危重病患者的持续肾脏替代治疗协和杜斌

危重病患者的持续肾脏替代治疗,北京协和医院杜斌,病例摘要,男性, 74岁, 病历号既往史I型糖尿病18年糖尿病肾病高血压病史5年口服络活喜, 倍他乐克等药物平素BP 160 180 / 70 90 mmHg,病例摘要,2007年7月25日入院发现恶心, 呕吐1周, 伴心前区疼痛及少尿3天1周前出现恶心, 呕吐, 予对症治疗3天前出现心前区疼痛, 憋闷, 尿量减少静脉泵入NG 100 g/min, 控制BP 134/56 mmHg血Cr 861 mol/L, UO 500 ml/d (速尿400 mg/d)血液透析, 透析过程中出现心绞痛, 持续不缓解,病例摘要: 体格检查,GCSE4V5M6BT36.2CHR70 bpmRR20 bpmBP103/45 mmHgSpO298 100% (鼻导管吸氧5 lpm),病例摘要: 实验室检查,CBC: WCC 14.79, Hb 102, plt 215Chemistry (Aug 2):Na140mmol/LCl 97mmol/LK 4.2mmol/LCr745mol/LBUN 31.14mmol/LCK-MB 6.8u/LcTnI 11.56g/LGLU 21.5mmol/L,病例摘要: 尿量,心绞痛*,*发作时EKG: V3-6导联ST段压低0.1 0.2 mv,病例摘要: 临床决策,下一步的治疗措施:输液治疗?升压药物?利尿药物?间断肾脏替代(IHD)?持续肾脏替代(CRRT)?,病例摘要: MAP与组织灌注,心绞痛*,*发作时EKG: V3-6导联ST段压低0.1 0.2 mv,病例摘要: MAP与组织灌注,心绞痛*,*发作时EKG: V3-6导联ST段压低0.1 0.2 mv,内容,急性肾功能衰竭的定义与诊断,1,急性肾脏功能衰竭的治疗原则,2,持续肾脏替代治疗的原理介绍,3,4,持续肾脏替代治疗的实际应用,内容,急性肾脏功能衰竭的治疗原则,2,持续肾脏替代治疗的原理介绍,3,4,持续肾脏替代治疗的实际应用,急性肾功能衰竭的定义与诊断,1,ICU中的急性肾功能衰竭*: BEST Kidney,患病率1738/29269(5.7%, 95%CI 5.5 6.0%)诱发因素感染性休克(47.5%, 95%CI 45.2 49.5%)住院病死率60.3%(95%CI 58.0 62.6%)*少尿( 84 mg/dL),Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005; 294: 813-818,ICU中的急性肾功能衰竭*: BEST Kidney,Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005; 294: 813-818,2000年9月至2001年12月23个国家54个ICU29,269名危重病患者,急性肾功能衰竭(n = 1738, 5.7%),住院病死率60.3%,住院存活率39.7%,出院时依赖RRT13.8%,ARF患病率(Vincent JL. Contr Nephrol 2001; 132: 1-6),患病率: 差异极大 (1 25%)可能由于不同人群以及定义的差异导致,定义: 尚缺乏公认的统一诊断标准肌酐升高20%肌酐升高30%综合考虑各种指标需要进行透析,急性肾功能衰竭的定义,近期回顾28篇有关手术后急性肾功能衰竭的文章28个定义无一相同妨碍了急性肾功能衰竭的流行病学及干预治疗的研究,急性肾功能的定义,问卷调查接受调查者的基本情况ARF的定义RRT的选择560名接受调查者西欧(75%), 东欧(11%)肾内科医生(52%), ICU医生(36%),Ricci Z, Ronco C, Damico G, et al. Practice patterns in the management of acute renal failure in the critically ill patient: an international survey. Nephrol Dial Transplant 2006; 21: 690-696,急性肾功能的定义,共计199个不同的ARF定义肌酐: 58个临界值(1.5 10 mg/dl)尿量: 33个临界值(0 950 ml/24 h),Ricci Z, Ronco C, Damico G, et al. Practice patterns in the management of acute renal failure in the critically ill patient: an international survey. Nephrol Dial Transplant 2006; 21: 690-696,199,45,30,91,135,ARF的定义与诊断: RIFLE标准,Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure: definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8: R204-R212,Pubmed检索检索词: RIFLE AND renal failure终点根据RIFLE标准对患者进行分类病死率资料,RIFLE标准 & 预后,RIFLE标准 & 预后,检索结果(n = 42)临床试验综述述评信件,无关研究(n = 9),述评(n = 2),综述(n = 11),未报告研究终点(n = 6),入选研究(n = 14),RIFLE标准 & 预后,急性肾损伤(AKI): 患病率,RIFLE标准 & 预后,155/3008,1964/10112,2779/7681,2830/5941,RIFLE标准 & 预后,病死率的比数比(OR)RIFLE-无AKI1.000 (reference)RIFLE-Risk3.030 (1.732 5.299)RIFLE-Injury6.598 (3.141 13.860)RIFLE-Failure18.325 (9.147 36.713),内容,持续肾脏替代治疗的原理介绍,3,4,持续肾脏替代治疗的实际应用,急性肾功能衰竭的定义与诊断,1,急性肾脏功能衰竭的治疗原则,2,心脏外科手术后ARF的原因(n = 646),Perez-Valdivieso JR, Bes-Rastrollo M, Monedero P, et al. Prognosis and serum creatinine levels in acute renal failure at the time of nephrology consultation: an observational cohort study. BMC Nephrology 2007; 8: 14-22,心脏外科手术后ARF的治疗(n = 646),Perez-Valdivieso JR, Bes-Rastrollo M, Monedero P, et al. Prognosis and serum creatinine levels in acute renal failure at the time of nephrology consultation: an observational cohort study. BMC Nephrology 2007; 8: 14-22,ARF的治疗措施,1,纠正肾前性因素,2,利尿药物,ARF的治疗: 肾前性因素,肾脏灌注RPP = MAP IAP影响因素血管内容量灌注压,ARF的治疗: 肾脏灌注压,平均动脉压的目标并无绝对数值, 应当根据患者基础水平个体化治疗仅当补充足够容量后才能使用升压药物维持灌注压用于治疗低血压时, 无证据显示去甲肾上腺素增加AKI的危险腹腔内高压可导致肾脏灌注降低, 从而产生AKI,Venkataraman R. Can we prevent acute kidney injury? Crit Care Med 2008; 36Suppl: S166-S171,健康及疾病状态下的自身调节机制,0,150,50,100,Organ blood flow(% Baseline),0,100,20,40,60,80,Organ artery pressure (mmHg),Autoregulatory threshold,Subautoregulatory slope,疾病时自身调节机制丧失,0,150,50,100,Organ blood flow(% Baseline),0,100,20,40,60,80,Organ artery pressure (mmHg),control,3 weeks,1 week,MAP应当维持在何水平?,无创血压不准确高压时读数过低低压时读数过高有创血压及无创血压的数值并不相等,MAP的维持: 技巧,核实患者平时的MAP患者家属病历资料检查目前MAP的测定方法无创 vs. 有创测定无创与有创血压的差值,内容,急性肾脏功能衰竭的治疗原则,2,4,持续肾脏替代治疗的实际应用,急性肾功能衰竭的定义与诊断,1,持续肾脏替代治疗的原理介绍,3,肾脏的生理功能,肾脏替代治疗 vs. 肾脏,heparin,V,V,PV,PA,high-flux,肾小球,原尿,肾小管,滤器剖面图,滤器清除物质的原理,超滤(ultrafiltration)对流(convection)弥散(diffusion)吸附(adsorption),超滤作用的原理: 跨膜压,跨膜压(TMP): 半透膜两侧的压力差溶剂的移动从压力高的一侧向压力低的一侧增加压力差可以增加溶剂的超滤,超滤作用的原理: 跨膜压,跨膜压(TMP): 半透膜两侧的压力差溶剂的移动从压力高的一侧向压力低的一侧增加压力差可以增加溶剂的超滤压力差消失时超滤作用终止,UFR = BFRin BFRout,超滤作用的原理: 超滤率,通过超滤作用清除的溶剂量(UFR),BFRin,BFRout= BFRin UFR,超滤作用的原理,压强,半透膜,超滤液,The transfer of solute in a stream of solvent, across a semi-permeable membrane, mediated by a hydrostatic force,超滤液,超滤作用的应用: 缓慢持续超滤(SCUF),heparin,V,V,PV,PA,对流作用的原理,跨膜压(TMP): 半透膜两侧的压力差溶质的移动随溶剂移动从压力高的一侧向压力低的一侧,对流作用的原理,UFR = Lp.A.P = Kuf.P,超滤率的影响因素,Lp: 膜超滤系数ml/(hr.mmHg.m2)Kuf: 滤器超滤系数ml/(hr.mmHg),P: TMP,高通量滤器,低通量滤器,超滤率的影响因素: 膜超滤系数,Lp (ml/(hr.mmHg.m2),10,20,膜对溶剂(水)的通透性,超滤率的影响因素: 跨膜压,超滤率的影响因素: 跨膜压,CVVH: “体外”超滤(后稀释), (values 15%) (牛血, 37 C, Hct 32%, Cp 60g/l),超滤率的影响因素: 滤过分数,FF% = UFR x 100 / QpQp = BFR x (1 Hct),FF% 30%以防止血液滤器凝血,超滤率的影响因素: 滤过分数,BFR = 100 ml/min, Hct = 0.30Qp = BFR x (1 Hct) = 70 ml/minFF 30%,UFR FF x Qp = 21 ml/min,血流量是影响超滤率的最主要因素*后稀释,SCUF,Coffee maker analogy of ultrafiltrationRemoval of large volumes of solute and fluid via convection,对流作用的原理,对流作用的原理: 溶质的清除,半透膜,血液,透析液/超滤液,对流作用的原理: 溶质的清除,半透膜,血液,超滤液,对流作用的原理: 溶质的清除,半透膜,血液,超滤液,SCUF,CVVH,置换液,Coffee maker analogy of hemofiltrationRemoval of large volumes of solute and fluid via convectionReplacement of excess UF with sterile replacement fluid,对流作用的原理: 溶质的清除,对流作用的原理: 筛选系数,筛选系数(S, sieving coefficient)S = UF / plasma,plasma,UF,对流作用的原理: 对流清除率,C = S.UFR,Kuf.P = Lp.A.P,筛选系数: UF / plasma,不同分子量物质的划分,小分子物质,中分子物质,大分子物质,对流作用的原理: 滤器对溶质的通透,血液滤器小分子物质自由通透MW 50,000 daltons,对流作用的原理: 筛选系数,Hemofilter Sieving CoefficientsSchaeffer et al., Nephron 1996,*P 0.05 vs 1 hr. value,对流作用的原理: 溶质的清除,0,40,80,120,10,102,103,104,105,urea,creatinine,Vit. B12,2-M,albumine,clearance ml/min,MW dalton,HF,Kidney,Cut-off,IL-1,TNF,IL-6,IL-8,对流作用的原理: 不同膜的清除能力,对流作用的应用: 持续血液滤过(CVVH),heparin,V,V,PV,PA,high-flux,滤器中的血液浓缩,0,20,40,60,80,100,血液滤器,mmHg,滤器出口,滤器入口,Pi,Po,静水压,胶体渗透压,o,i,弥散作用的原理: 浓度梯度,半透膜两侧的溶质浓度梯度溶质的移动从浓度高的一侧向浓度低的一侧浓度差消失时溶质的移动停止,弥散作用的原理: 浓度梯度,弥散作用的原理,弥散作用的原理: 溶质的清除,半透膜,血液,透析液,弥散作用的原理: 溶质的清除,半透膜,血液,透析液,弥散作用的原理: 逆流,半透膜,血液,透析液,弥散作用的原理: 透析液饱和度,透析液饱和度Sd = dialysate / plasma,plasma,dialysate,弥散作用的原理: 弥散清除率,Kd = Sd.Qd = f (Qb, Qd, KoA),透析液饱和度dialysate / plasma,影响溶质清除的因素,质量转运系数(Ko)中空纤维对溶质的弥散阻力溶质大小滤器通透性膜面积(A)血流量(Qb)透析液流量(Qd),溶质分子量与清除,Jeffrey RF, Khan AA, Prabhu P, et al. A comparison of molecular clearance rates during continuous hemofiltration and hemodialysis with a novel volumetric continuous renal replacement system. Artif Organs 1994; 18(6): 425-428,影响溶质清除的因素: KoA & Qb,Qb, ml/min,Kurea, ml/min,Qd = 500,KoA = 900,KoA = 700,KoA = 500,影响溶质清除的因素: Qd,Qd, ml/min,Kurea, ml/min,KoA = 765 ml/min,Qb = 500,Qb = 450,Qb = 350,Qb = 250,Qb = 100,影响溶质清除的因素: MW,Qb, ml/min,Kd, ml/min,PMNA膜KoA = 765 ml/min,尿素,肌酐,尿酸,VitB12,菊酚,弥散作用的原理: 溶质的清除,0,40,80,120,10,102,103,104,105,urea,creatinine,Vit. B12,2-M,albumine,clearance ml/min,MW dalton,HD,Kidney,IL-1,TNF,IL-6,IL-8,弥散作用的应用: 持续血液透析(CVVHD),V,V,PV,PA,low-flux,吸附作用的原理,膜对溶质的吸附能力疏水性多孔结构与膜面积无关,增加对流清除溶质能力的方法,增加UFR提高跨膜压(TMP)超滤液一侧的负压血液一侧的正压增加膜超滤系数(Lp)增加滤器膜面积(A)提高血流量(BFR)采用前稀释方式增加弥散清除,C = S.UFR = S.Lp.A.P,C = S.UFR.BFR / (BFR + RFR),KT = KD + UFR.S.(1 KD/BFR),对流清除能力的影响因素: 滤过分数,R,heater,heparin,V,V,PV,PA,UF,BLD,SAD,FF% = UFR x 100 / QpQp = BFR x (1 Hct),FF% 160 或 115 mEq/L)高热药物过量(药物能够经透析清除),急性肾脏损伤替代治疗的传统适应证,利尿治疗无效的血管内容量过多内科治疗无效的高钾血症内科治疗无效的代谢性酸中毒经透析可清除的药物或毒素中毒明显的尿毒症症状(脑病, 心包炎, 尿毒症性出血倾向)没有特异性表现的进展性氮质血症,Palevsky PM. Indications and timing of renal replacement therapy in acute kidney injury. Crit Care Med 2008; 36Suppl: S224-S228,肾脏替代治疗的剂量: Ronco,筛选患者(n = 492),随机分组(n = 425),排除患者(n = 67),UFR 35 ml/kg/hr(n = 139),UFR 20 ml/kg/hr(n = 146),UFR 45 ml/kg/hr(n = 140),Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: A prospective randomised trial. Lancet 2000; 356: 26-30,肾脏替代治疗的剂量: Ronco,Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: A prospective randomised trial. Lancet 2000; 356: 26-30,肾脏替代治疗的剂量: Ronco,Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: A prospective randomised trial. Lancet 2000; 356: 26-30,肾脏替代治疗的剂量: Ronco,Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: A prospective randomised trial. Lancet 2000; 356: 26-30,肾脏替代治疗的剂量: Bouman,Bouman CS, Oudemans-Van Straaten HM, Tijssen JG, et al. Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial. Crit Care Med 2002; 30: 2205-2211,肾脏替代治疗的剂量: Bouman,肾脏替代治疗的剂量: Saudan,Saudan P, Niederberger M, De Seigneux S, et al: Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure. Kidney Int 2006; 70: 1312-1317,肾脏替代治疗的剂量: Saudan,42 mL/kg/hr,25 mL/kg/hr,Saudan P, Niederberger M, De Seigneux S, et al: Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure. Kidney Int 2006; 70: 1312-1317,肾脏替代治疗的剂量: Kellum,Ronco 425 CVVH 20/h vs. 35-45 ml/kg/h*,Bouman 106 CVVH 20ml/kg/h* vs. 48 ml/kg/h,Schiffl 160 Alternate day vs. daily hemodialysis,Saudan 206 CVVH 25 ml/kg/h vs. CVVHDF 42 ml/kg/h,Total (fixed effects),Total (random effects),1,10,odds ratio,Study n treatment groups,Favors increased dose,Odds Ratio: 1.95 (95% CI 1.48 - 2.58, p 0.001),ARF的治疗剂量: Kellum,“Patients with ARF should be treated with at least 35 mL/kg/h of hemofiltration/ hemodiafiltration or daily hemodialysis until or unless ongoing multi-center clinical trials show otherwise.”,肾脏替代治疗的时机,Palevsky PM. Indications and timing of renal replacement therapy in acute kidney injury. Crit Care Med 2008; 36Suppl: S224-S228,肾脏替代治疗的时机,Palevsky PM. Indications and timing of renal replacement therapy in acute kidney injury. Crit Care Med 2008; 36Suppl: S224-S228,肾脏替代治疗的时机: Ronco,Ronco C, Bellomo R, Homel P, et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: A prospective randomised trial. Lancet 2000; 356: 26-30,肾脏替代治疗的时机: Gettings,Gettings LG, Reynolds HN, Scalea T, et al. Outcome in post-traumatic acute renal failure when continuous renal replacement therapy is applied early vs late. Intensive Care Med 1999; 25: 805-813,肾脏替代治疗的时机: Gettings,Gettings LG, Reynolds HN, Scalea T, et al. Outcome in post-traumatic acute renal failure when continuous renal replacement therapy is applied early vs late. Intensive Care Med 1999; 25: 805-813,肾脏替代治疗的时机: Piccinni,Piccinni P, Dan M, Barbacini S, et al. Early isovolaemic haemofiltration in oliguric patients with septic shock. Intensive Care Med 2006; 32: 80-86,肾脏替代治疗的时机: Pi