Abstract
BackgroundAxonal damage in large myelinated nerve fibres occurs in about 70% of patients with severe sepsis, known as critical illness polyneuropathy and contributes significantly to an increased short- and long-term morbidity and mortality in this population. Among other pathophysiological mechanisms, autonomic dysregulation, characterized by high concentrations of circulating catecholamines in the presence of impaired sympathetic modulation of heart and vessels have been discussed. We hypothesize that autonomic small fibre neuropathy play an important role in autonomic failure.Methods/DesignSingle center, non-randomized, controlled, observational study. Skin biopsies of patients with severe sepsis and/or septic shock are compared with those of age-matched controls. In order to assess impairment of small nerve fibres, skin biopsies are taken at onset of severe sepsis, and two and 16 weeks later. Intraepidermal nerve fibre densities are histologically analyzed using anti protein gene product (PGP) 9.5 immunostaining. In addition, standardized clinical examinations, as Medical Research Council (MRC) scores of muscle strength, Rankin scores, and standardized nerve conduction studies of the right median nerve, the right tibial nerve, the left fibular nerve, and both sural nerves are performed, to identify critical illness polyneuropathy and to neurophysiologically quantify the damage of large nerve fibres.DiscussionThe study will allow to describe the frequency of small fibre neuropathy in patients with severe sepsis up to four months after onset of severe sepsis and to evaluate its relationship to critical illness polyneuropathy.Trial registrationThe trial has been registered to the German Clinical Trials Register. The trial registration number is DRKS-ID: DRKS00000642.
Highlights
Axonal damage in large myelinated nerve fibres occurs in about 70% of patients with severe sepsis, known as critical illness polyneuropathy and contributes significantly to an increased short- and long-term morbidity and mortality in this population
The study will allow to describe the frequency of small fibre neuropathy in patients with severe sepsis up to four months after onset of severe sepsis and to evaluate its relationship to critical illness polyneuropathy
Due to the explorative character of the secondary analyses, no α correction will be performed. This is to our knowledge the first study to address the frequency of small fibre neuropathy in patients with severe sepsis/septic shock, treated in intensive care units
Summary
This is to our knowledge the first study to address the frequency of small fibre neuropathy in patients with severe sepsis/septic shock, treated in intensive care units. Gaining informed consent from the legal representative of severe sepsis/septic shock patients is difficult to obtain in the acute care setting and may limit patient recruitment. First results of the prospective severe sepsis/septic shock registry of the Centre of Sepsis Control and Care (CSCC) at the study center Jena University Hospital revealed higher mortality rates as suspected [29], so that relatively few patients may be available for follow-up examinations. The drop-out rate at 4 months is high due patient’s preferences and decisions This is highly important for planning further studies on long-term sequelae in severe sepsis/septic shock patients.
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