BackgroundNeuromuscular electrical stimulation (NMES) with high protein supplementation (HPRO) to preserve muscle mass and function has not been assessed in ICU patients. We compared the effects of combining NMES and HPRO with mobility and strength rehabilitation (NMES+HPRO+PT) to standardized ICU care. ObjectivesTo assess the effectiveness of combined NMES+HPRO+PT in mitigating sarcopenia as evidenced by CT volume and cross-sectional area when compared to usual ICU care. Additionally, we assessed the effects of the combined therapy on select clinical outcomes, including nutritional status, nitrogen balance, delirium and days on mechanical ventilation. MethodsParticipants were randomized by computer generated assignments to receive either NMES+HPRO+PT or standard care. Over 14 days the standardized ICU care group (N = 23) received usual critical care and rehabilitation while the NMES+HPRO+PT group (N = 16) received 30 min neuromuscular electrical stimulation of quadriceps and dorsiflexors twice-daily for 10 days and mean 1.3 ± 0.4 g/kg body weight of high protein supplementation in addition to standard care. Nonresponsive participants received passive exercises and, once responsive, were encouraged to exercise actively. Primary outcome measures were muscle volume and cross-sectional area measured using CT-imaging. Secondary outcomes included nutritional status, nitrogen balance, delirium and days on mechanical ventilation. ResultsThe NMES+HPRO+PT group (N = 16) lost less lower extremity muscle volume compared to the standard care group (N = 23) and had larger mean combined thigh cross-sectional area. The nitrogen balance remained negative in the standard care group, while positive on days 5, 9, and 14 in the NMES+HPRO+PT group. Standard care group participants experienced more delirium than the NMES+HPRO+PT group. No differences between groups when comparing length of stay or mechanical ventilation days. ConclusionsThe combination of neuromuscular electrical stimulation, high protein supplementation and mobility and strength rehabilitation resulted in mitigation of lower extremity muscle loss and less delirium in mechanically ventilated ICU patients.Trial Registration: Clinicaltrials.gov identifier: NCT02509520. Registered July 28, 2015