Abstracts From the Literature-Surgery Selected by Robert H. Bartlett

The Effect of Stress Level, Amino Acid Formula, and

Nitrogen Dose on Nitrogen Retention in Traumatic and Septic Stress. Cerra F, Hirsch J, Mullen K. et al. Ann Surg, 205:282. 1987.

Eighty-seven patients were entered into a randomized, prospective, double-blind, six-center study to evaluate the effect of amino acid loading and a formula that was branched chain enriched (50%) on nitrogen retention in metabolic stress. The patients had varying levels of metabolic stress (O-3) after major surgery, polytrauma, or surgical sepsis. The study was isocaloric and isonitrogenous and lasted for 7 days. The patients received either a standard amino acid formula (SAA) (Travasole) or a 50% branched chain enriched for- mula that was equimolar, leucine, isoleucine, and valine (MAA) (Travasol + Branchamin@ concentrate) at a dose of I .O-2.0 g/kg/day in a fixed ratio with 114 glucose calories per gram of nitrogen administered. The nitrogen retention was proportionate to the nitrogen (and, therefore, caloric) load in both groups. The MAA group, however, had better nitrogen retention, reached nitrogen equilibrium at a lower dose of amino acids, and had less urinary nitrogen excretion per gram of nitrogen administered. Since the groups were isonitrogenous and the calorie to nitrogen ratios were fixed, it appears that nitrogen equilibrium in surgical stress is propor- tionate to the amino acid load over a range of 0.05-0.4 g/kg/day of nitrogen; and that MAA are more efficient at inducing nitrogen retention and a reduction in urea excretion. These effects on nitrogen retention were more significant at level 2 stress or greater. At these higher stress levels, a dose of 2 t 0.2 g/kg/day of MAA seemed most efficient in promot- ing nitrogen retention. (Reprinted with permission.)

Growth Hormone Stimulates Protein Synthesis During

Hypocaloric Parenteral Nutrition: Role of Hormonal-Sub- strate Environment. Manson JMcK; Smith RJ, Wilmore DIV. Ann Surg 208:136, 1988.

The influence of growth hormone (GH) on protein metab- olism and fuel utilization was investigated in eight paired studies of normal volunteers. GH (10 mg) was given daily during one period, and saline was injected during control studies. For 6 days, subjects received parenteral nutrition that provided adequate dietary nitrogen, vitamin, and miner- als, but energy intake varied to provide 30-100% of require- ments. On Day 7, the feedings were discontinued and an oral glucose load (100 g) was administered. The level of energy intake did not markedly influence the actions of GH. During nutrient infusions, GH caused positive nitrogen balance (1.0 i 0.3 g/m2/day vs. - 1.2 + 0.3 in controls, p < 0.001) and increased protein synthesis (16.8 + 0.7 g N/m’/day vs. 13.9 i 0.8, p < 0.01). No change in the rate of protein breakdown or excretion of 3-methylhistidine occurred. GH was associated with an increase in insulin and insulin-like growth factor-l concentrations (IGF-I, 9.1 + 0.6 IU/ml vs. 3.3 t 0.5, p < 0.001). After discontinuation of the parenteral nutrition and administration of the oral glucose load, glucose concentrations tended to be higher after GH; however, despite a two- to threefold increase in insulin response,

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muscle glucose uptake was attenuated (I.10 -I 0.19 g/kg forearm vs. 1.64 i 0.30 in controls, p s_ 0.05). Compared with control conditions, GH appeared to attenuate the increase in amino acid nitrogen efflux from muscle after the administration of oral glucose. These data demonstrate that the protein anabolic effect of GH, which occurs even during hypocaloric feedings, is related to multiple mechanisms that favor protein synthesis. These include the increase in plasma concentrations of GH, insulin, IGF-I and fat utilization. GH administration results in a hormonal-substrate environment that favors nitrogen retention and protein synthesis. GH may be beneficial in promoting protein synthesis in surgical patients, particularly in association with hypocaloric glucose infusions that allow utilization of body fat as an energy source. (Reprinted with permission.)

Metabolic Effects of Recombinant Human Growth Hormone

in Patients Receiving Parenteral Nutrition. Ziegler TR. Young LS, Manson JMcK, et al. Ann Surg 208:6. 19X8.

Recombinant human methionyl growth hormone (Protro- pin@) (Genetech, Inc., San Francisco, CA) administered to normal volunteers receiving hypocaloric parenteral nutrition minimized weight loss and induced positive nitrogen balance. To evaluate whether growth hormone (GH) can promote anabolism in surgical patients, 11 stable malnourished indi- viduals were studied. In the initial trial, subjects received a constant parenteral infusion of a hypocaloric diet that pro- vided approximately 1100 kca1/24 hr and 1.3 g protein/ kg/24 hr for at least 2 weeks. During 1 week, GH IO mg was given subcutaneously daily, whereas the other week served as the control. Daily balance studies demonstrated that admin- istration of GH resulted in significant retention of nitrogen (+3.4 g/24 h) and phosphorus (+218 mg/24 h). despite provision of only 60% of caloric requirements With GH, serum blood urea nitrogen (BUN) and potassium fell. whereas glucose and insulin tended to rise, and levels of insulin-like growth factor 1 increased three to fourfold. Weight gain occurred with GH and was associated with positive mineral and water balance. Six patients received GH (IO mg subcutaneously daily) for 13-25 consecutive days after an initial control week. Significant nitrogen and phos- phorus retention occurred over the entire period of GH administration, and no significant side effects were observed. In these depleted patients, GH caused significant and sus- tained nitrogen retention over a wide range of nutritional support. GH appears to enhance the efficacy of parenteral nutrition in stable individuals requiring repletion of body protein. (Reprinted with permission.)

Evidence That Cathepsin B Contributes to Skeletal Muscle

Protein Breakdown During Sepsis. Hummel 111 RP. James JH. Warner BU: et al. Arch Surg 123:221, 1988

The mechanisms of accelerated skeletal muscle protein degradation during sepsis have not been fully elucidated. Activity of the lysosomal protease cathepsin B is increased in skeletal muscle during various catabolic states other than sepsis. In the present study the protein degradation rate and

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