The Effect of Muscle Stimulation and Amino Acid Intake on Protein Metabolism During Critical Illness

The Effect of a Single Session of Whole-body Neuromuscular Electrical Stimulation (NMES), With or Without Subsequent Intake of an Amino Acid Bolus, on Whole-body Protein Turnover in Sedated Intensive Care Unit (ICU) Patients

The goal of this clinical trial is to study how whole-body electrical stimulation combined with amino acid intake affects muscle health in ventilated ICU patients. The main questions to answer are:

• Does electrostimulation improve the balance of muscle protein in ICU patients?
• Does combining electrostimulation with amino acid help build muscle and prevent muscle loss?

Researchers will compare three groups of patients:

1. Sham electrostimulation (no current applied) + the standard nutrition
2. Electrostimulation + the standard nutrition
3. Electrostimulation + a 20g amino acid bolus

Participants will:

• Receive either real or sham electrostimulation
• Get their standard nutrition or a 20g amino acid bolus
• Have marked amino acids given through an IV
• Have blood samples taken to measure the amino acids and glucose in the blood
• Undergo ultrasound of the upper arm to measure the blood flow

This clinical trial aims to investigate the effects of whole-body neuromuscular electrical stimulation (NMES) on muscle protein metabolism in mechanically ventilated ICU patients. The study will examine whether NMES, combined with or without amino acid intake, can positively affect muscle protein synthesis and help prevent muscle wasting, which is a common issue in critically ill patients. ICU patients often experience muscle wasting due to prolonged immobility and impaired muscle protein metabolism.

Participants will be randomly assigned to one of three groups:

1. Sham-NMES + Standard Enteral Nutrition (CON): In this group, participants will receive sham NMES (inactive stimulation) followed by standard nutritional support.
2. Whole-body NMES + Standard Enteral Nutrition (WB-NMES): This group will receive active whole-body NMES followed by standard nutritional support.
3. Whole-body NMES + 20g Amino Acid Bolus (WB-NMES+AA): Participants in this group will receive active whole-body NMES followed by a 20g bolus of amino acids.

The main goal of the study is to measure whole-body protein net balance (WPNB), which is the difference between muscle protein synthesis and muscle protein breakdown.

Secondary outcomes include measuring whole-body protein synthesis, protein breakdown, protein oxidation, and muscle glucose uptake, a key indicator of muscle insulin sensitivity.

To assess these outcomes, participants will receive a continuous intravenous infusion of labelled amino acids, and their blood will be sampled at various points. Doppler ultrasound will be used to measure amino acid and glucose balances in the forearm muscles.

This study is crucial for understanding how NMES combined with amino acid intake can improve muscle health and metabolic function in ICU patients, potentially leading to better clinical outcomes, such as reduced muscle wasting and improved recovery during and after an ICU stay.

Inclusion Criteria:

• Aged ≥18 years
• Expected to need mechanical ventilation for at least 48 hours, judged by physician
• Expected to reach a Richmond Agitation-Sedation Scale (RASS) score of -4 or -5 (complete sedation), judged by physician
• Informed consent obtained from the next-of-kin
• Able to or are receiving gastric tube feeding
• Have an arterial and a venous line in situ

Exclusion Criteria:

• Spinal cord injury
• Previous surgery/local wounds that prohibit whole-body NMES
• Conditions that prohibit NMES (such open wounds)
• Chronic neuromuscular disorders (such as Amyotrophic lateral sclerosis (ALS))
• Acute Kidney Injury (AKI) II and III
• Undergoing continuous veno-venous hemofiltration (CVVH)
• Rhabdomyolysis
• Neuromuscular blocking agents
• In the caloric restriction period of refeeding syndrome
• In prone position
• Burn wounds
• ICD/pacemaker
• Pregnant
• Deemed not suitable to participate based upon the judgement of the treating intensivist