Schricker T, Kugler B, Träger K, Anhäupl T, Vogt J, Georgieff M
Clinic of Anesthesiology, Ulm University, Germany.
Nutr Hosp. 1993 Nov;8(8):471-8.
Total parenteral nutrition (TPN) after trauma and during sepsis has two major goals. One is the reduction of increased protein catabolism, the second is to avoid hyperglycemia and enhanced hepatic gluconeogenesis. Glucose and xylitol differ in their utilization rates after trauma and during sepsis. Whole-body glucose utilization is reduced during such states, while the utilization of xylitol is more than doubled. In order to investigate whether these differences are associated with beneficial effects on hepatic glucose production and protein sparing, we conducted two animal and two clinical studies.
For the analysis of glucose and protein turnover radioactive and stable isotope techniques were applied. In burned rats primed constant infusions of 6-[3H]-glucose, 1-[14C]-alanine, 3-[14C]-alanine and U-[14C]-acetate were used to determine whole body glucose turnover, gluconeogenesis from C3-precursors and alanine flux. In septic rats nitrogen balance was calculated after determination of 24-hour-urine nitrogen content measured by micro-Kjeldahl digestion. 24-hour urinary 3-methyl-histidine excretion was analysed by amino acid autoanalyser. In human studies hepatic glucose production and urea synthesis rates were measured using primed continuous infusions of [6,6-d2]-glucose and [2-N15]-urea, respectively.
In the first trauma model we demonstrated that hypocaloric xylitol in contrast to glucose significantly reduced hepatic glucose production and gluconeogenesis from C3-carbons. In the septic rat exchange of glucose calories by xylitol in a proportion of 1:1 was associated with a significantly ameliorated nitrogen retention and lower 3-methyl-histidine excretion. In two studies on surgical intensive care patients we were able to confirm these nitrogen sparing properties of xylitol. Hepatic glucose production and urea synthesis rates were significantly reduced during xylitol infusion after trauma, whereas equicaloric glucose had no effects. In septic patients xylitol led to significant lower lactate concentrations and gluconeogenesis rates than isocaloric glucose.
In animal as well as in human studies hypocaloric xylitol and the mixture of glucose/xylitol (1:1) were more efficient in preserving body protein than glucose alone. Hepatic gluconeogenesis was significantly reduced when compared to isocaloric glucose. During the acute phase after trauma we therefore recommend a carbohydrate supplementation of 3 g/kg BW/d by xylitol. During long-term TPN a glucose/xylitol mixture (1:1) in a dosage of 6 g/kg BW/d is recommended together with amino acids and, if necessary, lipids.
创伤后及脓毒症期间的全胃肠外营养（TPN）有两个主要目标。一是减少蛋白质分解代谢增加，二是避免高血糖和增强肝脏糖异生。创伤后及脓毒症期间，葡萄糖和木糖醇的利用率有所不同。在此类状态下，全身葡萄糖利用率降低，而木糖醇的利用率增加了一倍多。为了研究这些差异是否与对肝脏葡萄糖生成和蛋白质节省的有益作用相关，我们进行了两项动物研究和两项临床研究。
应用放射性和稳定同位素技术分析葡萄糖和蛋白质周转。在烧伤大鼠中，通过持续输注6-[³H]-葡萄糖、1-[¹⁴C]-丙氨酸、3-[¹⁴C]-丙氨酸和U-[¹⁴C]-乙酸盐来测定全身葡萄糖周转、C3前体的糖异生和丙氨酸通量。在脓毒症大鼠中，通过微量凯氏定氮法测定24小时尿氮含量后计算氮平衡。用氨基酸自动分析仪分析24小时尿3-甲基组氨酸排泄量。在人体研究中，分别通过持续输注[6,6-d₂]-葡萄糖和[2-N¹⁵]-尿素来测量肝脏葡萄糖生成和尿素合成率。
在第一个创伤模型中，我们证明与葡萄糖相比，低热量木糖醇显著降低了肝脏葡萄糖生成和C3碳的糖异生。在脓毒症大鼠中，用木糖醇按1:1比例替代葡萄糖热量与氮潴留显著改善和3-甲基组氨酸排泄降低有关。在两项针对外科重症监护患者的研究中，我们能够证实木糖醇的这些蛋白质节省特性。创伤后输注木糖醇期间，肝脏葡萄糖生成和尿素合成率显著降低，而等热量葡萄糖则无此作用。在脓毒症患者中，木糖醇导致的乳酸浓度和糖异生率显著低于等热量葡萄糖。
在动物和人体研究中，低热量木糖醇以及葡萄糖/木糖醇混合物（1:1）在保存机体蛋白质方面比单独使用葡萄糖更有效。与等热量葡萄糖相比，肝脏糖异生显著降低。因此，在创伤后的急性期，我们建议通过木糖醇补充3 g/kg体重/天的碳水化合物。在长期TPN期间，建议使用剂量为6 g/kg体重/天的葡萄糖/木糖醇混合物（1:1），同时补充氨基酸，必要时补充脂肪。
