Predictors of muscle protein synthesis after severe pediatric burns

Abstract

Background Following a major burn, skeletal muscle protein synthesis rate increases, but is often insufficient to compensate for massively elevated muscle protein breakdown rates. Given the long-term nature of the pathophysiologic response to burn injury, we hypothesized that muscle protein synthesis rate would be chronically elevated in severely burned children. The objectives of this study were to characterize muscle protein synthesis rate of burned children over a period of 24 months post-injury, and identify predictors that influence this response. Study design 87 children with ≥40% total body surface area (TBSA) burn were included. Patients participated in stable isotope infusion studies at 1, 2 and ~ 4 weeks post-burn, and at 6, 12 and 24 months post-injury to determine skeletal muscle fractional synthesis rate. Generalized estimating equations with log link normal distribution were applied to account for clustering of patients and control for patient characteristics. Results Patients (8±6 years) had large (62, 51–72% TBSA) and deep (47±21% TBSA third degree) burns. Muscle fractional synthesis rate was elevated throughout the first 12 months post-burn compared to established values from healthy young adults. Muscle fractional synthesis rate was lower in boys, children >3 years old, and when burns were >80% TBSA. Conclusions Muscle protein synthesis is elevated for at least one year after injury, suggesting that greater muscle protein turnover is a component of the long-term pathophysiological response to burn trauma. Muscle protein synthesis is highly affected by gender, age and burn size in severely burned children. These findings may explain the divergence in net protein balance and lean body mass in different populations of burn victims.

Body Composition Changes in Severely Burned Children During ICU Hospitalization*

“…When combined with immobilization, high serum levels of catecholamines, glucocorticoids, and pro-inflammatory cytokines contribute to the breakdown of lean muscle in severely burned children [34]. Of these factors, immobilization is most easily addressed through strength-building physical activity that can start within the first 5 days post injury [35].…”

Long-term effects of physical exercise during rehabilitation in patients with severe burns

“…The major contributor to the sometimes poor and in most cases late sequelae is the hypermetabolic response to burns, which is modulated by high serum levels of catecholamines, glucocorticoids, and proinflammatory cytokines (2). These acute inflammatory and endocrine responses are associated with a vast loss of lean body mass, muscle protein breakdown, and prolonged immobilization (3). Despite advances in burn care, these systemic responses are still present 2 years post burn and maybe beyond (4).…”

Severe burn increased skeletal muscle loss in mdx mutant mice

“…Prior studies have demonstrated that increased whole body protein turnover, specifically from breakdown of skeletal muscle, provides amino acid substrates for wound healing after burn (3). However, shunting of amino acids to the burn wound cannot account for muscle loss entirely as net protein loss with elevated catabolism is known to persist nine months to one year after burn, well after wound closure (4, 5). …”