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Published in: Critical Care 1/2016

Open Access 01-12-2016 | Research

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

Authors: Hubertus Axer, Alexander Grimm, Christine Pausch, Ulrike Teschner, Jan Zinke, Sven Eisenach, Sindy Beck, Orlando Guntinas-Lichius, Frank M. Brunkhorst, Otto W. Witte

Published in: Critical Care | Issue 1/2016

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Abstract

Background

A decrease of small nerve fibers in skin biopsies during the course of critical illness has been demonstrated recently. However, the diagnostic use of skin biopsies in sepsis and its time course is not known.

Methods

Patients (n=32) with severe sepsis or septic shock were examined using skin biopsies, neurological examination, nerve conduction studies, and sympathetic skin response in the first week after onset of sepsis, 2 weeks and 4 months later and compared to gender- and age-matched healthy controls.

Results

Skin biopsies at the ankle and thigh revealed a significant decrease of intraepidermal nerve fiber density (IENFD) during the first week of sepsis and 2 weeks later. All patients developed critical illness polyneuropathy (CIP) according to electrophysiological criteria and 11 showed IENFD values lower than the 0.05 quantile. Four patients were biopsied after 4 months and still showed decreased IENFD. Results of nerve conduction studies and IENFD did considerably change over time. No differences for survival time between patients with IEFND lower and larger than 3.5 fibers/mm were found.

Conclusions

Skin biopsy is able to detect an impairment of small sensory nerve fibers early in the course of sepsis. However, it may not be suited as a prognostic parameter for survival.

Trial registration

German Clinical Trials Register, DRKS-ID: DRKS00000642, 12/17/2010
Appendix
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Literature
1.
go back to reference Engel C, Brunkhorst FM, Bone H-G, Brunkhorst R, Gerlach H, Grond S, et al. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med. 2007;33:606–18.CrossRefPubMed Engel C, Brunkhorst FM, Bone H-G, Brunkhorst R, Gerlach H, Grond S, et al. Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med. 2007;33:606–18.CrossRefPubMed
2.
go back to reference Cawcutt KA, Peters SG. Severe sepsis and septic shock: clinical overview and update on management. Mayo Clin Proc. 2014;89:1572–8.CrossRefPubMed Cawcutt KA, Peters SG. Severe sepsis and septic shock: clinical overview and update on management. Mayo Clin Proc. 2014;89:1572–8.CrossRefPubMed
3.
go back to reference Kress JP, Hall JB. ICU-Acquired Weakness and Recovery from Critical Illness. N Engl J Med. 2014;370:1626–35.CrossRefPubMed Kress JP, Hall JB. ICU-Acquired Weakness and Recovery from Critical Illness. N Engl J Med. 2014;370:1626–35.CrossRefPubMed
4.
go back to reference Fan E, Cheek F, Chlan L, Gosselink R, Hart N, Herridge MS, et al. An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit-acquired weakness in adults. Am J Respir Crit Care Med. 2014;190:1437–46.CrossRefPubMed Fan E, Cheek F, Chlan L, Gosselink R, Hart N, Herridge MS, et al. An official American Thoracic Society Clinical Practice guideline: the diagnosis of intensive care unit-acquired weakness in adults. Am J Respir Crit Care Med. 2014;190:1437–46.CrossRefPubMed
5.
go back to reference Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013;310:1591–600.CrossRefPubMed Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, et al. Acute skeletal muscle wasting in critical illness. JAMA. 2013;310:1591–600.CrossRefPubMed
6.
go back to reference Zink W, Kollmar R, Schwab S. Critical illness polyneuropathy and myopathy in the intensive care unit. Nat Rev Neurol. 2009;5:372–9.CrossRefPubMed Zink W, Kollmar R, Schwab S. Critical illness polyneuropathy and myopathy in the intensive care unit. Nat Rev Neurol. 2009;5:372–9.CrossRefPubMed
7.
go back to reference Visser LH. Critical illness polyneuropathy and myopathy: clinical features, risk factors and prognosis. Eur J Neurol. 2006;13:1203–12.CrossRefPubMed Visser LH. Critical illness polyneuropathy and myopathy: clinical features, risk factors and prognosis. Eur J Neurol. 2006;13:1203–12.CrossRefPubMed
8.
9.
go back to reference Stevens RD, Dowdy DW, Michaels RK, Mendez-Tellez PA, Pronovost PJ, Needham DM. Neuromuscular dysfunction acquired in critical illness: a systematic review. Intensive Care Med. 2007;33:1876–91.CrossRefPubMed Stevens RD, Dowdy DW, Michaels RK, Mendez-Tellez PA, Pronovost PJ, Needham DM. Neuromuscular dysfunction acquired in critical illness: a systematic review. Intensive Care Med. 2007;33:1876–91.CrossRefPubMed
10.
go back to reference Garnacho-Montero J, Madrazo-Osuna J, García-Garmendia JL, Ortiz-Leyba C, Jiménez-Jiménez FJ, Barrero-Almodóvar A, et al. Critical illness polyneuropathy: risk factors and clinical consequences. A cohort study in septic patients. Intensive Care Med. 2001;27:1288–96.CrossRefPubMed Garnacho-Montero J, Madrazo-Osuna J, García-Garmendia JL, Ortiz-Leyba C, Jiménez-Jiménez FJ, Barrero-Almodóvar A, et al. Critical illness polyneuropathy: risk factors and clinical consequences. A cohort study in septic patients. Intensive Care Med. 2001;27:1288–96.CrossRefPubMed
11.
go back to reference Garnacho-Montero J, Amaya-Villar R, García-Garmendía JL, Madrazo-Osuna J, Ortiz-Leyba C. Effect of critical illness polyneuropathy on the withdrawal from mechanical ventilation and the length of stay in septic patients. Crit Care Med. 2005;33:349–54.CrossRefPubMed Garnacho-Montero J, Amaya-Villar R, García-Garmendía JL, Madrazo-Osuna J, Ortiz-Leyba C. Effect of critical illness polyneuropathy on the withdrawal from mechanical ventilation and the length of stay in septic patients. Crit Care Med. 2005;33:349–54.CrossRefPubMed
12.
13.
go back to reference Latronico N, Bolton CF. Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis. Lancet Neurol. 2011;10:931–41.CrossRefPubMed Latronico N, Bolton CF. Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis. Lancet Neurol. 2011;10:931–41.CrossRefPubMed
14.
go back to reference Khan J, Harrison TB, Rich MM, Moss M. Early development of critical illness myopathy and neuropathy in patients with severe sepsis. Neurology. 2006;67:1421–5.CrossRefPubMed Khan J, Harrison TB, Rich MM, Moss M. Early development of critical illness myopathy and neuropathy in patients with severe sepsis. Neurology. 2006;67:1421–5.CrossRefPubMed
15.
go back to reference Latronico N, Bertolini G, Guarneri B, Botteri M, Peli E, Andreoletti S, et al. Simplified electrophysiological evaluation of peripheral nerves in critically ill patients: the Italian multi-centre CRIMYNE study. Crit Care. 2007;11:R11.CrossRefPubMedPubMedCentral Latronico N, Bertolini G, Guarneri B, Botteri M, Peli E, Andreoletti S, et al. Simplified electrophysiological evaluation of peripheral nerves in critically ill patients: the Italian multi-centre CRIMYNE study. Crit Care. 2007;11:R11.CrossRefPubMedPubMedCentral
16.
go back to reference Axer H, Zinke J, Axer M, Grimm A. Electrophysiological assessment of critical illness polyneuropathy and critical illness myopathy. Neurophysiol Lab. 2013;35:18–33.CrossRef Axer H, Zinke J, Axer M, Grimm A. Electrophysiological assessment of critical illness polyneuropathy and critical illness myopathy. Neurophysiol Lab. 2013;35:18–33.CrossRef
17.
go back to reference Bednarik J, Lukas Z, Vondracek P. Critical illness polyneuromyopathy: the electrophysiological components of a complex entity. Intensive Care Med. 2003;29:1505–14.CrossRefPubMed Bednarik J, Lukas Z, Vondracek P. Critical illness polyneuromyopathy: the electrophysiological components of a complex entity. Intensive Care Med. 2003;29:1505–14.CrossRefPubMed
18.
go back to reference Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. J Peripher Nerv Syst. 2010;15:79–92. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. J Peripher Nerv Syst. 2010;15:79–92.
19.
go back to reference Devigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain. 2008;131:1912–25.CrossRefPubMedPubMedCentral Devigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain. 2008;131:1912–25.CrossRefPubMedPubMedCentral
20.
go back to reference Lauria G, Bakkers M, Schmitz C, Lombardi R, Penza P, Devigili G, et al. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv Syst. 2010;15:202–7.CrossRefPubMed Lauria G, Bakkers M, Schmitz C, Lombardi R, Penza P, Devigili G, et al. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv Syst. 2010;15:202–7.CrossRefPubMed
21.
go back to reference Lauria G, Devigili G. Skin biopsy as a diagnostic tool in peripheral neuropathy. Nat Clin Pract Neurol. 2007;3:546–57.CrossRefPubMed Lauria G, Devigili G. Skin biopsy as a diagnostic tool in peripheral neuropathy. Nat Clin Pract Neurol. 2007;3:546–57.CrossRefPubMed
22.
go back to reference Lauria G, Cornblath DR, Johansson O, McArthur JC, Mellgren SI, Nolano M, et al. EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol. 2005;12:747–58.CrossRefPubMed Lauria G, Cornblath DR, Johansson O, McArthur JC, Mellgren SI, Nolano M, et al. EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol. 2005;12:747–58.CrossRefPubMed
23.
go back to reference Latronico N, Shehu I, Seghelini E. Neuromuscular sequelae of critical illness. Curr Opin Crit Care. 2005;11:381–90.CrossRefPubMed Latronico N, Shehu I, Seghelini E. Neuromuscular sequelae of critical illness. Curr Opin Crit Care. 2005;11:381–90.CrossRefPubMed
24.
go back to reference Annane D, Trabold F, Sharshar T, Jarrin I, Blanc AS, Raphael JC, et al. Inappropriate sympathetic activation at onset of septic shock: a spectral analysis approach. Am J Respir Crit Care Med. 1999;160:458–65.CrossRefPubMed Annane D, Trabold F, Sharshar T, Jarrin I, Blanc AS, Raphael JC, et al. Inappropriate sympathetic activation at onset of septic shock: a spectral analysis approach. Am J Respir Crit Care Med. 1999;160:458–65.CrossRefPubMed
25.
go back to reference Sagui E, Cordier PY, Nau A, Rogier C, Bregigeon M, Brosset C. Is critical illness polyneuropathy associated with decreased heart rate variability? Rev Neurol (Paris). 2014;170:32–6.CrossRef Sagui E, Cordier PY, Nau A, Rogier C, Bregigeon M, Brosset C. Is critical illness polyneuropathy associated with decreased heart rate variability? Rev Neurol (Paris). 2014;170:32–6.CrossRef
26.
go back to reference Schmidt H, Müller-Werdan U, Hoffmann T, Francis DP, Piepoli MF, Rauchhaus M, et al. Autonomic dysfunction predicts mortality in patients with multiple organ dysfunction syndrome of different age groups. Crit Care Med. 2005;33:1994–2002.CrossRefPubMed Schmidt H, Müller-Werdan U, Hoffmann T, Francis DP, Piepoli MF, Rauchhaus M, et al. Autonomic dysfunction predicts mortality in patients with multiple organ dysfunction syndrome of different age groups. Crit Care Med. 2005;33:1994–2002.CrossRefPubMed
27.
go back to reference Schmidt H, Hoyer D, Hennen R, Heinroth K, Rauchhaus M, Prondzinsky R, et al. Autonomic dysfunction predicts both 1- and 2-month mortality in middle-aged patients with multiple organ dysfunction syndrome. Crit Care Med. 2008;36:967–70.CrossRefPubMed Schmidt H, Hoyer D, Hennen R, Heinroth K, Rauchhaus M, Prondzinsky R, et al. Autonomic dysfunction predicts both 1- and 2-month mortality in middle-aged patients with multiple organ dysfunction syndrome. Crit Care Med. 2008;36:967–70.CrossRefPubMed
28.
go back to reference Novak V, Freimer ML, Kissel JT, Sahenk Z, Periquet IM, Nash SM, et al. Autonomic impairment in painful neuropathy. Neurology. 2001;56:861–8.CrossRefPubMed Novak V, Freimer ML, Kissel JT, Sahenk Z, Periquet IM, Nash SM, et al. Autonomic impairment in painful neuropathy. Neurology. 2001;56:861–8.CrossRefPubMed
29.
30.
go back to reference Skorna M, Kopacik R, Vlckova E, Adamova B, Kostalova M, Bednarik J. Small nerve fiber pathology in critical illness documented by serial skin biopsies. Muscle Nerve. 2015;52:28–33.CrossRefPubMed Skorna M, Kopacik R, Vlckova E, Adamova B, Kostalova M, Bednarik J. Small nerve fiber pathology in critical illness documented by serial skin biopsies. Muscle Nerve. 2015;52:28–33.CrossRefPubMed
31.
go back to reference Axer H, Grimm A, Porzelius C, Teschner U, Schumacher U, Witte OW, et al. 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. BMC Neurol. 2013;13:159.CrossRefPubMedPubMedCentral Axer H, Grimm A, Porzelius C, Teschner U, Schumacher U, Witte OW, et al. 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. BMC Neurol. 2013;13:159.CrossRefPubMedPubMedCentral
32.
go back to reference Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358:125–39.CrossRefPubMed Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358:125–39.CrossRefPubMed
33.
go back to reference Schmidt K, Gensichen J, Thiel P, Ludewig K, Bahr V, Rissner F, et al. A prospective observational web-based registry for assessment of long-term outcome in patients with severe sepsis. Infection. 2013;41:S84–5. Schmidt K, Gensichen J, Thiel P, Ludewig K, Bahr V, Rissner F, et al. A prospective observational web-based registry for assessment of long-term outcome in patients with severe sepsis. Infection. 2013;41:S84–5.
34.
go back to reference Preston D, Shapiro B. Electromyography and Neuromuscular Disorders, Clinical–Electrophysiological Correlations. New York: Elsevier Saunders; 2013. Preston D, Shapiro B. Electromyography and Neuromuscular Disorders, Clinical–Electrophysiological Correlations. New York: Elsevier Saunders; 2013.
35.
go back to reference Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5.CrossRefPubMed Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5.CrossRefPubMed
37.
38.
go back to reference Storm H, Myre K, Rostrup M, Stokland O, Lien MD, Raeder JC. Skin conductance correlates with perioperative stress. Acta Anaesthesiol Scand. 2002;46:887–95.CrossRefPubMed Storm H, Myre K, Rostrup M, Stokland O, Lien MD, Raeder JC. Skin conductance correlates with perioperative stress. Acta Anaesthesiol Scand. 2002;46:887–95.CrossRefPubMed
39.
go back to reference Kerbaul F, Brousse M, Collart F, Pellissier J-F, Planche D, Fernandez C, et al. Combination of histopathological and electromyographic patterns can help to evaluate functional outcome of critical ill patients with neuromuscular weakness syndromes. Crit Care. 2004;8:R358–366.CrossRefPubMedPubMedCentral Kerbaul F, Brousse M, Collart F, Pellissier J-F, Planche D, Fernandez C, et al. Combination of histopathological and electromyographic patterns can help to evaluate functional outcome of critical ill patients with neuromuscular weakness syndromes. Crit Care. 2004;8:R358–366.CrossRefPubMedPubMedCentral
40.
go back to reference Grimm A, Teschner U, Porzelius C, Ludewig K, Zielske J, Witte OW, et al. Muscle ultrasound for early assessment of critical illness neuromyopathy in severe sepsis. Crit Care. 2013;17:R227.CrossRefPubMedPubMedCentral Grimm A, Teschner U, Porzelius C, Ludewig K, Zielske J, Witte OW, et al. Muscle ultrasound for early assessment of critical illness neuromyopathy in severe sepsis. Crit Care. 2013;17:R227.CrossRefPubMedPubMedCentral
41.
go back to reference Koch S, Wollersheim T, Bierbrauer J, Haas K, Mörgeli R, Deja M, et al. Long-term recovery In critical illness myopathy is complete, contrary to polyneuropathy. Muscle Nerve. 2014;50:431–6.CrossRefPubMed Koch S, Wollersheim T, Bierbrauer J, Haas K, Mörgeli R, Deja M, et al. Long-term recovery In critical illness myopathy is complete, contrary to polyneuropathy. Muscle Nerve. 2014;50:431–6.CrossRefPubMed
42.
go back to reference Battle CE, Lovett S, Hutchings H. Chronic pain in survivors of critical illness: a retrospective analysis of incidence and risk factors. Crit Care. 2013;17:R101.CrossRefPubMedPubMedCentral Battle CE, Lovett S, Hutchings H. Chronic pain in survivors of critical illness: a retrospective analysis of incidence and risk factors. Crit Care. 2013;17:R101.CrossRefPubMedPubMedCentral
Metadata
Title
The impairment of small nerve fibers in severe sepsis and septic shock
Authors
Hubertus Axer
Alexander Grimm
Christine Pausch
Ulrike Teschner
Jan Zinke
Sven Eisenach
Sindy Beck
Orlando Guntinas-Lichius
Frank M. Brunkhorst
Otto W. Witte
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2016
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-016-1241-5

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