Inhibition of Post-traumatic Septic Proteolysis and Ureagenesis and Stimulation of Hepatic Acute-phase Protein Production by Branched-chain Amino Acid TPN

Previous studies have shown that severe sepsis after major trauma results in the reprioritization of release of hepatic acute-phase proteins (APP). They suggest competition for leucine for nutritional utilization may be responsible. To test this hypothesis, a branched-chain enriched (46.6%) amino acid mixture (BCAA) was administered on a prospective randomized basis with standard TPN therapy to 16 septic post-trauma patients. After sepsis was diagnosed, a randomized therapy (control-TPN or BCAA-TPN) was given for 12 days, or until death occurred. Total calories and amino acid nitrogen (N) administered were not different in the two groups (f-test) and q 8 h (347 study periods) amino acid clearances, urinary urea nitrogen excretion, muscle proteolysis from 3-methyl-histidine (3-MH) excretion, and standard indices of sepsis severity and hepatic function were measured, as well as platelets (PLAT), leucocytes (WBC), albumin (ALB), and six acute-phase proteins: C-reactive protein (CRP), alpha-1-antitrypsin (A1TRIP), fibrinogen (FIBRIN), alpha-2- macroglobulin (AMACRO), ceruloplasmin (CERUL), and transferrin (TRANS). Using Scheffe analysis of all contrasts the data showed: BCAA resulted in a fall in 24-hour urea N excretion (24.0 to 20.0 gm/24 hr) and in proteolysis (138 to 126 gm/24 hr) (p<0.0001). Prestudy CRP levels were all elevated, but compared to control where APP reprioritization occurred, over the initial 10 days of therapy BCAA patients had a more rapid fall in CRP with a more rapid rise in FIBRIN, TRANS, CERUL, ALBUMIN, AMACRO, and A1TRIP (all p<0.0001) relative to CRP. Also, the sepsis-reduced clearances of glutamine and glutamate, alanine, and proline were increased (p<0.0001) during BCAA even though urea nitrogen production was reduced (p<0.0001). The increase in leucine clearance with BCAA-enriched TPN was positively correlated (r2=0.601; p<0.0001) with the increase in the sum of all APP and ALB and was also associated with an increase both in FIBRIN and in platelets (p<0.0001). The BCAA-related increase in FIBRIN (9.1 to 11.9 mg/ml) occurred at the same time as a fall in prothrombin time (p<0.0001). BCAA-enriched TPN reduced proteolysis and amino acid catabolism and appeared to increase the levels of the more rapidly appearing anti-inflammatory and nutritional hepatic APP and formed coagulation elements in post-traumatic sepsis.