Comment to “Very late intubation in COVID-19 patients: A forgotten prognosis factor?”,Critical Care

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Comment to “Very late intubation in COVID-19 patients: A forgotten prognosis factor?”
Critical Care ( IF 8.8 ) Pub Date : 2022-07-11 , DOI: 10.1186/s13054-022-04033-w
Ricard Mellado-Artigas _{1,

2} , Luigi Zattera ₁ , Enric Barbeta _{1,

2} , Carlos Ferrando _{1,

2}

Affiliation

Dear Editor,

We have read the manuscript published by Camous and colleagues in this journal [1]. We want to congratulate the authors for their effort in describing outcomes in ventilated COVID-19 patients and its relationship to the time of intubation. The authors showed that intubation after 7 days of dexamethasone start was associated with a dismal outcome, while intubation between days 1 and 7, as compared to intubation before day 1, was not linked to worse results.

The optimal timing for mechanical ventilation initiation, including COVID-19 patients, has been a matter of debate with studies supporting or refuting the effect of a delay in intubation on outcomes, and overall uncertain results [2, 3]. In the absence of clinical trials to provide high-quality evidence, observational studies are used to sustain daily practice. Unfortunately, observational studies often present with large imbalances in relevant variables between treatment groups that preclude an easy estimation of treatment effects. In other words, groups tend to differ at baseline in the degree of severity of their illness. Nonetheless, if confounding can be controlled for, these data might offer valuable information on a particular treatment effect.

In the present work, very late intubation was associated with higher mortality. While the potential role of a delay in intubation on outcome cannot be ruled out, we want to highlight that patients among groups largely differed in important variables: first, the early intubation group presented at baseline a median ROX index as low as 3, as well as higher illness severity, as reported by higher SOFA score, while the very late group displayed a median ROX of 6, making these patients populations not comparable in terms of both baseline severity and probability to be intubated. We suggest therefore an analysis after adjusting for these important covariates [4]. Second, the very late group received more frequently tocilizumab as an adjunctive therapy: although the authors hypothesized that this was due to a longer time between steroid treatment and intubation, intubation is not a formal contraindication for such treatment. Usually, patients receiving tocilizumab show a higher inflammatory burden despite steroid treatment which has been identified as marker of disease severity [5].

In conclusion, we think that the data presented in this brief report, although of great interest, might present important limitations as residual confounding could not be excluded.

Laurent Camous,
Jean-David Pommier,
Frederic Martino,
Benoît Tressieres,
Alexandre Demoule &
Marc Valette

Dear Editor,

We thank Mellado-Artigas et al. for their interest in our work and for their suggestions. As these authors underline, timing and indications of mechanical ventilation of SARS-CoV-2 pneumonia are still debated. We tried to understand the high mortality of lately intubated COVID patients, after careful studies of the potential bias and not comparing strategies of care.

For Mellado-Artigas et al. groups of our study are not comparable because of the baseline differences in ROX and SOFA. However, the description of our groups was based on the day of mechanical ventilation. As ROX scores at intubation were not different in between the three groups of intubated patients, we believe that respiratory condition at intubation was similar. Another potential bias discussed by Mellado-Artigas et al. was the difference in-between groups in the use of tocilizumab. However, as there are no robust data on mortality, incidence of nosocomial infection and ventilator-free days after tocilizumab treatment, we chose in our center not to use tocilizumab in mechanically ventilated patients in view of the potential infectious risk. There was no difference in inflammatory markers (CRP and D-dimer levels) at baseline between groups.

The impact on prognosis of late intubation in COVID patients has been discussed by others [2, 6]. The different hypotheses were discussed in our study: potential patient-self-induced lung injury (p-SILI) due to prolonged high flow nasal oxygen therapy or worsening of lung damages during steroid treatment.

Randomized trials are needed to confirm our data and to better understand the mechanisms of mortality in late intubated COVID patients. Mellado-Artigas et al. proposed the use of a propensity score-based cohort analysis as a tool to compare patients. We think that pairing of ARDS patients is difficult, as PaO₂/FiO₂ ratio or radiological abnormalities on CT-scan are rough markers of lung damage severity.

No applicable.

Camous L, Pommier J-D, Martino F, Tressieres B, Demoule A, Valette M. Very late intubation in COVID-19 patients: A forgotten prognosis factor? Crit Care. 2022;26(1):1–4. https://doi.org/10.1186/S13054-022-03966-6.
Article Google Scholar
González J, Benítez ID, de Gonzalo-Calvo D, et al. Impact of time to intubation on mortality and pulmonary sequelae in critically ill patients with COVID-19: a prospective cohort study. Crit Care. 2022;26(1):18. https://doi.org/10.1186/S13054-021-03882-1.
Article PubMed PubMed Central Google Scholar
Papoutsi E, Giannakoulis VG, Xourgia E, et al. Effect of timing of intubation on clinical outcomes of critically ill patients with COVID-19: a systematic review and meta-analysis of non-randomized cohort studies. Crit Care. 2021;25(1):121. https://doi.org/10.1186/s13054-021-03540-6.
Article PubMed PubMed Central Google Scholar
Austin PC. A tutorial and case study in propensity score analysis: an application to estimating the effect of in-hospital smoking cessation counseling on mortality. Multivar Behav Res. 2011;46(1):119–51. https://doi.org/10.1080/00273171.2011.540480.
Article Google Scholar
Lasso G, Khan S, Allen SA, et al. Longitudinally monitored immune biomarkers predict the timing of COVID-19 outcomes. PLOS Comput Biol. 2022;18(1):e1009778. https://doi.org/10.1371/JOURNAL.PCBI.1009778.
CAS Article PubMed PubMed Central Google Scholar
Fayed M, Patel N, Yeldo N, et al. Effect of intubation timing on the outcome of patients with severe respiratory distress secondary to COVID-19 pneumonia. Cureus [Internet] 2021 [cited 2022 May 20].

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CF is funded by Instituto de Salud Carlos III, Madrid, Spain (#CB06/06/1088; #PI16/00049; #PI18/01611; #PI19/00141).

Authors and Affiliations

Surgical ICU (Department of Anaesthesiology), Hospital ClínicInstitut D’investigació August Pi i Sunyer, Villarroel 170, 08025, Barcelona, Spain
Ricard Mellado-Artigas, Luigi Zattera, Enric Barbeta & Carlos Ferrando
CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain
Ricard Mellado-Artigas, Enric Barbeta & Carlos Ferrando

Authors

Ricard Mellado-ArtigasView author publications
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Luigi ZatteraView author publications
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Enric BarbetaView author publications
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Carlos FerrandoView author publications
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Contributions

RMA, CF, LZ and EB have participated in the writing of this manuscript and have approved the final version.

Corresponding author

Correspondence to Ricard Mellado-Artigas.

Ethics approval and consent to participate

Not applicable.

Competing interests

RMA declares having received lecturing fees from Medtronic and Fisher & Paykel. No other authors declare competing interests.

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Mellado-Artigas, R., Zattera, L., Barbeta, E. et al. Comment to “Very late intubation in COVID-19 patients: A forgotten prognosis factor?”. Crit Care 26, 212 (2022). https://doi.org/10.1186/s13054-022-04033-w

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Received: 06 May 2022
Accepted: 11 May 2022
Published: 11 July 2022
DOI: https://doi.org/10.1186/s13054-022-04033-w

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中文翻译：

对“COVID-19 患者非常晚插管：一个被遗忘的预后因素？”的评论

亲爱的编辑，

我们已经阅读了 Camous 及其同事在该期刊上发表的手稿 [1]。我们要祝贺作者在描述通气 COVID-19 患者的结果及其与插管时间的关系方面所做的努力。作者表明，地塞米松开始 7 天后插管与令人沮丧的结果相关，而与第 1 天之前的插管相比，第 1 天和第 7 天之间的插管与更差的结果无关。

开始机械通气的最佳时机（包括 COVID-19 患者）一直是一个争论的问题，研究支持或反驳插管延迟对结果的影响，以及总体不确定的结果 [2, 3]。在缺乏临床试验来提供高质量证据的情况下，观察性研究被用来维持日常实践。不幸的是，观察性研究通常会出现治疗组之间相关变量的巨大不平衡，从而无法轻松估计治疗效果。换言之，各组在疾病严重程度方面往往存在基线差异。尽管如此，如果可以控制混杂，这些数据可能会提供有关特定治疗效果的有价值信息。

在目前的工作中，非常晚的插管与较高的死亡率相关。虽然不能排除插管延迟对结果的潜在影响，但我们想强调各组患者在重要变量上存在很大差异：首先，早期插管组在基线时的 ROX 指数中位数也低至 3正如较高的 SOFA 评分所报告的那样，疾病严重程度较高，而晚期组的 ROX 中位数为 6，这使得这些患者群体在基线严重程度和插管概率方面不具有可比性。因此，我们建议在调整这些重要协变量后进行分析 [4]。其次，晚期组更频繁地接受托珠单抗作为辅助治疗：尽管作者假设这是由于类固醇治疗和插管之间的时间较长，但插管并不是此类治疗的正式禁忌症。通常，尽管类固醇治疗已被确定为疾病严重程度的标志物，但接受托珠单抗治疗的患者仍表现出较高的炎症负担 [5]。

总之，我们认为这份简短报告中提供的数据虽然非常有趣，但可能存在重要的局限性，因为不能排除残余混杂因素。

劳伦特·卡穆斯，
让-大卫·波米耶，
弗雷德里克·马蒂诺
贝努瓦·特雷西埃，
亚历山大·德穆勒 &
马克·瓦莱特

亲爱的编辑，

我们感谢Mellado-Artigas等人。感谢他们对我们工作的兴趣和他们的建议。正如这些作者所强调的，SARS-CoV-2 肺炎机械通气的时机和指征仍然存在争议。在仔细研究了潜在的偏倚而不是比较护理策略之后，我们试图了解新近插管的 COVID 患者的高死亡率。

对于Mellado-Artigas等人。由于 ROX 和 SOFA 的基线差异，我们的研究组不具有可比性。然而，我们组的描述是基于机械通气的日子。由于插管时的 ROX 评分在三组插管患者之间没有差异，我们认为插管时的呼吸状况相似。Mellado-Artigas讨论的另一个潜在偏见等。是使用托珠单抗的组间差异。然而，由于没有关于托珠单抗治疗后死亡率、医院感染发生率和无呼吸机天数的可靠数据，鉴于潜在的感染风险，我们中心选择不在机械通气患者中使用托珠单抗。在基线时，各组之间的炎症标志物（CRP 和 D-二聚体水平）没有差异。

其他人已经讨论了 COVID 患者晚期插管对预后的影响 [2, 6]。在我们的研究中讨论了不同的假设：由于长期高流量鼻氧治疗或类固醇治疗期间肺损伤恶化，可能导致患者自身诱发的肺损伤 (p-SILI)。

需要进行随机试验来确认我们的数据并更好地了解晚期插管 COVID 患者的死亡率机制。梅拉多-阿蒂加斯等人。提出使用基于倾向评分的队列分析作为比较患者的工具。我们认为 ARDS 患者的配对很困难，因为 PaO ₂ /FiO ₂比率或 CT 扫描上的放射学异常是肺损伤严重程度的粗略标志。

不适用。

Camous L、Pommier JD、Martino F、Tressieres B、Demoule A、Valette M. COVID-19 患者的极晚插管：一个被遗忘的预后因素？暴击护理。2022；26（1）：1-4。https://doi.org/10.1186/S13054-022-03966-6。
文章谷歌学术
González J、Benítez ID、de Gonzalo-Calvo D 等人。插管时间对 COVID-19 重症患者死亡率和肺部后遗症的影响：一项前瞻性队列研究。暴击护理。2022;26(1):18。https://doi.org/10.1186/S13054-021-03882-1。
文章 PubMed PubMed Central Google Scholar
Papoutsi E、Giannakoulis VG、Xourgia E 等。插管时间对 COVID-19 重症患者临床结局的影响：非随机队列研究的系统评价和荟萃分析。暴击护理。2021；25(1):121。https://doi.org/10.1186/s13054-021-03540-6。
文章 PubMed PubMed Central Google Scholar
奥斯汀电脑。倾向评分分析的教程和案例研究：估计院内戒烟咨询对死亡率影响的应用。多变量行为水库。2011;46(1):119-51。https://doi.org/10.1080/00273171.2011.540480。
文章谷歌学术
套索 G、汗 S、艾伦 SA 等。纵向监测的免疫生物标志物可预测 COVID-19 结果的时机。PLOS 计算机生物学。2022;18(1):e1009778。https://doi.org/10.1371/JOURNAL.PCBI.1009778。
CAS 文章 PubMed PubMed Central Google Scholar
Fayed M、Patel N、Yeldo N 等。插管时间对继发于 COVID-19 肺炎的严重呼吸窘迫患者结局的影响。Cureus [互联网] 2021 [引自 2022 年 5 月 20 日]。

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CF 由西班牙马德里的 Instituto de Salud Carlos III 资助（#CB06/06/1088；#PI16/00049；#PI18/01611；#PI19/00141）。

作者和附属机构

外科 ICU（麻醉科），Hospital ClínicInstitut D'investigació August Pi i Sunyer, Villarroel 170, 08025, Barcelona, Spain
Ricard Mellado-Artigas、Luigi Zattera、Enric Barbeta 和 Carlos Ferrando
CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, 马德里, 西班牙
Ricard Mellado-Artigas、Enric Barbeta 和 Carlos Ferrando

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贡献

RMA、CF、LZ 和 EB 参与了本手稿的撰写，并批准了最终版本。

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