Neurologic Complications of Patients With COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

Cathy Meng Fei Li, Xiaoxiao Densy Deng, Yu Fei Ma, Emily Dawson, Carol Li, Dong Yao Wang, Lynn Huong, Teneille Gofton, Atul Dave Nagpal, Marat Slessarev
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Abstract

In COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO), our primary objective was to determine the frequency of intracranial hemorrhage (ICH). Secondary objectives were to estimate the frequency of ischemic stroke, to explore association between higher anticoagulation targets and ICH, and to estimate the association between neurologic complications and in-hospital mortality.

Data sources: We searched MEDLINE, Embase, PsycINFO, Cochrane, and MedRxiv databases from inception to March 15, 2022.

Study selection: We identified studies that described acute neurological complications in adult patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring ECMO.

Data extraction: Two authors independently performed study selection and data extraction. Studies with 95% or more of its patients on venovenous or venoarterial ECMO were pooled for meta-analysis, which was calculated using a random-effects model.

Data synthesis: Fifty-four studies (n = 3,347) were included in the systematic review. Venovenous ECMO was used in 97% of patients. Meta-analysis of ICH and ischemic stroke on venovenous ECMO included 18 and 11 studies, respectively. The frequency of ICH was 11% (95% CI, 8-15%), with intraparenchymal hemorrhage being the most common subtype (73%), while the frequency of ischemic strokes was 2% (95% CI, 1-3%). Higher anticoagulation targets were not associated with increased frequency of ICH (p = 0.06). In-hospital mortality was 37% (95% CI, 34-40%) and neurologic causes ranked as the third most common cause of death. The risk ratio of mortality in COVID-19 patients with neurologic complications on venovenous ECMO compared with patients without neurologic complications was 2.24 (95% CI, 1.46-3.46). There were insufficient studies for meta-analysis of COVID-19 patients on venoarterial ECMO.

Conclusions: COVID-19 patients requiring venovenous ECMO have a high frequency of ICH, and the development of neurologic complications more than doubled the risk of death. Healthcare providers should be aware of these increased risks and maintain a high index of suspicion for ICH.

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COVID-19患者需要体外膜氧合的神经系统并发症:系统综述和荟萃分析
在需要体外膜氧合(ECMO)的COVID-19患者中,我们的主要目的是确定颅内出血(ICH)的频率。次要目的是估计缺血性脑卒中的频率,探讨较高的抗凝指标与脑出血之间的关系,以及估计神经系统并发症与住院死亡率之间的关系。数据来源:我们检索了MEDLINE、Embase、PsycINFO、Cochrane和MedRxiv数据库,检索时间从成立到2022年3月15日。研究选择:我们确定了描述严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)感染成人患者需要ECMO的急性神经系统并发症的研究。数据提取:两位作者独立进行研究选择和数据提取。95%或95%以上患者接受静脉-静脉或静脉-动脉ECMO的研究纳入荟萃分析,使用随机效应模型计算。数据综合:系统评价纳入54项研究(n = 3347)。97%的患者采用静脉-静脉ECMO。静脉-静脉ECMO对脑出血和缺血性卒中的meta分析分别包括18项和11项研究。脑出血的发生率为11% (95% CI, 8-15%),其中肺实质内出血是最常见的亚型(73%),而缺血性脑卒中的发生率为2% (95% CI, 1-3%)。较高的抗凝指标与脑出血频率增加无关(p = 0.06)。住院死亡率为37% (95% CI, 34-40%),神经系统原因排在第三位。有神经系统并发症的COVID-19患者与无神经系统并发症的患者相比,经静脉-静脉ECMO的死亡率风险比为2.24 (95% CI, 1.46-3.46)。对COVID-19患者进行静脉动脉ECMO的meta分析研究不足。结论:需要静脉-静脉ECMO的COVID-19患者脑出血发生率高,神经系统并发症的发生使死亡风险增加一倍以上。医疗保健提供者应意识到这些增加的风险,并保持对脑出血的高度怀疑。
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