Tan Hannah B, Danilla Stefan, Murray Alexandra, Serra Ramón, El Dib Regina, Henderson Tom O W, Wasiak Jason
Victorian Adult Burns Service, The Alfred Hospital, Commercial Road, Prahran, Victoria, (2) Monash University, Melbourne, Australia.
Cochrane Database Syst Rev. 2014;2014(12):CD007174. doi: 10.1002/14651858.CD007174.pub2. Epub 2014 Dec 23.
With burn injuries involving a large total body surface area (TBSA), the body can enter a state of breakdown, resulting in a condition similar to that seen with severe lack of proper nutrition. In addition, destruction of the effective skin barrier leads to loss of normal body temperature regulation and increased risk of infection and fluid loss. Nutritional support is common in the management of severe burn injury, and the approach of altering immune system activity with specific nutrients is termed immunonutrition. Three potential targets have been identified for immunonutrition: mucosal barrier function, cellular defence and local or systemic inflammation. The nutrients most often used for immunonutrition are glutamine, arginine, branched-chain amino acids (BCAAs), omega-3 (n-3) fatty acids and nucleotides.
To assess the effects of a diet with added immunonutrients (glutamine, arginine, BCAAs, n-3 fatty acids (fish oil), combined immunonutrients or precursors to known immunonutrients) versus an isonitrogenous diet (a diet wherein the overall protein content is held constant, but individual constituents may be changed) on clinical outcomes in patients with severe burn injury.
The search was run on 12 August 2012. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), ISI WOS SCI-EXPANDED & CPCI-S and four other databases. We handsearched relevant journals and conference proceedings, screened reference lists and contacted pharmaceutical companies. We updated this search in October 2014, but the results of this updated search have not yet been incorporated.
Randomised controlled trials comparing the addition of immunonutrients to a standard nutritional regimen versus an isonitrogenated diet or another immunonutrient agent.
Two review authors were responsible for handsearching, reviewing electronic search results and identifying potentially eligible studies. Three review authors retrieved and reviewed independently full reports of these studies for inclusion. They resolved differences by discussion. Two review authors independently extracted and entered data from the included studies. A third review author checked these data. Two review authors independently assessed the risk of bias of each included study and resolved disagreements through discussion or consultation with the third and fourth review authors. Outcome measures of interest were mortality, hospital length of stay, rate of burn wound infection and rate of non-wound infection (bacteraemia, pneumonia and urinary tract infection).
We identified 16 trials involving 678 people that met the inclusion criteria. A total of 16 trials contributed data to the analysis. Of note, most studies failed to report on randomisation methods and intention-to-treat principles; therefore study results should be interpreted with caution. Glutamine was the most common immunonutrient and was given in seven of the 16 included studies. Use of glutamine compared with an isonitrogenous control led to a reduction in length of hospital stay (mean stay -5.65 days, 95% confidence interval (CI) -8.09 to -3.22) and reduced mortality (pooled risk ratio (RR) 0.25, 95% CI 0.08 to 0.78). However, because of the small sample size, it is likely that these results reflect a false-positive effect. No study findings suggest that glutamine has an effect on burn wound infection or on non-wound infection. All other agents investigated showed no evidence of an effect on mortality, length of stay or burn wound infection or non-wound infection rates.
AUTHORS' CONCLUSIONS: Although we found evidence of an effect of glutamine on mortality reduction, this finding should be taken with care. The number of study participants analysed in this systematic review was not sufficient to permit conclusions that recommend or refute the use of glutamine. Glutamine may be effective in reducing mortality, but larger studies are needed to determine the overall effects of glutamine and other immunonutrition agents.
当烧伤累及大面积总体表面积（TBSA）时，机体可进入分解代谢状态，导致出现类似于严重营养不良的状况。此外，有效的皮肤屏障遭到破坏会导致正常体温调节功能丧失，感染风险和液体丢失增加。营养支持在严重烧伤治疗中很常见，通过特定营养素改变免疫系统活性的方法被称为免疫营养。免疫营养已确定三个潜在靶点：黏膜屏障功能、细胞防御以及局部或全身炎症。免疫营养最常使用的营养素为谷氨酰胺、精氨酸、支链氨基酸（BCAAs）、ω-3（n-3）脂肪酸和核苷酸。
评估添加免疫营养素（谷氨酰胺、精氨酸、BCAAs、n-3脂肪酸（鱼油）、复合免疫营养素或已知免疫营养素前体）的饮食与等氮饮食（一种总蛋白质含量保持恒定但个别成分可能改变的饮食）对严重烧伤患者临床结局的影响。
检索于2012年8月12日进行。我们检索了Cochrane损伤组专业注册库、Cochrane图书馆、MEDLINE（OvidSP）、Embase（OvidSP）、ISI WOS SCI-EXPANDED & CPCI-S以及其他四个数据库。我们手工检索了相关期刊和会议论文集，筛选了参考文献列表并联系了制药公司。我们于2014年10月更新了此检索，但此次更新检索的结果尚未纳入。
比较在标准营养方案中添加免疫营养素与等氮饮食或另一种免疫营养剂的随机对照试验。
两名综述作者负责手工检索、审查电子检索结果并识别潜在符合条件的研究。三名综述作者检索并独立审查了这些研究的完整报告以确定是否纳入。他们通过讨论解决分歧。两名综述作者独立从纳入研究中提取并录入数据。第三名综述作者检查了这些数据。两名综述作者独立评估每个纳入研究的偏倚风险，并通过讨论或与第三和第四综述作者协商解决分歧。感兴趣的结局指标为死亡率、住院时间、烧伤创面感染率和非创面感染率（菌血症、肺炎和尿路感染）。
我们识别出16项涉及678人的试验符合纳入标准。共有16项试验为分析提供了数据。值得注意的是，大多数研究未报告随机化方法和意向性分析原则；因此，对研究结果的解释应谨慎。谷氨酰胺是最常用的免疫营养素，在16项纳入研究中有7项使用了谷氨酰胺。与等氮对照相比，使用谷氨酰胺可使住院时间缩短（平均缩短 -5.65天，95%置信区间（CI） -8.09至 -3.22）并降低死亡率（合并风险比（RR）0.25，95%CI 0.08至0.78）。然而，由于样本量小，这些结果可能反映了假阳性效应。没有研究结果表明谷氨酰胺对烧伤创面感染或非创面感染有影响。所研究的所有其他制剂均未显示对死亡率、住院时间、烧伤创面感染或非创面感染率有影响的证据。
尽管我们发现了谷氨酰胺对降低死亡率有影响的证据，但对此发现应谨慎对待。本系统综述中分析的研究参与者数量不足以得出推荐或反驳使用谷氨酰胺的结论。谷氨酰胺可能有效降低死亡率，但需要更大规模的研究来确定谷氨酰胺和其他免疫营养剂的总体效果。
