Prone positioning in acute respiratory distress syndrome during venovenous extracorporeal membrane oxygenation,Critical Care

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Prone positioning in acute respiratory distress syndrome during venovenous extracorporeal membrane oxygenation
Critical Care ( IF 15.1 ) Pub Date : 2021-10-18 , DOI: 10.1186/s13054-021-03760-w
Shiping Zhu ₁

Affiliation

Dear Editor,

We read with respect the recent study by Dr. Poon [1], which investigated the potential benefit of prone positioning (PP) during venovenous extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome (ARDS). Total of 11 studies were included and the pooled result showed a non-significant increasing trend of survival rate in patients receiving PP during ECMO (RR 1.2, 95% CI 0.9–1.5). We would like to add some comments.

First, in the forest plot, we noted that the result from Garcia-2020’s study was significantly different from others. We performed a sensitivity analysis by excluding Garcia-2020’s study (Fig. 1), and the pooled result became statistically significant (RR 1.28, 95% CI 1.08–1.52). We believe several reasons may help to explain this finding. 1 > In Garcia-2020’s study, the overall mortality rate was significantly higher than others (85% vs. 30–60%), which suggested potential heterogeneity within these ARDS cohorts. Therefore, whether PP during ECMO presented different efficacy in different ARDS phenotypes needs to be further investigated. 2 > PP during ECMO is still not routinely applied to patients during ECMO, due to risk of life-threatening complications, such as cannula dislodgement. In all these included studies, the indications for PP differed significantly. In Garcia-2020’s study, PP was only used in case of severe hypoxemia or extensive lung consolidation, which generated an inter-relationship between PP and disease severity due to selection bias. However, in Giani-2020’s and Schmidt’s studies, PP is routinely performed or encouraged during ECMO. The indications in Chaplin-2020, Guervilly-2020, Yang-2021 and Rilinge-2020’s studies were unclear. Therefore, we suggest that these conditions should be considered when interpreting the pooled result of the current study.

Second, a meta-analysis aims to pool studies with similar design, cohort, intervention, and outcomes. This also one reason for the debate that whether observational studies and randomized controlled studies should be included in one meta-analysis [2, 3]. In the current study, both the unadjusted findings from four studies and results after propensity score matching (PSM) from three studies were included in one forest plot. We suggest that the unadjusted findings and adjusted result (PSM or regression) should be separated [4].

Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Reply

Wynne Hsing Poon,
Kollengode Ramanathan,
Ryan Ruiyang Ling,
Matthieu Schmidt &
Kiran Shekar

Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
Wynne Hsing Poon, Kollengode Ramanathan & Ryan Ruiyang Ling
Cardiothoracic Intensive Care Unit, National University Heart Centre, National University Hospital, Singapore, Singapore
Kollengode Ramanathan
Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
Matthieu Schmidt
Sorbonne Université, GRC 30, Reanimation Et Soins Intensifs du Patient en Insuffisance Respiratoire aigüE, AP-HP, Hôpital de La Pitié Salpêtrière, 75013, Paris, France
Matthieu Schmidt
Adult Intensive Care Services, Prince Charles Hospital, Brisbane, QLD, Australia
Kiran Shekar
Queensland University of Technology, Brisbane, Australia
Kiran Shekar
University of Queensland, Brisbane, Australia
Kiran Shekar
Bond University, Gold Coast, QLD, Australia
Kollengode Ramanathan & Kiran Shekar

Wynne Hsing Poon and Kollengode Ramanathan have contributed equally to this work

We thank Dr Zhu for the attention and valuable comments provided regarding our article. The indications for prone positioning (PP) during extracorporeal membrane oxygenation (ECMO) were indeed variable across studies, as outlined in our Supplementary Table 2 of our original manuscript [1]. Based on our a priori criteria for sensitivity analyses (Joanna Briggs Institute score < 8), the exclusion of study by Garcia et al., which primarily focused on COVID-19 patients, was not indicated. While we note that the sensitivity analysis suggested found significant survival benefits, this would be an unplanned post-hoc analysis, which should be considered exploratory and interpreted carefully [5].

Despite varied indications for PP, the baseline PF ratio reported by Garcia et al. (82.3 ± 22.5) was relatively similar to Giani et al. (73 ± 29) and Schmidt et al. (all patients, 60 [54–68]), suggesting a similar degree of refractory hypoxemia despite ECMO support. Additionally, metaregression analysis found that PF ratio did not independently influence patient survival. Though establishing an inter-relationship between disease severity or ARDS phenotypes and concurrent PP during ECMO goes beyond the scope of our meta-analysis, we wholly agree with Dr. Zhu that further studies should be conducted to shed light on these thought-provoking insights.

A plausible reason for the increased mortality reported by Garcia et al. could be related to the planning and provision of ECMO services during the COVID-19 pandemic [6]. With a pandemic-stricken and overwhelmed healthcare system, it is possible that patient outcomes are affected. Our subgroup analysis, albeit insignificant, also found a trend towards decreased survival in patients with COVID-19 (37%) compared to those without (64%).

This meta-analysis of observational studies aimed to summarize all available information on the application of PP with ECMO. The Cochrane recommendations suggest that in a meta-analysis of non-randomized data, adjusted results should be collected where possible [7]. However, we appreciate the suggestion to separate adjusted and unadjusted data, for which an additional analysis found no significant difference between groups (Table 1).

Table 1 Subgroup analysis based on study data type for chance of cumulative survival

Full size table

While the adjusted data suggest significant survival benefit, this should be interpreted with caution as the conclusions are based on observational study-level data from three studies. As we understand ARDS and its therapeutic interventions better, the clinical outcomes of patients are likely to improve. Clinical decisions for these patients should evolve with time, while being evidence based. Better evidence should be obtained from well-conducted clinical trials to elucidate whether PP during ECMO demonstrates a survival benefit and identify patients who are most likely to benefit.

Not applicable.

1.
Poon WH, Ramanathan K, Ling RR, Yang IX, Tan CS, Schmidt M, Shekar K. Prone positioning during venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome: a systematic review and meta-analysis. Crit Care. 2021;25(1):292. https://doi.org/10.1186/s13054-021-03723-1.
Article PubMed PubMed Central Google Scholar
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Shrier I, Boivin JF, Steele RJ, Platt RW, Furlan A, Kakuma R, Brophy J, Rossignol M. Should meta-analyses of interventions include observational studies in addition to randomized controlled trials? A critical examination of underlying principles. Am J Epidemiol. 2007;166(10):1203–9.
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Kunz R, Khan KS, Neumayer HH. Observational studies and randomized trials. N Engl J Med 2000;343(16):1194–1195; author reply 1196–1197.
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Peters J, Mengersen K. Selective reporting of adjusted estimates in observational epidemiology studies: reasons and implications for meta-analyses. Eval Health Prof. 2008;31(4):370–89.
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Curran-Everett D, Milgrom H. Post-hoc data analysis: benefits and limitations. Curr Opin Allergy Clin Immunol. 2013;13(3):223–4.
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Ramanathan K, Antognini D, Combes A, Paden M, Zakhary B, Ogino M, MacLaren G, Brodie D, Shekar K. Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases. Lancet Respiratory Med. 2020;8(5):518–26.
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Reeves BCDJ, Higgins JPT, Shea B, Tugwell P, Wells GA. Chapter 24: including non-randomized studies on intervention effects. Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editors. Cochrane handbook for systematic reviews of interventions. Hoboken: Wiley; 2021.
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Department of Respiratory Medicine, Hangzhou Hospital of Traditional Chinese Medicine, No. 453, Tiyuchang Road, Hangzhou, 310000, Zhejiang, China
Shiping Zhu

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SZ came up with the question and was responsible for writing.

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Correspondence to Shiping Zhu.

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Zhu, S. Prone positioning in acute respiratory distress syndrome during venovenous extracorporeal membrane oxygenation. Crit Care 25, 361 (2021). https://doi.org/10.1186/s13054-021-03760-w

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Received: 18 August 2021
Accepted: 20 August 2021
Published: 18 October 2021
DOI: https://doi.org/10.1186/s13054-021-03760-w

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Keywords

ARDS
Prone positioning
Mortality
Meta-analysis

中文翻译：

静脉体外膜肺氧合期间急性呼吸窘迫综合征的俯卧位

亲爱的编辑，

我们尊重 Poon 博士最近的研究 [1]，该研究调查了在急性呼吸窘迫综合征 (ARDS) 患者的静脉体外膜肺氧合 (ECMO) 期间俯卧位 (PP) 的潜在益处。共纳入 11 项研究，汇总结果显示 ECMO 期间接受 PP 患者的生存率无显着增加趋势（RR 1.2，95% CI 0.9-1.5）。我们想补充一些意见。

首先，在森林图中，我们注意到 Garcia-2020 的研究结果与其他研究有显着差异。我们通过排除 Garcia-2020 的研究（图 1）进行了敏感性分析，汇总结果变得具有统计学意义（RR 1.28，95% CI 1.08–1.52）。我们认为有几个原因可能有助于解释这一发现。1 > 在 Garcia-2020 的研究中，总体死亡率显着高于其他研究（85% 对 30-60%），这表明这些 ARDS 队列中存在潜在的异质性。因此，ECMO期间PP是否在不同ARDS表型中表现出不同的疗效需要进一步研究。2 > ECMO 期间 PP 仍不常规应用于 ECMO 期间的患者，因为存在危及生命的并发症的风险，例如套管移位。在所有这些纳入的研究中，PP 的适应症有显着差异。在 Garcia-2020 的研究中，PP 仅用于严重低氧血症或广泛肺实变的情况，由于选择偏倚，PP 与疾病严重程度之间存在相互关系。然而，在 Giani-2020 和 Schmidt 的研究中，在 ECMO 期间常规执行或鼓励 PP。Chaplin-2020、Guervilly-2020、Yang-2021 和 Rilinge-2020 的研究中的迹象尚不清楚。因此，我们建议在解释当前研究的汇总结果时应考虑这些条件。ECMO 期间常规进行或鼓励 PP。Chaplin-2020、Guervilly-2020、Yang-2021 和 Rilinge-2020 的研究中的迹象尚不清楚。因此，我们建议在解释当前研究的汇总结果时应考虑这些条件。ECMO 期间常规进行或鼓励 PP。Chaplin-2020、Guervilly-2020、Yang-2021 和 Rilinge-2020 的研究中的迹象尚不清楚。因此，我们建议在解释当前研究的汇总结果时应考虑这些条件。

其次，荟萃分析旨在汇集具有相似设计、队列、干预和结果的研究。这也是争论是否应将观察性研究和随机对照研究纳入一项荟萃分析的原因之一 [2, 3]。在当前的研究中，四项研究的未调整结果和三项研究的倾向评分匹配 (PSM) 后的结果都包含在一个森林图中。我们建议将未调整的结果和调整的结果（PSM 或回归）分开 [4]。

急性呼吸窘迫综合征的静脉体外膜氧合期间的俯卧位：回复

温星潘，
科伦戈德·拉马纳坦
瑞安瑞阳玲，
马修·施密特 &
基兰·谢卡尔

Yong Loo Lin 医学院，新加坡国立大学，新加坡，新加坡
Wynne Hsing Poon, Kollengode Ramanathan & Ryan Ruiyang Ling
新加坡新加坡国立大学医院国立大学心脏中心心胸重症监护室
科伦戈德·拉马纳坦
Service de Médecine Intensive-Réanimation, Institut de Cardiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, 巴黎, 法国
马修·施密特
Sorbonne Université, GRC 30, Reanimation Et Soins Intensifs du Patient en Insuffisance Respiratoire aigüE, AP-HP, Hôpital de La Pitié Salpêtrière, 75013, Paris, France
马修·施密特
澳大利亚昆士兰州布里斯班查尔斯王子医院成人重症监护服务
基兰·谢卡尔
澳大利亚布里斯班昆士兰科技大学
基兰·谢卡尔
澳大利亚布里斯班昆士兰大学
基兰·谢卡尔
澳大利亚昆士兰黄金海岸邦德大学
Kollengode Ramanathan & Kiran Shekar

Wynne Hsing Poon 和 Kollengode Ramanathan 对这项工作做出了同等贡献

我们感谢朱博士对我们文章的关注和宝贵意见。如我们原始手稿的补充表 2 所述，体外膜肺氧合 (ECMO) 期间俯卧位 (PP) 的指征在不同研究中确实不同。根据我们的敏感性分析的先验标准（Joanna Briggs Institute 评分 < 8），没有指出排除 Garcia 等人主要针对 COVID-19 患者的研究。虽然我们注意到敏感性分析表明发现了显着的生存获益，但这将是一项计划外的事后分析，应被视为探索性分析并仔细解释 [5]。

尽管 PP 的适应症各不相同，但 Garcia 等人报告的基线 PF 比率。(82.3 ± 22.5) 与 Giani 等人相对相似。(73 ± 29) 和 Schmidt 等人。（所有患者，60 [54-68]），表明尽管 ECMO 支持，但难治性低氧血症的程度相似。此外，元回归分析发现 PF 比并不能独立影响患者的生存率。尽管在 ECMO 期间建立疾病严重程度或 ARDS 表型与并发 PP 之间的相互关系超出了我们的荟萃分析的范围，但我们完全同意朱博士的观点，即应该进行进一步的研究以阐明这些发人深省的见解。

Garcia 等人报告的死亡率增加的合理原因。可能与 COVID-19 大流行期间 ECMO 服务的规划和提供有关 [6]。由于大流行病肆虐和不堪重负的医疗保健系统，患者的治疗效果可能会受到影响。我们的亚组分析虽然不显着，但也发现 COVID-19 患者（37%）与没有患者（64%）相比存在生存率下降的趋势。

这项观察性研究的荟萃分析旨在总结有关 PP 与 ECMO 应用的所有可用信息。Cochrane 建议建议，在非随机数据的荟萃分析中，应尽可能收集调整后的结果[7]。然而，我们感谢将调整后数据和未调整数据分开的建议，额外的分析发现组间没有显着差异（表 1）。

表 1 基于研究数据类型的累积生存机会亚组分析

全尺寸表

虽然调整后的数据表明显着的生存获益，但应谨慎解释，因为结论是基于三项研究的观察性研究级数据。随着我们更好地了解 ARDS 及其治疗干预措施，患者的临床结果可能会有所改善。这些患者的临床决策应随着时间的推移而发展，同时以证据为基础。应从进行良好的临床试验中获得更好的证据，以阐明 ECMO 期间的 PP 是否显示出生存获益并确定最有可能受益的患者。

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