Improved Muscle Metabolism by Combination of Muscle Activation and Protein Substitution ( IMEMPRO )

Intensive Care Unit Acquired Weakness (ICUAW) describes the clinically diagnosed manifestation of a neuromuscular organ dysfunction. It develops in approximately 40% of all intensive care unit patients amounting to at least 1.2 million patients annually in Germany. All these patients face a broad range of sequeleae and an increased mortality up to 5 years after ICU discharge. A characteristic pathophysiological phenomenon is an early severe muscle atrophy reaching 10% during the first days after ICU admission.

The current preventative and therapeutic approach for ICUAW is a combination of targeted risk factor management as well as early activation of muscles, i.e. neuromuscular electrical stimulation (NMES) and early mobilization as they have been shown to counteract the muscle atrophy and mediate different outcome benefits such as shorter ICU stay.

Nutrition is a key element of our daily life. Protein intake has been shown to affect lean mass and muscle mass. Research into specific nutritional strategies to treat or prevent ICUAW are scarce and the combination with early muscle activation has not been adequately explored.

The study will include 40 patients (20 intervention, 20 observation) who were admitted to an intensive care unit within the last 48 hours. A basic requirement for inclusion is an indication for enteral (via the gastrointestinal tract) nutrition at time of inclusion. In the intervention group, the ability to mobilize is assessed daily and the maximum possible level of mobilization is carried out and additional muscles are activated twice a day using neuromuscular electrical stimulation (NMES). The nutrition plan of the intervention group is based on the applicable guidelines for intensive care medicine. In this study, protein intake is increased in the interventional group. The control group receives therapy without deviating from the standard according to the SOP and DGEM guideline: "Clinical nutrition in intensive care medicine" 2018.

The study aims to show that the decrease in muscle mass is significantly less than in the control group (primary hypothesis) via ultrasound of the rectus femoris muscle and muscle biopsy. As a second hypothesis it is examined whether the combination of early high protein intake and muscle activation improves muscle strength and endurance compared to the control group.

Further exploratory analyses will investigate changes in the skeletal muscle glycogen content, skeletal muscle histology, skeletal muscle gene expression, skeletal muscle protein level, as well as metabolomic changes in blood and urine.

An additional blood sample will be taken after 90 days as part of a follow-up.

• change in muscle thickness of the rectus femoris [Срок оценки: day 1 (study inclusion) until 90-day Follow-up]
• change in echogenicity of the rectus femoris [Срок оценки: day 1 (study inclusion) until 90-day Follow-up]
• change of the pennation angle of the rectus femoris [Срок оценки: day 1 (study inclusion) until 90-day Follow-up]
• change of the muscle strength, measured by the Medical Research Council score (MRC-score) [Срок оценки: day 1 (study inclusion) until 90-day Follow-up]
• change of the muscle strength, measured by handgrip dynamometry [Срок оценки: day 1 (study inclusion) until 90-day Follow-up]
• change in muscle endurance [Срок оценки: up to 90 day follow up]
• change in physical physical function [Срок оценки: up to 90-day follow-up]
• development of quality of life [Срок оценки: up to 90-day follow-up]
• change in Skeletal muscle mass [Срок оценки: day 1 (study inclusion) until 90-day Follow-up]
• change in extracellular volume [Срок оценки: day 1 (study inclusion) until 90-day Follow-up]
• change in the REE (Resting Energy Expenditure) [Срок оценки: day 1 (study inclusion) until 90-day Follow-up]
• urea-to-creatinine ratio [Срок оценки: day 1 (study inclusion) until 90-day Follow-up]