Support of the metabolic response to burn injury

Objective To determine if long-term (7 days) infusion of insulin can ameliorate altered protein kinetics in skeletal muscle of severely burned patients and to investigate the hypothesis that changes in protein kinetics during insulin infusion are associated with an increased rate of transmembrane amino acid transport from plasma into the intracellular free amino acid pool. Background Data In critically ill patients, vigorous nutritional support alone may often fail to entirely curtail muscle catabolism ; insulin stimulates muscle protein synthesis in normal volunteers. Methods Nine patients with severe burns were studied once during enteral feeding alone (control period), and once after 7 days of high-dose insulin. The order of treatment with insulin was randomized. Data were derived from a model based on a primed-continuous infusion of L-[ 15 N]phenylalanine, sampling of blood from the femoral artery and vein, and biopsies of the vastus lateralis muscle. Results Net leg muscle protein balance was significantly (p < 0.05) negative during the control period. Exogenous insulin eliminated this negative balance by stimulating protein synthesis approximately 350% (p < 0.01). This was made possible in part by a sixfold increase in the inward transport of amino acids from blood (p < 0.01). There was also a significant increase in leg muscle protein breakdown. The new rates of synthesis, breakdown, and inward transport during insulin were in balance, such that there was no difference in the intracellular phenylalanine concentration from the control period. The fractional synthetic rate of protein in the wound was also stimulated by insulin by approximately 50%, but the response was variable and did not reach significance. Conclusions Exogenous insulin may be useful in promoting muscle protein synthesis in severely catabolic patients.

Stimulation of muscle protein synthesis by long-term insulin infusion in severely burned patients.

Pathophysiology of the burn wound and pharmacological treatment. The Rudi Hermans Lecture, 1995

The Hypermetabolic Response to Burn Injury and Interventions to Modify This Response

Objective To determine the effects of recombinant human insulin-like growth factor-1 (IGF-1) complexed with its principal binding protein, IGFBP-3, on skeletal muscle metabolism in severely burned children. Background Data Severe burns are associated with a persistent hypermetabolic response characterized by hyperdynamic circulation and severe muscle catabolism and wasting. Previous studies showed that nutritional support and pharmacologic intervention with anabolic agents such as growth hormone and insulin abrogated muscle wasting and improved net protein synthesis in the severely burned. The use of these agents, however, has several adverse side effects. A new combination of IGF-1 and IGFBP-3 is now available for clinical study. Methods Twenty-nine severely burned children were prospectively studied before and after treatment with 0.5, 1, 2, or 4 mg/kg/ day IGF-1/IGFBP-3 to determine net balance of protein across the leg, muscle protein fractional synthetic rates, and glucose metabolism. Another group was studied in a similar fashion without IGF-1/IGFBP-3 treatment as time controls. Results Seventeen of 29 children were catabolic before starting treatment. The infusion of 1.0 mg/kg/day IGF-1/IGFBP-3 increased serum IGF-1, which did not further increase with 2.0 and 4.0 mg/kg/day. IGF-1/IGFBP-3 treatment at 1 to 4 mg/ kg/day improved net protein balance and increased muscle protein fractional synthetic rates. This effect was more pronounced in catabolic children. IGF-1/IGFBP-3 did not affect glucose uptake across the leg or change substrate utilization. Conclusions IGF-1/IGFBP-3 at doses of 1 to 4 mg/kg/day attenuates catabolism in catabolic burned children with negligible clinical side effects.

Muscle Protein Catabolism After Severe Burn: Effects of Igf-1/igfbp-3 Treatment

ObjectiveThe effect of insulin-like growth factor-1 (IGF-1) on energy expenditure and protein and glucose metabolism in a group of patients with thermal injury was determined.Summary Background DataAccelerated protein catabolism is a constant feature of the hypermetabolic response to thermal injury.

https://apps.dtic.mil/dtic/tr/fulltext/u2/a289566.pdf

Basil A. Pruitt

Papers

Insulin-Like Growth Factor-1 Lowers Protein Oxidation in Patients with Thermal Injury,