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The role of endotoxin and nutritional support on peripheral tissue amino acid metabolism during critical illness
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THE ROLE OF ENDOTOXIN AND NUTRITIONAL SUPPORT ON PERIPHERAL TISSUE AMINO ACID METABOLISM DURING CRITICAL ILLNESS. D.G. Hesse, K.J. Tracey, Y. Fong, J.D. Albert, A. Legaspi, P.S. Barie, S.F. Lowry, Department of Surgery, The New York Hospital-Cornell Medical Center, New York City, USA The role of endotoxin(LPS) in altering tissue protein metabolism during critical illness is unknown. Seven critically ill patients(ICU pts) were studied while on dextrose 5% (D5W) infusion, and again on the 5th day of intravenous feeding(TPN). Three normal volunteers(VL) were fed a regular weight-maintaining in-hospital diet for 6 days and given LPS in the post-absorptive(PA) state, while four VL were studied after LPS challenge during the 7th day of weight-maintaining TPN. Leg amino acid(AA) flux(F1) was measured in ICU pts under both feedin conditions and in VL before (t = 0) and following (t = 2 hr) LPS injection (20 units/kg3 . Leg AA Fl (nmol/min-IOOml tissue) was calculated from simultaneous arterial(art) and venous(ven) blood samples as: [AAart - AA (1 - hematocrit) x extremity blood flow(Bf). Bf was measured by electrocapaci!$ex plethysmography and AA concentrations were measured bycolumnchromatography. Data are shown as total AA(TAA), essential AA(EAA), and branched chain AA(BCAA) flux. (-) = extremity efflux. Data are mean f SEM. ICU pts D5W
TPN
t=o
VL: D5W t=2hr
-569 f 4 -429 + 25 -245 + 203** TAA -1400 + 162 -168 * 11 -122 + 13 35 5 10"" EAA -360 f 63 -38 c 2 -19 + 2 86 + 32** BCAA -117 + 32 ** pc.001 compared to D5W; *p<.O5 compared to t = 0 by ANOVA
t=o
VL: TPN
-9 !Z 71 64 f 25 60 f 14
t=2hr -525 + 127* -35 i-40 50 + 9
In comparison to orally fed cohorts, VL-TPN exhibited an increase in leg AA efflux after LPS. Against the complex background of critical illness, TPN-induced gut rest may sensitize peripheral tissue protein to the net catabolic effects of endotoxin.
0. ,74 THE EFFECT OF EXOGENOUS INSULIN ON WHOLE BODY PROTEIN METABOLISM DURING THE TOTAL PARENTERAL NUTRITION (TPN) OF CRITICALLY ILL INTENSIVE CARE PATIENTS. MJ Glynn, S Metzner, D Halliday, J Powell-Tuck. Gastrointestinal Unit, Charing Cross Hospital, London ~6 8RF and Clinical Research Centre, Harrow, Middlesex. U.K.. Previous studies of the effect of exogenous insulin during TPN have not shown any beneficial effect on protein metabolism in patients with simple gastrointestinal disease but there may be benefit (reduction of urea production) in patients with high basal urea production rates. For this reason we have studied the effect of exogenous insulin on whole body protein (WBP) metabolism in critically ill patients receiving TPN. 6 patients were studied (5 ventilated) suffering from septicasmia after perforated viscus (4 pts), necrotising fasciitis or mediastinitis. One was premorbidly diabetic and all needed insulin to control hyperglycaemia during TPN in spite of half the energy being given as fat. WBP turnover was measured by the single dose 15N-glycine method with both urea and ammonia as end products. For each patient the insulin infusion was adjusted to try and keep the blood glucose between 8-lOmmol/l during one study and 4-6mmolfl during another (in randomised order 2 days apart). The TPN was unaltered between the studies (averaging 288mgNfkgld and 32kcallkgfd) as were other parameters as far as was possible. Results: mean (and SEM) Insulin infused units/h Plasma insulin mUI1 Blood glucose mmol/l Urea N production mglkgf9h N balance mgfkgl9h WBP flux - urea end product mg/kg/9h WBP flux - ammonia end product mg/kg/9h 3-methylhistidine excretion mg/kg/9h
High insulin (0.96) 5.75 (8.7) 78.0 (1.1) 6.34 (29) 151 -48.7 (-16.8) (225) 808 (365) 1446 0.23 (0.05)
Low insulin paired t test P
Using more insulin than is needed to keep the blood glucose below lOmmol/l confers no benefit on whole body protein metabolism in parenterally fed critically ill patients. 45
THE ROLE OF ENDOTOXIN AND NUTRITIONAL SUPPORT ON PERIPHERAL TISSUE AMINO ACID METABOLISM DURING CRITICAL ILLNESS. D.G. Hesse, K.J. Tracey, Y. Fong, J.D. Albert, A. Legaspi, P.S. Barie, S.F. Lowry, Department of Surgery, The New York Hospital-Cornell Medical Center, New York City, USA The role of endotoxin(LPS) in altering tissue protein metabolism during critical illness is unknown. Seven critically ill patients(ICU pts) were studied while on dextrose 5% (D5W) infusion, and again on the 5th day of intravenous feeding(TPN). Three normal volunteers(VL) were fed a regular weight-maintaining in-hospital diet for 6 days and given LPS in the post-absorptive(PA) state, while four VL were studied after LPS challenge during the 7th day of weight-maintaining TPN. Leg amino acid(AA) flux(F1) was measured in ICU pts under both feedin conditions and in VL before (t = 0) and following (t = 2 hr) LPS injection (20 units/kg3 . Leg AA Fl (nmol/min-IOOml tissue) was calculated from simultaneous arterial(art) and venous(ven) blood samples as: [AAart - AA (1 - hematocrit) x extremity blood flow(Bf). Bf was measured by electrocapaci!$ex plethysmography and AA concentrations were measured bycolumnchromatography. Data are shown as total AA(TAA), essential AA(EAA), and branched chain AA(BCAA) flux. (-) = extremity efflux. Data are mean f SEM. ICU pts D5W
TPN
t=o
VL: D5W t=2hr
-569 f 4 -429 + 25 -245 + 203** TAA -1400 + 162 -168 * 11 -122 + 13 35 5 10"" EAA -360 f 63 -38 c 2 -19 + 2 86 + 32** BCAA -117 + 32 ** pc.001 compared to D5W; *p<.O5 compared to t = 0 by ANOVA
t=o
VL: TPN
-9 !Z 71 64 f 25 60 f 14
t=2hr -525 + 127* -35 i-40 50 + 9
In comparison to orally fed cohorts, VL-TPN exhibited an increase in leg AA efflux after LPS. Against the complex background of critical illness, TPN-induced gut rest may sensitize peripheral tissue protein to the net catabolic effects of endotoxin.
0. ,74 THE EFFECT OF EXOGENOUS INSULIN ON WHOLE BODY PROTEIN METABOLISM DURING THE TOTAL PARENTERAL NUTRITION (TPN) OF CRITICALLY ILL INTENSIVE CARE PATIENTS. MJ Glynn, S Metzner, D Halliday, J Powell-Tuck. Gastrointestinal Unit, Charing Cross Hospital, London ~6 8RF and Clinical Research Centre, Harrow, Middlesex. U.K.. Previous studies of the effect of exogenous insulin during TPN have not shown any beneficial effect on protein metabolism in patients with simple gastrointestinal disease but there may be benefit (reduction of urea production) in patients with high basal urea production rates. For this reason we have studied the effect of exogenous insulin on whole body protein (WBP) metabolism in critically ill patients receiving TPN. 6 patients were studied (5 ventilated) suffering from septicasmia after perforated viscus (4 pts), necrotising fasciitis or mediastinitis. One was premorbidly diabetic and all needed insulin to control hyperglycaemia during TPN in spite of half the energy being given as fat. WBP turnover was measured by the single dose 15N-glycine method with both urea and ammonia as end products. For each patient the insulin infusion was adjusted to try and keep the blood glucose between 8-lOmmol/l during one study and 4-6mmolfl during another (in randomised order 2 days apart). The TPN was unaltered between the studies (averaging 288mgNfkgld and 32kcallkgfd) as were other parameters as far as was possible. Results: mean (and SEM) Insulin infused units/h Plasma insulin mUI1 Blood glucose mmol/l Urea N production mglkgf9h N balance mgfkgl9h WBP flux - urea end product mg/kg/9h WBP flux - ammonia end product mg/kg/9h 3-methylhistidine excretion mg/kg/9h
High insulin (0.96) 5.75 (8.7) 78.0 (1.1) 6.34 (29) 151 -48.7 (-16.8) (225) 808 (365) 1446 0.23 (0.05)
Low insulin paired t test P
Using more insulin than is needed to keep the blood glucose below lOmmol/l confers no benefit on whole body protein metabolism in parenterally fed critically ill patients. 45