Research Article| Volume 58, P229-235, March 2023

Combining exercise, protein supplementation and electric stimulation to mitigate muscle wasting and improve outcomes for survivors of critical illness—The ExPrES study

Published:December 03, 2022DOI:


      • Combining physical therapy, NMES and high protein nutrition with standard care restored positive nitrogen balance in critically ill subjects.
      • The intervention group experienced less muscle lower extremity muscle loss (volume and cross-sectional area) when compared to standard care.
      • The intervention group experienced less delirium compared to the group who received standard care.



      Neuromuscular 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.


      To 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.


      Participants 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.


      The 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.


      The 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: identifier: NCT02509520. Registered July 28, 2015



      NMES (neuromuscular electrical stimulation), HPRO (high protein supplementation), PT (physical therapy), SC (standard care), LOS (length of stay), EMR (electronic medical record), NUTRIC (Nutrition Risk in Critically ill), MRC (medical research council), LTACH (long-term acute care hospital), PD (pulse duration), PR (pulse rate), CAM (confusion Assessment Method), CSA (cross-sectional area), SPPB (short physical performance battery)
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      Linked Article

      • Exercise and nutrition in critically ill patients-What is the correct formula?
        Heart & Lung: The Journal of Cardiopulmonary and Acute CareVol. 58
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          ICU-acquired weakness is diagnosed in approximately 1 million mechanically ventilated patients annually.1 This weakness is secondary to multiple mechanisms including myopathy, neuropathy, deconditioning and protein malnutrition. In addition, ICU-acquired weakness is associated with decreased quality of life and increased mortality.2 Physical rehabilitation and nutritional support have the potential to improve muscle strength and help maintain functional status.
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