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1、Blood Purification in the ICU: State of the ArtICU中的血液净化治疗：最新进展,A/Prof. Rinaldo BellomoAustin & Repatriation Medical CentreMelbourneAustralia,Similarities between sepsis and renal failure感染与肾功能衰竭之间的相似之处,“Uremia”尿毒症Organ dysfunction induces “toxemia”器官功能不全导致的“毒血症”“Toxemia” induces widespread injury毒血
2、症导致的广泛损伤The mediators of “toxemia” are ill-defined关于毒血症的因子定义是错误的Continuous removal beneficial持续清除是有益的Use Hemofiltration使用血滤,“Septicemia”败血症Organ dysfunction induces “toxemia”器官功能不全导致的“毒血症”“Toxemia” induces widespread injury毒血症导致的广泛损伤The mediators of “toxemia” are ill-defined关于毒血症的因子定义是错误的Continuous
3、removal beneficial ?持续地清除是否有益？Use Hemofiltration? 是否可使用血滤？,The Mediators of Sepsis (the Humoral Theory of Sepsis),TNF (MW 17,500-trimer)IL-1 (MW 17,000); IL-8 (MW9,000); IL-6 (MW22,000)Complement: Factor D (MW 25,000), C3a, C5a (MW 11,500)Eicosanoids: TxB2, PGE2 (MW 500)PAF: MW 600血小板活化因子Others: VIP
4、, vasopressin, endorphin, myocardial depressant factors (MW5,000), Phospholipase其它：Vasoactive intestinal peptide,血管活性药物，内皮素，心肌抑制因子小于5千道尔顿，磷脂酶,The CRRT Membranes,Nominal Pore size: 20- 30 kD普通孔径为23万道尔顿Highly absorptive capacity高黏附性Can bind many mediators in vitro在体外试验中可以黏附许多因子Can bind mediators in vi
5、vo在体内试验中也可以黏附细胞因子Can filter some mediators in vitroCan filter some mediators in vivo在体内及体外试验均可滤出一定的因子,CRRT and complementCRRT与补体,ng/ml for C3a(/ 10 for C5a),Time on CVVH at 2L / h UF rate,p 0.001,p 0.01,C3a SC = 0.2C5a SC = 0.02,Hoffman et al. Intensive Care Med 1996,TNF levels: CVVH vs. CVVHD,p 0.0
6、2,PATIENTS,%Change,No TNF in UF!,J Kellum, Crit Care Med 1998,High Volume Hemofiltration,The term was first used by Grootendorst in 1992这一术语是在1992年，由Grootendorst 首次提出的Animal experiments in pigs (weight 36-39 kg)所选动物为体重在3639公斤的猪Blood flow 300 ml/minUF flow 6000 ml/hrReplacement fluid given pre-filter
7、Polysulfone filters (Amicon, USA)多聚砜膜IV endotoxin over 30 minutes,HVHF and RVEF右室,p0.001,Grootendorst et al, Intensive Care Med 1992,HVHF and MAP,p0.001,Grootendorst et al, Intensive Care Med 1992,Effect of septic UF on MAP,2L Normal UF,2L LPS UF,Change in MAP(mmHg),Grootendorst et al, J Crit Care 1
8、993,p 0.05,Effect of HVHF on ischemic gut injury,HVHF,No CVVH,Gut injuryscore,Mucosal injury粘膜损伤,Sloughing腐烂,Ulcers溃疡,Perforation穿孔,p 400 ml/min)在一个70公斤的病人进行前置换时，超滤量（UF）11L/hr，小于后置换，但后置换需要更大的血流速度（400ml/min）,HVHF,11L/hr of UF is technically demanding/very difficult in human beings病人身上实现11L/hr的超滤量，在技术
9、上是极难实现的Can we achieve similar results at lower UF rates?是否我们能够使用较小一点的超滤量而达到相似的治疗效果呢？Dog experiment in 20 kg dogs and UF rate of 2000ml/min (blood flow 200 ml and pre-dilution)在体重为20KG的狗身上，使用2L/hr的超滤量（血流速度为200ml/min并采用前置换）Small solute clearance = approx. 80 ml/kg/hr小分子物质的清除率（SC）80ml/kg/hr,Change in M
10、AP after IV LPS,Time after IV LPS (minutes),MAP(mmHg),p 0.05,Bellomo et al AJRCCM 2000; 161: 1429-1436,HVHF vs. CVVH,10 patients with septic shock and ARFNoradrenaline dependentRandomized to 8 hrs of HVHF (6L/hr) or CVVH (1L/hr) in random orderPhysiological outcome: hemodynamic responseBiological ou
11、tcome: Complement and cytokines这里是一项10个病人的试验，他们均患有感染中毒性休克和急性肾功能衰竭去甲肾、8小时6、1L/hr血滤生理指标：血流动力学的影响生物学指标：补体系统和细胞因子,Technique for HVHF,Filtral 16 (1.6 m2)- AN 69 membraneBlood flow: 300 ml/minCatheter: 13.5 Fr double lumen Niagara (Bard)Replacement fluid: 2 L/hr pre and 4L/hr postAnticoagulation: heparin/
12、protamine regional approachBuffer: lactate使用乳酸盐作为缓冲剂Estimate small solute clearance: approx. 85 ml/min (70 ml/kg/hr)评价小分子物质的清除率85ml/min(70ml/kg/hr),Cole, Bellomo et al. Intensive Care Med 2001; 27: 978-986,Norepinephrine Requirements: HVHF vs. CVVH,Change (g/min)over 8 h.,p 0.02,Cole, Bellomo et al.
13、 Intensive Care Med 2001 ; 27: 978-986,% Change in NorepinephrineDose: HVHF vs CVVH,% change over 8 h.,Cole, Bellomo et al. Intensive Care Med 2001 ; 27: 978-986,C3a: HVHF (6 L) vs. CVVH (1 L),ng /ml,p 0.017,*,*,TIME (hrs.),Cole, Bellomo et al. Intensive Care Med 2001 ; 27: 978-986,C5a: HVHF (6 L) v
14、s. CVVH (1 L),ng/ml,Time (hrs.),*,*,*,p0.017,Cole, Bellomo et al. Intensive Care Med 2001,IL-10 during CVVH,pg / ml,TIME (hrs),HVHF,Cole, Bellomo et al. Intensive Care Med 2001,CVVH,HVHF:C3a: Serum vs. UF concentration,ng/ml,TIME (hrs.),Maximum C3a Clearance = 3.3 mil/min,Cole, Bellomo et al. Intens
15、ive Care Med 2001,TNF: HVHF vs. CVVH,pg / ml,TIME (hrs.),Cole, Bellomo et al. Intensive Care Med 2001,IL-8: HVHF vs. CVVH,pg / ml,TIME (hrs.),*,p 8-9 kD it results in adsorptive removal, not filtration of inflammatory mediators使用AN69的滤器，对于分子量89千道尔顿的物质主要是靠黏附来清除，而不是靠滤出There is now a rationale for phase II studies现在可以进行二期临床试验,
