Arnold J, Campbell I T, Hipkin L J, Keegan M, Jenkins S, O'Sullivan E, Chadwick S
Intensive Therapy Unit, Royal Liverpool Hospital, UK.
Crit Care Med. 1995 Jan;23(1):71-7. doi: 10.1097/00003246-199501000-00014.
To determine whether glucose utilization and metabolic substrate (glucose and fat) oxidation could be manipulated in patients with secondary multiple organ dysfunction syndrome.
Prospective study.
Intensive care units (ICU) of two university hospitals.
Eight adults free of hepatic disease and hemodynamically stable at the time of study, but with failed respiratory and gastrointestinal systems, who thus required mechanical ventilation and intravenous nutrition.
Patients were infused with 20% dextrose through 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 and third hours of the clamp to reduce plasma concentrations of endogenous insulin and glucagon. Exogenous insulin was administered together with somatostatin during the third hour to restore basal insulin concentrations. Energy expenditure was measured by indirect calorimetry throughout the study and blood samples were withdrawn regularly for determination of metabolite and hormone concentrations. Main statistical comparisons were made between the baseline data (first hour of the study) and data collected during the second and third hours of the clamp.
Plasma glucagon concentrations were reduced by nearly 50% (p < .05) toward the end of the study, whereas no significant changes in plasma concentrations of cortisol or growth hormone occurred. Energy expenditure did not change significantly at any time during the clamp procedure. Glucose utilization (6.1 mg/kg/min [34 mumol/kg/min]) during the first hour of the hyperglycemic clamp, decreased by 53% (p < .05) with the infusion of somatostatin during the second hour of the clamp. However, once exogenous insulin was infused during the third hour, glucose utilization increased by 55% (p < .05) when compared with the baseline (hour 1) rate. Glucose oxidation was nearly doubled during the third hour of the study when compared with oxidation rates during the first and second hours. Fat oxidation decreased steadily during the 3-hr clamp.
Glucagon has a significant inhibitory effect on glucose utilization during intravenous glucose infusion in the multiple organ dysfunction syndrome patient. Pharmacologic intervention with somatostatin and insulin (physiologic dose) can facilitate glucose utilization and oxidation in these patients. Further 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.
确定在继发性多器官功能障碍综合征患者中，葡萄糖利用及代谢底物（葡萄糖和脂肪）氧化是否可被调控。
前瞻性研究。
两家大学医院的重症监护病房（ICU）。
8名成年患者，研究时无肝脏疾病且血流动力学稳定，但呼吸和胃肠系统功能衰竭，因此需要机械通气和静脉营养。
通过中心静脉导管以递增并维持（钳夹）血浆葡萄糖浓度在216 mg/dL（12 mmol/L）的速率给患者输注20%葡萄糖，持续3小时。在钳夹的第二小时和第三小时持续输注生长抑素，以降低内源性胰岛素和胰高血糖素的血浆浓度。在第三小时将外源性胰岛素与生长抑素一起给予，以恢复基础胰岛素浓度。在整个研究过程中通过间接测热法测量能量消耗，并定期采集血样以测定代谢物和激素浓度。主要统计学比较在基线数据（研究的第一小时）与钳夹的第二小时和第三小时收集的数据之间进行。
在研究接近结束时，血浆胰高血糖素浓度降低了近50%（p < 0.05），而血浆皮质醇或生长激素浓度无显著变化。在钳夹过程中的任何时间，能量消耗均无显著变化。高血糖钳夹第一小时的葡萄糖利用率为6.1 mg/kg/min [34 μmol/kg/min]，在钳夹的第二小时输注生长抑素后降低了53%（p < 0.05）。然而，在第三小时输注外源性胰岛素后，与基线（第一小时）速率相比，葡萄糖利用率增加了55%（p < 0.05）。与第一小时和第二小时的氧化速率相比，研究的第三小时葡萄糖氧化几乎增加了一倍。在3小时的钳夹过程中，脂肪氧化稳步下降。
在多器官功能障碍综合征患者静脉输注葡萄糖期间，胰高血糖素对葡萄糖利用具有显著抑制作用。用生长抑素和胰岛素（生理剂量）进行药物干预可促进这些患者的葡萄糖利用和氧化。需要进一步研究以确定葡萄糖和脂肪代谢的长期改变对继发性多器官功能障碍综合征患者是否有益。
