Kinetic of body nitrogen loss during a whole day infusion and withdrawal of glucose and insulin in injured patients.

OBJECTIVE: To investigate the kinetics of body nitrogen (N) excretion during 24 h glucose infusion (relating glycemia with insulin supply) and during subsequent 24 h saline infusion in injured patients during a full blown stress reaction. To define the lag time between the start of the withdrawal of glucose and insulin infusion, and the modification in the N loss from the body, and the time span to reach the maximum effect and its size. The knowledge of these variables is mandatory to plan short term studies in critically ill patients, while assuring the stability of the metabolic condition during the study period, and also to assess the possible weaning of the effect on protein breakdown during prolonged glucose and insulin infusion. DESIGN: 24-36 h after injury, patients were fasted ( < 100 g glucose) for 24 h (basal day). Thereafter, a 24 h glucose infusion in amount corresponding to measured fasting energy production rate (EPR), clamping glycemia at normal level with insulin supply followed by 24 h saline infusion, was performed. Total N, urea and 3-methyl-histidine (3-MH) in urine were measures on 4 h samples starting from 20th h of the basal day. SETTING: Multipurpose ICU in University Hospital. PATIENTS: 6 consecutive patients who underwent accidental and/or surgical injury, immediately admitted for respiratory assistance (FIO2 < 0.04). Excluded patients were those with abnormal nutritional status, cardiovascular compromise and organ failures. MAIN RESULTS: Patients showed a 33% increase in measured versus predicted fasting EPR and a consistent increase in N and 3-MH urinary loss. An infusion of glucose at 5.95 +/- 0.53 mg/kg x min (97.20 +/- 0.03% of the fasting measured EPR) with 1.22 +/- 0.18 mU/kg x min insulin infusion reduced N and 3-MH loss after a time lag of 12 h. The peak decrease in body N (-36%) and 3-MH loss (-38%) was reached during the first 12 h of glucose withdrawal period. Thereafter, during the following 12 h, the effect completely vanished confirming that it is therapy-dependent and that the metabolic environment of the patients did not change during the three days study period. CONCLUSION: 24 h glucose withdrawal reduces N and 3-MH loss injured patients, the drug-like effect is maintained during the first 12 h of withdrawal and thereafter disappears. The study suggests that at least a 24 h study period is necessary when planning studies exploring energy-protein metabolism relationship in injured patients, and, again 24 h before changing protocol in a crossover study.

[Energy metabolism and metabolite flow from muscle tissue during TPN of trauma patients]. / Metabolismo energetico e flusso di metaboliti dal tessuto muscolare durante TPN di pazienti traumatizzati.

AIM: We evaluated muscle-visceral interorgan flux of substrates in 8 critically ill patients in the flow phase after injury. SETTING: This study was conducted on critically ill patients admitted in ICU. PATIENTS: 8 patients were studied immediately after injury. RESULTS: We measured leg flux for oxygen, amino acids, glucose, lactate pyruvate, keton bodies, free fatty acids (FFA), free and total carnitine, and whole body oxygen consumption, nitrogen (N) balance and 3-methyl hystidine (3MEH) excretion during fasting and the second day of metabolic treatment (10.7 +/- 0.06 g x N x m-2 e 1035.5 +/- 3.9 kcal x m-2 x die). During fast the leg shows a net release of N, pyruvate, FFA and free carnitine while glucose, lactate and keton bodies fluxes are not different from zero. The energy balance of the leg is markedly negative (substrate for 79 kcal x m-2 burned for leg energy requirement and 347 kcal x m-2 released as a such). Assuming the body muscle tissue 4.5 times the leg tissue and knowing whole body energy balance, we were able to assess that the non muscular (visceral) part of the body resulted in a consistently positive energy balance. The metabolic treatment is able to match the energy expenditure and the substrate efflux of the leg (and the whole body muscle tissue). In fact the efflux of amino acids and FFA is reduced pyruvate blunted while glucose is remarkably taken up (the uptake of the whole muscle tissue accounted for 72% of the daily load). At the same time, the treatment blunts leg free carnitine and reduces body 3MEH output. Moreover, the caloric balance of the non muscular part of the body remains positive even if the qualiquantitative uptake of substrates is different from fasting. CONCLUSION: Substrates for energy requirements of visceral tissue came from muscular tissue. The metabolic treatment is able to modulate this process.

[Body, muscle, and visceral nitrogen balance in catabolic patients. Modification with metabolic treatment]. / Bilancio azotato corporeo, muscolare e viscerale in pazienti catabolici. Modificazioni col trattamento metabolico.

In sixteen severely catabolic patients, two different nutritional treatments with the same nitrogen input (0.30 gN.kg-1.die-1) but with a different caloric support: 30 kcal.kg-1.die-1 foe group A and 15 kcal.kg-1.die-1 for group B were infused. Body nitrogen balance (BN), muscle nitrogen balance (BNm) and, calculated as a difference of the two, visceral nitrogen balance were measured in every patient on basal day and on the second day of total parenteral nutrition. Both nutritional treatment reduced the catabolic state in the same amount: this was confirmed by a less negative body BN and by the reduced excretion of 3-MEH and amino acidic catabolic markers. Otherwise in the other compartments the treatments showed different effects: the metabolic support was more reduced by treatment A than it was by B, supplying to visceral compartment a lower nitrogen amount: the nitrogen dismission from muscle compartment, available for visceral tissues, is greater with treatment B than with treatment A. In conclusion, even if both treatments show the same effect on body nitrogen balance, they penalize either one of the examined compartment or the other. To avoid this problem, the study and the use of tissue-specific nutrients are desiderable. Tissue-specific solutions may warrant the balance among body compartment without any further increase of the nitrogen rate.

Peripheral, visceral and body nitrogen balance of catabolic patients, without and with parenteral nutrition.

The effect of major trauma and sepsis on skeletal muscle, central tissue and whole body nitrogen (N) metabolism was investigated in 5 patients before and during TPN (30 kcal, 0.30 g N kg-1 day-1). Fasting 3-methylhistidine (MEH) urinary excretion was elevated (407.9 +/- 67.6 mumol m-2 day-1), muscle and body N balances (NB) were markedly negative (-28.2 +/- 4.6 g m-2 day-1 and -15.7 +/- 3.1 g m-2 day-1), while central tissue NB was positive (13.0 +/- 2.4 g m-2 day-1). TPN effected a reduction in MEH excretion (261.8 +/- 27.5 mmol m-2 day-1 - p less than 0.05) and decreased the release of almost all amino acids from muscle tissue, some of them acting as catabolic markers. Muscle (-7.2 +/- 1.2 g m-2 day-1 - p less than 0.01) as well as body NB (-4.8 +/- 1.4 g m-2 day-1 - p less than 0.01) improved, whilst central tissue NB worsened, even though still positive (3.1 +/- 1.6 g m-2 day-1 - p less than 0.05). Gathering fasting and TPN data MEH excretion was significantly related to both body (r = 0.89) and muscle (r = 0.73) NB, that were highly related to each other (r = 0.93), being muscle always worse than body NB. In conclusion, the anticatabolic activity of TPN is confirmed, although our setting did not achieve muscle NB, it was consistently improved and seems to be the major determinant of body NB, in contrast central NB and central N utilization (46.4% +/- 5.4 vs 15.8% +/- 8.4 - p less than 0.05) worsened.