Impact of Human Blood Serum From Critically Ill Patients on Human Colon Neuronal Networks.

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:

1. 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
2. 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)

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.

From all patients basic demographic data, illness severity scores (APACHE-II, SOFA) laboratory results, pre-morbidity data and clinical outcome for the study cohort will be recorded. At day 3 and 10 patients will be examined by neurologic examination, nerve conduction study, neuromyosonography and laboratory tests (inflammation, coagulation, organ function, blood parameters including TNF-alpha, IL-6, S100b, oxidative stress markers, neurofilaments, C-type natriuretic peptide).

Eligibility Criteria:
Inclusion Criteria:

* 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

Exclusion Criteria:

* Diagnosis of pre-existing neuromuscular diseases other than CIP
* High-dose glucocorticosteroid therapy (\> 300 mg Hydrocortisone/die)
* Age \< 18