Burn-induced hypermetabolism and skeletal muscle dysfunction

Abstract

Critical illnesses, including sepsis, cancer cachexia and burn injury, invoke a milieu of systemic metabolic and inflammatory derangements that ultimately results in increased energy expenditure leading to fat and lean mass catabolism. Burn injuries present a unique clinical challenge given the magnitude and duration of the hypermetabolic response in comparison to other forms of critical illness, which drastically increase the risk of morbidity and mortality. Skeletal muscle metabolism is particularly altered as a consequence of burn-induced hypermetabolism as it primarily provides a main source of fuel in support of wound healing. Interestingly, muscle catabolism is sustained long after the wound has healed, indicating that additional mechanisms beyond wound healing are involved. In this review, we discuss the distinctive pathophysiological response to burn injury with a focus on skeletal muscle function and metabolism. We first examine the diverse consequences on skeletal muscle dysfunction between thermal, electrical and chemical burns. We then provide a comprehensive overview of the known mechanisms underlying skeletal muscle dysfunction that may be attributed to hypermetabolism. Lastly, we review the most promising current treatment options to mitigate muscle catabolism, and by extension improve morbidity and mortality, and end with future directions which have the potential to significantly improve patient care.

Burns: Classification, Pathophysiology, and Treatment: A Review

“…The body’s hypermetabolic response has detrimental effects at the cellular and systemic level [ 26 ]. At the systemic level, the structure and function of major organs (heart, liver, skeletal muscle, skin), the immune system and the transmembrane transport system are compromised.…”

“…At the systemic level, the structure and function of major organs (heart, liver, skeletal muscle, skin), the immune system and the transmembrane transport system are compromised. Wound healing is impaired, which increases the risk of infection, hampers rehabilitation and delays the reintegration of patients back into society [ 26 , 27 ]. At the cellular level, hypermetabolic response increases thermogenesis [ 28 ] by uncoupling mitochondrial respiration from phosphorylation of ADP to ATP, resulting in heat generation [ 29 ].…”

“…The endocrine disruption that occurs after a burn alters metabolic pathways. Catecholamines drive hypermetabolism, while an increase in the secretions of cortisol, adrenaline and glucagon (which are catabolic hormones), together with an increase in pro-inflammatory cytokines, inhibits protein and fat synthesis [ 26 , 32 ]. The observed negative nitrogen balance in burn patients [ 25 ] suggests that skeletal muscles are used as the main energy source [ 33 ].…”

“…The observed negative nitrogen balance in burn patients [ 25 ] suggests that skeletal muscles are used as the main energy source [ 33 ]. Accelerated protein degradation leads to a significant loss of lean body mass (LBM) and muscle atrophy, resulting in reduced strength and compromised rehabilitation outcomes [ 26 , 34 ]. Depending on the magnitude of LBM loss, certain dysfunctions occur.…”

“…In addition, patients with severe burns exhibit increased glucose production through activation of the gluconeogenesis pathway, with alanine as the main substrate (next to lactic acid). In this situation, amino acids become the main “fuel”, resulting in a deficit of amino acids for building proteins, as well as an increase in nitrogen excretion, mainly in the form of urea [ 26 ].…”