| Objective: Sever sepsis is the main cause of death in critically ill patients in ICU. The morbidity and mortality is 0.3% and 28%-50%,repectively. It has been recently demonstrated that plasma angiopoietin-2,Matrix metalloproteinases-9,and interleukin-18 levels were significantly elevated in severe septic patients. Angiopoietin-2 and interleukin-18 were associated with worse outcome in patients with severe sepsis, The higher the Ang-2 levels at the onset of severe sepsis, the worse the outcome of the patients. It has been reported that Ang-2 was superior to APACHEⅡscore in predicting the outcome of patients with sepsis. Publication have shown that through different mechanism,Ang-2 and MMP-9 impaired microvascular endothelial cells resulting in capillary permeability increase, especially on pulmonic capillaries, which contributed to poor oxygenation. Although existing controversy, continuous blood purification(CBP) has been currently refered to as an optional crucial therapeutic measure for sever septic patients. Theoretically,CBP maintains homeostasis and improves outcome of septic patients by removing the pro-inflammatory and anti-inflammatory mediators though ways of diffusion, convection and adsorption as well.In this study, Angiopoietin-2, matrix metalloproteinase-9, IL-18 levels in plasma and ultrafiltrate were measured by ELISA. We hypothesed that Ang-2, MMP-9 and IL-18 could be cleared during continuous veno-venous hemofiltration (CVVH) in patients with severe sepsis. We also aimed to: 1) investigate the effect of continuous blood purification on the treatment of severe sepsis and its mechanisms: 2) explore whether angiopoietin-2 or IL-18 could be biomarkers in predicting severity of disease and mortality in severe septic patients.Methods:Nineteen severe septic patients receiving CBP were recruited in this study. Changes of temperature (T), heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), C-reactive protein (CRP), alveolo-arterial oxygen partial pressure difference [(A-a)DO2], blood urea nitrogen (BUN), serum creatinine (SCr), buffuer excess (BE), PaO2, FiO2, blood routine, and electrolyte analysis were recorded at the time points of: pre-CBP (0hr), 4hr, 24hr and 48hr of CBP. Oxygenation Index (OI=PaO2/FiO2), acute physiology and chronic health evaluation (APACHEⅡ) and sepsis-related organ failure assessment (SOFA) scores were calculated within 48 hours after CBP. the outcome of 28 days was surveyed as well. Simutaneously, peripheral venous blood and ultrafiltrate (UF) sample were collected at the time points. Ang-2,MPP-9 and IL-18 levels in plasma and ultrafiltrate were measured by enzyme linked immunosorbent assay (ELISA). Oxygenation Index and alveolo-arterial oxygen partial pressure difference were used as indicators of pulmonary function.Statistical analysis was performed using SPSS13.0 software package. Data were shown as mean±SD; The relationship between Ang-2,MMP-9,IL-18,APACHEⅡ,and OI were analyzed by linear regression analysis. A statistical significance was assumed at a P-value<0.05.Results:1.The changes of Ang-2,MMP-9 and IL-18 levels in severe septic patients pre and post-continuous blood purification CBPCompaired with the value at T0, plasma Ang-2 concentrations were significant decreased at the following three time points (P<0.05); There were no significant differences among T0 and other three time points in MMP-9 and IL-18, but both MMP-9 and IL-18 levels were gradually decreased. Ang-2,MMP-9 and IL-18 are positively detected in ultrafiltrate.2.The course of Ang-2,MMP-9 and IL-18 levesl in survivors and non-survivors Ang-2,MMP-9 and IL-18 were significantly increased in nonsurvivors compared with survivors; the higher of Ang-2 and MMP-9 levels and the lower of oxygenation Index. However,there is no statistical difference.3.The correlation analysis of Ang-2,MMP-9,IL-18 and APACHE II,PaO2/FiO2 ratioAng-2 levels related positively to the APACHE II (r=0.545,P=0.016), Ang-2 levels and APACHEII gradually decreased in survivors. MMP-9 and IL-18 levels did not relate to APACHEII (P>0.05). Ang-2 and IL-18 levels inversely related to PaO2/FiO2 ratio.4.Changes of haemodynamics, temperature and oxygenation of severe septic patients during CBPThe haemodynamics of all patients were stable, and the doses of dopamine and norepinephrine which were used in 7 of 19 patients were reduced gradually. There was a significant decrease in T, HR and P(A-a) O2 (P<0.05 or P<0.01). There was a significant increase in OI during CBP (P<0.05).5.Changes of metabolism of severe septic patients pre- and post-CBP BUN and SCr levels of patients with severe septic patients were significantly decreased, while the values of pH and BE were gradually increased (P<0.05 or P<0.01).6.Changes of CRP of severe septic patients during CBPCRP level was decreased significantly after CBP (P<0.05).7.Changes of APACHE II and SOFA score during CBP APACHE II score was decreased with significant difference during CBP (P<0.05 or P<0.01).,however, SOFA has no statistical difference was observed between T0 and other three time points (P>0.05).8.Clinical outcomesSeven patients died and twelve patients were survived within 28 days in ICU. The actual mortality was 36.84%.Conclusions:1 The concentration of circulation Ang-2 and IL-18 were elevated in sever septic patients. Those two mediators were significantly increased in nonsurvivors compared with survivors.Circulating Ang-2 levels in septic patients correlation with low PaO2/FIO2 and mortality.2 Ang-2 levels inversely related to PaO2/FIO2 ratio and positively related to the APACHE II, which is a better predictor of outcome and mortality in sever septic patients.3 Ang-2 and MMP-9 were cleared by convection and adsorption mechanism; IL-18 was cleared by convection. By clearing the mediators which induced capillary permeability increase to improve the pulmonary function.4 CBP could stabilize haemodynamics, improve renal function and oxygenation, correct metabolic acidosis and retain homeostasis of severe septic patients. |
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