Anabolic responsiveness in critically ill children: a narrative review and conceptual perspective on nutrient...

Critical illness alters energy metabolism, substrate use, and protein turnover in children, while skeletal muscle loss may continue despite apparently adequate energy and protein delivery. Nutritional adequacy may depend not only on nutrient delivery but also on how effectively nutrients are utilized to preserve muscle and support anabolic responsiveness. This hypothesis-generating narrative review synthesizes evidence on metabolic alterations and anabolic responsiveness in critically ill children, focusing on indirect calorimetry, respiratory quotient (RQ), non-protein RQ (npRQ), nitrogen balance, and quadriceps and diaphragm ultrasound. PubMed/MEDLINE was searched from inception to July 2026, prioritizing pediatric evidence and incorporating adult studies when pediatric data were insufficient. Indirect calorimetry remains the reference bedside method for measuring resting energy expenditure but cannot determine whether nutrients are incorporated into skeletal muscle protein. RQ and npRQ provide information on whole-body substrate oxidation but lack validated pediatric thresholds. Nitrogen balance estimates whole-body protein retention or loss but does not directly reflect skeletal muscle protein balance. Serial ultrasound can track regional muscle changes, although quadriceps and diaphragm measurements reflect different physiological influences. Pediatric studies demonstrate early peripheral muscle loss, while direct measurements of muscle protein synthesis and breakdown remain limited. No routinely available bedside method can directly assess anabolic responsiveness or confirm anabolic resistance. Integrating metabolic measurements with serial muscle assessment may identify mismatches between nutrient delivery and tissue response but remains hypothesis-generating. Prospective studies incorporating direct protein kinetics are needed to determine when anabolic responsiveness is restored and whether this can guide nutritional and rehabilitation strategies.