Effect Of Early Continuous Enteral Nutrition And Selective Decontamination Of The Digestive Tract By Using "Hu-chang He Ji" In Patients With Severe Acute Pancreatitis

PART IA Pilot Study for the Clinical Evaluation of Gut Barrier DysfunctionAbstractObjective To investigate the potential influencing factors which possibly affect the gut barrier function. To establish a clinical evaluation system of diagnosing gut barrier dysfunction.Methods Fifty three patients who were undergone critical ill with an APACHE II score of 8 or more were recruited randomly from ICU, 27 patients which APACHE II score was 6 or less than were also recruited. Clinical features, symptoms and signs of these 80 cases were recorded. Endotoxin, tumor necrosis factor - α , diamine oxidase, D-lactic acid and high-sensitive C reactive protein of plasma sample were measured. Urinary lactulose/mannitol ratios, the urinary concentration and content of intestinal fatty acid binding protein were examined as well. Multivariate logistic regression analysis was performed to screen the factors related to gut barrier dysfunction intimately. The optimal operating point and doubtable interval were determined by receiver operating characteristic curve ( ROC curve) .Results In the logistic regression models, urinary lactulose/mannitol ratios, the urinary content of intestinal fatty acid binding proteinof 24 hours (IFABP-t) and the exposure of endotoxin of plasma were identified as the most intimately factors which could affect gut barrier function. These three factors were evaluate by receiver operating characteristic curve. The optimal operating point of plasma endotoxin, L/M and IFABP-t were 0.145, 17ng and 55.34Eu/ml respectively, the sensitivity and specificity were 84.5% vs 88%, 78 % vs 88%, 78% vs 78%. The doubtable value interval of urinary ratio of lactulose and mannitol was determined as 0.178 to 0.082.Conclusion Gut barrier dysfunction could be suspected when critical ill patients have the symptoms and signs of digestive system, and the proofs of increasing intestinal permeability (L/M>1.78, or gut hypoperfusion (IFABP-t >17ng), or higher exposure of endotoxin(> 55.34Eu/ml) in plasma.PART IIEffect of Early Continuous Enteral Nutrition and SelectiveDecontamination of the Digestive Tract by Using "Hu-chang he ji" inPatients With Severe Acute Pancreatitis—A Multicenter ProspectiveRandomized Controlled TrialAbstractObjective A prospective randomized controlled trial was conducted to determine the effect of early continuous enteral nutrition and selective decontamination of the digestive tract by using "Hu-chang he ji" in patients with severe acute pancreatitis (SAP). Gut barrier function, systemic inflammatory response, immune status, nitrogen balance and amino acids in plasma were investigated after nasojejunal feeding or total parenteral nutrition with SAP patients.Methods Sixty three patients with acute pancreatitis were enrolled and randomized into early enteral nutrition (EEN) group (29 cases) and total parenteral nutrition (TPN) group(34 cases). EEN or TPN were initiated when homeostasis were achieved within 72 hours after attack. Both group received isocaloric isonitrogenous nutrition. The nasojejunal feeding tubes were placed distal to the ligament of Treitz by endoscopic or fluoroscopic techniques. Pepti-2000 variant, combined with glutamine, arginine and "Hu-chang he ji" were administered into jejunum of SAP patients of EEN group, TPN were administered through a central vein. APACHE-II score were recorded every week, abdominal computerized tomography were performed at admission day, day 7, 14, 28, 42. Measurement of serum amylase, albumin, prealbumin, transferrin, plasma diamine oxidase (DAO), endotoxin, C-reactive protein (CRP), tumor necrosis factor- α (TNF- α ), interleukin-1 β (IL-1 β ) concentrations were performed at day 1, 7, 14, 21 of EEN or TPN support. Urinary excretion of lactulose (L) and mannitol (M) and plasma amino acids were measured by pulsed electrochemical detection (HPLC-PED) at day 1, 7, 14, 21 as well. The total DNA of microbial communities in fecal samples was amplified by ERIC (enterobacterial repetitive intergenic consensus) primers to generate community fingerprint. The percentage of CD₃⁺, CD₄⁺, CD₈⁺ cells were determined by flow cytometry, and CD₄⁺:CD₈⁺ ratios were calculated. IgA,IgG,IgM,C3, C4 were measured by immunochemical assay. Nitrogen balance, body weightand body mass index (BMI) were determined at day 1, 7, 14, 21. Complications, length and cost of hospitalization were recorded as well.Results 1. Both EEN and TPN were toleranced well. The APACHE II score decreased in both group, at day 7, it decreased significantly in EEN group(6.00± 1.60 vs. 7.08 ± 2.34) compared with TPN group(P<0.05), CTSI (computed tomography severity index) and serum amylase were no difference in two group. Plasma DAO, endotoxin, urinary L/M ratio, IFABP-t and IFABP-c were decreased at day 7, and became lower after that. There were significantly difference between EEN and TPN group of these 4 parameters (P<0.05). ERIC-PCR showed that EEN maintained the composition of flora fecal while TPN had a negative effect on it. The length of stay and cost also decreased significantly in EEN group, the average cost were RMB 25, 900±14, 200 and 46, 800±4,030.The mean length of hospitalization was 20±5.7 and 34.5 + 12.94 days.2. There were no differences between EEN and TPN group with the concentration of IgA, IgG, IgM, C3 and C4. The percentage of CD₄⁺cell and CD₄⁺/CD₈⁺ ratio were increased in EEN group which significantly higher than that of TPN group in day 7. Prealbumin was higher in EEN group at 14 and 21day. Infectious complications developed in 9/34 (26.47%) of TPN group and 1/29 (3.44%) of EEN group (P<0.05). TNF- α and IL-1β were no differences between two group. CRP of EEN was lower than that of TPN in dayl4 and 21.3. Both group achieved the positive nitrogen balance at day 14, BMI of EEN at day 21 was higher than that of TPN (P<0.05). Nineteen amino acids altered after the onset of SAP, both the total amino acids and BCAA/AAA (branched-chain amino acid/aromatic amino acid) level were lower in patients with SAP compared with health control group (P<0.05). The glutamine concentrations of TPN were decreased when compared with EEN group at day 1, 17, 21. Phe/Try were increase in both EEN and TPN group.Conclusion l.It was clearly established in this trial the safety and feasibility of early continuous enteral nutrition and "Hu-chang he ji" with severe acute pancreatitis. EEN improved gut barrier function by reducing the gut permeability, improved the hypoperfusion, maintaining the integrity and gut fecal flora. EEN initially decreased plasma endotoxin levels in SAP. 2. EEN improved immunological response and enhanced systemic immunity. EEN was associated with a significantly lower incidence of infections and a reduced length of hospital stay, but EEN had no effecton the inflammatory responses in early stage of SAP. 3. EEN and TPN reversed the negative nitrogen balance. In the early phase of SAP, amino acids concentration and BCAA/AAA were low in plasma; nutrition support might be helpful in maintaining the level of amino acids in plasma. Glutamine enriched enteral nutrition might maintaine the glutamine in plasma. EEN might shorten the course of hypermetablism in patients with SAP. Enteral nutrition should be the preferred route of nutritional support in patients with severe acute pancreatitis.