Elusive guidance to dosing of protein in critical illness

Provision of adequate protein in the nutritional regimen remains a concern for clinicians in the intensive care setting, to counteract the accelerated catabolism, breakdown of skeletal muscle, and functional impairment with acquired weakness that occurs.

The plasticity of skeletal muscle leads to complexity in determining optimal protein dosing, where steps to sustain protein synthesis are offset by anabolic resistance, disuse atrophy, intramuscular inflammation, and blunted mammalian target of rapamycin (mTOR) sensing with poor incorporation of exogenous amino acids into new muscle formation. High protein dosing in the early phases of critical illness is ineffective at improving clinical outcomes and may be toxic in an environment of mitochondrial dysfunction, where an elevated urea/creatinine ratio can be interpreted as a biomarker for poor tolerance, elevated ammonia production, and increasing muscle proteolysis.

The most effective strategy to mitigate the adverse consequences of reduced muscle mass and strength is to provide low dose protein during the acute phases of critical illness, combine nutrient delivery with exercise and early mobilization, consider fish oil or specialized pro-resolving mediators to enhance resolution of inflammation, and subsequently increase protein provision to standard doses or higher as the patient progresses to recovery and rehabilitation.