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1.血液净化溶质清除机制及膜材料、模式对溶质清除影响
2.高肌红蛋白血症患者血液净化治疗：模式选择及其研究
P1
血液净化溶质清除机制及膜材料、模式对溶质清除影响
=[溶质]Ultrafiltration/[溶质]Plasma=1-PB
Convective Clearance( CICVVH(Post)) =Sc×QUF (Ultrafiltration rate)
Convective Clearance(CI CVVH(Pre))
=Sc×QUF×CF(Correction factor)
横轴作为流速，纵轴作为溶质的清除率，发现前稀释溶质的清除效率明显低于后稀释滤过。
Saturation Coefficient(Sd)
=[溶质]Utrafiltration/[溶质]Plasma
CICVVHD≈Qd×Sd ；CICVVHDF=(Qf Qd)×Sd
上图所示纵轴是溶质清除率，绿色的曲线是透析模式，黑色的曲线是滤过模式，红色的曲线是模仿人对不同分子质量的溶质清除率。大于5000Da，清除效率都不好。肌红蛋白的分子质量大概在17000Da多一点，它的滤过清除要差一些。如果滤器的孔径再大一些，它的清除效率就会更高一点。
·High Flux：高通量Kuf>20ml/h/mmHg
·High Cut Off (HCO)：40-100Kda
·CRRT滤器对溶质的筛选系数(SC, Sieving Coefficient)：超滤液中溶质浓度与滤器前血浆溶质浓度的比值，是溶质透过滤器膜能力的定量指标；SC越高表明滤器膜材料对该溶质清除能力越强，SC接近1时提示溶质近乎可自由通过
超高通量其实相当于高截留分子量，截留的分子量在40000-60000Da。
高通量的对不同分子质量的清除率，要是10000Da大概清除效率能够达到0.5左右筛选系数。如果是高截留分子量10000Da ，大概就能达到0.8/0.9，几乎所有的都能通过。
第一种CTA，三醋酸纤维素膜，这种膜的生物相溶性差一点。第二种PMMA，聚甲基丙烯酸甲酯膜，吸附性非常强。第三种PAN，聚丙烯晴膜，这个膜的吸附作用非常强，无论是内侧膜的中间带，还有膜的外侧，对这些炎症因子蛋白的吸附都非常强，所以这样的吸附作用，我们要去关注。
AN-69膜明显对肿瘤坏死因子TNF-α吸附作用非常强。
把PMMA膜和PAN膜列为急性透析膜，也就是在急性病人中去用这样的膜，它的吸附性更强。
本意是要让它吸附肝素，延长滤器的寿命。但是滤器寿命没有延长，对各种炎症因子的吸附增强了。
The in vitro experimental setup was comprised of a solution reservoir.
The investigated hollow-fiber hemofilters were AN69ST, PMMA, and a polysulfone (PS)hemofilter.
The first layer is composed of a polyacrylonitrile copolymer made up of acrylonitrile and methallylsulfonate. The negative charge of the sulfonate helps in adsorbing the cytokines.
The second layer is composed of positively charged polyethyleneimine(聚乙酰亚胺)， which adsorbs the endotoxins.
The third layer is pre grafted with heparin conferring antithrombogenic property.
DAMPs damage-associated molecular patterns,FGF fibroblast growth factor,HMGB-1 high-mobility group box 1，MCP-1 monocyte chemoattractant protein 1，MIP macrophage inflammatory protein,PAI-1 plasminogen activator-inhibitor 1.PAMPs pathogen-associated molecular patterns.PCT procalcitonin,TSST-1 toxic shock syndrome toxin 1.
P2
高肌红蛋白血症患者血液净化治疗：模式选择及其研究
严重的低血容量；致死性电解质紊乱：高钾、高磷和低钙血症等；高代谢状态；高肌红蛋白血症：加重肾血管收缩、管型形成堵塞远端肾小管以及直接毒性引起的小管损伤，致AKI。
酸性条件下比如肌红蛋白管型，它本身是直接的肾小管堵塞。它会直接刺激血管痉挛狭窄，导致灌注不强，出现明显的炎症因子释放炎症。所以这三重机制导致肾损伤加重，是肾损伤的主要原因。干预的措施里，如果血流动力学稳定，可以选择这样的一个RT治疗会更好一点，但是一定要考虑用高通量的膜。
The first factor we need to recognize is that the greatest filter for removing myoglobin is the kidney, and in critical care nephrology there is no preventive kidney replacement therapy.
However, the kidneys need a perfusion pressure and fluid volume to help them eliminate the toxin.
The initiation of renal replacement therapy in clinical practice should not be managed by the myoglobin or CK serum concentration but by the status of renal impairment, with complications such as life-threatening hyperkalemia, hypercalcemia, hyperazotemia, anuria or hyperhydration without response to diuretic therapy.
Objective: To test the ability of a novel super high-flux (SHF) membrane with a larger pore size to clear myoglobin from serum.
Setting: The ICU of a university teaching hospital.
Subject: A patient with serotonin syndrome complicated by severe rhabodomyolysis and oliguric acute renal failure.
Method: Initially CVVH was performed at 2 /hour ultrafiltration (UF) with a standard polysulphone 1.4 m2 membrane (cutoff point, 20 kDa), followed by CVVH with a SHF membrane (cutoff point, 100 kDa) at 2 hour UF, then at 3 /hour UF and then at 4 /hour UF, in an attempt to clear myoglobin.
Progressive reduction of serum myoglobin concentration over a 48-hour period using super high-flux(SHF) continuous veno-venous hemo-filtration (CVVH). The serum concentration of myoglobin remained>100,000 ug/l until commencement of SHF CVVH.
Images of ultrafiltration fluid demonstrating progressive reduction in pigmentation over a 3-day period concurrent with treatment using super high-flux continuous veno-venous hemofiltration. ICU, intensive care unit.
Conclusions: SHF hemofiltration achieved a much greater clearance of myoglobin than conventional hemofiltration, and it may provide a potential modality for the treatment of myoglobinuric acute renal failure.
17例病例经过了这样的治疗，发现它都明显的清除，而且肌红蛋白很高时，肾脏也是完全恢复的。大家要去特别关注这样的一些问题。
Bars indicate mean percentage baseline myoglobin concentration at respective time points for different types of RRT and filters.
White bars=Standard high-flux filter
Grey bars =HCO filter (1.1 m 2)
black bars =HCO filter (2.1 m2)
Conclusions: As a novel approach, HCO RRT allows for rapid and effective removal of myoglobin from the circulation. In light of the pathogenic role in AKI, reducing exposure of the kidney to myoglobin may improve renal recovery and patient outcome. Our data pave the way for prospective trials, addressing this issue.
Conclusions: Myoglobin clearance using continuous veno-venous hemodialysis with high cutoff dialyzer and regional citrate anticoagulation is better than that with continuous veno-venous hemodiafiltration with regional citrate anticoagulation.
CK creatine kinase,Myo myoglobin
-1: day-1, 0：day 0， 1：day 1，green beams: decrease of CK during CS treatment (=group 1)，red beams: increase of CK during CS treatment (-group 2)
Conclusion: Blood purification with Cytosorb during high-flux dialysis led to a significant reduction of myoglobin in patients with severe rhabdomyolysis.
The effect might be obscured by sustained rhabdomyolysis, which was seen in patients with rising CK during treatment. Prospective clinical trials would be useful in investigating its benefits in avoiding permanent kidney damage.
Background: Rhabdomyolysis can cause AKI. It remains controversial whether or not myoglobin can be removed from the circulation with extracorporeal therapy and decrease the incidence of AKI. Therefore, we examined myoglobin removal in a series of 11 patients with oliguric AKI treated with HVHE.
Methods: Patients received prefilter hemofiltration using a polysulphone filter with a molecular size cutoff of 65 kDa and a surface area of 1.7 m2. Sieving coefficients and myoglobin clearances were calculated at 6， 12， and 24 h after the start of hemofiltration.
Replacement fluid was administered before filter at a rate of at least 40 ml/kg/h. Blood flow rates were 200-250 ml/min.
Results: The mean sieving coefficient was 0.158， and the mean myoglobin clearance was 8.7 ml/min.
有一些血凝块蛋白粘附或者粘附在滤器表面，使得滤器随着治疗时间延长，溶质的清除效率下降，因此滤器性能的衰减可能是清除率下降的最主要原因。
血浆置换能清除一部分肌红蛋白，如果还在继续产生的状态下，不建议做血浆置换来清除它。
血液净化溶质清除能力与治疗模式、剂量密切相关，膜材料尤为重要
肌红蛋白分子质量17KD，CRRT治疗选择高截留分子量滤器更具优势
吸附能力强的滤器/吸附柱对肌红蛋白清除更有利，关注滤器性能衰减！
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