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- Ahlbeck, Karsten
(författare)
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Muscle function in the critically ill : clinical and experimental investigations
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is common that critically ill patients develop muscle weakness in the intensive care unit (ICU), not only delaying mobilisation and increasing the risk of co-morbidities, but also prolonging rehabilitation after hospital care. The aim of this thesis was to describe the diagnosis, time course and possible risk factors for this weakness. When specific diseases such as CNS lesions, intoxication or other nerve and muscle disorders have been excluded in the ICU, a ”critical illness polyneuropathy and myopathy” (CIPNM) should be considered. The pathology behind this entity is unclear; among possible etiologic factors sepsis, corticosteroids and neuromuscular blocking agents (NMBAs) have been suggested. CIPNM consists of a nerve pathology (neuropathy) and/or a muscle pathology (myopathy) and is diagnosed by a clinical assessment in combination with neurophysiological examination. The latter can be cumbersome due to the challenging environment in the ICU and is in itself not a definitive method of differentiating between a polyneuropathy and a myopathy. We demonstrate a rapid method of electrophoresis, using an ultra-thin gel to evaluate the myosin to actin (M/A) ratio as a means of diagnosing critical illness myopathy (CIM). Using this diagnostic tool, there was a significant difference in M/A ratio between the patients having CIM, a control group, and patients having axonal neuropathies. To evaluate the prevalence of CIPNM and the temporal pattern of its two major components critical illness polyneuropathy (CIP) and CIM, a prospective study was conducted including ICU patients who had been mechanically ventilated for at least 72 hours. The eventual prevalence of CIPNM was investigated, including neurophysiological and clinical examination. Muscle biopsies were obtained, in order to study the myosin to actin ratio and mitochondrial function. All septic patients, who were also receiving corticosteroid treatment, had a CIPNM diagnosis, whereas none of the non-septic patients fulfilled the necessary criteria. As a marker of oxidative stress, mitochondrial superoxide dismutase was increased in all patients, with a marked elevation in the CIPNM group. To examine possible predisposing risk factors and mechanisms behind CIPNM in an experimental porcine ICU model over 5 days, groups were separated by interventions including corticosteroids, neuromuscular blocking agents and endotoxin, during mechanical ventilation. No group had a pathologic M/A ratio. All groups had significant changes in compound muscle action potential amplitude, including the inactivity/mechanical ventilation only group. The groups including corticosteroid treatment, endotoxin and the combination of all interventions had decreased muscle specific force and mitochondrial complex I activity, which were not seen in the mechanical ventilation group. In conclusion, this thesis demonstrates an alternative method of diagnosing a critical illness myopathy, which could prove to be both time-efficient and reliable. In ICU patients there was a high prevalence of CIPNM in patients mechanically ventilated for more than 72 hours. An experimental model showed both decreased specific muscle force and mitochondrial complex I activity in intervention groups receiving corticosteroids, endotoxin or a combination, for both respiratory and non-respiratory muscles.
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| 2. |
- Ochala, Julien, et al.
(författare)
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Diaphragm muscle weakness in an experimental porcine intensive care unit model
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit.
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| 3. |
- Ochala, Julien, et al.
(författare)
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Factors underlying the early limb muscle weakness in acute quadriplegic myopathy using an experimental ICU porcine model
- 2011
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6, s. e20876-
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Tidskriftsartikel (refereegranskat)abstract
- The basic mechanisms underlying acquired generalized muscle weakness and paralysis in critically ill patients remain poorly understood and may be related to prolonged mechanical ventilation/immobilization (MV) or to other triggering factors such as sepsis, systemic corticosteroid (CS) treatment and administration of neuromuscular blocking agents (NMBA). The present study aims at exploring the relative importance of these factors by using a unique porcine model. Piglets were all exposed to MV together with different combinations of endotoxin-induced sepsis, CS and NMBA for five days. Peroneal motor nerve conduction velocity and amplitude of the compound muscle action potential (CMAP) as well as biceps femoris muscle biopsy specimens were obtained immediately after anesthesia on the first day and at the end of the 5-day experimental period. Results showed that peroneal nerve motor conduction velocity is unaffected whereas the size of the CMAP decreases independently of the type of intervention, in all groups after 5 days. Otherwise, despite a preserved size, muscle fibre specific force (maximum force normalized to cross-sectional area) decreased dramatically for animals exposed to MV in combination with CS or/and sepsis. These results suggest that the rapid declines in CMAP amplitude and in force generation capacity are triggered by independent mechanisms with significant clinical and therapeutic implications.
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