烧伤患者肠内谷氨酰胺给药对血浆谷氨酰胺水平的影响与安全性

　　一些小样本随机研究表明，对烧伤患者给予补充标准剂量（0.3～0.5g/kg/d）的谷氨酰胺可降低死亡率并改善临床结局，而高剂量（＞0.5g/kg/d）谷氨酰胺或血浆谷氨酰胺浓度＞930μmol会导致死亡率增加。

　　在大样本多中心研究之前，美国科罗拉多大学医学院、瑞典卡罗林斯卡学院、加拿大维多利亚女王大学在美国国防部和美国烧伤学会资助下，对18例2～3度烧伤患者进行研究，两组患者入院后分别肠内给予0.5g/kg/d谷氨酰胺和麦芽糊精（对照），直到皮瓣移植后1周，对患者进行6个月随访。

　　结果发现烧伤患者的血浆谷氨酰胺水平降低并持续2周以上，外源性补充谷氨酰胺可使血浆谷氨酰胺水平升高，且无死亡报道，表明该研究较为安全。

JPEN J Parenter Enteral Nutr. 2016;40(4):124-125.

Safety and Effect of Enteral Glutamine Administration in Burn Patients on Plasma Glutamine Levels.

Paul Wischmeyer; Christine Baird; Olav Rooijackers; Daren Heyland.

University of Colorado School of Medicine, Aurora, CO, USA; Karolinska Institutet and University Hospital, Huddinge, Sweden; Queens University-Public Health, Kingston, Ontario, Canada.

Purpose: Glutamine (GLN) given in standard accepted doses (0.3-0.5 g/kg/d) has shown signals of reduced mortality and improved outcomes in burn injury in a number of small randomized trials of intravenous and enteral GLN supplementation. However, in trials (REDOXS) of patients with multiorgan failure at admit, high-dose GLN (>0.5 g/kg/d) is associated with a signal of increased mortality. Secondary analysis indicates that much of this increased mortality occurred in renal failure patients at intensive care unit admit not undergoing dialysis. Previous research by other groups and our REDOXS data suggest that admission GLN levels >930 μmol/L may be associated with increased mortality and that renal failure may correlate with increased GLN levels. We observed GLN levels >930 μmol /L in REDOXS in 10% of patients at admit. A major multicenter trial planned to examine GLN's effect on burn mortality. Prior to launching this large initiative, we conducted a multicenter randomized pilot trial to assess feasibility of larger trial, including an analysis of GLN levels.

Methods: A multicenter double-blind randomized pilot trial was conducted in 8 burn centers in Canada and the United States to demonstrate the feasibility of our larger planned trial. We included patients with deep second- and/or third-degree burns at moderate to high risk of death. For patients aged 18-59 years, we required a total burn surface area (TBSA) ≥20% or, in the presence of an inhalation injury, a minimum TBSA of 15%. For patients ≥60 years, we required a TBSA ≥10%. We excluded patients admitted >48 hours before screening and patients with advanced liver and kidney disease. Patients were randomized to receive either GLN via feeding tube every 4 hours for a total of 0.5 g/kg/d or maltodextrin (control). Study intervention continued until 7 days post-last graft. Patients were followed for 6 months to document survival. A substudy of patients had blood draws done at baseline and weekly thereafter to measure plasma GLN levels and other laboratory measures.

Results: In first 18 patients in which GLN levels were analyzed, significant GLN deficiency was noted overall and in both GLN and control groups (<420 μmol/L). Mean plasma GLN levels were consistently higher in the GLN group at 2 and 3 weeks post-burn injury, although this was/was not statistically significant. A few mild elevations of GLN >930 μmol/L were observed in the GLN and control groups at weeks 3 (n = 1) and week 4 (n = 4). The highest level was 1026 μmol/L. These mild elevations of GLN were not associated with increased blood urea nitrogen or creatinine levels at time of sample collection. No elevated GLN levels were observed at admission or in first 2 weeks post-burn injury. No deaths were observed in any patient with an elevated GLN level. Further patients are currently being analyzed.

Conclusions: Burn injury is associated with significant GLN deficiency that can persist for ≥2 weeks without GLN treatment. Unlike in REDOXS, we observed no marked elevations of GLN level at admission or in the first 2 weeks post-burn injury. Late mild elevations of GLN levels were seen in both GLN and control groups. Furthermore, none of the deaths observed in this subgroup were associated with an elevated GLN level. We hypothesize that these elevations may be related to a number of factors, including the large total protein load that burn patients receive in feeding, the potential for massive weight loss in burn injury over time leading to need for GLN and protein redosing at weekly intervals, and reduced GLN/protein losses when burn wound is closed and/or as it is debrided and covered. We feel that these data indicate that the full 2700-patient RE-ENERGIZE trial can be initiated safely, with proper exclusions for renal and liver failure.

Financial support: Department of Defense / American Burn Association Clinical Trial Grant.