Department of Neurology, New York University Grossman School of Medicine, New York, NY, USA.
Brown University School of Medicine, Providence, RI, USA.
Neurocrit Care. 2021 Dec;35(3):693-706. doi: 10.1007/s12028-021-01220-5. Epub 2021 Mar 16.
Toxic metabolic encephalopathy (TME) has been reported in 7-31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients.
We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission.
Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P < 0.001]). Excluding comfort care patients (n = 267 of 4491 [6%]) and after adjustment for confounders, TME remained associated with increased risk of in-hospital death (n = 128 of 425 [30%] patients with TME died, compared with n = 600 of 3799 [16%] patients without TME; adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.02-1.52, P = 0.031), and TME due to hypoxemia conferred the highest risk (n = 97 of 233 [42%] patients with HIE died, compared with n = 631 of 3991 [16%] patients without HIE; aHR 1.56, 95% CI 1.21-2.00, P = 0.001).
TME occurred in one in eight hospitalized patients with COVID-19, was typically multifactorial, and was most often due to hypoxemia, sepsis, and uremia. After we adjustment for confounding factors, TME was associated with a 24% increased risk of in-hospital mortality.
在患有 2019 年冠状病毒病（COVID-19）的住院患者中，有 7-31%的患者出现了毒性代谢性脑病（TME）；然而，一些报告包括与镇静相关的谵妄，并且关于 TME 的病因的资料很少。我们旨在确定严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）阳性患者中 TME 的患病率、病因和死亡率。
我们在同一医疗网络的四家纽约市医院进行了一项回顾性、多中心、观察性队列研究，研究对象为经逆转录酶-聚合酶链反应确诊的 SARS-CoV-2 感染住院患者。在没有镇静或镇静洗脱后，TME 是在精神状态改变的患者中诊断的。排除有结构性脑疾病、癫痫发作或原发性神经诊断的患者。主要转归是根据病因分层的 TME 患病率和住院死亡率（不包括仅接受舒适护理的患者），使用多变量时间依赖性 Cox 比例风险模型评估，调整因素包括年龄、种族、性别、插管、需要重症监护、序贯器官衰竭评估评分、医院位置和入院日期。
在 4491 例 COVID-19 患者中，559 例（12%）被诊断为 TME，其中 435 例（78%）在入院前立即发生脑病。最常见的病因是感染性脑病（n=559 例中的 247 例[62%]）、缺氧缺血性脑病（HIE）（n=559 例中的 331 例[59%]）和尿毒症（n=559 例中的 156 例[28%]）。435 例（78%）患者存在多种病因。与无 TME 患者（n=3932 例）相比，有 TME 的患者年龄更大（76 岁 vs. 62 岁）、有痴呆症（27% vs. 3%）或精神病病史（20% vs. 10%）、更常插管（37% vs. 20%）、住院时间更长（7.9 天 vs. 6.0 天）、更常出院回家（25% vs. 66%[所有 P<0.001]）。排除仅接受舒适护理的患者（n=4491 例中的 267 例[6%]），并调整混杂因素后，TME 与住院死亡风险增加仍相关（n=425 例中有 128 例[30%]的 TME 患者死亡，与 n=3799 例中有 600 例[16%]的无 TME 患者死亡；调整后的危险比[aHR] 1.24，95%置信区间[CI] 1.02-1.52，P=0.031），由缺氧引起的 TME 风险最高（n=233 例中有 97 例[42%]的 HIE 患者死亡，与 n=3991 例中有 631 例[16%]的无 HIE 患者死亡；aHR 1.56，95%CI 1.21-2.00，P=0.001）。
TME 发生在每 8 例住院 COVID-19 患者中一例，通常是多因素的，最常见的病因是缺氧、感染和尿毒症。在我们调整了混杂因素后，TME 与住院死亡率增加 24%相关。
