Early type II fiber atrophy in intensive care unit patients with nonexcitable muscle membrane

Objective: Intensive care unit-acquired weakness indicates increased morbidity and mortality. Nonexcitable muscle membrane after direct muscle stimulation develops early and predicts intensive care unit-acquired weakness in sedated, mechanically ventilated patients. A comparison of muscle histology at an early stage in intensive care unit-acquired weakness has not been done. We investigated whether nonexcitable muscle membrane indicates fast-twitch myofiber atrophy during the early course of critical illness. Design: Prospective observational study. Setting: Two intensive care units at Charite University Medicine, Berlin. Patients: Patients at increased risk for development of intensive care unit-acquired weakness, indicated by Sepsis-related Organ Failure Assessment scores >= 8 on 3 of 5 consecutive days within their first week in the intensive care unit. Interventions: None. Measurements and Main Results: Electrophysiological compound muscle action potentials after direct muscle stimulation and muscle biopsies were obtained at median days 7 and 5, respectively. Patients with nonexcitable muscle membranes (n = 15) showed smaller median type II cross-sectional areas (p <. 05), whereas type I muscle fibers did not compared with patients with preserved muscle membrane excitability (compound muscle action potentials after direct muscle stimulation >= 3.0 mV; n = 9). We also observed decreased mRNA transcription levels of myosin heavy chain isoform IIa and a lower densitometric ratio of fast-to-slow myosin heavy chain protein content. Conclusion: We suggest that electrophysiological nonexcitable muscle membrane predicts preferential type II fiber atrophy in intensive care unit patients during early critical illness. (Crit Care Med 2012; 40:647-650)