Impairment of small somatic and autonomic nerve fibres in intensive care unit patients with severe sepsis and critical illness polyneuropathy – a single center controlled observational study

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.

Electrophysiologic alterations in the excitability of the sciatic and vagus nerves during early stages of sepsis

“… 29 – 33 These nerves were chosen to evaluate the effect of sepsis on the excitability of a somatic (sciatic) and autonomic (vagus) nerves. 30 – 32 In the sciatic nerve, we measured parameters of the first and second CAP components in myelinated fibers. 33 The first component originated from fibers with motor and sensory functions (Types A α and A β fibers) with a large conduction velocity (70–120 m/s).…”

The impairment of small nerve fibers in severe sepsis and septic shock

“…In addition, the study had a high drop-out rate of patients over time due to high mortality rates and contraindications against skin biopsy (such as coagulopathy or anticoagulation). Therefore, the initial target number of patients (n = 200) as designated in the study protocol [ 31 ] was not reached although over 300 patients were screened. However, the extent the decrease in IENFD was much larger than expected and the results were statistically significant based on considerably fewer patients than initially scheduled.…”

“…The study protocol for this single-center, non-randomized, controlled, observational study has been published earlier in detail [ 31 ]. The study has been registered with the German Clinical Trials Register (DRKS-ID: DRKS00000642).…”

Small-nerve-fiber pathology in critical illness documented by serial skin biopsies

“…A controlled, observational study is presently underway investigating severe sepsis patients with serial skin biopsies at onset of sepsis and then 14 days and 2 months later. The study is scheduled to conclude in 2015 …”