Department of Anesthesiology, Section Interdisciplinary Surgical Intensive Care, University Hospital Ulm, Albert-Einstein-Allee 23, 89081, Ulm, Germany.
Ulm University, Institute of Epidemiology and Medical Biometry, Schwabstraße 13, 89075, Ulm, Germany.
BMC Anesthesiol. 2020 Nov 17;20(1):287. doi: 10.1186/s12871-020-01204-6.
Up to 70% of septic patients develop a diffuse brain dysfunction named "septic associated encephalopathy" which is often solely based on clinical impressions. However, the diagnosis of septic associated encephalopathy is outcome-relevant due to an increase in mortality in these patients. Neuroinflammation as well as a disturbance of cholinergic transmission are assumed to be the causes of both delirium and septic associated encephalopathy. An alteration in cholinergic activity can be objectified by measuring the erythrocytic acetylcholinesterase-activity. Single-point measurements of acetylcholinesterase-activity are of limited value because individual and dynamic changes over time have to be anticipated. Therefore, the hypothesis should be tested whether a longitudinal analysis of acetylcholinesterase-activity in critically ill patients can help to diagnose a suspected septic-associated encephalopathy and whether acetylcholinesterase-activity differs in comparison to non-septic patients.
In this prospective, observational, single-center study, 175 patients (45 with sepsis, 130 without sepsis) were included. All patients were admitted to the surgical Intensive Care Unit of the University hospital Ulm, Germany. Patients were examined daily for the presence of delirium using the CAM-ICU. Daily measurement of the acetylcholinesterase-activity was performed in all patients. The possible time-dependent change in acetylcholinesterase-activity was analyzed with a linear regression model considering repeated measurements. Using a time-adjusted model further factors able to affect AChE-activity were investigated. For nonparametric distributions quantitative data were compared using Wilcoxon matched-pairs test. For analysis of independent samples the Mann-Whitney test was performed.
About 90% of septic patients with suspected septic associated encephalopathy exhibited a statistically significant time-dependent in- or decrease in acetylcholinesterase-activity over a period of at least 5 consecutive days.
Longitudinal measurement of acetylcholinesterase-activity over several consecutive days revealed a change from baseline only in septic patients with suspected septic-associated encephalopathy. Therefore, longitudinal measurement of acetylcholinesterase-activity is able to diagnose septic associated encephalopathy in septic patients with delirious symptoms.
Retrospectively registered at German Clinical Trials Register, registration number DRKS00020542 , date of registration: January 27, 2020.
多达 70%的脓毒症患者会出现一种称为“脓毒症相关脑病”的弥漫性脑功能障碍,这种脑病通常仅基于临床印象。然而,由于这些患者的死亡率增加,脓毒症相关脑病的诊断与预后相关。神经炎症以及胆碱能传递的紊乱被认为是谵妄和脓毒症相关脑病的原因。通过测量红细胞乙酰胆碱酯酶活性可以客观地反映胆碱能活性的改变。单点测量乙酰胆碱酯酶活性的价值有限,因为需要预测个体和随时间的动态变化。因此,应该测试以下假设:对危重症患者乙酰胆碱酯酶活性进行纵向分析是否有助于诊断疑似脓毒症相关脑病,以及乙酰胆碱酯酶活性是否与非脓毒症患者不同。
在这项前瞻性、观察性、单中心研究中,纳入了 175 名患者(45 名脓毒症患者,130 名非脓毒症患者)。所有患者均入住德国乌尔姆大学医院外科重症监护病房。使用 ICU 意识模糊评估法(CAM-ICU)每天对患者进行谵妄检查。所有患者均进行每日乙酰胆碱酯酶活性测量。使用线性回归模型分析考虑重复测量的乙酰胆碱酯酶活性的可能时变。使用时间调整模型进一步研究能够影响 AChE 活性的其他因素。对于非参数分布,使用 Wilcoxon 配对检验比较定量数据。对于独立样本分析,使用 Mann-Whitney 检验。
约 90%的疑似脓毒症相关脑病的脓毒症患者在至少连续 5 天的时间内,乙酰胆碱酯酶活性表现出统计学上显著的时间依赖性升高或降低。
连续几天对乙酰胆碱酯酶活性进行纵向测量,仅在疑似脓毒症相关脑病的脓毒症患者中发现基线后发生变化。因此,对乙酰胆碱酯酶活性进行连续几天的纵向测量能够诊断出有谵妄症状的脓毒症患者的脓毒症相关脑病。
于 2020 年 1 月 27 日在德国临床试验注册中心(DRKS00020542)进行回顾性注册。