持续早期肠内营养联合肠黏膜保护对重症急性胰腺炎肠屏障功能影响的多中心随机对照临床试验

Effect of early continuous enteral nutrition combined with interstinal mucosal protective agents on gut barrier in patients with severe acute pancreatitis： A multicenter prospective randomized controlled trial

目的观察持续早期肠内营养（EEN）联合肠黏膜保护对重症急性胰腺炎（SAP）患者肠屏障功能的影响。方法选取2004年5月至2006年6月四个中心SAP患者79例，分为EEN联合肠黏膜保护组（联合组，39例）和完全肠外营养（TPN）组（40例）。在发病后72h内分别给予等氮源、等热量EEN和TPN。联合组给予肠内营养多聚合剂、精氨酸、谷氨酰胺和肠黏膜保护药物；TPN组采用中心静脉或外周静脉输注。入选后第l、7、14、21天行急性生理学及慢性健康状况（APACHE-Ⅱ）评分并检测血淀粉酶、二胺氧化酶（DAO）、内毒素、尿液肠脂肪酸结合蛋白浓度（IFABP-c）、肠脂肪酸结合蛋白含量（IFABPt）、乳果糖与甘露醇（L／M）比值和肠道菌群变化，并观察并发症和住院时间、费用。结果两组患者均无死亡。两组APAcHPⅡ评分随住院天数增加均呈递减趋势，联合组第7天APAcHE一Ⅱ评分为6．00±1．60，低于TPN组（7．08±2．34，P〈0．05）。第7，14，2l天联合组血内毒素分别为（39．30±l5．82）、（22．64±14．31）、（14．8l±10．93）Eu／L，L／M比值分别为0．28±0．25、0．2l±0．18和0．08±0．04，IFABP-c分别为（15．62±5．26）、（5．46±1．18）和（3．26±0．94）pg／ml，均明显低于TPN组（P值均d0．05）。联合组肠道菌群结构无明显变化，而TPN组出现肠道菌群结构变化。TPN组感染率（包括胰腺感染、腹腔感染和泌尿道、呼吸道感染）高于联合组（26．47％比3．44％，P〈O．01）。联合组住院费用为（25900±14200）元，平均住院天数为（20．0±5．7）d，均低于TPN组[（46800±4030）元和（34．5±19．9）d，P值均〈0.05）]。结论EEN联合肠黏膜保护可降低SAP患者肠道通透性，改善肠道灌注，保持肠道菌群，减少内毒素易位，对肠屏障功能有保护作用，且缩短病程、节约住院费用。

Objective To assess the effect of continuous early enteral nutrition （EEN） combined with intestinal mucosal protective agents on gut barrier function in patients with severe acute pancreatitis. Methods A total of 79 patients with severe acute pancreatitis selected from four centers between May 2004 to June 2006 were enrolled and divided into EEN combined with intestinal mucosal protective agents group （combined group,n：39） and total parenteral nutrition （TPN） group （n：40）. The patients were received either EEN or TPN when homeostasis were achieved within 72 hours after onset. The patients in combined group were administered pepti-2000 variant combined with glutamine, arginine and intestinal mucosal protective agents. The patients in TPN group were administered through a central vein.APACHE- II score was recorded every week; The concentration of serum amylase, plasmic diamine oxidase （DAO） and endotoxin were mesured on day 1, 7, 14 and 21 as well as urinary excretion of lactulose （L） and mannitol （M）. Complications, lenth and charges of hospital stay were recorded. Results There was no death in both groups. The APACHE- 11 score decreased on day 7, but lower in combined group （6.00＋1.60） than that inTPNgroup （7.08±2.34）（P〈0.05）. Onday 7, 14 and 21, the concentrations of endotoxin in combined group was（ 39.30 ± 15.82）, （ 22.64 ± 14. 31 ）, （ 14.81 ± 10.93 ） Eu/L, respectively, urinary L/M ratio was 0. 28±0.25,0. 21±0. 18 and 0.08±0.04, respectively, IFABP-c was 15.62±5.26）,（5.46±1. 18）and （3.26±0.94） pg/ml, respectively. All of these parameters were significantly lower than those in TPN group （P 〈 0. 05）. The infectious rates including pancreatic, peritoneal and respiratory infection in TPN group were much higher than that in combined group（26.47 vs 3.44% ,P〈0.01）. The composition of flora fecal remained unchange in combined group rather than TPN group. The mean hospital stay was shorter in combined group [（20.0±5. 7） days] compared to TPN groups [（34.5±12.9） days]. The charges were also significantly lower in combined group, with average cost of RMB 25,900!14,200, while it was 46, 800d：4,030 in TPN group. Conclusions EEN combined with intestinal mucosal protective agents can improve gut barrier function via reducing the gut permeability, improving the hypoperfusion, maintaining the integrity and gut fecal flora. It might reduce the course and charges of hospital stay.