高的患者中非选择性地使用 ECMO。我们同意 ECMO 是一种昂贵且资源密集型的支持选择。因此，它应该只用于经过仔细风险-收益评估的特定患者。该评估应考虑所有可用和相关的预后信息以及（假定的）患者意愿。在 COVID-19 大流行期间，还必须考虑训练有素的医务人员的可用性和可用重症监护资源的利用情况 [3]。

然而，患者选择的主要困难之一是足够准确地预测个体患者的预后。这对于有 ECMO 支持和没有 ECMO 支持的患者都是如此。即使没有 ECMO 也可能有良好结果的更健康的患者更自由地使用 ECMO 提高了归因于该程序的生存概率，正如在有或没有 ECMO 预后相当差的重病和老年患者中限制使用一样。图 1) [2, 4]。然而，在我们看来，扩大适应症范围可能是合理的，甚至是正当的。当经验丰富的医生基于对个体患者负责任的床边评估做出决定并期望在不使用 ECMO 的情况下会出现更差的结果时，可能会出现这种情况。这种方法最近被描述为“抢救 ECMO”[5]。

为了全面评估ECMO在治疗严重呼吸衰竭中的作用，我们认为仅关注最终接受ECMO的患者的生存率是不够的。相反，必须考虑具有明确严重程度标准的整个有创通气患者队列，包括未选择 ECMO 的患者，这既是由于徒劳无功，也是基于即使没有 ECMO 他们也会康复的评估。因此，实现最佳整体结果的方法应该被认为是优越的。这种方式可以帮助我们为每位患者提供最佳治疗，并改进我们的算法以决定是否使用 ECMO。

托马斯·贝恩
克里斯蒂安·卡拉吉安尼迪斯，
史蒂芬·韦伯-卡斯滕斯，
阿瑟·斯拉茨基，
沃尔夫拉姆·温迪施 &
丹尼尔布罗迪

雷根斯堡大学医学院，雷根斯堡，德国
托马斯·贝因
科隆-梅海姆医院科隆-梅海姆医院 ARDS 和 ECMO 中心呼吸内科和重症监护医学科，科隆科隆医院，Witten，德国
克里斯蒂安 Karagiannidis & Wolfram Windisch
Herdecke University Hospital, Ostmerheimer Strasse 200, 51109, Cologne, Germany
克里斯蒂安 Karagiannidis & Wolfram Windisch
德国柏林 Charité - Universitätsmedizin Berlin 麻醉学和手术重症监护医学系 (CCM, CVK)
史蒂芬·韦伯-卡斯滕斯
基南生物医学研究中心，李嘉诚知识研究所，圣迈克尔医院，多伦多大学，多伦多，加拿大
亚瑟·斯拉茨基
美国纽约哥伦比亚大学内外科医学院医学系
丹尼尔布罗迪
美国纽约长老会医院急性呼吸衰竭中心
丹尼尔布罗迪

我们感谢 Supady 博士及其同事就根据我们的数据证明在德国使用 ECMO 治疗 COVID-19 的高死亡率 [1] 判断谁应该接受 ECMO 的困难而深思熟虑的来信。他们的论点中隐含的是，宣布死亡率为高或低要求我们知道在 COVID-19 中不使用 ECMO 的情况下实际预期的死亡率是多少，这是不受控制的观察数据无法提供的信息 [6]。这是进行精心设计的随机临床试验的重要论据。但是，如果没有这些证据，我们应该如何进行呢？尽管如此，我们认为相对于资源投资而言，总体死亡率应被视为较高，这表明在该人群中使用 ECMO 确实可能过于宽松。

值得讨论的另一点是，而 Supady 等人。在决定实施 ECMO 时使用术语“选择”，我们更喜欢术语“指示。” 适应症是基于对患者实际康复潜力的仔细评估，并结合给定的干预措施（例如 ECMO），以使患者能够恢复合理的生活质量并实现明确的治疗目标。个体患者的目标和价值观[7]。这一概念还旨在平衡利益（生存）与伤害（侵入性治疗、疼痛、镇静、固定和代理人的心理负担）。因此，ECMO 的适应症应基于每个患者的几个记忆、人口统计学、医学和预后参数，以避免无效的治疗以及高住院死亡率。我们同意 Supady 博士关于平衡合理使用 ECMO 的构想；然而，德国的现实——正如我们在信中所表达的——表明我们离合理使用 ECMO 还很远。最近的一篇论文也明确强调了这一点，该论文显示，德国 40% 的 ECMO 病例是在每年只有 2 例或更少病例的医院进行的 [8] 没有关于 ECMO 交付质量的保证，这可能会合理地做出贡献致高死亡率。

由于这些原因，我们相信德国 ECMO 患者的高死亡率反映了一个坚持更合理的 ECMO 应用的机会，以反映其使用的组织方法和应该被广泛接受的适应症。

不适用。

1.
Karagiannidis C、Slutsky AS、Bein T、Windisch W、Weber-Carstens S、Brodie D。在大流行的前三波期间，德国接受 ECMO 的 COVID 患者在全国范围内完全死亡。暴击护理。2021;25(1):413。
文章谷歌学术
2.
Barbaro RP、MacLaren G、Boonstra PS、Combes A、Agerstrand C、Annich G、Diaz R、Fan E、Hryniewicz K、Lorusso R 等。COVID-19 的体外膜肺氧合：国际体外生命支持组织登记处不断演变的结果。柳叶刀。2021；398（10307）：1230-8。
CAS 文章谷歌学术
3.
Supady A、Badulak J、Evans L、Curtis JR、Brodie D. 我们是否应该在 COVID-19 大流行期间定量体外膜氧合？柳叶刀呼吸医学。2021;9(4):326-8。
CAS 文章谷歌学术
4.
Supady A、Taccone FS、Lepper PM、Ziegeler S、Staudacher DL。CO-S 组：严重 COVID-19 ARDS 体外膜肺氧合后的存活率：来自国际多中心登记的结果。暴击护理。2021 年；25(1):90。
文章谷歌学术
5.
Abrams D、Ferguson ND、Brochard L、Fan E、Mercat A、Combes A、Pellegrino V、Schmidt M、Slutsky AS、Brodie D. 用于 ARDS 的 ECMO：从抢救到护理标准？柳叶刀呼吸医学。2019;7(2):108-10。
文章谷歌学术
6.
MacLaren G、Fisher D、Brodie D. 治疗最危重的 COVID-19 患者：体外膜氧合的不断变化的作用。贾马。2022;327(1):31-2。https://doi.org/10.1001/jama.2021.22580。
文章 PubMed 谷歌学术
7.
Beauchamp T, Childress J. 生物医学伦理学原则。牛津：牛津出版社；2001 年。
谷歌学术
8.
Bercker S、Petroff D、Polze N、Karagianidis C、Bein T、Laudi S、Stehr SN、Voelker MT。ECMO 在德国的使用：对 29,929 次 ECMO 运行的分析。公共科学图书馆一。2021;16(12):e0260324。
CAS 文章谷歌学术

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隶属关系

医学 III 系（跨学科医疗重症监护），医学中心 – 弗莱堡大学，医学院，弗莱堡大学，Hugstetter Strasse 55, 79106, Freiburg, Germany
Alexander Supady、Paul M. Biever、Dawid L. Staudacher 和 Tobias Wengenmayer
德国弗莱堡大学心脏中心心脏病学和血管学 I 系
Alexander Supady、Paul M. Biever、Dawid L. Staudacher 和 Tobias Wengenmayer
海德堡全球健康研究所，海德堡大学，海德堡，德国
亚历山大·苏帕迪

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