Effect Of Preoperative Selected Decontamination Of The Digestive Tract On Endotoxemia Induced By Cardiopulmonary Bypass

Objective: Endotoxemia (ETM) has been a noticeable and severe problem of clinical medicine, which triggers systemic inflammatory response syndrome and leads to multiple organ dysfunction syndrome, and has great impact on treatment effectiveness and clinical prognosis. The previous studies have proven that cardiopulmonary bypass (CPB) gives rise to the significant increase of plasma endotoxin. Literatures have reported some mechanisms of ETM occurring and treatment means, but have seldom explored the effect of selected decontamination of the digestive tract (SDD) on ETM induced by CPB. Very limited research only focused on single point, thus the results may not be believable. In this study, a randomized and controlled trial was employed to evaluate the effects of preoperative SDD on endotoxemia, the increase of proinflammatory cytokine and activation of complement system, and some biochemical and clinical markers in patients undergoing CPB from different angles, and to provide scientific evidences for prevention of ETM.Methods:1.Thirty adults were randomly subjected into control group and SDD group. The patients in control group underwent preoperative bowel preparation—diet preparation and enema. And those in SDD group were administrated Tobramycin 100mg, Garlicin 40mg and 20% Lactulose 10ml three times per day in addition to routinely preoperative bowel preparation.2.Feces samples were sterilely collected at point of pre-operation in control group and at points of pre-SDD and post-SDD in SDD group. Bacteria cultivation and identification and Gram staining of feces were used to evaluate species of intestinal flora and their ratios.3.Radial arterial blood in two groups was sampled at four points of anesthetic induction, end of CPB, 2 h after CPB, 24 h after CPB to estimate the concentration of plasma D-lactate. After centrifugation of samples in heparin tubes at 3000rpm for 15 min, the supernatant was stored at -70℃ for enzyme-linked ultraviolet spectrophotometry.4. Radial arterial blood in two groups was sampled at same four points to estimate theplasma endotoxin concentration. After centrifugation of samples in pyrogen-free heparin tubes at 4"C, 800rpm for 10 min, the supernatant was stored at -70 °C for chromogenic Limulus Amebocyte Lysate and quantitative photometric assay. Correlation analysis between D-lactate and endotoxin was performed.5. Radial arterial blood in two groups was sampled at same four points to estimate the concentrations of plasma TNF-a and C3. After centrifugation of samples in heparin tubes at 3000rpm for 15 min , the supernatant was stored at -70'C. Plasma TNF-a was detected by enzyme-linked immunoadsordent assay and C3 was measured by transmission turbidimetry. Correlation analysis between endotoxin and TNF-a > C3 was performed.6. Peripheral venous blood in two groups was sampled at two points of pre-operation and 24 hours of post-operation to estimate the markers of blood cell count and analysis(WBC> NEUI\ MO), liver zymogramC ALT> AST> GGT> ALP, CPK^ LDH), myocardial zymogram (HBDKL CK-MB) and renal function (UREA> CREA) . Clinical markers of two groups, such as ICU stay, duration of mechanical ventilation, hospital stay, etc, were recorded.Results:1. The major pre-operative and intra-operative parameters were comparable in the two groups (P>0.05) . And no death occurred.2. The species of intestinal bacteria in two groups were common and similar (P>0.05). However , aerobic Gram-negative bacilli (AGNB) ratio in post-SDD group decreased significantly compared with that in control group and pre-SDD group (PO.05 ) , especially the Escherichia Coli.3. The post-CPB plasma D-lactate concentration was significantly higher than that of pre-CPB in two groups (PO.05) , and the level at end of CPB was highest. Moreover, the concentration of plasma D-lactate in SDD group was significantly less than that in control group at two points of anesthetic induction and 2 h after CPB (PO.05) .4. The post-CPB plasma endotoxin concentration was strikingly higher than that of pre-CPB in two groups (PO.05) , and the level at end of CPB was highest. In addition, the endotoxin concentration in SDD group decreased significantly compared with that in control group at two points of end of CPB (PO.01) and 24 h after CPB(PO.05). There was significant positive correlation between D-lactate and endotoxin.5. The post-CPB plasma TNF- a and C3 concentrations were significantly higher than that of pre-CPB in two groups (P<0.05) , and the level at end of CPB was highest. But the concentrations of TNF- a and complement 3 in two groups were similar at four points(P>0.05). There were significant positive correlation between endotoxin and TNF- a , and significant negative correlation between endotoxin and C3.6. The post-CPB values of blood cell count and analysis, liver zymogram, myocardia zymogram and renal function in two groups increased significantly than that of pre-CPB(P<0.05) . But the values between two groups had no statistical differences (P>0.05) . Moreover, the recorded clinical markers also had no statistical differences (PX).O5) . Conclusion:1. CPB induces the increase of gut permeability and the raise of plasma endotoxin concentration, and causes elevation of proinflammatory cytokine and activation of complement system.2. The regimen of SDD effectively decontaminated part of AGNB that is the origin of endotoxin, thus diminished endotoxin pool.3. The regimen of SDD significantly decreased gut permeability and reduces plasma endotoxin concentration. And it can protect intestinal mucosa to some extent. Whereas it seems that it may not influence the concentrations of plasma TNF- a and C3 and the values of biochemical and clinical markers.