Study On Treatment Timing Of Early Enteral Nutrition For Severe Acute Pancreatitis

Objective:Enteral nutrition (enteral nutrition, EN) support is one of important treatment means for severe acute pancreatitis, but the timing of enteral nutrition therapy is still controversial, the implementation of this study is to explore the perfect timing of early enteral nutrition. By animal experiments of early enteral nutrition at different time points, to investigate therapeutic action and the effects of early enteral nutrition on the intestinal mucosal barrier in the rats with severe acute pancreatitis. Through clinical research, to investigate therapeutic action of early enteral nutrition at different time points on the patients with severe acute pancreatitis.Methods:1.Experiment Study: 128 healthy male Sprague-Dawley rats (180-200g) were randomly allocated into four groups (n=24 for each group):sham operation group(S group);total parenteral nutrition group(TPN group);enteral nutrition 12h after operation (EEN group);enteral nutrition 24h after operation(EN group). In addition, the mortality of 8 rats in each group were observed .The model of SAP was induced by injection of lml of 3.8%sodium taurocholate beneath the pancreatic capsule.EEN group after operation 12h, EN group after operation 24h were intermittent pushed EN preparation in jejunum (injection 5ml per 1.5h, every 10min), gradually increased the total amount of 50ml up to 24h and maintained; TPN group after operation 8h were injected parenteral nutrition into external jugular vein by uniform micro-infusion pump in 24h, the speed was gradually increased from lml ? h-1 to 0.05L?d-1 and maintained.Rats were killed by abdominal aorta exsanguination at 24h,96h and 168h after nutrition support.The levels of serum amylase were measured,and part of the blood specimens(3~4ml) for diamine oxidase(diamine oxidase,DAO),D-lactate assay were restored at-80℃.Pancreatic and ileum tissues were fixed in 4%formalin to observe the pathological changes of pancreatic tissue and for pathological score,ileal mucosal morphology organizations changes in the light microscope after paraffin embedded sections,HE staining;expression of ileum mucosal tight junction occludin protein was examinated by immunohistochemistry.2.Clinical research:60 Patients with acute pancreatitis admitted between January 2008 and December 2009 to the Department of Gastroenterology, First Affiliated Hospital of Nanchang University were enrolled in the prospective study and were divided into: early enteral nutrition 1 group(EEN1 group) (enteral nutrition within2~ 4 days of the course of SAP,average 3.17±0.79d) 30 cases, and enteral nutrition 2 group (EEN2 group) 30 cases (enteral nutrition within 5~10 days of the course of SAP,average 7.85±1.53d). All patients were given custody, absolute diet, fluid infusion, acid suppression, anti-infection, somatostatin and other conventional basic therapy after admission.Each group were placed nasogastric tube after the resumption of intestinal function, and were given nasogastric infusion with Peptison after intestinal adaptation,the other lack nutrients were added through phleboclysis. At the beginning of nutritional support, the non-protein calories of (72.6±8.5)x103J·kg-1·d-1 was given, gradually increased to (116.7±19.3)x103J·kg-1·d-1 that the ratio of glucose and fat was from 1 to 2:1, the ratio of energy and nitrogen was (492.3±86.4)x103J:1g,adding the right amount of vitamins and trace elements.Observed APACHEⅡscore on the 2th d and 10th d,and complications, mortality, length of stay, hospital costs and changes of blood biochemical (serum amylase, C-reactive protein, D-lactate, diamine oxidase) in each group at the time of admission and on the 10th d after the course of SAP.Compared the differences between them.RESULTS:1.Experiment Study:(1).Serum amylase changes:At each time point, EEN, EN group and the TPN group compared between the groups, no statistical significance (P>0.05), but each group were significantly higher than S group (P <0.01).(2).Plasma D-lactic acid changes:S group, low levels of plasma D-lactate in the different time points after modeling was no significant change, and at each time point was significantly lower than TPN, EN, EEN group, there were significant differences statistically significant (P <0.01); the levels of plasma D-lactate of other groups were increased, on the 96h, 168h , the levels of plasma D-lactate of the EEN group was significantly lower than the TPN group, the difference was significant statistically (p <0.01); on the 96h and 168h, the EN group also are lower than the TPN group, the difference was statistically significant(P<0.05~0.01), the levels of plasma D-lactate of the EEN group were lower than those of the EN group (P <0.05) on the168h.(3).Changes of serum DAO levels:On the 96h and 168h,the levels of serum DAO were increased, the TPN group, EN group than the S group, the difference was statistically significant (P<0.05~0.01), and the EEN group was no significant difference (P>0.05). Relative to the TPN group, levels of serum DAO of EEN group and EN group after treatment decreased, the difference was statistically significant (P<0.05~0.01) . Compared with the EN group, levels of serum DAO of EEN group were lower than the EN on the 96h and 168h,the difference was statistically significant (P <0.05).(4). Mortality rate of four groups rats during 168h:the mortality rate of 4 groups rats was no significant difference (P> 0.05),it showed that early enteral nutrition is security.(5). Pancreatic histological score:The pancreatic histological score of TPN, EN, EEN group were significantly higher than the S group at each time point(P <0.01), and increased to the highest score on the 96h after modeling. The pancreatic histological score of EEN group on the 96h ,168h and EN group on the 168h were lower than TPN group at the corresponding time point(P <0.05 ~ 0.01). The score of EEN group lower than the EN groups on the 168h.(P <0.05).(6).Ileal morphological changes:On the 168h,the mucosa thickness,villus height of EEN group were significantly higher than that of TPN group(P<0.01);higher than that of EN group too(P<0.05).(7).Variations of average gray level of intestinal occludin protein content:Expression of occludin protein of epithelial cells of TPN,EN,EEN groups were significantly lower than that of the S group(P<0.01),with the exception of EEN 168h group;It showed that expression of occludin protein generally decreased in SAP;On the 96h and 168h,the average gray level of TPN group was higher than that of the EEN , EN group , the difference was statistically significant (P <0.05 ~ 0.01) .Compared with TPN group,the average gray level of EEN group was lower on the 168h, the difference was statistically significant (P<0.05) it showed occludin protein expression of EEN group was higher than that of EN group.2.Clinical research:(1).Changs of serum amylase and C-reactive protein among patients with SAP:the serum amylase and C-reactive protein of EEN1 and EEN2 group had decreased after treatment, Compared with the EEN2 group, EEN1 group were statistical difference (P <0.05) on the 10th d.(2).Changes of Serum D-lactate,and diamine oxidase of patients with SAP:The levels of serum D-lactate and diamine oxidase of EEN1 and EEN2 group were decreased after treatment, the difference was statistically significant(P<0.05~0.01). Paralleled with the EEN2 group,the levels of serum D-lactate and diamine oxidase of EEN1 group have statistical decreased (P <0.05) on the 10th d. The 10th d compared with the time of admission, the levels of serum D-lactate and diamine oxidase of EEN1 and EEN2 group had decreased,the difference was statistical significance (P<0.05).(3).Comparison of APACHE-Ⅱs core of patients with SAP:On the10th d, EEN1 group compared with EEN2 group, the APACHE-Ⅱscore had decreased more significantly on the 10th d, the difference was statistical significance(P<0.05~0.01).(4).Comparison of complication rate, mortality, hospital stay and hospital costs of patients with SAP:EEN1 group paralleled with EEN2 group, hospital stay, hospital costs were reduced significantly, the difference was statistical significance (P<0.05). The complication rate and mortality among 2 groups was not statistically different (P> 0.05).Conclusions:(1) EEN can reduce the damage of pancreas in rats with SAP.(2) EEN can protect the intestinal mucosal barrier of rats with SAP, reduce the levels of D-lactate, DAO in blood.(3) EEN can shorten the hospital stay and reduce hospital costs of patients with SAP.(4) The 4th d when EEN is safe and effective treatmen in the course of SAP is better time.