Critical illness polyneuropathy: clinical findings and cell culture assay of neurotoxicity assessed by a prospective study

Druschky, A.; Herkert, Matthias; Radespiel‐Tröger, Martin; Druschky, Katrin; Hund, Ernst; Becker, Cord‐Michael; Hilz, M. J.; Erbguth, Frank; Neundörfer, B.

doi:10.1007/s001340100890

Cited by 92 publications

(70 citation statements)

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“…Sepsis was the main suspect in the early days of the discovery of CIP, as it was a common feature in the first case reports (67,812), and the incidence of CIP reported in patients with sepsis was very high (52,333). Sepsis, multiple organ failure, and its severity were found to be associated with CIP (166,403,415,416). Sepsis, as such, was identified as an independent risk factor for neuromuscular complications (122,300) as well as bacteremia (499,738).…”

Section: A Risk Factors For the Development Of Icuacquired Neuromuscmentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

291

329

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Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca 2ϩ dysregulation is present through altered Ca 2ϩ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

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Section: A Risk Factors For the Development Of Icuacquired Neuromuscmentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

291

329

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“…Eleven out of the 29 (38%) 25,28,29,32,[36][37][38][39][40][41][42] observational studies were graded of low quality, 17 out of 29 (59%) 12,[14][15][16]20,24,26,27,30,[43][44][45][46][47][48][49][50] as medium and one (3%) 51 as high quality. There were four RCTs included; two studies were deemed of low risk, 22,23 one unclear risk 8 and one with high risk 31 of bias.…”

Section: Quality Of Included Studiesmentioning

confidence: 99%

The incidence of intensive care unit-acquired weakness syndromes: A systematic review

Appleton

Kinsella

Quasim

2014

Journal of the Intensive Care Society

150

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We conducted a literature review of the intensive care unit-acquired weakness syndromes (critical illness polyneuropathy, critical illness myopathy and critical illness neuromyopathy) with the primary objective of determining their incidence as a combined group. Studies were identified through MEDLINE, Embase, Cochrane Database and article reference list searches and were included if they evaluated the incidence of one or more of these conditions in an adult intensive care unit population. The incidence of an intensive care unit-acquired weakness syndrome in the included studies was 40% (1080/2686 patients, 95% confidence interval 38-42%). The intensive care unit populations included were heterogeneous though largely included patients receiving mechanical ventilation for seven or more days. Additional prespecified outcomes identified that the incidence of intensive care unit-acquired weakness varied with the diagnostic technique used, being lower with clinical (413/1276, 32%, 95% CI 30-35%) compared to electrophysiological techniques (749/1591, 47%, 95% CI 45-50%). Approximately a quarter of patients were not able to comply with clinical evaluation and this may be responsible for potential underreporting of this condition.

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“…As a number of cytokines are known to be neurotoxic, the increase in inflammatory cytokines found in ICUAW patients may contribute to the electrical excitability, although the scant data supporting this contention are difficult to interpret. For example, exposure of cultured neuronal cells to serum from patients with ICUAW resulted in neurotoxicity in 12 out of 16 cases in one study, but 50% of the control sera also caused neurotoxicity [97]. Membrane alterations also occur in ICUAW, resulting in chronic depolarisation and reduced excitability of the nerve [93], and therefore functional denervation of the adjacent muscle [98].…”

Section: Electrical Inexcitabilitymentioning

confidence: 99%

Molecular mechanisms of intensive care unit-acquired weakness

Bloch¹,

Polkey²,

Griffiths³

et al. 2011

Eur Respir J

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Intensive care unit-acquired weakness (ICUAW) is an increasingly recognised and important clinical consequence of critical illness. It is associated with significant morbidity and mortality. The aetiology of this disease is not well understood. The purpose of this article is to review our understanding of the molecular pathogenesis of ICUAW in the context of current knowledge of clinical risk factors and aetiology.Key features of the disease are loss of muscle mass resulting from a shift in the dynamic balance of muscle protein synthesis and breakdown and a reduction in force-generating capacity. These alternations are secondary to neuropathy, disruption of the myofilament structure and function, a disrupted sarcoplasmic reticulum, electrical inexcitability and bioenergenetic failure.As knowledge and understanding of ICUAW grows, potential therapeutic targets will be identified, hopefully leading to multiple strategies for prevention and treatment of this important condition.

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Critical illness polyneuropathy: clinical findings and cell culture assay of neurotoxicity assessed by a prospective study

Abstract: The results support the hypothesis of a multi-factorial aetiopathogenesis of CIP. We observed serum neurotoxicity in the majority of CIP patients, indicating the possible involvement of a so far unknown, low-molecular-weight neurotoxic agent in CIP pathogenesis.

Cited by 92 publications

References 0 publications

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

The incidence of intensive care unit-acquired weakness syndromes: A systematic review

Molecular mechanisms of intensive care unit-acquired weakness

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