高通量血液濾過(guò)在膿毒癥患者中的應(yīng)用價(jià)值--第1次修改

1、高容量血液濾過(guò)在膿毒癥治療中的臨床應(yīng)用及進(jìn)展王力軍 膿毒癥是感染引起的全身炎癥反應(yīng)綜合征，臨床上證實(shí)有細(xì)菌存在或有高度可疑感染灶。其病理機(jī)制為細(xì)胞因子的瀑布樣反應(yīng)，導(dǎo)致促炎/抗炎介質(zhì)之間的失衡。膿毒癥進(jìn)一步發(fā)展為嚴(yán)重膿毒癥/膿毒性休克，甚至多器官功能衰竭，近年來(lái)，盡管臨床醫(yī)生在嘗試多種治療手段 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.，嚴(yán)重膿毒癥患者死亡率仍高達(dá)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.。高容量血液濾過(guò)(High volume hemofiltration, HVHF)，也稱高通量血液濾過(guò)，或稱強(qiáng)化腎臟替代治療(High-intensity continuous renal replacement therapy)，是在常規(guī)容量血液濾過(guò)的基

6、礎(chǔ)上，衍生出一種新的血液凈化療法 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具有清除炎癥介質(zhì)，維持促炎/抗炎介質(zhì)間平衡、重建免疫穩(wěn)態(tài)、改善氧合、血流動(dòng)力學(xué)及器官功能狀態(tài)、穩(wěn)定內(nèi)環(huán)境和降低死亡率等作用，已應(yīng)用于膿毒癥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.。同時(shí)，HVHF治療中亦存在諸多問(wèn)題 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.。本文對(duì)HVHF在膿毒癥患者的臨床應(yīng)用及進(jìn)展做一綜述。1. HVHF與膿毒癥1. 1 HVHF概況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.首先將血液濾過(guò)應(yīng)用于臨床。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、癥患者的死亡率。HVHF是在持續(xù)靜-靜脈血液濾過(guò)(Continuous veno-venous hemofiltration, CVVH)的基礎(chǔ)上發(fā)展起來(lái)。CVVH的置換劑量達(dá)25 - 30 ml(kg·h)時(shí)，即可滿足清除中、小分子物質(zhì)和穩(wěn)定內(nèi)環(huán)境等作用，該劑量稱為標(biāo)準(zhǔn)(常規(guī))劑量或腎臟替代劑量。然而究竟置換劑量達(dá)到多少可視為HVHF，國(guó)際上尚無(wú)確切的標(biāo)準(zhǔn) Rimmelé T, Kellum JA. Clinical review: Blood purification for sepsis. Critical Care. 2011, 15:205.。近期學(xué)者就HVHF的

12、概念達(dá)成共識(shí)(Pardubice共識(shí))：即CVVH時(shí)置換劑量需達(dá)到50 - 70 ml(kg·h )；或者首先以100 -120 ml(kg·h)的置換劑量進(jìn)行CVVH 4-8 h，然后改為腎臟替代劑量 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.。近年來(lái)，出現(xiàn)了脈沖式高容量血液濾過(guò)(Pulse high volume hemofiltration, PHVHF)的概念：即每日首先以較大的置換劑量(通常超過(guò)85 ml(kg·h)進(jìn)行CVVH，然后改為較小的替代劑量(如35 ml(kg·h)繼續(xù)治療。PHVHF與HVHF相比，在保留HVHF治療益處的同時(shí)，降低了治療成本及醫(yī)護(hù)人員工作量，減少了出現(xiàn)邏輯錯(cuò)誤的概率，在臨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治療膿毒癥的優(yōu)勢(shì)1.2.1 清除炎癥介質(zhì)炎癥細(xì)胞因子是引起失控性炎癥反應(yīng)和組織損害的

16、關(guān)鍵介質(zhì) 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治療膿毒癥最主要的病理生理學(xué)機(jī)制，可能是通過(guò)對(duì)流及吸附等方法，非特異性的清除血液中炎癥細(xì)胞因子，緩解患者的急性狀態(tài)，為臨床有效性治療創(chuàng)造條件及贏得時(shí)間

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，有學(xué)者對(duì)膿毒癥患者進(jìn)行HVHF后發(fā)現(xiàn)，患者血流動(dòng)力學(xué)及存活率明顯改善的情況下，血液內(nèi)的細(xì)胞因子水平并沒(méi)有明顯降低，提示HVHF具有其他的機(jī)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“介質(zhì)傳遞假說(shuō)”，即在HVHF治療中，輸入大量(4872 L/d)置換液，顯著增加淋巴回流，達(dá)正常狀態(tài)的2080倍，提高組織間質(zhì)和血液介質(zhì)/細(xì)胞因子交換，改善淋巴細(xì)胞功能，間接增加從血液中清除炎癥介質(zhì)的機(jī)會(huì)。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.發(fā)現(xiàn)，HVHF組心輸出量、每搏輸出量及平均動(dòng)脈壓明顯改善，但兩組間血液中腫瘤壞死因子(Tumor necrosis factor-, TNF-)水平無(wú)統(tǒng)計(jì)學(xué)差異，而HVHF組心肌細(xì)胞內(nèi)TNF-明顯下降。推測(cè)血流動(dòng)力學(xué)的改善，可能是HVHF降低了心肌細(xì)胞內(nèi)，而非血液中的TNF-水平所致。吸附是HVHF時(shí)清除炎癥介質(zhì)的重要機(jī)制。血液灌流(Hemoperfusion, HP)通過(guò)活性炭或樹(shù)脂，吸附血液中的大分子、蛋白結(jié)合率高的炎癥介質(zhì)。目前，HP的安全性

23、及有效性得到驗(yàn)證，已應(yīng)用于急、危重病患者的治療 王力軍，余慕明，柴艷芬。血液灌流對(duì)急性中毒患者內(nèi)環(huán)境影響的研究。中華急診醫(yī)學(xué)雜志。2014，23(11)：1214-1217。 王力軍，柴艷芬。血液灌流技術(shù)在臨床上的應(yīng)用新進(jìn)展。中國(guó)醫(yī)師進(jìn)修雜志。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. 。理論上HP序貫HVHF治療膿毒癥，能更有效清除細(xì)胞因子，改善患者臨床癥狀及預(yù)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.將患者隨機(jī)分為兩組，治療組采取HP 2 h + HVHF

27、10 h(置換劑量4065 ml/(kg·h)，對(duì)照組采取HVHF 12 h(置換劑量與對(duì)照組相同)，連續(xù)治療3 d。結(jié)果發(fā)現(xiàn)，治療第5 d時(shí)，治療組患者血液中TNF-、白細(xì)胞介素-1(Interleukin-1, IL-1)和IL-6等水平低于對(duì)照組，提示HP序貫HVHF治療能更有效的清除炎癥介質(zhì)。1.2.2 改善血流動(dòng)力學(xué)及氧合HVHF不僅能清除炎癥介質(zhì)，尚能清除心肌抑制因子等血管活性物質(zhì)，改善患者的血流動(dòng)力學(xué)狀態(tài) 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.發(fā)現(xiàn)，HVHF(6L/h)可提高右室射血分?jǐn)?shù)、心輸出量及平均動(dòng)脈壓。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. 采用不同置換劑量對(duì)膿毒癥患者血管收縮藥物使用量的研究后指出，相對(duì)于35 ml(kg·

31、h)的置換劑量，65 ml(kg·h)組患者在維持平均動(dòng)脈壓65 mmHg的情況下，明顯減少了血管收縮藥物的使用，差異具有統(tǒng)計(jì)學(xué)意義(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可明顯降低肺毛細(xì)血管的通透性，減少血管外肺水，改善膿毒癥患者肺功能，提高氧合指數(shù)。然而，也有學(xué)者認(rèn)為HVHF未能有效改善膿毒癥患者的血流動(dòng)力學(xué)狀態(tài)，甚至在治療早期，可降低心輸出量，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 改善預(yù)后多數(shù)學(xué)者認(rèn)為，HVHF可改善膿毒癥患者預(yù)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.。遺憾的是，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. 學(xué)者在歐洲3個(gè)國(guó)家18個(gè)ICU，進(jìn)行了迄今為止規(guī)模最大的多中心、隨機(jī)對(duì)照的IVOIRE研究后指出，與35 ml(kg·h)相比，70 ml(kg·h) 的置換劑量在降低患者死亡率及減少住院時(shí)間等指標(biāo)上并無(wú)優(yōu)勢(shì)。此與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.等研究結(jié)果相似。究其原因，首先，膿毒癥是以炎癥介質(zhì)的大量生成為基本特征，使用傳統(tǒng)濾器的HVHF不能有效及持續(xù)地清除炎癥介質(zhì) 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，及時(shí)和足量的抗菌素是治療膿毒癥的關(guān)鍵，HVHF清除了大量的抗菌素，使其不能達(dá)到有效的血藥濃度，導(dǎo)致治療失敗和增加不良預(yù)后的風(fēng)險(xiǎn) 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時(shí)清除多種微量元素，導(dǎo)致電解質(zhì)紊亂，丟失營(yíng)養(yǎng)物質(zhì)，從而抵消了其正性治療作用 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治療膿毒癥存在的問(wèn)題2.1.1 HVHF的劑量選擇置換劑量超過(guò)35 ml(kgh)，即可被認(rèn)為HVHF。早期試驗(yàn)表明，置換劑量越高，血流動(dòng)力學(xué)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)作為截點(diǎn)，似乎太低，臨床上一般需達(dá)到50 70 ml(kgh)；如進(jìn)行PHVHF，可選擇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.。無(wú)限制的增加置換劑量，并不能改善患者預(yù)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.，反而增加護(hù)士工作量和患者經(jīng)濟(jì)負(fù)擔(dān) 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治療時(shí)機(jī)及濾器選擇關(guān)于何時(shí)對(duì)膿毒癥患者進(jìn)行HVHF治療，目前尚無(wú)統(tǒng)一的標(biāo)準(zhǔn) 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.對(duì)心外科術(shù)后伴有急性腎衰竭及心源性休克的患者進(jìn)行單因素研究后發(fā)現(xiàn)，與死亡組相比，術(shù)后實(shí)施HVHF越早(16±15) h vs (34±27) h)，術(shù)后72 h內(nèi)實(shí)施HVHF

53、越長(zhǎng)(58±13) h vs (34±18) h)，患者存活率越高，具有統(tǒng)計(jì)學(xué)差異(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.認(rèn)為，膿毒癥患者開(kāi)始HVHF治療時(shí)間越早，存活率越高。提示應(yīng)盡早開(kāi)始HVHF治療。濾器是決定HVHF治療效能的重要因素之一。某些特殊材質(zhì)的濾器(如聚丙烯腈(polyacrylonitrile)和聚甲基丙烯酸甲酯(polymethylmethacrylate)膜)能更有效的清除炎癥介質(zhì)，改善血流動(dòng)力學(xué)狀態(tài)，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.。相對(duì)于高通量(high-flux, HF，濾器孔徑0.01m)，高截留分子量 (high-molecular-weight cutoff, HCO，濾器孔徑0.02m) 的濾器，似乎

57、可更有效的清除細(xì)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.對(duì)膿毒癥患者進(jìn)行治療后發(fā)現(xiàn)，與HF組相比，HCO組患者的IL-6、IL-8和IL-10的水平出現(xiàn)具有統(tǒng)計(jì)學(xué)意義的下降(P值分別為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.認(rèn)為，HCO能高效清除高遷移率蛋白-1等晚期炎癥介質(zhì)。吸附是HVHF清除炎癥介質(zhì)的重要機(jī)制之一，理論上濾器具飽和吸附的時(shí)限。超出此時(shí)限，濾器吸附能力明顯降低。HVHF有效治療的時(shí)間，多在開(kāi)始6 h以內(nèi) 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研究中出現(xiàn)的陰性結(jié)果，很可能與較低的濾器更換頻率(48 h)有關(guān) 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