摘要
研究背景
儿童脓毒症是危重患儿死亡的第一位原因,是当今儿童危重病医学所面临的棘手难题。持续血液净化技术(CBP)在脓毒症和严重脓毒症患儿治疗中广泛应用和深入研究,但目前对CBP的治疗机制缺乏足够的理解,有必要对这一治疗过程中的相应机制进行研究。目前尚未见到CBP治疗脓毒症患儿前后典型蛋白标志物变化情况研究,本研究主要对CBP治疗脓毒症患儿前后临床疗效做比较,探讨CBP治疗脓毒症指证及时机,并对典型蛋白标志物软骨糖蛋白39(YKL-40)及C反应蛋白(CRP)动态变化做深入研究,探讨CBP治疗脓毒症机制。
目的
本课题研究CBP治疗脓毒症患儿前后临床疗效,CBP治疗脓毒症指证及时机,分析CBP治疗脓毒症前后病情危重程度、炎性因子及YKL-40和CRP动态变化情况,并分析比较YKL-40、CRP与IL-6、TNF-α和脓毒症患儿病情危重程度做相关性分析,探讨脓毒症患儿疾病严重程度、预后与典型蛋白标志物的关系,为临床评价CBP治疗脓毒症提供治疗依据。
第一部分
方法
根据2005年国际脓毒症会议发布小儿脓毒症诊断标准,收集北京军区总医院附属医院八一儿童重病中心2008年8月至2010年8月收治的符合严重脓毒症诊断标准的25例患儿,以同期门诊健康体检儿童25例为对照组。25例患儿在行CBP治疗前均进行了常规综合治疗、原发病的治疗、抗生素、营养对症支持治疗,维持水电解质酸碱平衡；25例患儿均需机械通气辅助呼吸,15例患儿需应用多巴胺及去甲肾上腺素维持血压。
(1)在持续血液净化治疗儿童脓毒性休克患儿开始治疗即0小时、治疗开始12小时、24小时、48小时从桡动脉端抽血5mL和2mL,5mL血样低温离心后取上层血清冻存；2mL血样做血常规生化检查肾功能、肝功能、血电解质、血乳酸,并测定4个时间点的动脉血气,对以上结果做统计分析。根据1995年5月中华医学会儿科学会急救学组讨论通过的《小儿危重病例评分法(草案)》(评分法)对CBP治疗前后脓毒症患儿评分,反映患儿危重病情程度和预测死亡风险。
(2)采用酶联免疫法测定4个时间点的IL-6、TNF-α水平值并做统计分析。
结果
(1)经CBP治疗,25例脓毒症患儿经临床好转18例,恶化死亡5例,放弃治疗2例,18例患儿经后续治疗后治愈出院,治愈率72%。
①在CBP治疗脓毒症患儿开始后,Oh、12h、24h和48h平均动脉压结果分别为42.84±8.84 mmHg,54.80±12.67mmHg,55.96±12.48mrnHg,58.27±13.00 mmHg,平均动脉压不断上升,治疗后平均动脉压与治疗前比较,有显著性差异(F=54.031,P<0.001); 0h、12h、24h和48h多巴胺使用量为17.61±4.07μg/kg min、14.24±2.36μg/kg·min、8.51±2.39μg/kg·min、4.31±1.47μg/kg·min,治疗后多巴胺使用量与治疗前比较,有显著性差异(F=159.681,P<0.001),治疗后12h(P<0.001)、24h(P<0.001)和48h(P<0.001)多巴胺使用量与治疗前比较,均有显著性差异；0h、12h、24h和48h肾上腺素使用量为1.41±0.34μg/kg·min、0.63±0.21μg/kg·min、0.08±0.03μg/kg·min、0.03±0.02μg/kg·min,治疗后肾上腺素使用量与治疗前比较,有显著性差异(F=277.775,P<0.001),治疗后12h(P<0.001)、24h (P<0.001)和48h(P<0.001)肾上腺素使用量与治疗前比较,均有显著性差异；Oh、12h、24h和48h尿量分别为0.86±0.58 mL/kg. h,0.88±0.42 mL/kg·h,0.90±0.45 mL/kg. h,1.36±0.61 mL/kg. h,治疗后尿量与治疗前比较,有显著性差异(F=27.752,P<0.001),治疗后48h尿量与开始CBP治疗前治疗前比较,有显著性差异(P<0.001)。
②在CBP治疗脓毒症患儿开始后,Oh、12h、24h和48h血肌酐水平分别为363.02±83.73μmol/L、230.20±58.39μmol/L、191.20±51.17μmol/L 103.71±30.89μmol/L,治疗后血肌酐水平与治疗前比较,有显著性差异(F146.343=,P<0.001),治疗后12h(P<0.001)、24h(P<0.001)和48h(P<0.001)血肌酐水平与治疗前比较,均有显著性差异；0h、12h、24h和48h尿素氮水平分别为39.83±8.72 mmol/L、23.55±6.44mmol/L、14.64±4.68mmol/L、7.71±1.61mmol/L,治疗后尿素氮水平与治疗前比较,有显著性差异(F=179.995=,P<0.001),治疗后12h(P<0.001)、24h(P<0.001)和48h(P<0.001)尿素氮水平与治疗前比较,均有显著性差异。
③在CBP治疗脓毒症患儿开始后,0h、12h、24h和48h血气PH分别为7.14±0.43、7.33±0.48、7.36±0.44、7.31±0.40,治疗后血气PH与治疗前比较,无显著性差异；0h、12h、24h和48h血气BE分别为19.72±4.71、8.32±2.33、4.61±1.62、0.61±0.17,治疗后血气BE与治疗前比较,有显著性差异(F=264.709,P<0.001),治疗后12h(P<0.001)、24h (P<0.001)和48h(P<0.001)血气BE与开始CBP治疗前治疗前比较,均有显著性差异；0h、12h、24h和48h血气PO2/FiO2分别为187.49±44.28、247.01±70.07、300.97±55.27、351.53±80.59,治疗后PO2/FiO2水平与治疗前比较,有显著性差异(F=70.274,P<0.001),治疗后12h (P<0.001)、24h(P<0.001)和48h(P<0.001)PO2/FiO2水平与治疗前比较,均有显著性差异。
④经CBP治疗后48h,患儿危重评分与治疗前比较,有显著性差异(t=-6.096,P<0.001)。
(2)在CBP治疗脓毒症患儿开始后,0h、12h、24h和48h IL-6水平分别为706.90±275.95 ng/L.325.18±126.94 ng/L.212.07±82.79 ng/L. 162.59±63.47ng/L,治疗后IL-6水平与治疗前比较,有显著性差异(F=164.057,P<0.001),治疗后12h(P<0.001).24h(P<0.001)和48h(P<0.001) IL-6水平与治疗前比较,均有显著性差异；Oh、12h、24h和48h TNF-α水平分别为989.67±386.33ng/L.872.27±209.28 ng/L.541.25±207.28ng/L.439.08±159.37 ng/L,治疗后TNF-α水平与治疗前比较,有显著性差异(F=106.836,P<0.001),治疗后12h(P=0.033).24h(P<0.001)和48h(P<0.001)TNF-α水平与治疗前比较,均有显著性差异。治疗后IL-6、TNF-α水平呈现下降趋势,经CBP治疗脓毒症患儿48h后,患儿血清中炎性因子IL-6(t=4.653,P<0.001)和TNF-α水平(t=9.008,P<0.001)与正常患儿比较,有显著性差异。
(3)8例存在肝功能衰竭患儿,CBP治疗前,患儿内环境严重紊乱,凝血机制差,总胆红素(258.98±117.38)U/L、血氨(189.31:±46.23)μg/dL. GPT(1281.19±363.18)U/L.GOT(1018.71±72.24)U/L.PTA(28.22±6.76)%. CBP治疗12h后症状减轻,内环境、出血指标显著改善,总胆红素(93.51±28.34)U/L、血氨(56.26±10.16)μg/dL.GPT(390.58±169.12)U/L.GOT(300.77±141.46)U/L.PTA(61.46±13.75)%.总胆红素(t=3.797,P=0.007)、血氨(t=9.391, P<0.001)、GPT(t=7.017,P<0.001)、GOT(t=13.897,P<0.001)、PTA (t=.12.553,P<0.001)治疗前后均有统计学意义。
(4)掌握好脓毒症患儿CBP治疗指证、时机及实施方法,可明显提高脓毒症患儿治愈率。
第二部分
方法
(1)采用酶联免疫法测定待测血清中YKL-40浓度,采用免疫比浊法测定血浆中CRP水平,根据标准品浓度与吸光度之间关系绘制标准曲线,算出回归方程,根据所测血清标本吸光度算出样本中YKL-40和CRP浓度。
(2)制备脓毒症患儿全血总RNA,以RT-PCR法测定全血中YKL-40 mRNA相对表达含量。
(3)获取脓毒症患儿外周血单核细胞,收集培养的细胞,加入PBS离心洗涤1遍,吸出上清,加入cell staining buffer,充分混匀,加抗人FITC-CD14抗体或FITC-CD16抗体,室温避光孵育,用cell staining buffer重悬后行FCM检测,每次重复3次,取平均值CXP软件分析；用细胞免疫化学法检测脓毒症患儿外周血单核细胞中YKL-40的定位表达。
结果
(1)在CBP治疗脓毒症患儿开始后,患儿外周血中0h、12h、24h和48h YKL-40蛋白浓度分别为177.93±58.74μg/L、100.57±37.37μg/L、80.16±28.46μg/L、59.75±21.03μg/L,治疗后YKL-40与治疗前比较,有显著性差异(F=172.466,P<0.001)；患儿外周血中0h、12h、24h和48h CRP蛋白浓度分别为664.49±259.40μg/L、619.01±206.81μg/L、201.13±75.42μg/L、120.17±46.91μg/L,治疗后CRP水平与治疗前比较,有显著性差异(F=172.262,P<0.001),治疗后12h (P=0.026).24h(P<0.001)和48h(P<0.001)CRP水平与治疗前比较,均有显著性差异。CBP治疗48h后脓毒症患儿外周血YKL-40浓度与健康儿童比较,无显著性差异。
(2)在CBP治疗后YKL-40mRNA△Ct表达含量与治疗前比较,无显著性差异；患儿外周血中0h、12h、24h和48h YKL-40 mRNA相对表达含量(2-△△CT)分别为1(0.6-1.7)、0.5(0.4-0.6)、0.5(0.3-0.7)、0.4(0.2-0.6)。
(3)YKL-40阳性外周血中CD14呈低表达,CD16呈阳性表达,且在CBP治疗脓毒症患儿开始后,患儿外周血中0h、12h、24h和48h CD16表达率分别为35.23±8.15%、26.42±6.11%、27.86±6.57%、23.67±4.85%,呈下降趋势,治疗前后有显著性差异(F=153.901,P<0.001);CBP治疗脓毒症患儿48h后,外周血中CD16表达率接近健康儿童；经细胞免疫化学法检测,外周血细胞单核细胞中YKL-40阳性表达。
(4)经CBP治疗恶化死亡5例脓毒症患儿外周血中YKL-40.CRP水平和CD16表达率较生存组患儿显著升高,与生存组患儿比较,有显著性差异(P<0.001)。
第三部分
方法
收集第一部分、第二部分CBP治疗脓毒症患儿YKL-40、CRP、IL-6、TNF-α、IL-6浓度及危重评分数据,经SPSS13.0统计分析,采用Pearson相关分析分别做YKL-40、CRP对TNF-α、IL-6和YKL-40、CRP对CBP治疗脓毒症患儿前后危重评分做相关性分析。
结果
经CBP治疗48小时后, YKL-40浓度与IL-6浓度相关具显著性,且呈密切正相关(r=0.905, P<0.001), YKL-40浓度与TNF-α浓度相关具显著性,且呈密切正相关(r=0.890, P<0.001); CRP浓度与IL-6浓度相关具显著性,且呈密切正相关(r=1.000, P<0.001), CRP浓度与TNF-α浓度相关具显著性,且呈密切正相关(r=0.987,P<0.001)。经CBP治疗48小时后, YKL-40浓度与危重评分相关具显著性,且呈中度正相关(r=0.662, P<0.001); CRP浓度与危重评分相关具显著性,且呈密切正相关(r=0.772,P<0.001)。
结论
1持续性血液净化技术治疗能明显提高脓毒症患儿氧合能力、纠正酸中毒、改善组织灌注、清除小分子物质、稳定血压并减少升压药用量,改善预后并降低死亡率。
2掌握好上CBP的指证及时机和实施方法是提高脓毒症患儿治愈率的重要一环。
3持续性血液净化技术是脓毒症患儿有效治疗手段,其清除体内炎性细胞因子是其治疗脓毒症的可能机制。合并急性肝功能衰竭的患儿,肝性脑病ⅡⅡ级以前及时行CBP是较好的时间点。
4 YKL-40和CRP均有可能成为评价持续性血液净化技术治疗脓毒症疗效的蛋白指标,CBP治疗后,外周血中YKL-40、CRP水平高及持续CD16高表达提示脓毒症患儿预后较差。
Backgrouds
Pediatric sepsis, a thornic problem in critically ill children, is the primary cause of death among children. Continuous blood purification technology (CBP) is much effective in treatment of pediatric sepsis and generally applied in pediatric sepsis. By far, there is not enough comprehension in treatment mechanism of CBP treatment in pediatric sepsis. It is essential to investigate the mechanism. The change of typical biomarkers in treatment mechanism of CBP treatment in pediatric sepsis has not been investigated by scientifically controlled studies. In the research, we investigated the curative effect, the therapeutic indications and juncture of CBP treatment in pediatric sepsis, the feasibility of 39 human cartilage glycoprotein-39 (YKL-40) and C-reactive protein (CRP) as typical biomarkers in treatment mechanism of CBP applied in pediatric sepsis.
Objectives
In the study, we report the curative effect, the therapeutic indications and juncture of CBP treatment in pediatric sepsis, the disease severity of ill children, the changes of inflammatory factors, YKL-40 and CRP concentration in peripheral blood when treated pediatric sepsis with CBP. Then made correlation analysis between YKL-40 concentration to IL-6, TNF-a concentration and disease severity scores, CRP concentration to IL-6, TNF-a concentration and disease severity scores. By the study, we investigated the relationship with prognosis and YKL-40 and CRP as typical biomarkers in treatment mechanism of CBP treatment in pediatric sepsis, offered treatment basis for clinical evaluation of CBP.
Part one
Methods
25 cases of pediatric sepsis children were collected from Byi Children's Hospital, Beijing Command Hospital People Liberation Army from August 2008 to August 2010, all ill children were selected in line with the 2005 Meeting of the International Sepsis published diagnostic criteria for severe sepsis in children, healthy children to the same period illness children as control group. All illness children received routine comprehensive treatment with primary disease treatment, antibiotic treatment, nutrition treatment, support treatment and liquid, electrolyte acid-alkali balancing before CBP treatment. All 25 cases of illness children required assist respiration with mechanical ventilation,15 cases needed maintain with dopamine and noradrenaline.
(1)Blood samples were collected from radial artery at four points of CBP treatment 0 hours,12 hours,24 hours,48 hours respectively. Each volume 5 mL blood samples were made blood serum with centrifugating in low temperature, then were cryopreserved. Each volume 2 mL blood samples were taken for conventional biochemical tests of the renal function, liver function, blood electrolyte and blood lactate at different time points. At the same time, arterial blood gas analysis was done at different time points. Score changes, in cases of pediatric critical illness before and after CBP, was calculated according with the pediatric critical illness score published by the subspecialty group of emergency medicine, society of pediatrics, Chinese medical association, was used to predict the ill children death risk.
(2)A euzymelinked immunosorbent assay was used to determine inflammation mediators of IL-6 and TNF-a concentration at different time points.
Results
(1) Evaluation of clinical outcome was done in 25 cases of illness children with 48 hours of CBP treatment. Clinical symptoms improved in 18 cases, deteriorated and resulted in death in 5 cases, treatment were given up in two case,72% cure rate.
①The mean arterial blood pressure in the four time points (the beginning if treatment,12 hour,24 hour and 48 hour) were 42±12.6 mmHg,54±9.6 mmHg, 55±7.9 mmHg,58±5.9 mmHg. The mean arterial blood pressure increased significantly (P<0.05) before and after CBP treatment. The dosages of dopamine in the four time points were 17.05±3.26μg/kg·min,14.19±4.95μg/kg·min, 8.60±6.51μg/kg·min,4.25±3.12μg/kg·min. The dosages of dopamine decreased significantly (P<0.05) before and after CBP treatment 12 hour. The dosages of noradrenaline were 1.41±0.39μg/kg·min,0.62±0.30μg/kg.min, 0.08±0.03μg/kg·min,0.03±0.02μg/kg·min. The dosages of noradrenaline decreased significantly (P<0.05) before and after CBP treatment 12 hour. The urine amount for illness children in the four time points were 0.85±0.54 mL/kg·h,0.86±0.55 mL/kg·h, 0.89±0.56 mL/kg. h,1.35±0.686 mL/kg. h. The difference was significant (P<0.05) compared at the beginning of treatment and 48 hour after treatment.
②The level of blood serum creatinine in the four time points were 361.95±70.26μmol/L,279.69±61.56μmol/L,189.64±50.36μmol/L,103.21±33.45μmol /L. The difference was significant (P<0.05) compared at the beginning of treatment and 12 hour after CBP treatment. The difference was very significant (P<0.01) compared at the beginning of treatment and 24hour and 48hour after CBP treatment. The level of urea nitrogen in the four time points were 39.21±10.24 mmol/L, 23.2±7.7mmol/L,14.76±2.12mmol/L,7.78±1.63mmol/L. The difference was significant (P<0.05) compared at the beginning of treatment and 12 hour after CBP treatment. The difference was very significant (P<0.01) compared at the beginning of treatment and 24hour and 48hour after CBP treatment.
③The blood gas PH level in the four time points were 7.14±0.22,7.33±0.12, 7.4±0.16,7.33±0.11. PH level increased significantly (P<0.05). The BE blood gas value in the four time points were-19.58±6.45,-8.21±2.73,-4.56±1.78,-0.61±1.75. BE value increased very significantly (P<0.01) compared at the beginning of treatment and CBP treatment. The oxygenation index (PO2/FiO2) in the four time points were 188.76±85.61,245.32±82.56,301.24±78.35,352.42±81.56. The difference was significant (P<0.05) compared at the beginning of treatment and 12 hour after CBP treatment. The difference was very significant (P<0.01) compared at the beginning of treatment and 24hour and 48hour after CBP treatment.
④Severity scores of illness cases increased significantly (P<0.05) before and after CBP treatment 48 hour.
(2) IL-6 concentration in the four time points were 705.21±87.62 ng/L, 324.31±86.34 ng/L,213.64±62.35 ng/L,164.35±51.23ng/L. IL-6 concentration decreased significantly (P<0.05) before and after CBP treatment 12 hour. IL-6 concentration was significant (P<0.05) compared at the beginning of treatment and CBP treatment 24 hour and 48 hour. TNF-a concentration in the four time points were 987.52±91.25ng/L,871.36±97.56 ng/L,541.23±111.25 ng/L,437.69±107.19 ng/L. TNF-a concentration was significant (P<0.05) compared at the beginning of treatment and CBP treatment 12 hour. TNF-a concentration was very significant (P<0.01) compared at the beginning of treatment and CBP treatment 24 hour and 48 hour.
(3) There were 8 cases liver failure in pediatric sepsis children. The total bilirubin concentration was 258.98±117.38 U/L and 93.51±28.34 U/L at the beginning of treatment and CBP treatment 12 hour. Blood ammonia concentration was 189.31±46.23μg/dL and 56.26±10.16μg/dL, glutamate-pyruvate transaminase (GPT) was 1281.19±363.18 U/L and 390.58±169.12 U/L, glutamic oxaloacetic transaminase(GOT) was 1018.71±72.24 U/L and 300.77±141.46 U/L, prothrombin activity(PTA) was 28.22±6.76% and 61.46±13.75%.There were all have very significant (P<0.01) compared at the beginning of treatment and CBP treatment12 hour.
(4) The cure rate of CBP treatment in pediatric sepsis maybe obiously increasing when we made best CBP treatment therapeutic indications, juncture and method.
Part two
Methods
(1) A euzymelinked immunosorbent assay was used to determine YKL-40 concentration blood serum and immunoturbidimetry assay to determine CRP concentration. The blood serum of YKL-40 and CRP concentration were calculated by regression equation made by standard curve of YKL-40 and CRP concentration.
(2) YKL-40 mRNA expression in pediatric sepsis illness blood was determined by RT-PCR.
(3) Peripheral blood monouclear cells (PBMC) in pediatric sepsis illness blood was obtained and then cultivated. The flow cytometry (FCM) was used to detect CD 14 and CD 16. The YKL-40 allocated expression in pediatric sepsis illness blood was detected by immunohistochemistry (IHC).
Results
(1) YKL-40 concentration of pediatric sepsis illness blood in the four time points were180.56±23.25μg/L,100.21±21.32μg/L,80.35±35.26μg/L, 60.53±26.21μg/L. YKL-40 concentration decreased significantly (P<0.05) before and after CBP treatment 12 hour. IL-6 concentration was very significant (P<0.01) compared at the beginning of treatment and CBP treatment. CRP concentration of pediatric sepsis illness blood in the four time points were 662.23±69.56μg/L, 620.21±58.32μg/L,200.32±42.36μg/L,120.56±29.21μg/L. CRP concentration was significant (P<0.05) compared at the beginning of treatment and CBP treatment 12 hour, was very significant (P<0.01) compared at the beginning of treatment and CBP treatment 24 hour and 48 hour.
(2) The YKL-40 mRNA of pediatric sepsis illness blood relative expression in the four time points were 1 (0.6-1.7),0.5 (0.4-0.6),0.5 (0.3-0.7),0.4 (0.2-0.6) CRP concentration was significant (P<0.05) compared at the beginning of treatment and CBP treatment 12 hour, was very significant (P<0.01) compared at the beginning of treatment and CBP treatment 24 hour and 48 hour. The YKL-40 mRNA relative expression was significant (P<0.05) compared at the beginning of treatment and CBP treatment 12 hour and 24 hour, was very significant (P<0.01) compared at the beginning of treatment and CBP treatment 48 hour.
(3) The YKL-40 protein was expressed in CD16+ monocytes with a dim expression of CD14. The FCM showed that the CD16 expression in the four time points were 35.2±5.930%、26.3±5.21%、27.8±6.92%、23.8±5.12%, the expression was decreased. The YKL-40 expression in histoleucocyte was positive by IHC.
(4) The YKL-40 concentration, CRP concentration and CD 16 expression of 5 pediatric sepsis death cases blood in the four time points were higher the live pediatric sepsis illness, there were very significant (P<0.01)
Part three
Methods
To make correlation analysis with Bivariate Correlation between YKL-40 concentration with IL-6, TNF-a concentration and disease severity scores, CRP concentration with IL-6, TNF-a concentration and disease severity scores.
Results
There were positive correlation between YKL-40 concentration with IL-6, TNF-a concentration and disease severity scores, CRP concentration with IL-6, TNF-a concentration and disease severity scores.
Conclusions
1 CBP can improve the treatment of pediatric sepsis, reduce the death rate of the treatment, was effective in the treatment by improving oxygenation improvement, correcting metabolic acidosis, increasing the tissue perfusion, stabilizing blood pressure and educing boosting pressure drugs usage.
2 The cure rate of CBP treatment in pediatric sepsis maybe obiously increasing when we made best CBP treatment therapeutic indications, juncture and method.
3 CBP is an effective treatment method for pediatric sepsis. It effectively removes blood cytokines which may be the possible mechanisms for the CBP treatment of pediatric sepsis.
4 YKL-40 and CRP may be as biomarkers to evaluate CBP treatment for pediatric sepsis. There are bad prognosis if the YKL-40,CRP concentration and CD16 expression keep in higher level.
引文
1. Angus, D.C., et al., Epidemiology of severe sepsis in the United States:analysis of incidence, outcome, and associated costs of care. Crit Care Med,2001.29(7):p.1303-10.
2. Andreu Ballester, J.C., et al., Epidemiology of sepsis in the Valencian Community (Spain), 1995-2004. Infect Control Hosp Epidemiol,2008.29(7):p.630-4.
3. Goldstein, B., B. Giroir, and A. Randolph, International pediatric sepsis consensus conference:definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med, 2005.6(1):p.2-8.
4. 许煊,连续血液净化治疗在危重症患儿中的应用.中国小儿急救医学,2010.17(4).
5. 封志纯,连续血液净化治疗儿童脓毒性休克.中华儿科杂志,2006·.44(8)：p.4.
6. Bock, K.R., Renal replacement therapy in pediatric critical care medicine. Curr Opin Pediatr, 2005.17(3):p.368-71.
7. Kornecki, A., et al., Continuous renal replacement therapy for non-renal indications: experience in children. Isr Med Assoc J,2002.4(5):p.345-8.
8. 常平,两种连续血液净化置换液的比较.中华急诊医学杂志,2005.14(6).
9. Goldstein, S.L., et al., Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int,2005.67(2):p.653-8.
10. Naran, N., M. Sagy, and K.R. Bock, Continuous renal replacement therapy results in respiratory and hemodynamic beneficial effects in pediatric patients with severe systemic inflammatory response syndrome and multiorgan system dysfunction. Pediatr Crit Care Med, 2010.11(6):p.737-40.
11. Brierley, J., et al., Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock:2007 update from the American College of Critical Care Medicine. Crit Care Med,2009.37(2):p.666-88.
12. Fortenberry, J.D. and M.L. Paden, Extracorporeal therapies in the treatment of sepsis: experience and promise. Semin Pediatr Infect Dis,2006.17(2):p.72-9.
13. Joannes-Boyau, O., et al., Impact of high volume hemofiltration on hemodynamic disturbance and outcome during septic shock. ASAIO J,2004.50(1):p.102-9.
14. Strazdins, V., A.R. Watson, and B. Harvey, Renal replacement therapy for acute renal failure in children:European guidelines. Pediatr Nephrol,2004.19(2):p.199-207.
15. Li, A.M., et al., A systematic review of antibiotic dosing regimens for septic patients receiving continuous renal replacement therapy:do current studies supply sufficient data? J Antimicrob Chemother,2009.64(5):p.929-37.
16. Cremaschi E, Maggiore U, Maccari C, Cademartiri C, Andreoli R, Fiaccadori E. Linezolid levels in a patient with biliary tract sepsis, severe hepatic failure and acute kidney injury on sustained low-efficiency dialysis (SLED). Minerva Anestesiol.2010 Nov;76(11):961-4. PubMed PMID:21102392.
17.Duszynska W. [Antimicrobial therapy in severe infections with multidrug-resistant Gram-negative bacterias]. Anestezjol Intens Ter.2010 Jul-Sep;42(3):160-6. Polish. PubMed PMID:21413423.
18. Johnson MT, Reichley R, Hoppe-Bauer J, Dunne WM, Micek S, Kollef M. Impact of previous antibiotic therapy on outcome of Gram-negative severe sepsis. Crit Care Med.2011 Apr 14. [Epub ahead of print] PubMed PMID:21499086.
19. Karpel E, Madej A, Buldak L, Dulawa-Buldak A, Nowakowska-Dulawa E, Labuzek K, Haberka M, Stojko R, Okopien B. Bile bacterial flora and its in vitro resistance pattern in patients with acute cholangitis resulting from choledocholithiasis. Scand J Gastroenterol.2011 Apr 20. [Epub ahead of print] PubMed PMID:21504380.
20. Morales-Molina JA, Mateu-de Antonio J, Grau S, Segura M, Acosta P. [Stability:a factor to consider in antibiotic-lock solutions]. Enferm Infecc Microbiol Clin.2010 Feb;28(2):104-9. Epub 2009 May 1. Review. Spanish. PubMed PMID:19409671.
21. Fernando RR, Krishnan S, Fairweather MG, Ericsson CD. Vibrio parahemolyticus septicaemia in a liver transplant patient:a case report. J Med Case Reports.2011 May 6;5(1):171. [Epub ahead of print] PubMed PMID:21548914. J Med Case Reports.2011 May 6;5(1):171. [Epub ahead of print]
22. de Oliveira, C.F., et al., ACCM/PALS haemodynamic support guidelines for paediatric septic shock:an outcomes comparison with and without monitoring central venous oxygen saturation. Intensive Care Med,2008.34(6):p.1065-75.
1. Angus, D.C., et al., Epidemiology of severe sepsis in the United States:analysis of incidence, outcome, and associated costs of care. Crit Care Med,2001.29(7):p.1303-10.
2. Andreu Ballester, J.C., et al., Epidemiology of sepsis in the Valencian Community (Spain), 1995-2004. Infect Control Hosp Epidemiol,2008.29(7):p.630-4.
3. Goldstein, B., B. Giroir, and A. Randolph, International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med,2005.6(1):p. 2-8.
4. 康白,感染的分类和微生态机制,ed.康白.Vo1.第1版.2002,北京：人民卫生出版社.
5. Opal, S.M., Concept of PIRO as a new conceptual framework to understand sepsis. Pediatr Crit Care Med,2005.6(3 Suppl):p. S55-60.
6. Bang, A.T., et al., Simple clinical criteria to identify sepsis or pneumonia in neonates in the community needing treatment or referral. Pediatr Infect Dis J,2005.24(4):p.335-41.
7. Bang, A.T., et al., Effect of home-based neonatal care and management of sepsis on neonatal mortality:field trial in rural India. Lancet,1999.354(9194):p.1955-61.
8. Levy, M.M., et al.,2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med,2003.31(4):p.1250-6.
9. Goldenberg, R.L., J.C. Hauth, and W.W. Andrews, Intrauterine infection and preterm delivery. N Engl J Med,2000.342(20):p.1500-7.
10. Jacobs, R.F., et al., Septic shock in children:bacterial etiologies and temporal relationships. Pediatr Infect Dis J,1990.9(3):p.196-200.
11. Paul, D.A., et al., Maternal antibiotics and decreased periventricular leukomalacia in very low-birth-weight infants. Arch Pediatr Adolesc Med,2003.157(2):p.145-9.
12. Wills, B.A., et al., Comparison of three fluid solutions for resuscitation in dengue shock syndrome. N Engl J Med,2005.353(9):p.877-89.
13. Ngo, N.T., et al., Acute management of dengue shock syndrome:a randomized double-blind comparison of 4 intravenous fluid regimens in the first hour. Clin Infect Dis,2001.32(2):p. 204-13.
14. Marshall, J.C., et al., Measures, markers, and mediators:toward a staging system for clinical sepsis. A report of the Fifth Toronto Sepsis Roundtable, Toronto, Ontario, Canada, October 25-26,2000. Crit Care Med,2003.31(5):p.1560-7.
15. Ninis, N., et al., The role of healthcare delivery in the outcome of meningococcal disease in children:case-control study of fatal and non-fatal cases. BMJ,2005.330(7506):p.1475.
16. Kramer, P., et al., [Arteriovenous haemofiltration:a new and simple method for treatment of over-hydrated patients resistant to diuretics]. Klin Wochenschr,1977.55(22):p.1121-2.
17. 许元文,连续性肾脏替代治疗与间歇性血液透析治疗多器官功能障碍综合征的疗效比较.中华肾脏病杂志,2001(5).
18. Hakala, B.E., C. White, and A.D. Recklies, Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem,1993.268(34):p.25803-10.
19. Fusetti, F., et al., Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39. J Biol Chem,2003.278(39):p.37753-60.
20. Dehn, H., et al., Plasma YKL-40, as a prognostic tumor marker in recurrent ovarian cancer. Acta Obstet Gynecol Scand,2003.82(3):p.287-93.
21. Renkema, G.H., et al., Purification and characterization of human chitotriosidase, a novel member of the chitinase family of proteins. J Biol Chem,1995.270(5):p.2198-202.
22. Kronborg, G, et al., Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae bacteremia and is associated with the outcome of the disease. Scand J Infect Dis, 2002.34(5):p.323-6.
23. Nordenbaek, C., et al., YKL-40, a matrix protein of specific granules in neutrophils, is elevated in serum of patients with community-acquired pneumonia requiring hospitalization. J Infect Dis,1999.180(5):p.1722-6.
24. Pulliam, P.N., M.W. Attia, and K.M. Cronan, C-reactive protein in febrile children 1 to 36 months of age with clinically undetectable serious bacterial infection. Pediatrics,2001.108(6): p.1275-9.
25. Somech, R., et al., Procalcitonin correlates with C-reactive protein as an acute-phase reactant in pediatric patients. Isr Med Assoc J,2000.2(2):p.147-50.
26. Huang, S.Y., et al., Serum interleukin-6 level as a diagnostic test in children with sepsis. J Chin Med Assoc,2003.66(9):p.523-7.
27. Latifi, S.Q., et al., Persistent elevation of serum interleukin-6 in intraabdominal sepsis identifies those with prolonged length of stay. J Pediatr Surg,2004.39(10):p.1548-52.
28. 中华急诊医学会儿科学组,第六届全国儿科危重症研讨会纪要.小儿急救医学,2000.7(3).
29. 常平,两种连续血液净化置换液的比较.中华急诊医学杂志,2005.14(6).
30. 中华医学会儿科学会急救学组,第四届全国小儿急救医学研讨会纪要.中华儿科杂志,1995.33(6).
31. 马文成,小儿危重病例评分法在危重儿童院间转运中的应用.中国妇幼保健,2005.20(21).
32. Alves-Filho, J.C., et al., The role of neutrophils in severe sepsis. Shock,2008.30 Suppl 1:p. 3-9.
33. Okajima, K., Regulation of inflammatory responses by natural anticoagulants. Immunol Rev, 2001.184:p.258-74.
34. Peng, Y, Z. Yuan, and H. Li, Removal of inflammatory cytokines and endotoxin by veno-venous continuous renal replacement therapy for burned patients with sepsis. Burns, 2005.31(5):p.623-8.
35. de Oliveira, C.F., et al., ACCM/PALS haemodynamic support guidelines for paediatric septic shock:an outcomes comparison with and without monitoring central venous oxygen saturation. Intensive Care Med,2008.34(6):p.1065-75.
36. Strazdins, V., A.R. Watson, and B. Harvey, Renal replacement therapy for acute renal failure in children:European guidelines. Pediatr Nephrol,2004.19(2):p.199-207.
37. Kornecki, A., et al., Continuous renal replacement therapy for non-renal indications: experience in children. Isr Med Assoc J,2002.4(5):p.345-8.
38. Li, A.M., et al., A systematic review of antibiotic dosing regimens for septic patients receiving continuous renal replacement therapy:do current studies supply sufficient data? J Antimicrob Chemother,2009.64(5):p.929-37.
39. Naran, N., M. Sagy, and K.R. Bock, Continuous renal replacement therapy results in respiratory and hemodynamic beneficial effects in pediatric patients with severe systemic inflammatory response syndrome and multiorgan system dysfunction. Pediatr Crit Care Med, 2010.11(6):p.737-40.
40. Brierley, J., et al., Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock:2007 update from the American College of Critical Care Medicine. Crit Care Med,2009.37(2):p.666-88.
41. 封志纯,连续血液净化治疗儿童脓毒性休克.中华儿科杂志,2006.44(8)：p.4.
42. Bock, K.R., Renal replacement therapy in pediatric critical care medicine. Curr Opin Pediatr, 2005.17(3):p.368-71.
43. Goldstein, S.L., et al., Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int,2005.67(2):p.653-8.
44. Lavery, J.V., Ethical issues in international biomedical research:a casebook.2007, Oxford; New York:Oxford University Press, ⅹⅹⅶ,371 p.
45. Joannes-Boyau, O., et al., Impact of high volume hemofiltration on hemodynamic disturbance and outcome during septic shock. ASAIO J,2004.50(1):p.102-9.
46. Zivanovic, S., et al., Human cartilage glycoprotein 39--biomarker of joint damage in knee osteoarthritis. Int Orthop,2009.33(4):p.1165-70.
47. Johansen, J.S., et al., Circulating YKL-40 levels during human endotoxaemia. Clin Exp Immunol,2005.140(2):p.343-8.
48. Ziegler-Heitbrock, L., The CD14+CD16+blood monocytes:their role in infection and inflammation. J Leukoc Biol,2007.81(3):p.584-92.
49. Cecchetti, S., et al., Functional role of phosphatidylcholine-specific phospholipase C in regulating CD16 membrane expression in natural killer cells. Eur J Immunol,2007.37(10):p. 2912-22.
50. Baeten, D., et al., Human cartilage gp-39+,CD16+monocytes in peripheral blood and synovium:correlation with joint destruction in rheumatoid arthritis. Arthritis Rheum,2000. 43(6):p.1233-43.
51. Goldstein B, G.B., Randolph A, International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference:definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med,2005. Jan;6(1):p.2-8.
52. Fischer, J.E., Physicians'ability to diagnose sepsis in newborns and critically ill children. Pediatr Crit Care Med,2005.6(3 Suppl):p. S120-5.
53. Brilli, R.J. and B. Goldstein, Pediatric sepsis definitions:past, present, and future. Pediatr Crit Care Med,2005.6(3 Suppl):p. S6-8.
54. Randolph, A.G.M., MSc, The purpose of the 1st International Sepsis Forum on Sepsis in Infants and Children. Pediatric Critical Care Medicine,2005.6(3):p.2.
55. Bonsu, B.K., M. Chb, and M.B. Harper, Identifying febrile young infants with bacteremia:is the peripheral white blood cell count an accurate screen? Ann Emerg Med,2003.42(2):p. 216-25.
56. Carrol, E.D., et al., Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash. Arch Dis Child,2002.86(4):p.282-5.
57. Maruna, P., K. Nedelnikova, and R. Gurlich, Physiology and genetics of procalcitonin. Physiol Res,2000.49 Suppl 1:p. S57-61.
58. Mariscalco, M.M., Is plasma procalcitonin ready for prime time in the pediatric intensive care unit? Pediatr Crit Care Med,2003.4(1):p.118-9.
59. Arkader, R., et al., Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome. Arch Dis Child,2006.91(2):p.117-20.
60. Pavcnik-Arnol, M., S. Hojker, and M. Derganc, Lipopolysaccharide-binding protein in critically ill neonates and children with suspected infection:comparison with procalcitonin, interleukin-6, and C-reactive protein. Intensive Care Med,2004.30(7):p.1454-60.
61. Athhan, F., et al., Procalcitonin:a marker of neonatal sepsis. J Trop Pediatr,2002.48(1):p. 10-4.
62. Sauer, M., et al., Procalcitonin, C-reactive protein, and endotoxin after bone marrow transplantation:identification of children at high risk of morbidity and mortality from sepsis. Bone Marrow Transplant,2003.31(12):p.1137-42.
63. Casado-Flores, J., et al., Serum procalcitonin in children with suspected sepsis:a comparison with C-reactive protein and neutrophil count. Pediatr Crit Care Med,2003.4(2):p.190-5.
64. Han, Y.Y., et al., Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis. Pediatr Crit Care Med,2003.4(1):p.21-5.
65. Fernandez Lopez, A., et al., Procalcitonin in pediatric emergency departments for the early diagnosis of invasive bacterial infections in febrile infants:results of a multicenter study and utility of a rapid qualitative test for this marker. Pediatr Infect Dis J,2003.22(10):p.895-903.
66. Enguix, A., et al., Comparison of procalcitonin with C-reactive protein and serum amyloid for the early diagnosis of bacterial sepsis in critically ill neonates and children. Intensive Care Med,2001.27(1):p.211-5.
67. Oude Nijhuis, C.S., et al., Lipopolysaccharide-binding protein:a possible diagnostic marker for Gram-negative bacteremia in neutropenic cancer patients. Intensive Care Med,2003. 29(12):p.2157-61.
68. Stryjewski, G.R., et al., Interleukin-6, interleukin-8, and a rapid and sensitive assay for calcitonin precursors for the determination of bacterial sepsis in febrile neutropenic children. Pediatr Crit Care Med,2005.6(2):p.129-35.
69. Barton, P., et al., Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis. Pediatrics,2004.113(1 Pt 1):p.7-17.
70. Fijnvandraat, K., et al., Coagulation activation and tissue necrosis in meningococcal septic shock:severely reduced protein C levels predict a high mortality. Thromb Haemost,1995. 73(1):p.15-20.
71. Weiss, K.D., Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis. Pediatrics,2004.113(1 Pt 1):p.134.
72. Macias, W.L., et al., Pharmacokinetic-pharmacodynamic analysis of drotrecogin alfa (activated) in patients with severe sepsis. Clin Pharmacol Ther,2002.72(4):p.391-402.
73. Scherpereel, A., et al., Endocan, a new endothelial marker in human sepsis. Crit Care Med, 2006.34(2):p.532-7.
74. Neuman, M.I. and M.B. Harper, Evaluation of a rapid urine antigen assay for the detection of invasive pneumococcal disease in children. Pediatrics,2003.112(6 Pt 1):p.1279-82.
75. Rittichier, K.R., et al., Diagnosis and outcomes of enterovirus infections in young infants. Pediatr Infect Dis J,2005.24(6):p.546-50.
76. Heim, A., et al., Rapid and quantitative detection of human adenovirus DNA by real-time PCR. J Med Virol,2003.70(2):p.228-39.
77. Golden, S.M., et al., Evaluation of a real-time fluorescent PCR assay for rapid detection of Group B Streptococci in neonatal blood. Diagn Microbiol Infect Dis,2004.50(1):p.7-13.
78. Tirodker, U.H., et al., Detection of fungemia by polymerase chain reaction in critically ill neonates and children. J Perinatol,2003.23(2):p. 117-22.
79. Dahmer, M.K., et al., Genetic polymorphisms in sepsis. Pediatr Crit Care Med,2005.6(3 Suppl):p. S61-73.
80. Brandtzaeg, P. and M. van Deuren, Current concepts in the role of the host response in Neisseria meningitidis septic shock. Curr Opin Infect Dis,2002.15(3):p.247-52.
81. Emonts, M., et al., Host genetic determinants of Neisseria meningitidis infections. Lancet Infect Dis,2003.3(9):p.565-77.
82. Sikora, J.P., D. Chlebna-Sokol, and A. Krzyzanska-Oberbek, Proinflammatory cytokines (IL-6, IL-8), cytokine inhibitors (IL-6sR, sTNFRII) and anti-inflammatory cytokines (IL-10, IL-13) in the pathogenesis of sepsis in newborns and infants. Arch Immunol Ther Exp (Warsz),2001.49(5):p.399-404.
83. Cocks, J.R., Perforated peptic ulcer--the changing scene. Dig Dis,1992.10(1):p.10-6.
84. Gravett, M.G., et al., Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA,2004.292(4):p.462-9.
85. Giannoulias, D., et al., Localization of prostaglandin H synthase, prostaglandin dehydrogenase, corticotropin releasing hormone and glucocorticoid receptor in rhesus monkey fetal membranes with labor and in the presence of infection. Placenta,2005.26(4):p. 289-97.
86. Wang, H., et al., Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med,2004.10(11):p.1216-1221.
87. Abraham, E., Cytokine modifiers:pipe dream or reality? Chest,1998.113(3 Suppl):p. 224S-227S.
88. Fisher, C.J., Jr., et al., Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med,1996.334(26): p.1697-702.
89. Moerer, O., et al., A German national prevalence study on the cost of intensive care:an evaluation from 51 intensive care units. Crit Care,2007.11(3):p. R69.
90. Adrie, C., et al., Epidemiology and economic evaluation of severe sepsis in France:age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost. J Crit Care,2005.20(1):p.46-58.
91. Kollef, M.H., et al., Inadequate antimicrobial treatment of infections:a risk factor for hospital mortality among critically ill patients. Chest,1999.115(2):p.462-74.
92. Kalenka, A., et al., Changes in the serum proteome of patients with sepsis and septic shock. Anesth Analg,2006.103(6):p.1522-6.
93. Wasinger, V.C., et al., Progress with gene-product mapping of the Mollicutes:Mycoplasma genitalium. Electrophoresis,1995.16(7):p.1090-4.
94. Gorg, A., W. Weiss, and M.J. Dunn, Current two-dimensional electrophoresis technology for proteomics. Proteomics,2004.4(12):p.3665-85.
95. Mpamhanga, C.P., et al., Knowledge-based interaction fingerprint scoring:a simple method for improving the effectiveness of fast scoring functions. J Chem Inf Model,2006.46(2):p. 686-98.
96. Garbis, S., G. Lubec, and M. Fountoulakis, Limitations of current proteomics technologies. J Chromatogr A,2005.1077(1):p.1-18.
97. Muller, B.T., et al., Gene expression profiles in the acutely dissected human aorta. Eur J Vase Endovasc Surg,2002.24(4):p.356-64.
98. Kasthuri, R.S., et al., Potential biomarkers of an exaggerated response to endotoxemia. Biomarkers,2007.12(3):p.287-302.
99. Service, R.F., Proteomics. Can Cclera do it again? Science,2000.287(5461):p.2136-8.
100. Walley, K.R. and J.A. Russell, Protein C-1641 AA is associated with decreased survival and more organ dysfunction in severe sepsis. Crit Care Med,2007.35(1):p.12-7.
101. Mokart, D., et al., Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS):early markers of postoperative sepsis after major surgery. Br J Anaesth,2005.94(6):p. 767-73.
102. McEver, R.P., Adhesive interactions of leukocytes, platelets, and the vessel wall during hemostasis and inflammation. Thromb Haemost,2001.86(3):p.746-56.
103. Andrews, R.K., et al., Platelet adhesion receptors and (patho)physiological thrombus formation. Histol Histopathol,2001.16(3):p.969-80.
104. Kolesnik, V. and A. Biskop, Long-term inhibition of platelet aggregation. Lancet,2000. 356(9231):p.768.
105. Eichacker, P.Q., et al., Risk and the efficacy of antiinflammatory agents:retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med,2002.166(9):p.1197-205.
106. Ronco, C., et al., A pilot study of coupled plasma filtration with adsorption in septic shock. Crit Care Med,2002.30(6):p.1250-5.
107. Gangloff, M., A.N. Weber, and N.J. Gay, Conserved mechanisms of signal transduction by Toll and Toll-like receptors. J Endotoxin Res,2005.11(5):p.294-8.
108. Morath, S., A. Geyer, and T. Hartung, Structure-function relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus. J Exp Med,2001.193(3):p.393-7.
109. Seydel, U., et al., Intrinsic conformation of lipid A is responsible for agonistic and antagonistic activity. Eur J Biochem,2000.267(10):p.3032-9.
110. Vasselon, T. and P.A. Detmers, Toll receptors:a central element in innate immune responses. Infect Immun,2002.70(3):p.1033-41.
111. Inohara, N., Y. Ogura, and G. Nunez, Nods:a family of cytosolic proteins that regulate the host response to pathogens. Curr Opin Microbiol,2002.5(1):p.76-80.
112. Aderem, A. and R.J. Ulevitch, Toll-like receptors in the induction of the innate immune response. Nature,2000.406(6797):p.782-7.
113. 许元文,连续性肾脏替代治疗与间歇性血液透析治疗多器官功能障碍综合征的疗效比较.中华肾脏病杂志,2001(5)：p.4.
114. Cole, L., et al., A phase II randomized, controlled trial of continuous hemofiltration in sepsis. Crit Care Med,2002.30(1):p.100-6.
115. 吴立峰,早期血液净化治疗对全身炎症反应综合征及脓毒症患者治疗作用的研究.现代实用医学,2009.21(2)：p.4.
116. Shoji, H., Extracorporeal endotoxin removal for the treatment of sepsis:endotoxin adsorption cartridge (Toraymyxin). Ther Apher Dial,2003.7(1):p.108-14.
117. 黎磊石,季.,连续性血液净化.2004,南京：东南大学出版社.
118. Cho, K.C., et al., Survival by dialysis modality in critically ill patients with acute kidney injury. J Am Soc Nephrol,2006.17(11):p.3132-8.
