谷氨酰胺增强型肠内营养对危重病患者临床结局的影响:随机对照试验的系统评价

目的 系统评价谷氨酰胺(Gln)增强型肠内营养治疗对危重病患者预后及治疗费用的影响.方法 检索8个生物医学数据库(<中国生物医学文献数据库>、、<科学引文索引数据库>等)1976年以后的文献资料.鉴定随机对照试验(RCT),纳人研究的标准包括:(1)采用随机对照的临床研究,设立平行对照;(2)危重病患者,急性生理与慢性健康评估评分Ⅱ大于10分或烧伤面积大于30%TBSA者;(3)以肠内营养中是否添加Gln作为研究组与对照组的惟一差别;(4)临床结局指标包括患者死亡、院内感染、器官功能衰竭发生情况、住院日及费用.研究方法学质量按照Cochrane系统评价员手册及Jadad评分量表进行评定.用Rev Man 5.0软件进行Meta分析.结果 224篇相关文献中,共7项RCT符合全部纳入标准.死亡情况:共5项研究报告了545例患者中的死亡例数,研究间无异质性(P=0.46),合并相对危险度(RR)为0.94,95%置信区间(CI)为0.68～1.30,P=0.70.Gln组死亡风险与对照组比较,差异无统计学意义(P>0.05).院内感染:共3项研究报告了489例患者中的院内感染发生情况.研究间无异质性(P=0.08),采用固定效应模型,合并RR=0.72,95%CI为0.52～0.99,P=0.04.与对照组比较,Gln组院内感染率下降了28%.器官功能衰竭:共3项研究报告了460例患者中发生器官功能衰竭或MODS的情况,研究间无异质性(P=0.65),采用固定效应模型,合并RR=1.27,95%CI为0.70～2.30,P=0.43.Gln组与对照组比较,差异无统计学意义(P>0.05).住院时间:4项研究报告了患者入住重症监护病房(ICU)的时间,其中3项研究以中位数(四分位间距)形式表示结果,2组患者比较差异无统计学意义(P>0.05);另1项研究给出了2组患者入住ICU时间的x±s,差异亦无统计学意义(P>0.05).此外,有3项关于重症烧伤患者的研究给出了住院时间,研究间无异质性(P=0.08),采用固定效应模型,合并均数差值为-7.24,95%CI为-13.28～-1.19,P=0.02.与对照组比较,Gln组住院时间约缩短7.24 d.结论 Gln增强型肠内营养用于危重病患者,可以降低院内感染的发生率,有可能缩短重症烧伤患者住院时间,但病死率及经济学指标尚需进行更多大样本研究进一步验证.

The impact of glutamine-enhanced enteral nutrition on clinical outcome of patients with critical illness: a systematic review of randomized controlled trials

Objective To systematically evaluate the influence of glutamine-enhanced enteral nutri-tion on clinical prognosis and treatment cost of patients with critical illness. Methods Randomized con-trolled trials (RCTs) since 1976 were searched in 8 biomedical databases, such as MEDLINE, EMBASE, SCI, Cochran Library, and Chinese Biomedicine Database. Bibliography of retrieved papers and personal files were searched as well. RCTs were evaluated with inclusion criteria: (1) RCTs were enrolled, parallel control was set up; (2) Patients with critical illness, with their acute physiology and chronic health evalua-tion score over 10, or with total burn surface area over 30% TBSA ; (3) The only difference between experi-mental and control groups was the addition of glutamine in enteral nutrition; (4) Clinical outcome index in-cluded mortality, nosocomial infection rate, length of hospital stay, organ dysfunction rate, and treatment cost. Methodological quality of the study was assessed based on Cochrane Reviewers' Handbook and Jadad's Score Scale. Statistical software RevMan 5.0 was used for Meta-analysis. Results Among 224 related ar-ticles, 7 RCTs met all inclusion criteria. Mortality: death events among 545 patients were reported in 5 RCTs. There was no heterogeneity among the 5 RCTs (P = 0.46) , relative risk (RR) = 0.94, 95% confi-dence interval (CI) 0.68-1.30, P = 0.70. No statistical difference was found between glutamine group and control group in respect of death risk (P > 0.05). Nosocomial infection rate : nosocomial infection events a-mong 489 patients were reported in 3 RCTs. No heterogeneity was found among the 3 RCTs (P = 0. 08). Fixed-effect model was applied. RR =0.72, 95% CI 0.52-0.99, P =0.04. Nosocomial infection rate of glutamine group was 28% lower than that of control group. Organ dysfunction rate: organ dysfunction events among 460 patients were reported in 3 RCTs. No heterogeneity was found among the 3 RCTs (P = 0. 65). Fixed-effect model was applied. RR = 1.27, 95% CI 0.70-2.30, P = 0.43. No statistical difference was found between glutamine group and control group in respect of organ dysfunction rate (P > 0.05). Length of hospital stay:length of intensive care unit (ICU) stay of patients were reported in 4 RCTs, but 3 of them re-ported by median (interquartile ranges) and thus made Meta-analysis unavailable. No statistical difference was found between glutamine group and control group in respect of length of ICU stay. The other RCT repor-ted length of ICU stay by mean standard deviation and showed no statistical difference between glutamine group and control group. Length of hospital stay was reported in 3 RCTs with severely burned patients. No heterogeneity was found among the 3 RCTs (P = 0. 08). Fixed-effect model (Inverse Variance method) was applied, and it was shown that length of hospital stay of patients in glutamine group was 7.24 days fewer than that of control group by a mean difference of -7.24, 95%CI - 13.28 to - 1.19, P =0.02. Conclusions Administration of Glutamine-enhaneed enteral nutrition in patients with critical illness may reduce nosocomial infection rate, and shorten length of hospital stay. Studies with a large sample are needed to verify the efficien-cy of glutamine-enhanced enteral nutrition on lowering mortality of patients with critical illness and its cost-ef-fectiveness.