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To investigate the predictive value of electrophysiological measurements including validation of muscle membrane excitability on the development of intensive care unit (ICU)-aquired paresis.Prospective observational study.University ICU.Surgical ICU patients selected upon a simplified acute physiology score ≥20 on three successive days within 1 wk after ICU admission.We performed serial electrophysiological measurements with onset of critical illness including conventional electrophysiological parameters and compound muscle action potentials after direct muscle stimulation (dmCMAP). Patients’ awareness and muscle strength were measured sequentially by Ramsay sedation scale and an additional questionnaire and by Medical Research Council score, respectively.Among 56 sedated patients 34 patients revealed reduced dmCMAP values <3 mV indicating a myopathic process within 7.5 (5 of 11) days after admission to the ICU. Abnormal dmCMAP anticipated ICU-acquired paresis upon emergence from sedation with a sensitivity and specificity of 83.3% and 88.8%, respectively (positive predictive value of 0.91). Multivariate logistic regression analyses revealed that validating dmCMAP during early course of critical illness had significant diagnostic utility to anticipate ICU-acquired paresis (p = .004; odds ratio = .47; 95% confidence interval = .28–.79).Abnormal dmCMAP occurred within the first week after admission to the ICU and pointed towards a myopathic process as the primary cause of ICU-acquired paresis. Validation of dmCMAP with onset of critical illness allows an early prediction of ICU-acquired paresis and adds important information to clinical estimation of the patients’ motor function.