Protein nutritional support in critically ill patients: pathophysiological basis, clinical evidence, and areas of uncertainty - a narrative review.

Protein metabolic derangement is a hallmark of critical illness and contributes to adverse outcomes and delayed recovery. This narrative review synthesises current evidence on protein metabolism, requirement assessment, and supplementation strategies in critically ill adults, with emphasis on sepsis and severe burns as representative hypercatabolic phenotypes. Sepsis and major burns are characterised by accelerated skeletal muscle breakdown, negative nitrogen balance, and sustained functional impairment. Current guidelines generally support progressive enteral-first protein delivery after haemodynamic stabilisation, targeting at least 1.2-1.3 g/kg/day, whereas higher targets are more consistently justified in severe burns because of prolonged hypermetabolism, exudative losses, and wound-healing demands. However, randomised trials and meta-analyses do not show a uniform mortality benefit from higher protein provision, and very high early doses may be harmful in selected patients, particularly those with acute kidney injury or poor metabolic tolerance. Evidence for specific protein sources, functional amino acids, micronutrients, probiotics, and metabolic modulators remains heterogeneous. Future research should define phenotype-specific protein strategies using metabolic, structural, functional, and long-term patient-centred outcomes.