MANIPULATION OF SUBSTRATE UTILIZATION WITH SOMATOSTATIN IN PATIENTS WITH SECONDARY MULTIPLE ORGAN DYSFUNCTION SYNDROME

Objectives: To determine whether glucose utilization and metabolic sub strate (glucose and fat) oxidation could be manipulated in patients wi th secondary multiple organ dysfunction syndrome. Design: Prospective study. Setting: Intensive care units (ICU) of two university hospitals . Patients: Eight adults free of hepatic disease and hemodynamically s table at the time of study, but with failed respiratory and gastrointe stinal systems, who thus required mechanical ventilation and intraveno us nutrition. Interventions: Patients were infused with 20% dextrose t hrough central venous cannulas at rates that increased and maintained (clamped) their plasma glucose concentration at 216 mg/dL, (12 mmol/L) for 3 hrs. Somatostatin was infused continuously during the second an d third hours of the clamp to reduce plasma concentrations of endogeno us insulin and glucagon, Exogenous insulin was administered together w ith somatostatin during the third hour to restore basal insulin concen trations. Energy expenditure was measured by indirect calorimetry thro ughout the study and blood samples were withdrawn regularly for determ ination of metabolite and hormone concentrations. Main statistical com parisons were made between the baseline data (first hour of the study) and data collected during the second and third hours of the clamp. Me asurements and Main Results: Plasma glucagon concentrations were reduc ed by nearly 50% (p < .05) toward the end of the study, whereas no sig nificant changes in plasma concentrations of cortisol or growth hormon e occurred. Energy expenditure did not change significantly at any tim e during the clamp procedure. Glucose utilization (6.1 mg/kg/min [34 m u mol/kg/min]) during the first hour of the hyperglycemic clamp, decre ased by 53% (p < .05) with the infusion of somatostatin during the sec ond hour of the clamp. However, once exogenous insulin was infused dur ing the third hour, glucose utilization increased by 55% (p < .05) whe n compared with the baseline (hour 1) rate. Glucose oxidation was near ly doubled during the third hour of the study when compared with oxida tion rates during the first and second hours. Fat oxidation decreased steadily during the 3-hr clamp. Conclusions: Glucagon has a significan t inhibitory effect on glucose utilization during intravenous glucose infusion in the multiple organ dysfunction syndrome patient. Pharmacol ogic intervention with somatostatin and insulin (physiologic dose) can facilitate glucose utilization and oxidation in these patients. Furth er investigations are needed to determine whether long-term alteration of glucose and fat metabolism would be beneficial in the patient with secondary multiple organ dysfunction syndrome.