Determinants of skeletal muscle protein turnover following severe burn trauma in children

Malagaris, Ioannis; Herndon, David N.; Polychronopoulou, Efstathia; Rontoyanni, Victoria G.; Andersen, Clark R.; Suman, Oscar E.; Porter, Craig; Sidossis, Labros S.

doi:10.1016/j.clnu.2018.05.027

Cited by 9 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[9][10][11]24,25,27,28 Although we did not directly measure protein flux (Q) in this trial, one can speculate based on published data that, during severe stress, an increase in protein flux results from both an increase in protein intake and in protein breakdown on one side of the flux equation and an increase in synthesis and oxidation on the other side. 14,22,29,30 The majority of the additional amino acids in the EMS group were predominately oxidized via traditional pathways including the tricarboxylic acid cycle, gluconeogenesis, ketogenesis, and then excretion in the urine as urea. This is well supported by metabolomics and our data that show a significantly greater increase in urinary urea nitrogen and total nitrogen excretion in the EMS group.…”

Section: Discussionmentioning

confidence: 99%

Early metabolic support for critically ill trauma patients: A prospective randomized controlled trial

Stolarski

Young

Weinberg

et al. 2021

J Trauma Acute Care Surg

View full text Add to dashboard Cite

BACKGROUND:There is a lack of consensus regarding the optimal nutritional support for trauma patients. We hypothesize that early postinjury metabolic support focusing on adequate protein would modify the metabolic signature and alter the inflammatory environment for critically ill trauma patients. METHODS:We conducted a prospective randomized controlled pilot trial for adult patients admitted to the surgical intensive care unit following traumatic injury. Patients were randomized to receive early metabolic support (EMS) (peripheral amino acid infusions) or standard of care (enteral nutrition as soon as feasible). Routine laboratory assessments, nitrogen balance, cytokines, and metabolomic analyses were assessed at baseline and day 5 after intervention. RESULTS:A total of 42 trauma patients were randomized into well-balanced groups with similar age (32 years), Injury Severity Score (25), and body mass index (27.4 kg/m 2 ). Early metabolic support provided significantly more protein (1.43 g/kg vs. 0.35 g/kg; p < 0.0001) and more calories (12.6 kcal/kg vs. 7.5 g/kg; p = 0.0012) over the first 5 days as compared with the standard of care.Early metabolic support modified protein catabolism and synthesis as demonstrated by a larger median negative nitrogen balance (−16.3 g vs. −5.3 g; p = 0.03) and a unique metabolomic profile at day 5. The biochemical profile of patients who received EMS was defined by greater declines in circulating levels of stress hormone precursors and increased levels of amino acids. The inflammatory response following EMS resulted in a greater decrease in interleukin-1B ( p = 0.02) and increase in soluble interleukin-6 receptor ( p = 0.01) between baseline and day 5 as compared with the standard of care. The EMS group had a decreased length of stay (15 vs. 22 days) and decreased surgical intensive care unit length of stay (8 vs. 9 days); however, this disappeared after adjustment for Injury Severity Score in this small population. CONCLUSIONS:Early metabolic support with amino acid is safe, modifies metabolism, and may downregulate the inflammatory state associated with significant trauma, warranting a larger trial to assess for improved outcomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Early metabolic support for critically ill trauma patients: A prospective randomized controlled trial

Stolarski

Young

Weinberg

et al. 2021

J Trauma Acute Care Surg

View full text Add to dashboard Cite

show abstract

“…However, recent evidence suggests that the net negative balance persists for over 1 year in pediatric patients with burns, whereas a reduction in lean body mass may be observed for 2-3 years postburn (17,45). These findings were subsequently confirmed in adult patients with burns compared with healthy control subjects using a combination of amino acid isotope labeling, muscle biopsies, femoral blood flow, and blood sampling over time (8,26). Furthermore, the increased rates of protein synthesis and degradation are not dependent on the presence of a wound, as a negative net protein balance was shown in both the burned and the contralateral unburned leg (8).…”

Section: Burn-induced Proteolysismentioning

confidence: 95%

“…These inconsistencies may be attributed to differences in observational periods, as it has been suggested that scald burns may have a greater short-term impact on morbidity and mortality, whereas flame burns may produce a more prolonged inflammatory response resulting in greater long-term complications (25). However, the type of burn injury does not appear to have a direct influence on muscle catabolism or muscle protein kinetics (26), although more studies are necessary to tease out these discrepancies.…”

Section: Thermal Burnsmentioning

confidence: 99%

Burn-induced hypermetabolism and skeletal muscle dysfunction

Knuth

Auger

Jeschke

2021

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

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.

show abstract

“…Study inclusion criteria were: age ≤ 18 years at admission; within 1 week of burn injury; ≥ 30% of total body surface area (TBSA) burned; randomization into the placebo arm of prospective pharmacological studies. 14 The study protocol was approved by the Institutional Review Board at the University of Texas Medical Branch, Galveston, TX, and the studies were conducted at Shriners Hospitals for Children, Galveston, TX. Informed written consent was obtained from legal guardians prior to participation and guiding principals outlined in the Declaration of Helsinki were followed.…”

Section: Participantsmentioning

confidence: 99%

“…13 This study uses data from children with burns who participated in the control arm of larger published pharmacological studies. 14 These studies provide the opportunity to simultaneously assess both muscle FSR and FBR to compare the A-V balance and two-bolus tracer incorporation methods in children with burns; this is the purpose of the current analysis. We hypothesized the FSR and FBR from the A-V balance method would not be different from the two-bolus method.…”

mentioning

confidence: 99%

Comparison of Arterial-Venous Balance and Tracer Incorporation Methods for Measuring Muscle Fractional Synthesis and Fractional Breakdown Rates

Hudson

Cotter

Herndon

et al. 2021

Journal of Burn Care &Amp; Research

View full text Add to dashboard Cite

Loss of muscle mass in response to injury or immobilization impairs functional capacity and metabolic health, thus hindering rehabilitation. Stable isotope techniques are powerful in determining skeletal muscle protein fluxes. Traditional tracer incorporation methods to measure muscle protein synthesis and breakdown are cumbersome and invasive to perform in vulnerable populations such as children. To circumvent these issues, a two-bolus stable isotope amino acid method has been developed; although, measured rates of protein synthesis and breakdown have not been validated simultaneously against an accepted technique such as the arterial-venous balance method. The purpose of the current analysis was to provide preliminary data from the simultaneous determination of the arteriovenous balance and two-bolus tracer incorporation methods on muscle fractional synthesis and breakdown rates in children with burns. Five were administered a primed-constant infusion of L-[ 15N]Threonine for 180 minutes (Prime: 8 µmol/kg; constant: 0.1 µmol·kg -1·min -1). At 120 and 150 minutes, bolus injections of L-[ring- 13C6]Phenylalanine and L-[ 15N]Phenylalanine (50 µmol/kg each) were administered, respectively. Blood and muscle tissue samples were collected to assess mixed muscle protein synthesis and breakdown rates. The preliminary results from this study indicate there is no difference in either fractional synthesis rate (mean ± SD; arteriovenous balance: 0.19 ± 0.17 %/h; tracer incorporation: 0.14 ± 0.08 %/h; P = 0.42) or fractional breakdown rate (arteriovenous balance: 0.29 ± 0.22 %/h; tracer incorporation: 0.23 ± 0.14 %/h; P = 0.84) between methods. These data support the validity of both methods in quantifying muscle amino acid kinetics; however, the results are limited and adequately powered research is still required.

show abstract

Determinants of skeletal muscle protein turnover following severe burn trauma in children

Cited by 9 publications

References 30 publications

Early metabolic support for critically ill trauma patients: A prospective randomized controlled trial

Early metabolic support for critically ill trauma patients: A prospective randomized controlled trial

Burn-induced hypermetabolism and skeletal muscle dysfunction

Comparison of Arterial-Venous Balance and Tracer Incorporation Methods for Measuring Muscle Fractional Synthesis and Fractional Breakdown Rates

Contact Info

Product

Resources

About