高通量血液滤过在脓毒症患者中的应用价值--第1次修改

1、高容量血液滤过在脓毒症治疗中的临床应用及进展王力军 脓毒症是感染引起的全身炎症反应综合征，临床上证实有细菌存在或有高度可疑感染灶。其病理机制为细胞因子的瀑布样反应，导致促炎/抗炎介质之间的失衡。脓毒症进一步发展为严重脓毒症/脓毒性休克，甚至多器官功能衰竭，近年来，尽管临床医生在尝试多种治疗手段 Opal SM, Laterre PF, Francois B, LaRosa SP, Angus DC, Mira JP, Wittebole X, Dugernier T, Perrotin D, Tidswell M, Jauregui L, Krell K, Pachl J, Takahashi

2、 T, Peckelsen C, Cordasco E, Chang CS, Oeyen S, Aikawa N, Maruyama T, Schein R, Kalil AC, Van Nuffelen M, Lynn M, Rossignol DP, Gogate J, Roberts MB, Wheeler JL, Vincent JL; ACCESS Study Group. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS ran

3、domized trial. JAMA. 2013, 309(11):1154-62. Bernard GR, Francois B, Mira JP, Vincent JL, Dellinger RP, Russell JA, Larosa SP, Laterre PF, Levy MM, Dankner W, Schmitt N, Lindemann J, Wittebole X. Evaluating the efficacy and safety of two dos

4、es of the polyclonal anti-tumor necrosis factor- fragment antibody AZD9773 in adult patients with severe sepsis and/or septic shock: randomized, double-blind, placebo-controlled phase IIb study. Crit Care Med. 2014; 42(3):504-11.，严重脓毒症患者死亡率仍高达30%50% Stevenson EK, Rubenstein AR, Radin

5、GT, Wiener RS, Walkey AJ. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis. Crit Care Med. 2014, 42(3):625-31.。高容量血液滤过(High volume hemofiltration, HVHF)，也称高通量血液滤过，或称强化肾脏替代治疗(High-intensity continuous renal replacement therapy)，是在常规容量血液滤过的基

6、础上，衍生出一种新的血液净化疗法 Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Kim I, Lee J, Lo S, McArthur C, McGuinness S, Norton R, Myburgh J, Scheinkestel C. The relationship between hypophosphataemia and outcomes during low-intensity and high-intensity continuousrenal replacement therapy. Crit Care Resusc.

7、 2014; 16(1):34-41.。HVHF具有清除炎症介质，维持促炎/抗炎介质间平衡、重建免疫稳态、改善氧合、血流动力学及器官功能状态、稳定内环境和降低死亡率等作用，已应用于脓毒症及多器官衰竭患者的救治 Rimmelé T, Kellum JA. Clinical review: Blood purification for sepsis. Critical Care. 2011, 15:205.。同时，HVHF治疗中亦存在诸多问题 Schiffl H. The dark side of high-intensity renal replacement therapy of a

8、cute kidney injury in critically ill patients. Int Urol Nephrol. 2010; 42(2):435-40.。本文对HVHF在脓毒症患者的临床应用及进展做一综述。1. HVHF与脓毒症1. 1 HVHF概况1977年，Kramer等 Kramer P, Wigger W, Rieger J, Matthaei D, Scheler F. Arteriovenous haemofi ltration: a new and simple method for treatment of over-hydrated patients resi

9、stant to diuretics. Klin Wochenschr 1977, 55:1121-1122.首先将血液滤过应用于临床。1992年，Grootendorst等 Grootendorst AF, van Bommel EF, van der Hoven B, van Leengoed LA, van Osta AL. High volume hemofiltration improves right ventricular function in endotoxin-induced shock in the pig. Intensive Care M

10、ed. 1992;18(4):235-40.首次提出HVHF的概念。2000年，Ronco等 Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, La Greca G. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet. 2000; 356:26-30.首次描述了HVHF可降低危重

11、症患者的死亡率。HVHF是在持续静-静脉血液滤过(Continuous veno-venous hemofiltration, CVVH)的基础上发展起来。CVVH的置换剂量达25 - 30 ml(kg·h)时，即可满足清除中、小分子物质和稳定内环境等作用，该剂量称为标准(常规)剂量或肾脏替代剂量。然而究竟置换剂量达到多少可视为HVHF，国际上尚无确切的标准 Rimmelé T, Kellum JA. Clinical review: Blood purification for sepsis. Critical Care. 2011, 15:205.。近期学者就HVHF的

12、概念达成共识(Pardubice共识)：即CVVH时置换剂量需达到50 - 70 ml(kg·h )；或者首先以100 -120 ml(kg·h)的置换剂量进行CVVH 4-8 h，然后改为肾脏替代剂量 Honoré PM, Jacobs R, Boer W, Joannes-Boyau O, De Regt J, De Waele E, Van Gorp V, Collin V, Spapen HD. New insights regarding rationale, therapeutic target and dose of hemofiltration a

13、nd hybrid therapies in septic acute kidney injury. Blood Purif. 2012, 33(1-3):44-51.。近年来，出现了脉冲式高容量血液滤过(Pulse high volume hemofiltration, PHVHF)的概念：即每日首先以较大的置换剂量(通常超过85 ml(kg·h)进行CVVH，然后改为较小的替代剂量(如35 ml(kg·h)继续治疗。PHVHF与HVHF相比，在保留HVHF治疗益处的同时，降低了治疗成本及医护人员工作量，减少了出现逻辑错误的概率，在临床上可能更具可行性 Ratanarat

14、 R, Brendolan A, Ricci Z, Salvatori G, Nalesso F, de Cal M, Cazzavillan S, Petras D, Bonello M, Bordoni V, Cruz D, Techawathanawanna N, Ronco C. Pulse high-volume hemofiltration in critically ill patients: a new approach for patients with septic shock. Semin Dial. 2006; 19(1):69-74. Rimmelé T,

15、Wey PF, Bernard N, Monchi M, Semenzato N, Benatir F, Boselli E, Etienne J, Goudable J, Chassard D, Bricca G, Allaouchiche B. Hemofiltration with the Cascade system in an experimental porcine model of septic shock. Ther Apher Dial. 2009; 13(1):63-70.。1.2 HVHF治疗脓毒症的优势1.2.1 清除炎症介质炎症细胞因子是引起失控性炎症反应和组织损害的

16、关键介质 Reis Machado J, Soave DF, da Silva MV, de Menezes LB, Etchebehere RM, Monteiro ML, Antônia Dos Reis M, Corrêa RR, Celes MR.Neonatal Sepsis and Inflammatory Mediators. Mediators Inflamm. 2014; 2014:269681.。HVHF治疗脓毒症最主要的病理生理学机制，可能是通过对流及吸附等方法，非特异性的清除血液中炎症细胞因子，缓解患者的急性状态，为临床有效性治疗创造条件及赢得时间

17、De Vriese AS, Colardyn FA, Philippe JJ, Vanholder RC, de Sutter JH, Lameire NH. Cytokine Removal during Continuous Hemofiltration in Septic Patients. J Am Soc Nephrol. 1999, 10: 846853. Peng Z, Pai P, Hong-Bao L, Rong L, Han-Min W, Chen H. The impacts of continuous veno-venous hemofiltration on plas

18、ma cytokines and monocyte human leukocyte antigen-DR expression in septic patients. Cytokine. 2010; 50(2):186-91.。但是，有学者对脓毒症患者进行HVHF后发现，患者血流动力学及存活率明显改善的情况下，血液内的细胞因子水平并没有明显降低，提示HVHF具有其他的机制 Peng ZY, Wang HZ, Carter MJ, Dileo MV, Bishop JV, Zhou FH, Wen XY, Rimmelé T, Singbartl K, Federspiel WJ, C

19、lermont G, Kellum JA. Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis. Kidney Int. 2012; 81(4): 363369.。Di Carlo JV等 Di Carlo JV, A1exander SR. Hemofi1tration for cytokine- driven illnesses: the mediator delivery hypot

20、hesis. Int J Artif Organs. 2005, 28: 777786. Honoré PM, Jacobs R, Boer W, Joannes-Boyau O, De Regt J, De Waele E, Van Gorp V, Collin V, Spapen HD. New insights regarding rationale, therapeutic target and dose of hemofiltration and hybrid therapies in sept

21、ic acute kidney injury. Blood Purif. 2012; 33(1-3):44-51.提出“介质传递假说”，即在HVHF治疗中，输入大量(4872 L/d)置换液，显著增加淋巴回流，达正常状态的2080倍，提高组织间质和血液介质/细胞因子交换，改善淋巴细胞功能，间接增加从血液中清除炎症介质的机会。Li C等 Li C, Zhang P, Cheng X, Chen J. High-volume hemofiltration reduces the expression of myocardial tumor necrosis

22、factor-alpha in septic shock pigs. Artif Organs. 2013, 37(2):196-202.发现，HVHF组心输出量、每搏输出量及平均动脉压明显改善，但两组间血液中肿瘤坏死因子(Tumor necrosis factor-, TNF-)水平无统计学差异，而HVHF组心肌细胞内TNF-明显下降。推测血流动力学的改善，可能是HVHF降低了心肌细胞内，而非血液中的TNF-水平所致。吸附是HVHF时清除炎症介质的重要机制。血液灌流(Hemoperfusion, HP)通过活性炭或树脂，吸附血液中的大分子、蛋白结合率高的炎症介质。目前，HP的安全性

23、及有效性得到验证，已应用于急、危重病患者的治疗 王力军，余慕明，柴艳芬。血液灌流对急性中毒患者内环境影响的研究。中华急诊医学杂志。2014，23(11)：1214-1217。 王力军，柴艳芬。血液灌流技术在临床上的应用新进展。中国医师进修杂志。2013，36(15)：74-76。 Basu R, Pathak S, Goyal J, Chaudhry R, Goel RB, Barwal A. Use of a novel hemoadsorption device for cytokine removal as adjuvant therapy in a patient with septi

24、c shock with multi-organ dysfunction: A case study. Indian Journal of Critical Care Medicine. 2014,18(12):822-824. 。理论上HP序贯HVHF治疗脓毒症，能更有效清除细胞因子，改善患者临床症状及预后 Joannes-Boyau O, Honoré PM, Perez P, Bagshaw SM, Grand H, Canivet JL, Dewitte A, Flamens C, Pujol W, Grandoulier AS, Fleureau C, Jacobs R,

25、Broux C, Floch H, Branchard O, Franck S, Rozé H, Collin V, Boer W, Calderon J, Gauche B, Spapen HD, Janvier G, Ouattara A. High-volume versus standard-volume haemoltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Car

26、e Med. 2013; 39(9):1535-46. 。Liu LY等 Liu LY, Zhu YJ, Li XL, Liang YF, Liang ZP, Xia YH. Blood hemoperfusion with resin adsorption combined continuous veno-venous hemoltration for patients with multiple organ dysfunction syndrome. World J Emerg Med. 2012, 3(1):44-48.将患者随机分为两组，治疗组采取HP 2 h + HVHF

27、10 h(置换剂量4065 ml/(kg·h)，对照组采取HVHF 12 h(置换剂量与对照组相同)，连续治疗3 d。结果发现，治疗第5 d时，治疗组患者血液中TNF-、白细胞介素-1(Interleukin-1, IL-1)和IL-6等水平低于对照组，提示HP序贯HVHF治疗能更有效的清除炎症介质。1.2.2 改善血流动力学及氧合HVHF不仅能清除炎症介质，尚能清除心肌抑制因子等血管活性物质，改善患者的血流动力学状态 Ronco C, Ricci Z, Bellomo R, Bedogni F. Extracorporeal ultrafiltration for the trea

28、tment of overhydration and congestive heart failure. Cardiology. 2001, 96: 155-68. Bellomo R, Lipcsey M, Calzavacca P,et al. Early acid-base and blood pressure effects of continuous renal replacement therapy intensity in patients with metabolic acidosis. Intensive Care Med. 2013; 39(3):429

29、-36.。Grootendorst AF等 Grootendorst AF, van Bommel EF, van der Hoven B, van Leengoed LA, van Osta AL. High volume hemofiltration improves right ventricular function in endotoxin-induced shock in the pig. Intensive Care Med. 1992;18(4):235-40.发现，HVHF(6L/h)可提高右室射血分数、心输出量及平均动脉压。Bouss

30、ekey N等 Boussekey N, Chiche A, Faure K, Devos P, Guery B, d'Escrivan T, Georges H, Leroy O. A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock. Intensive Care Med. 2008; 34(9):1646-53. 采用不同置换剂量对脓毒症患者血管收缩药物使用量的研究后指出，相对于35 ml(kg·

31、h)的置换剂量，65 ml(kg·h)组患者在维持平均动脉压65 mmHg的情况下，明显减少了血管收缩药物的使用，差异具有统计学意义(P=0.004)。Ren H等 Ren H, Jiang J, Chu Y, Ding M, Qie G, Zeng J, Wang P, Zhu W, Meng M, Wang C. Study of the effects of high volume hemofiltration on extra vascular lung water and alveolar-arterial oxygen exchange in patients with

32、septic shock. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014; 26(9):609-14.提出，HVHF可明显降低肺毛细血管的通透性，减少血管外肺水，改善脓毒症患者肺功能，提高氧合指数。然而，也有学者认为HVHF未能有效改善脓毒症患者的血流动力学状态，甚至在治疗早期，可降低心输出量，增加全身血管阻力 Sander A, Armbruster W, Sander B, Daul AE, Lange R, Peters J. Hemofiltration increases IL-6 clearance in early systemic in

33、flammatory response syndrome but does not alter IL-6 and TNF alpha plasma concentrations. Intensive Care Med. 1997, 23(8):878-84. De Vriese AS, Colardyn FA, Philippe JJ, Vanholder RC, de Sutter JH, Lameire NH. Cytokine Removal during Continuous Hemofiltration in Septic Patients. J Am Soc Nephrol. 19

34、99, 10: 846853. Joannes-Boyau O, Honoré PM, Perez P, Bagshaw SM, Grand H, Canivet JL, Dewitte A, Flamens C, Pujol W, Grandoulier AS, Fleureau C, Jacobs R, Broux C, Floch H, Branchard O, Franck S, Rozé H, Collin V, Boer W, Calderon J, Gauche B, Spapen HD, Janvier G, Ouattara A. High-volume

35、versus standard-volume haemoltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Care Med. 2013; 39(9):1535-46. 。1.2.3 改善预后多数学者认为，HVHF可改善脓毒症患者预后 Honore PM, Jamez J, Wauthier M, Lee PA, Dugernier T, Pirenne B, Hanique G,

36、 Matson JR. Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock. Crit Care Med. 2000; 28(11):3581-7. Peng ZY, Wang HZ, Carter MJ, Dileo MV, Bishop JV, Zhou FH, W

37、en XY, Rimmelé T, Singbartl K, Federspiel WJ, Clermont G, Kellum JA. Acute removal of common sepsis mediators does not explain the effects of extracorporeal blood purification in experimental sepsis. Kidney Int. 2012; 81(4): 363369. Ren H, Jiang J, Chu Y, Ding M, Qie G, Zeng J, Wang P, Zhu W, M

38、eng M, Wang C. Study of the effects of high volume hemofiltration on extra vascular lung water and alveolar-arterial oxygen exchange in patients with septic shock. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2014; 26(9):609-14.。遗憾的是，Joannes-Boyau O等 Joannes-Boyau O, Honoré PM, Perez P, Bagshaw SM, G

39、rand H, Canivet JL, Dewitte A, Flamens C, Pujol W, Grandoulier AS, Fleureau C, Jacobs R, Broux C, Floch H, Branchard O, Franck S, Rozé H, Collin V, Boer W, Calderon J, Gauche B, Spapen HD, Janvier G, Ouattara A. High-volume versus standard-volume haemoltration for septic shock patients with acu

40、te kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Care Med. 2013; 39(9):1535-46. 学者在欧洲3个国家18个ICU，进行了迄今为止规模最大的多中心、随机对照的IVOIRE研究后指出，与35 ml(kg·h)相比，70 ml(kg·h) 的置换剂量在降低患者死亡率及减少住院时间等指标上并无优势。此与Clark E Cornejo R, Romero C, Ugalde D, Bustos P, Diaz G, Galv

41、ez R, Llanos O, Tobar E. High-volume hemofiltration and prone ventilation in subarachnoid hemorrhage complicated by severe acute respiratory distress syndrome and refractory septic shock. Crit Care. 2014, 18:R7.及Zhang P Zhang P, Yang Y, Lv R, Zhang Y, Xie W, Chen J. Effect of the intensity of contin

42、uous renal replacement therapy in patients with sepsis and acute kidney injury: a single-center randomized clinical trial. Nephrol Dial Transplant. 2012; 27(3):967-73.等研究结果相似。究其原因，首先，脓毒症是以炎症介质的大量生成为基本特征，使用传统滤器的HVHF不能有效及持续地清除炎症介质 Atan R, Crosbie D, Bellomo R. Techniques of extracorporeal cy

43、tokine removal: a systematic review of the literature. Blood Purif. 2012, 33(1-3):88-100.；其次，及时和足量的抗菌素是治疗脓毒症的关键，HVHF清除了大量的抗菌素，使其不能达到有效的血药浓度，导致治疗失败和增加不良预后的风险 Joannes-Boyau O, Honoré PM, Perez P, Bagshaw SM, Grand H, Canivet JL, Dewitte A, Flamens C, Pujol W, Grandoulier AS, Fleureau C, Jaco

44、bs R, Broux C, Floch H, Branchard O, Franck S, Rozé H, Collin V, Boer W, Calderon J, Gauche B, Spapen HD, Janvier G, Ouattara A. High-volume versus standard-volume haemoltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensi

45、ve Care Med. 2013; 39(9):1535-46. ；再者，HVHF时清除多种微量元素，导致电解质紊乱，丢失营养物质，从而抵消了其正性治疗作用 Schiffl H, Lang SM. Severe acute hypophosphatemia during renal replacement therapy adversely affects outcome of critically ill patients with acute kidney injury. Int Urol Nephrol. 2013, 45(1):191-7.。2. HVH

46、F治疗脓毒症存在的问题2.1.1 HVHF的剂量选择置换剂量超过35 ml(kgh)，即可被认为HVHF。早期试验表明，置换剂量越高，血流动力学的改善程度越高 Vidal S, Richebé P, Barandon L, Calderon J, Tafer N, Pouquet O, Fournet N, Janvier G. Evaluation of continuous veno-venous hemofiltration for the treatment of cardiogenic shock in conjunction with acute failure afte

47、r cardiac surgery. European Journal of Cardio-thoracic Surgery. 2009,36:572-279.。提示以35 ml(kgh)作为截点，似乎太低，临床上一般需达到50 70 ml(kgh)；如进行PHVHF，可选择100 -120 ml(kg·h) Honoré PM, Jacobs R, Boer W, Joannes-Boyau O, De Regt J, De Waele E, Van Gorp V, Collin V, Spapen HD. New insights regarding rationale

48、, therapeutic target and dose of hemofiltration and hybrid therapies in septic acute kidney injury. Blood Purif. 2012, 33(1-3):44-51.。无限制的增加置换剂量，并不能改善患者预后 Zhang P, Yang Y, Lv R, Zhang YT, Xie WQ, Chen JH. Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acu

49、te kidney injury: a single-center randomized clinical trial. Nephrol Dial Transplant. 2012, 27: 967973. RENAL Replacement Therapy Study Investigators. RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009; 361(

50、17):1627-38.，反而增加护士工作量和患者经济负担 Paterson AL, Johnston AJ, Kingston D, Mahroof R. Clinical and economic impact of a switch from high- to low-volume renal replacement therapy in patients with acute kidney injury. Anaesthesia. 2014; 69(9):977-82.。2.1.2 HVHF治疗时机及滤器选择关于何时对脓毒症患者进行HVHF治疗，目前尚无统一的标准 Payen D, M

51、ateo J, Cavaillon JM et al. Impact of continuous venovenous hemoltration on organ failure during the early phsae of severe sepsis: a randomized controlled trail. Crit Care Med.2009, 37:803-810.。Vidal S等 Vidal S, Richebé P, Barandon L, Calderon J, Tafer N, Pouquet O, Fournet N, Janvier G. Evalua

52、tion of continuous veno-venous hemofiltration for the treatment of cardiogenic shock in conjunction with acute failure after cardiac surgery. European Journal of Cardio-thoracic Surgery. 2009,36:572-279.对心外科术后伴有急性肾衰竭及心源性休克的患者进行单因素研究后发现，与死亡组相比，术后实施HVHF越早(16±15) h vs (34±27) h)，术后72 h内实施HVHF

53、越长(58±13) h vs (34±18) h)，患者存活率越高，具有统计学差异(P 值均小于0.001)。Honore等 Honore PM, Jamez J, Wauthier M, Lee PA, Dugernier T, Pirenne B, Hanique G, Matson JR. Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractabl

54、e circulatory failure resulting from septic shock. Crit Care Med. 2000; 28(11):3581-7.认为，脓毒症患者开始HVHF治疗时间越早，存活率越高。提示应尽早开始HVHF治疗。滤器是决定HVHF治疗效能的重要因素之一。某些特殊材质的滤器(如聚丙烯腈(polyacrylonitrile)和聚甲基丙烯酸甲酯(polymethylmethacrylate)膜)能更有效的清除炎症介质，改善血流动力学状态，降低死亡率 Rimmelé T, Assadi A, Cattenoz M, Desebbe O, Lamber

55、t C, Boselli E, Goudable J,´Etienne J, Chassard D, Bricca G, Allaouchiche B. High-volume haemofiltration with a new haemofiltration membrane having enhanced adsorption properties in septic pigs. Nephrol Dial Transplant. 2009, 24: 421427. Matsumura Y, Oda S, Sadahiro T, Nakamura M, Hirayama Y, W

56、atanabe E, Abe R, Nakada TA, Tateishi Y, Oshima T, Shinozaki K, Hirasawa H. Treatment of septic shock with continuous HDF using 2 PMMA hemofilters for enhanced intensity. Int J Artif Organs. 2012; 35(1):3-14.。相对于高通量(high-flux, HF，滤器孔径0.01m)，高截留分子量 (high-molecular-weight cutoff, HCO，滤器孔径0.02m) 的滤器，似乎

57、可更有效的清除细胞因子 Rimmelé T, Kellum JA. Clinical review: Blood purification for sepsis. Critical Care. 2011, 15:205.。Haase M等 Haase M, Bellomo R, Baldwin I, Haase-Fielitz A, Fealy N, Davenport P, Morgera S, Goehl H, Storr M, Boyce N, Neumayer HH. Hemo

58、dialysis membrane with a high-molecular-weight cutoff and cytokine levels in sepsis complicated by acute renal failure: a phase 1 randomized trial. Am J Kidney Dis. 2007, 50(2):296-304.对脓毒症患者进行治疗后发现，与HF组相比，HCO组患者的IL-6、IL-8和IL-10的水平出现具有统计学意义的下降(P值分别为0.05、0.02和0.04)。此外Naka T等 Naka T, Haase M

59、, Bellomo R. 'Super high-flux' or 'high cut-off' hemofiltration and hemodialysis. Contrib Nephrol. 2010, 166:181-9.认为，HCO能高效清除高迁移率蛋白-1等晚期炎症介质。吸附是HVHF清除炎症介质的重要机制之一，理论上滤器具饱和吸附的时限。超出此时限，滤器吸附能力明显降低。HVHF有效治疗的时间，多在开始6 h以内 Boussekey N, Chiche A, Faure K, Devos P, Guery B, d&#

60、39;Escrivan T, Georges H, Leroy O. A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock. Intensive Care Med. 2008; 34(9):1646-53. 。IVOIRE研究中出现的阴性结果，很可能与较低的滤器更换频率(48 h)有关 Joannes-Boyau O, Honoré PM, Perez P, Bagshaw SM, Grand H, Canivet JL, Dewitte A, Flamens C, Pujol W, Grandoulier AS, Fleureau C, Jacobs R, Broux C, Floch H, Branchard O, Franck S, Rozé H, Collin V, Boer W, Calderon J, Gauche B, Spapen HD, Janvier G, Ouattara A. High-volume versus standard-volume haemoltration for septic shock patients with acute kidne