Pilot Observation of the Impact of Human Blood Serum From Critically Ill Patients With or Without Critical-illness-polyneuropathy on Intramural Neuronal Networks of Human Colon Samples
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- Changes in the frequency and the amplitude of spontaneous contractions of colonic smooth muscle preparations induced by incubation with serum from critically ill patients with CIP, without CIP and healthy controls
研究概览
简要总结
Critical illness in the ICU setting has high medical and socioeconomic importance. Critically ill patients frequently develop severe neurologic impairment during their course of disease, typically presenting as critical-illness-polyneuropathy (CIP), which is associated with an increased mortality rate. To date neither strategies are available to predict nor to specifically treat CIP.
Diagnostic tests to determine CIP during the course of critical illness are available through nerve conduction studies. Further research is needed to find diagnostic tools to identify patients who are on high risk to develop CIP, which could encourage the evolution of new therapeutic strategies for CIP patients.
The aims of the study are:
- An early detection of changes in intramural neuronal networks of human colon samples induced by human blood serum from critically ill patients in order to predict the development of CIP
- The comparison of different diagnostic tests to diagnose and monitor CIP during the course of critical illness (neurologic examination versus nerve conduction study versus neuromyosonography)
详细描述
All patients with critical illness and fulfilling the inclusion criteria should be screened for the study on two surgical ICUs at the university hospital of Rostock, Germany.
The inclusion of patients will be started if written informed consent was obtained from all participants or their representatives (if direct consent could not be obtained).
The aim of the study is a prediction or an earlier detection of CIP in critically ill patients before nerve conduction studies are able to diagnose CIP. We hypothesize that upregulated circulating neurotoxic factors in human serum of critically ill patients cause neuronal damage and play an important role in the pathogenesis of CIP. Time from upregulation of neurotoxic factors to the clinical appearance of neuronal damage (CIP) is unknown.
An experimental part of the study aims at establishing enteric neuronal networks as functional bioassays for the qualitative detection of neurotoxic humoral factors. Human colon samples will be exposed to the serum of critically ill patients with and without CIP in an organ bath (100% serum) under standardized physiologic conditions. Alterations to neuronal functions (contractions, spontaneous activity) will be studied between serum from patients with CIP, without CIP and serum probes from healthy volunteers (without critical illness).
In a clinical part of the study critically ill patients with and without CIP (detected by nerve conduction studies as the gold standard for the diagnosis of CIP) will be examined by neurologic examination, nerve conduction study and neuromyosonography of peripheral nerves. The incidence, the extent and the time from the beginning of critical illness to the clinical appearance of nerval alterations will be compared between the 3 diagnostic tests.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with critical illness, defined as a SOFA-Score ≥ 8 on 3 consecutive days within the first 5 days of ICU stay
- •Informed consent by patient or legal proxy
排除标准
- •Diagnosis of pre-existing neuromuscular diseases other than CIP
- •High-dose glucocorticosteroid therapy (> 300 mg Hydrocortisone/die)
- •Age < 18
结局指标
主要结局
Changes in the frequency and the amplitude of spontaneous contractions of colonic smooth muscle preparations induced by incubation with serum from critically ill patients with CIP, without CIP and healthy controls
时间窗: Baseline and 3 Hours
The parameters will be measured in colonic smooth muscle preparations before and after three hours of incubation with serum from healthy controls as well as critically ill patients with or without CIP. The observed changes in the respective parameter over the three-hour period will be estimated in each tested preparation as measured by absolute values of frequency (contractions per minute) and force (millinewton).
Changes in the amplitude, the integrated force and the time to first and last peak of contractions evoked by electric field stimulation in colonic smooth muscle preparations incubated with the above mentioned sera
时间窗: Baseline and 3 Hours
Applying the same time protocol as described above for point 1, except for the use of electric field stimulation as an exogenous trigger of contractions, changes in the respective parameter over the three-hour period will be estimated in each tested preparation as measured by absolute values of force (millinewton), integrated force (millinewton\*second) and time (seconds).
次要结局
- Incidence of peripheral nerve abnormalities assessed by neuromyosonography(Day 10)
- Incidence of abnormalities of muscle echogenicity assesed by neuromyosonography(Day 10)
- Length of ICU stay(Day 100)
- The number of participants with death(Day 100)
- Incidence of CIP assessed by standardized nerve conduction study(Day 10)
- Incidence of CIP assessed by standardized neurological examination(Day 10)
- Time of respirator-therapy(Day 100)
研究者
Dr. Johannes Ehler, MD
Dr. med. Johannes Ehler
University of Rostock