Effect of Endotoxin on the Peripheral Nerve Leading to Critical Illness Polyneuropathy

Introduction: Critical illness polyneuropathy (CIP) is a mixed motor and sensory axonal polyneuropathy which complicates sepsis or hypotension and occurs with the development of multiple organ failure. CIP is a relatively common problem in intensive care units. It has a frequency of 33% to 100% depending on the criteria used for the diagnosis and the type of patients. Patients who survive recover within weeks, in case of mild CIP, or within months, in case of severe CIP. In this study we investigated electrophysiological, microbiological and inflammatory parameters to evaluate factors possibly associated with the pathogenesis of CIP in patients with severe sepsis or septic shock. Methods: This prospective study was performed in the interdisciplinary intensive care unit (ICU) of the Medical School of Hannover, Germany. Twenty patients with severe sepsis or septic shock were enrolled into the study as early as possible after admission to ICU. Electrophysiological tests were performed at different days (1, 7 and 14 day) after diagnosis of sepsis. In parallel, to investigate the development of CIP the plasma concentration of different endotoxins, as well as activation of inflammatory and coagulation cascades were determined. Results: The median age of patients was 51.5 (range 19–74) years, and total median Acute Physiology And Chronic Health Evaluation II (APACHE II) score was 19 (range 0–32). Total median Sequential Organ Failure Assessment (SOFA) score was 10.55 (range 1–17). The mortality during this study was 25%. The main electrophysiological finding of the study was a reduction of the amplitude of the compound muscle action potentials (CMAP) at all three nerves studied. The values of other parameters (sensible nerve action potential, nerve conduction velocity and distal latencies) were mostly normal. Interestingly, there was a significant correlation between the axonal damage of motor nerves and the serum concentration of endotoxin. Discussion: This study shows the onset of CMAP reduction as an early sign for beginning of CIP. The correlation between CMAP and endotoxin points to a direct effect of endotoxin on the peripheral nerve. Thus, inhibition of the biological effects of endotoxin might be an effective therapy of CIP in vivo.