ICU中的血液净化治疗最新进展.ppt
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Blood Purification in the ICU: State of the Art
ICU中的血液净化治疗：最新进展
A/Prof. Rinaldo Bellomo
Austin & Repatriation Medical Centre
Melbourne
Australia
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 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 (MW<9,000); IL-6 (MW<22,000)
? 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, vasopressin, endorphin, myocardial depressant factors (MW<5,000), 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2-3万道尔顿
? 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 vivo
? 在体内试验中也可以黏附细胞因子
? Can filter some mediators in vitro
? Can filter some mediators in vivo
? 在体内及体外试验均可滤出一定的因子
CRRT and complement
CRRT与补体
TNF levels: CVVH vs. CVVHD
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36-39公斤的猪
? Blood flow 300 ml/min
? UF flow 6000 ml/hr
? Replacement fluid given pre-filter
? Polysulfone filters (Amicon, USA)
? 多聚砜膜
? IV endotoxin over 30 minutes
HVHF and RVEF右室
HVHF and MAP
Effect of septic UF on MAP
Effect of HVHF on ischemic gut injury
HVHF
? HVHF may be beneficial in human septic shock
? 高容量血滤可能对感染性休克病人有益
? If Hct of 30% and blood flow of 300 ml/min and pre-dilution...small solute clearance = approx. 60-70 ml/min (110ml/kg/hr)
? 假设HCT＝30%，血流速度＝300ml/min,而且采用前置换...那么小分子物质的清除率(SC)≈60-70ml/min(110ml/kg/hr)
? In 70 kg patient in pre-dilution......need about 11 L/hr of UF rate.....less if post-dilution but need big blood flows (>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 MAP after IV LPS
HVHF vs. CVVH
? 10 patients with septic shock and ARF
? Noradrenaline dependent
? Randomized to 8 hrs of HVHF (6L/hr) or CVVH (1L/hr) in random order
? Physiological outcome: hemodynamic response
? Biological outcome: 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 membrane
? Blood flow: 300 ml/min
? Catheter: 13.5 Fr double lumen Niagara (Bard)
? Replacement fluid: 2 L/hr pre and 4L/hr post
? Anticoagulation: heparin/protamine regional approach
? Buffer: 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)
Norepinephrine Requirements:
HVHF vs. CVVH
% Change in Norepinephrine
Dose: HVHF vs CVVH
C3a: HVHF (6 L) vs. CVVH (1 L)
C5a: HVHF (6 L) vs. CVVH (1 L)
IL-10 during CVVH
HVHF:
C3a: Serum vs. UF concentration
TNF: HVHF vs. CVVH
IL-8: HVHF vs. CVVH
Conclusions
? HVHF has beneficial short term effects in human septic shock similar to those in animals
? 高容量血滤对感染中毒性休克病人在一段时间内是有益的，这一点与动物试验结果类似
? With AN69 and molecules >8-9 kD it results in adsorptive removal, not filtration of inflammatory mediators
? 使用AN69的滤器，对于分子量>8-9千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
Short Term-Very HVHF
? Patrick Honore et al. (Crit Care Med 2000; 28: 3581-3587)
? 20 patients in severe refractory septic shock
? 20例严重的难以控制的感染中毒性休克病人
? 4 hours of HVHF (blood flow 450 ml/min, 1.6 m2 Fresenius polysulfone filter, bicarbonate buffer, post-dilution, UF rate 8750 ml/hr)
? 4小时HVHF(血流450ml/min,1.6m2多聚砜膜，后置换，UF＝8750ml/hr)
? Approx. small solute clearance: 116ml/kg/hr
? 小分子物质的清除率≈116ml/kg/hr
Results
? 11 responders (rapid increase in CI, MVSO2, pH>7.3 and 50% reduction in adrenaline dose)
? 11例有反应的病人
? 9 of 11 responders survived
? Responders weighed less : 66 vs. 83 kg
? 有反应的病人体重较无反应者体重偏轻
? Responders got more UF: 132 ml/kg/min vs. 107 ml/kg/min
? 那么有反应的病人UF则要高于无反应者
? Responders were treated earlier: 6.5 vs. 13.8 hrs
? 同时也发现，有反应的病人治疗要早于无反应者
Comments
注解
? 但这一试验本身存在问题：
? No controls
? No randomization
? No predefined criteria of response
? 没有预先制定有反应组的诊断标准
? However.....
? Provocative study
? 研究是具有煽动性的
? Findings consistent with expectations
? 与期望的结果一致
Conclusions
? We have no consensus definition for the term "HVHF" but we have several phase I studies suggesting that "more" UF might be better.......（后略) ......
Blood Purification in the ICU: State of the Art
ICU中的血液净化治疗：最新进展
A/Prof. Rinaldo Bellomo
Austin & Repatriation Medical Centre
Melbourne
Australia
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 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 (MW<9,000); IL-6 (MW<22,000)
? 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, vasopressin, endorphin, myocardial depressant factors (MW<5,000), 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2-3万道尔顿
? 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 vivo
? 在体内试验中也可以黏附细胞因子
? Can filter some mediators in vitro
? Can filter some mediators in vivo
? 在体内及体外试验均可滤出一定的因子
CRRT and complement
CRRT与补体
TNF levels: CVVH vs. CVVHD
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36-39公斤的猪
? Blood flow 300 ml/min
? UF flow 6000 ml/hr
? Replacement fluid given pre-filter
? Polysulfone filters (Amicon, USA)
? 多聚砜膜
? IV endotoxin over 30 minutes
HVHF and RVEF右室
HVHF and MAP
Effect of septic UF on MAP
Effect of HVHF on ischemic gut injury
HVHF
? HVHF may be beneficial in human septic shock
? 高容量血滤可能对感染性休克病人有益
? If Hct of 30% and blood flow of 300 ml/min and pre-dilution...small solute clearance = approx. 60-70 ml/min (110ml/kg/hr)
? 假设HCT＝30%，血流速度＝300ml/min,而且采用前置换...那么小分子物质的清除率(SC)≈60-70ml/min(110ml/kg/hr)
? In 70 kg patient in pre-dilution......need about 11 L/hr of UF rate.....less if post-dilution but need big blood flows (>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 MAP after IV LPS
HVHF vs. CVVH
? 10 patients with septic shock and ARF
? Noradrenaline dependent
? Randomized to 8 hrs of HVHF (6L/hr) or CVVH (1L/hr) in random order
? Physiological outcome: hemodynamic response
? Biological outcome: 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 membrane
? Blood flow: 300 ml/min
? Catheter: 13.5 Fr double lumen Niagara (Bard)
? Replacement fluid: 2 L/hr pre and 4L/hr post
? Anticoagulation: heparin/protamine regional approach
? Buffer: 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)
Norepinephrine Requirements:
HVHF vs. CVVH
% Change in Norepinephrine
Dose: HVHF vs CVVH
C3a: HVHF (6 L) vs. CVVH (1 L)
C5a: HVHF (6 L) vs. CVVH (1 L)
IL-10 during CVVH
HVHF:
C3a: Serum vs. UF concentration
TNF: HVHF vs. CVVH
IL-8: HVHF vs. CVVH
Conclusions
? HVHF has beneficial short term effects in human septic shock similar to those in animals
? 高容量血滤对感染中毒性休克病人在一段时间内是有益的，这一点与动物试验结果类似
? With AN69 and molecules >8-9 kD it results in adsorptive removal, not filtration of inflammatory mediators
? 使用AN69的滤器，对于分子量>8-9千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
Short Term-Very HVHF
? Patrick Honore et al. (Crit Care Med 2000; 28: 3581-3587)
? 20 patients in severe refractory septic shock
? 20例严重的难以控制的感染中毒性休克病人
? 4 hours of HVHF (blood flow 450 ml/min, 1.6 m2 Fresenius polysulfone filter, bicarbonate buffer, post-dilution, UF rate 8750 ml/hr)
? 4小时HVHF(血流450ml/min,1.6m2多聚砜膜，后置换，UF＝8750ml/hr)
? Approx. small solute clearance: 116ml/kg/hr
? 小分子物质的清除率≈116ml/kg/hr
Results
? 11 responders (rapid increase in CI, MVSO2, pH>7.3 and 50% reduction in adrenaline dose)
? 11例有反应的病人
? 9 of 11 responders survived
? Responders weighed less : 66 vs. 83 kg
? 有反应的病人体重较无反应者体重偏轻
? Responders got more UF: 132 ml/kg/min vs. 107 ml/kg/min
? 那么有反应的病人UF则要高于无反应者
? Responders were treated earlier: 6.5 vs. 13.8 hrs
? 同时也发现，有反应的病人治疗要早于无反应者
Comments
注解
? 但这一试验本身存在问题：
? No controls
? No randomization
? No predefined criteria of response
? 没有预先制定有反应组的诊断标准
? However.....
? Provocative study
? 研究是具有煽动性的
? Findings consistent with expectations
? 与期望的结果一致
Conclusions
? We have no consensus definition for the term "HVHF" but we have several phase I studies suggesting that "more" UF might be better.......（后略) ......
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