INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Sorbonne Université, Paris, France; Service de Médecine Intensive-Réanimation, Institut de Cardiologie, AP-HP Sorbonne Université Hôpital Pitié-Salpêtrière, Paris, France.
Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpitaux Universitaires Pitié Salpêtrière-Charles Foix, Département de Santé Publique, Centre de Pharmacoépidémiologie (Cephepi), Paris, France.
Lancet Respir Med. 2023 Feb;11(2):163-175. doi: 10.1016/S2213-2600(22)00438-6. Epub 2023 Jan 11.
To inform future research and practice, we aimed to investigate the outcomes of patients who received extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) due to different variants of SARS-CoV-2.
This retrospective study included consecutive adult patients with laboratory-confirmed SARS-CoV-2 infection who received ECMO for ARDS in 21 experienced ECMO centres in eight European countries (Austria, Belgium, England, France, Germany, Italy, Portugal, and Spain) between Jan 1, 2020, and Sept 30, 2021. We collected data on patient characteristics, clinical status, and management before and after the initiation of ECMO. Participants were grouped according to SARS-CoV-2 variant (wild type, alpha, delta, or other) and period of the pandemic (first [Jan 1-June 30] and second [July 1-Dec 31] semesters of 2020, and first [Jan 1-June 30] and second [July 1-Sept 30] semesters of 2021). Descriptive statistics and Kaplan-Meier survival curves were used to analyse evolving characteristics, management, and patient outcomes over the first 2 years of the pandemic, and independent risk factors of mortality were determined using multivariable Cox regression models. The primary outcome was mortality 90 days after the initiation of ECMO, with follow-up to Dec 30, 2021.
ECMO was initiated in 1345 patients. Patient characteristics and management were similar for the groups of patients infected with different variants, except that those with the delta variant had a younger median age and less hypertension and diabetes. 90-day mortality was 42% (569 of 1345 patients died) overall, and 43% (297/686) in patients infected with wild-type SARS-CoV-2, 39% (152/391) in those with the alpha variant, 40% (78/195) in those with the delta variant, and 58% (42/73) in patients infected with other variants (mainly beta and gamma). Mortality was 10% higher (50%) in the second semester of 2020, when the wild-type variant was still prevailing, than in other semesters (40%). Independent predictors of mortality were age, immunocompromised status, a longer time from intensive care unit admission to intubation, need for renal replacement therapy, and higher Sequential Organ Failure Assessment haemodynamic component score, partial pressure of arterial carbon dioxide, and lactate concentration before ECMO. After adjusting for these variables, mortality was significantly higher with the delta variant than with the other variants, the wild-type strain being the reference.
Although crude mortality did not differ between variants, adjusted risk of death was highest for patients treated with ECMO infected with the delta variant of SARS-CoV-2. The higher virulence and poorer outcomes associated with the delta strain might relate to higher viral load and increased inflammatory response syndrome in infected patients, reinforcing the need for a higher rate of vaccination in the population and updated selection criteria for ECMO, should a new and highly virulent strain of SARS-CoV-2 emerge in the future. Mortality was noticeably lower than in other large, multicentre series of patients who received ECMO for COVID-19, highlighting the need to concentrate resources at experienced centres.
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为了为未来的研究和实践提供信息,我们旨在调查因不同 SARS-CoV-2 变体而接受体外膜氧合(ECMO)治疗急性呼吸窘迫综合征(ARDS)的患者的结局。
本回顾性研究纳入了 2020 年 1 月 1 日至 2021 年 9 月 30 日期间,在欧洲 8 个国家(奥地利、比利时、英国、法国、德国、意大利、葡萄牙和西班牙)的 21 个有经验的 ECMO 中心,因 SARS-CoV-2 感染而接受 ECMO 治疗 ARDS 的连续成年患者。我们收集了患者特征、临床状况和 ECMO 启动前后的管理数据。根据 SARS-CoV-2 变体(野生型、alpha、delta 或其他)和大流行时期(2020 年第一学期[1 月 1 日至 6 月 30 日]和第二学期[7 月 1 日至 12 月 31 日],以及 2021 年第一学期[1 月 1 日至 6 月 30 日]和第二学期[7 月 1 日至 9 月 30 日])对参与者进行分组。描述性统计和 Kaplan-Meier 生存曲线用于分析大流行前 2 年的演变特征、管理和患者结局,使用多变量 Cox 回归模型确定死亡率的独立危险因素。主要结局为 ECMO 启动后 90 天的死亡率,随访至 2021 年 12 月 30 日。
共启动了 1345 例 ECMO。除了 delta 变体感染的患者中位年龄更小且高血压和糖尿病发病率更低外,感染不同变体的患者组的患者特征和管理相似。总体 90 天死亡率为 42%(569/1345 例死亡),野生型 SARS-CoV-2 感染患者为 43%(297/686),alpha 变体为 39%(152/391),delta 变体为 40%(78/195),其他变体(主要是 beta 和 gamma)感染患者为 58%(42/73)。2020 年第二学期(当野生型变体仍占主导地位时)的死亡率(50%)比其他学期(40%)高 10%。死亡率的独立预测因素为年龄、免疫功能低下状态、从重症监护病房入院到插管的时间较长、需要肾脏替代治疗以及更高的序贯器官衰竭评估血流动力学成分评分、动脉血二氧化碳分压和乳酸浓度。在调整这些变量后,delta 变体感染的患者死亡率明显高于其他变体,野生型 SARS-CoV-2 为参照。
尽管变体之间的死亡率没有差异,但感染 delta 变体的患者接受 ECMO 治疗的死亡风险调整后明显更高。与 delta 株相关的更高毒力和更差结局可能与感染患者的病毒载量更高和炎症反应综合征增加有关,这强调了需要在人群中提高疫苗接种率,并在未来出现新的、高毒力的 SARS-CoV-2 株时更新 ECMO 的选择标准。死亡率明显低于接受 COVID-19 治疗的其他大型、多中心 ECMO 系列患者,这突显了需要在有经验的中心集中资源。
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