Critical illness myopathy unrelated to corticosteroids or neuromuscular blocking agents

Risk factors for critical illness polyneuromyopathy

“…Several parameters obtained at the end of the first week and reflecting the duration of SIRS (1 st week duration of SIRS) and severity of multiple organ failure (admission SOFA and summed 1 st week SOFA) are able to predict correctly the CIPM development in about 80 % of critically ill patients. CIPM-subgroup of patients without electrophysiological signs of CIPM; CIPM+ subgroup of patients with electrophysiological signs of CIPM; SIRS systemic inflammatory response syndrome; CI confidence interval Quantitative parameters are expressed as median supplied with the 10 th and 90 th percentiles (in parentheses); gender is expressed as a percentage; corticosteroids and muscle-blocking agents are expressed both as median cumulative dosage and as percentage of treated cases; respiratory support is expressed as median duration and as the percentage of cases with support 1 SIRS occurred in 61.5 % of cases without CIPM and in 100 % of cases with CIPM 2 Significance level of tests comparing patients with and without CIPM expressed as p value: Kruskal-Wallis test for continuous variables and Fisher's exact test for binary variables Parameters as single predictors 1 SIRS is believed to be the most important causal factor in CIP development [5,10,31], and in concert with other factors (denervation, NDMBA, corticosteroids) is considered as a potential cause of CIM. Recently, the presence of SIRS has been found to increase the risk of clinically symptomatic CIPM development leading to artificial ventilation and, together with the APACHE III score, has been used to estimate this risk [12].…”

Critical illness myopathy serum fractions affect membrane excitability and intracellular calcium release in mammalian skeletal muscle

“…On a subcellular level myosin isoforms have been shown to be subject to calpain-mediated proteolysis in patients with CIM [22].In a rat animal model, loss of myosin filaments and reduced electrical excitability were produced by glucocorticoid treatment only after denervation of the muscle, by muscle relaxing agents or other pro-inflammatory low-molecular weight mediators in the peripheral blood [23].An example of such mediators might be peptides and toxins involved in the innate immune response during sepsis (e. g. [24,25]). So far, studies done in patients with CIM can indicate a more puzzling situation as administration of glucocorticoids and neuromuscular blocking agents has been found not always to result in the development of CIM [26] although these drugs are widely accepted as trigger agents which have been tested on established animal models [27][28][29][30]. Moreover, patients given steroids may recover from CIM even when steroids were not discontinued [26].Also, cytokines (tumour necrosis factor-α and interleukin-6) which it has been suggested are involved in the pathogenesis of CIM [3] were not convincingly increased in the sera of affected patients [31].Direct electrical stimulation revealed reduced muscular excitability in clinical patients [27].…”

“…So far, studies done in patients with CIM can indicate a more puzzling situation as administration of glucocorticoids and neuromuscular blocking agents has been found not always to result in the development of CIM [26] although these drugs are widely accepted as trigger agents which have been tested on established animal models [27][28][29][30]. Moreover, patients given steroids may recover from CIM even when steroids were not discontinued [26].Also, cytokines (tumour necrosis factor-α and interleukin-6) which it has been suggested are involved in the pathogenesis of CIM [3] were not convincingly increased in the sera of affected patients [31].Direct electrical stimulation revealed reduced muscular excitability in clinical patients [27]. In an animal model, abnormalities of sodium channel inactivation have been found [28] whereas in animals having undergone high-dose corticosteroid treatment the membrane effects seemed to be more complex [29].Very recently,inactivation of sodium channels has been correlated with depolarised resting potentials and to be crucially responsible for reduced membrane excitability in the rat animal model of critical illness myopathy for steroid denervated muscle fibres [30].…”

Analysis of muscle proteins in acute quadriplegic myopathy

“…11 A similar myopathy has also been reported in patients with critical illnesses who have not been administered steroids or NMBAs. 1,4,8,23,24 The manner in which these drugs or critical illnesses are involved in the occurrence of AQM remains unclear.…”