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) a nd during subsequent 24 h saline infusion in injured patients during a full blown stress reaction. To define the lag time between the start or the withdrawal of glucose and insulin infusion, and the modificatio n 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 als o to assess the possible weaning of the effect on protein breakdown du ring prolonged glucose and insulin infusion. Design: 24-36h after inju ry, patients were fasted (<100 g glucose) for 24 h (basal day). Therea fter, a 24 h glucose infusion in amount corresponding to measured fast ing energy production rate (EPR), clamping glycemia at normal level wi th insulin supply followed by 24 h saline infusion, was performed. Tot al N, urea and 3-methyl-histidine (3-MH) in urine were measured on 4 h samples starting from 20th h of the basal day. Setting: Multipurpose ICU in University Hospital. Patients: 6 consecutive patients who under went accidental and/or surgical injury, immediately admitted for respi ratory assistance (FIO2 < 0.4). Excluded patients were those with abno rmal nutritional status, cardiovascular compromise and organ failures. Main results: Patients showed a 33% increase in measured versus predi cted fasting EPR and a consistent increase in N and 3-MH urinary loss. An infusion of glucose at 5.95 +/- 0.53 mg/kg min (97.20 +/- 0.03% of the fasting measured EPR) with 1.22 +/- 0.18 mU/kg . min insulin infu sion reduced N and 3-MH loss after a time lag of 12 h. The peak decrea se in body N (-36%) and 3-MH loss (-38%) was reached during the first 12h of glucose withdrawal period. Thereafter, during the following 12 h, the effect completely vanished confirming that it is therapy-depend ent and that the metabolic environment of the patients did not change during the three days study period. Conclusion: 24 h glucose withdrawa l reduces N and 3-MH loss in injured patients, the drug-like effect is maintained during the first 12h of withdrawal and thereafter disappea rs. 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 cr ossover study.