| As a systemic inflammatory response syndrome caused by infection. Sepsis is the most common cause of septic shock and multiple organ dysfunction (MODS), which is also characteristiced by high prevalence, high mortality, high cost of treatment. The intestinal barrier consists of a mechanical barrier, a biological barrier, a chemical barrier as well as a immunologic barrier. The mechanical barrier is specifically composed by integrated epithelial cells and tight junctions, the epithelial basement membrane, lamina propria of submucosal and thick mucus barrier covering the epithelial surface; the biological barrier composed by the intestinal permanent flora in an interdependent as well as mutual restraint way to form a micro-ecological environment; the chemical barrier constituted by gastrointestinal secretion of gastric acid, bile, digestive enzymes, lysozyme, mucopolysaccharides, protein decomposition enzymes with certain bactericidal effect; and the immune barrier formed by a variety of immune cells within the intestinal mucosa and submucosa and secretory IgA produced by intestinal lymphoid tissue and distributed to the surface of the mucous membranes. Intestinal tract is one of the most vulnerable organs to the damage during sepsis, as intestinal ischemia, hypoxia, reperfusion injury, the release of inflammatory mediators and other mechanisms contribute to intestinal barrier dysfunction, intestinal bacteria and toxins translocation, thus further aggravate sepsis, leading to severe sepsis, and eventually the occurrence of MODS. Therefore, the intestinal mucosal barrier is not only the victim of the occurrence and development of sepsis, but also triggers and aggravates sepsis. Considering their ages, low immunity, and a variety of underlying diseases, the elderly are easy to co-infect and develop into sepsis, severe sepsis, multiple organ dysfunction syndrome, which is also the main cause of death among elderly patients in critical condition. Elderly patients with sepsis are not only with intestinal anatomy structure subject to ischemic, but also the elderly gut is degradation and easily damaged, furthermore, the intestinal barrier as one of the primary target organs of sepsis hit, so the elderly patients with sepsis are more often complicated with intestinal barrier dysfunction. However,from bench to bed, there are only few studies on intestinal barrier dysfunction in elderly patients at present.Laboratory detection of intestinal barrier function is mainly concentrated on the examination of the intestinal permeability, the intestinal mucosal injury, intestinal ischemia index, and pathological examination. Studies have shown that intestinal fatty acid binding protein (IFABP), diamine oxidase (DAO) and D-lactate are ideal diagnostic indicators. IFABP is a small (14～15kDa) cytosolic, water-soluble protein, which is in particular highly expressed in the mature small intestinal epithelial cells and constitutes up to2%～3%of the cytoplasmic protein content of the mature enterocyte. And its activity was stable at room temperature. DAO as intracellular oxidase is highly active in the intestinal villus epithelial cells, with the highest content and the strongest activity in villous epithelial cells of the jejunum, ileum, while both the content and activity are low in other organizations. In circumstances of intestinal mucosal ischemia, hypoxia, and injury, intestinal epithelial structural protein IFABP and intracellular oxidase DAO release into the blood. D-lactate is mainly derived from glycolysis of gastrointestinal tract bacteria, while under normal circumstances are rarely absorbed, and not yet confirmed that the human body posses enzyme systems to rapidly degradate it. When intestinal epithelial damaged and cell permeability increased, D-lactate goes into the blood circulation through damaged intestinal mucosa. Thus the detection of plasma levels of IFABP, DAO, D-lactate can be used to reflect the intestinal mucosa injury and permeability, respectively. Elderly patients with sepsis are more often complicated with intestinal barrier dysfunction, but the changes of intestinal barrier function have not been reported in elderly patients with sepsis.In recent years, anti-infection treatment and organ support technology on sepsis have made great strides, but the mortality of sepsis remains high. To seek treatment aimed at the etiology and the pathophysiological characteristics of sepsis is always been the current research focus. With the continuous improvement and perfection of continuous blood purification (CBP) technology, it plays a role which traditional medicine can not be matched in the treatment of serious infections in critically ill patients. CBP can not only remove inflammatory mediators, but also improve hemodynamics, which contribute to stabilize the homeostasis of the body and rebuild the immune steady state. High volume hemofiltration (HVHF) is a blood purification technology developed by standard continuous renal replacement therapy (CRRT), with the current definition that the replacement dose of more than35ml/(kg·h), even as high as75to120ml/(kg·h). The most important theory of application of HVHF is based on that both inflammatory mediators and cytokines play an important role in the pathophysiological process of critically ill patients, especially in sepsis patients; through blood purification techniques such as convection and adsorption to clear these pathogenic substances may be beneficial mitigation of patients with acute state, which help to create conditions and gain time for the clinical effective treatment. Compared with traditional CRRT, it is better able to remove soluble inflammatory mediators, down-regulate the inflammatory response, thus significantly improve the hemodynamic status and tissue perfusion, reduce the amount of positive inotropic drugs and effectively reduce mortality. In recent years, our clinical observations have shown that HVHF exserted significant efficacy in the elderly sepsis, septic shock, multiple organ dysfunction syndrome. However, its effect on intestinal barrier function remains to be further studied. This study designed to observe the changes of the intestinal barrier function in elderly patients with sepsis and the effect of HVHF with aim to provide clinical guidance for the prognosis and effective treatment of intestinal barrier dysfunction.In our study,73cases of elderly patients with sepsis consecutively admitted to our MICU from March2010to March2011, are divided into sepsis group (n=19), severe sepsis group (n=54) according to whether complicated with tissue hypoperfusion or organ dysfunction, and also divided into the survival group (n=45), the non-survival group (n=28) based on the survival condition by day28. And according to whether high volume hemofiltration performed, the patients with severe sepsis were further devided into the conventional therapy group (n=31) and hemofiltration group (n=23). The establishment of control group (n=31) are those health examined elderly. Peripheral blood of sepsis patients were routinely collected at days0,2,3,7after admission, using enzymatic spectrophotometer method, enzymatic, enzyme-linked immunosorbent assay to detect the levels of IFABP, DAO and D-lactate, respectively. And we also record the patients’APACHEII score, days of mechanical ventilation, length of stay in ICU, and each organ function parameters at the same time.The main results were as follows:1. The changes of plasma IFABP, DAO, D-lactate values in elderly patients with sepsis in control group, sepsis group and severe sepsis group. The plasma values of IFABP, DAO, D-lactate in control group (n=31) were (954.55±210.55) pg/ml. (3.96±1.21) mg/ml and (0.100±0.039) mmol/L, respectively. In sepsis group, at admission, and days2,3,7after admisson, the plasma values of IFABP were (2026.32±341.93) pg/ml,(1831.84±356.52) pg/ml,(1152.37±198.80) pg/ml,(1110.84±244.94) pg/ml, respectively; the plama values of DAO were (15.37±2.54) mg/ml (8.78±0.76) mg/ml (4.81±0.79mg/ml,(4.73±0.98) mg/ml, respectively; the plasma values of D-lactate were (0.251±0.026) mmol/L,(0.231±0.013mmol/L,(O.138±O.O3O) mmol/L,(0.112±0.031) mmol/L, respectively. In severe sepsis group, at admission, and days2,3,7after admisson, the plasma values of IFABP were (5419.24±567.94) pg/ml,(3788.98±693.37) pg/ml,(2776.07±645.92) pg/ml,(2072.98±1033.11) pg/ml, respectively; the plasma values of DAO were (20.97±2.19) m/ml,(13.95±4.37) mg/ml,(11.83±4.66) mg/ml,(9.45±4.81) mg/ml, respectively; the plasma values of D-lactate were (0.359±0.105) mmol/L,(0.256±0.084) mmol/L,(0.182±0.069) mmol/L,(0.171±0.071) mmol/L, respectively. Compared with the control group, the plasma levels of IFABP, DAO and D-lactate of both the sepsis group and the severe sepsis group, were significantly increased at the time of admission (P <0.05), with severe sepsis group higher than in sepsis group (P <0.001). Followed by plasma IFABP, DAO and D-lactate levels gradually decreased, the values of them in sepsis group returned to normal by day3, day3,day7respectively after admission (P>0.05), while the severe sepsis group were still significantly higher than control group (P <0.05).2. The changes of plasma IFABP, DAO, D-lactate values in elderly patients with sepsis in the survival group and nonsurvial sepsis group.In the survival group, at admission and days2,3,7after admisson, the plama values of IFABP were (3893.47±1685.18) pg/ml,(2808.73±995.74) pg/ml,(1994.33±896.04) pg/ml,(1440.64±77940) pg/ml, respectively; the plasm values of DAO were (18.30±3.43) mg/ml,(11.05±3.57) mg/ml,(7.98±4.34) mg/ml.(6.50±4.12) mg/ml, respectively; the plasma values of D-lactate were(0.301±0.090) mmol/L,(0.230±0.060) mmol/L,(0.152±0.054) mmol/L,(0.134±0.057) mmol/L, respectively. In the death group, at admission and days2,3,7after admisson, the plasma values of IFABP were (5667.35±475.66) pg/ml,(4171.06±608.00) pg/ml,(3030.65±542.23) pg/ml,(2671.47±890.39) pg/ml, respectively; the plasma values of DAO were (21.81±1.94) mg/ml,(15.87±4.48) mg/ml,(14.19±4.10) mg/ml,(11.20±3.23) mg/ml, respectively; the plasma values of D-lactate were (0.393±0.102) mmol/L,(0.297±0.075) mmol/L (0.212±0.066) mmol/L,(0.203±0.068) mmol/L, respectively. Compared with the control group, plasma levels of IFABP, DAO and D-lactate of both the survival group and the death group at admission was significantly increased (P<0.05), and the death group was higher than the survival group (P<0.001), followed by the plasma levels of IFABP, DAO and D-lactate gradually decreased.3. There are strong relationships between plasma values of IFABP and DAO and D-lactate, plasma values of DAO and D-lactate (at admission and days2,3,7after admisson for IFABP and DAO, r=0.890, r=0.853, r=0.878, respectively, P=0.000; for IFABP and D-lactate:r=0.714,r=0.638,r=0.702,r=0.813, respectively, P=0.000; for DAO and D-lactate:r=0.832, r=0.918, r=0.925, r=0.880, respectively, P=0.000). The levels of IFABP, DAO and D-lactic acid at admission and APACHEII score, duration of mechanical ventilation were positively correlated (for IFABP and APACHEII score:r=0.569, P=0.000; for DAO and APACHEII score:r=0.712, P=0.000; for D-lactate and APACHEII score:r=0.730,P=0.001; for IFABP and number of days on the ventilator:r=0.360, P=0.003; for DAO and number of days on the ventilator:r=0.345, P=0.003; for D-lactic acid and the duration of mechanical ventilation:r=0.351, P=0.002).4. HVHF has effects on intestinal barrier function in eldly patients with sepsis: In conventional treatment group(n=31), treated according to international guidelines for management of severe sepsis, the plasma values of IFABP at admission and days2.3,7after admisson were (5505.67±571.96) pg/ml,(4070.62±669.05) pg/ml,(2960.10±579.86) pg/ml,(2515.95±1004.08) pg/ml, respectively; the plasm values of DAO were (21.31±2.16) mg/ml,(15.99±4.21) mg/ml,(14.12±4.10) mg/ml,(11.47±4.15mg/ml, respectively; the plasma values of D-lactate were (0.372±0.107) mmol/L,(0.294±0.076) mmol/L,(0.212±0.064) mmol/L.(0.207±0.063) mmol/L, respectively.(2) In the hemofiltration group (n=23), treated according to international guidelines for management of severe sepsis and received HVHF, the plasma values of IFABP at admission and days2,3,7after admisson were (5337.82±564.93) pg/ml,(3500.59±607.44) pg/ml,(2600.41+669.33) pg/ml,(1650.14±889.33) pg/ml, respectively: the plasma values of DAO were(20.65±2.22) mg/ml,(12.01±3.63) mg/ml.(9.65±4.16) mg/ml,(7.53±4.69) mg/ml, respectively; the plasma values of D-lactate were (0.347±0.104) mmol/L.(0.220±0.076) mmol/L,(0.152±0.062) mmol/L,(0.136±0.062) mmol/L, respectively. There was no difference between the two groups before treatment. However, compared writh the conventional treatment group, the plasm levels of IFABP, DAO and D-lactate of hemofiltration group after treatment were significantly decreased except for IFABP at day3(P<0.05). And the28-day mortality was significantly reduced in the hemofiltration group than the conventional treatment group (71%vs26.1%,.P=0.001).The conclusions are as follows: Firstly, elderly patients with sepsis have intestinal barrier dysfunction at early stage, and the severity of intestinal barrier dysfunction and sepsis are positively correlated. Secondly, intestinal barrier dysfunction was closely related to the clinical outcome in elderly patients with sepsis. Thirdly, high volume hemofiltration can help to recovery of intestinal barrier dysfunction, reduce the mortality, and improve clinical outcome in elderly patients with sepsis. |
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