Resting trans-membrane potential difference (Em) of skeletal muscle is correlated to the energy status of the organism: the more severe the illness, the lower the Em. In 1971, Cunningham demonstrated this association with severely debilitating medical conditions, showing an increase in intracellular sodium concentration possibly due to a “generalized cellular abnormality”. The study posed the basis for considering local (muscle) bio-electrical events generated by excitable tissues as indicative of the well-being of the entire organism. In 1995, Leijten showed that patients with electrophysiological signs of polyneuropathy had increased intensive care unit (ICU) mortality, more prolonged rehabilitation, and persistent 1-year motor handicap than those without.

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