CRRT_严重脓毒症与MODS(邱海波).ppt

CRRT CRRT Severe sepsis and Severe sepsis and MODSMODS邱海波邱海波东南大学附属中大医院东南大学附属中大医院ICU东南大学急诊与危重医学研究所东南大学急诊与危重医学研究所1. CRRT vs IRRT2. Early vs late CRRT 3. High vs normal flow4.Possible ways to increase mediators clearanceCurrent opinion in CRRT Current opinion in CRRT Mode of RRT differences among continentsBellomo, et al. 2001Understanding Renal Replacement Therapy and Acute Renal Failure in the ICU (The B.E.S.T kidney study)•Retrospective cohort study •Pats with ARF and required dialysis between April 1,1996, and March 31, 1999•2 ICU in Canada.•N=261CRRT对对ARF肾功能恢复的影响肾功能恢复的影响－－CRRTCRRT促进肾功能恢复促进肾功能恢复CRRTIHDPAPACHE II2725.10.10Baseline SCr1361800.002MAP Before RRT74.787.2<0.001Hosp Mortality71.9%42.2%<0.01Renal recovery in hosp80.0%62.5%0.06Duration of RRT14.7d14.5d0.91Cost per week (Can $)3486-51171341Survivor (Cost per y) No-RRT RRT $11,192 $73,273Crit Care Med 2003; 31:449 –455IHD vs CRRTICU RRTn=116 RRT for overdosen=7Pre-existing CRFn=16ICU RRT for ARF/MOFn=66Initial CRRTn=66Initial IHDn=28Jacka MJ, Ivancinova X, Gibney RTN. Can J Anaesth 2005;52:327-332•Munns et al观察危重急性肾衰竭患者 IHD CRRT•CCr下降25%7%•尿量下降50%10%•钠排泄分数下降46%12%肾功能下降的原因: IHD平均动脉压下降，导致肾脏低灌注，加重肾脏缺血性损伤，延迟急性肾衰竭肾功能的恢复 为什么为什么CRRT促进肾功能恢复促进肾功能恢复? ?•160 pats with ARF: Daily vs every-other-160 pats with ARF: Daily vs every-other-day IHDday IHD•Mean Mean ultrafiltration volumeultrafiltration volume–Daily: 1.2 ± 0.5 L Daily: 1.2 ± 0.5 L –Every-other-day: 3.5 ± 0.3 L (P <0.001).Every-other-day: 3.5 ± 0.3 L (P <0.001).•HypotensionHypotension occurred in occurred in –Daily: 5 ± 2% Daily: 5 ± 2% –Every-other-day: 25 ± 5% (P < 0.001)Every-other-day: 25 ± 5% (P < 0.001)•Time to recovery of renal function Time to recovery of renal function –Daily: 9 ± 2 days Daily: 9 ± 2 days N Engl J Med 2002; 346:305-310为什么为什么CRRTCRRT有助于肾脏功能的恢复？？有助于肾脏功能的恢复？？Effect of Effect of RRT doseRRT dose on recovery on recovery of renal function?of renal function?P = NS•Ronco C et al. Effects of different doses in CVVH on outcomes of ARF:A prospective RCT20ml/h/kg 35/ml/kg/h45ml/kg/h95% 92% 90%N=425SurvivalLancet 2000; 356: 26 -30lCRRT vs IRRTØon return of renal functionØOn mortalityMortality:Which is better CRRT or IHD?Swzrtz. RD. Comparing continuous HF with HD in patients with severe ARF Am J Kidney 1999; 34: 424 - 432Mehti. RL. Collaborative Group for Treatment of ARF in ICU:A RCT of continuous versus IHD for ARF. Kidney Int 2001; 60: 1154 - 63Kellum JA. Continuous versus intermittent RRT. A meta-analysis. Intensive Care Med 2002; 162: 197- 202 Conclusion :There is no conclusive evidence to support the superiority of CRRT vs IHD. Both techniques are complimentaryCRRT vs IRRT对危重病患者的影响对危重病患者的影响－－CRRT可降低危重病患者病死率可降低危重病患者病死率nQuality score 5: definitely equalCRRT vs IRRT对危重病患者的影响对危重病患者的影响－－CRRT可降低危重病患者病死率可降低危重病患者病死率Hospital mortality:CRRT was associated with a reduced risk of hospital death in the six studies in which baseline severity of illness was similar RR 0.48, 0.34–0.69, p<0.0005 Intensive Care Med, 2002, 28: 29-371. CRRT vs IRRT2. Early vs late CRRT 3. High vs normal flow4.Possible ways to increase mediators clearanceCurrent opinion in CRRT Current opinion in CRRT •1989－1997：100例创伤后ARF•早期－后期的临界：BUN 60mg/dl•两组病人创伤评分、GCS、发生休克的比例、年龄、性别和创伤分布均无差异早期－后期早期－后期CRRT对危重病患者的影响对危重病患者的影响－早期或预防性－早期或预防性CRRT可降低可降低ARF患者病死率患者病死率Gettings LG. Intensive Care Med, 1999, 25: 805-813早期－后期早期－后期CRRT对危重病患者的影响对危重病患者的影响－早期或预防性－早期或预防性CRRT可降低可降低ARF患者病死率患者病死率n生存率－明显差异生存率－明显差异Gettings LG. Intensive Care Med, 1999, 25: 805-813OutcomeOutcomeEarly start 39% survival Early start 39% survival Late start  20% survivalLate start  20% survivalEarly vs. Late RRT•RCT (n =106)•Oliguria (< 30cc/hr) refractory to high-dose furosemide (500mg over 6hrs)•Randomized to 3 groups: –Early (<12h) high-volume hemofiltration (n=35; 72-96L/24 h) –Early (<12h) low-volume hemofiltration (n=35; 24-36L/24 h) –Late low-volume hemofiltration (n=36; 24-36 L/24 h)Bouman et al. Crit Care Med 30:2205-2211, 2002 Dose and Timing of CVVH in ARFBouman CS, et al. Critical Care Med 2002; 30:2205-221174.3%68.8%75.0%0%20%40%60%80%100%28-Day SurvivalLV-LateLV-EarlyHV-EarlyTreatment Groupn=35SOFAn=36SOFAn=35SOFA1. CRRT vs IRRT2. Early vs late CRRT 3. High vs normal flow4.Possible ways to increase mediators clearanceCurrent opinion in CRRT Current opinion in CRRT High-volume hemofilitration (HVHF)•Ronco C et al. Effects of different doses in CVVH on outcomes of ARF:A prospective RCT20ml/h/kg 35/ml/kg/h45ml/kg/h41% 57% 58%N=425SurvivalLancet 2000; 356: 26 -30RCT of HVHF in Septic Shock5919 ICUadmissionsOliguric ARFN=248Non-oliguric ARFN=130Not randomized in studyN=142RandomizedIn studyN-106EHVn=35ELVn=35LLVn=36Hemofiltrationn=352No hemofiltrationN=6Bouman CS et al. Effects of early high-volume CVVH on survival and recovery of renal function in IC patients with ARF. Crit Care Med 2002; 30: 2205 (n=106)EHV 74.3%LLV 75%ELV 68.8%ELV= Early low vol hemofiltration=1-1.5 L/hrELV= Early low vol hemofiltration=1-1.5 L/hrLLV= Late low vol hemofiltration=1-1.5 L/hrLLV= Late low vol hemofiltration=1-1.5 L/hrEHV= Early high vol hemofiltration=3-4 L/hrEHV= Early high vol hemofiltration=3-4 L/hrEarly=within 12 hours of Early=within 12 hours of diagnosis of septic shockdiagnosis of septic shockSurvival %Survival %No difference renal recovery or 28-d mortality •160 pats with ARF: Daily vs every-other-day ID160 pats with ARF: Daily vs every-other-day IDN Engl J Med 2002; 346:305-310Survival vs dialysis dose in IHDSurvival vs dialysis dose in IHDCRRT: Impact on outcomesSeverity of DiseaseSeverity of DiseaseSurvival rate %Survival rate %High Dose (CRRT)High Dose (CRRT)Low DoseLow Dose(IHD)(IHD)The Cleveland Clinic ObservationThe Cleveland Clinic Observation1001009090808070706060505040403030202010100 0ATN (n=1260)•Multi-center RCT in the USA. Patients with ARF randomized to:Multi-center RCT in the USA. Patients with ARF randomized to:Intensive Management Strategy:Intensive Management Strategy:•If hemodynamically stable (SOFA CVS score: 0-2) IHD 6-times/week (target Kt/V =1.2-1.4/session)• If hemodynamically unstable (SOFA CVS score: 3-4) CVVHDF at 35 ml/kg/hr or SLED 6-times/week (target Kt/V = 1.2-1.4/session)Conventional Management Strategy: Conventional Management Strategy: •If hemodynamically stable (SOFA CVS score: 0-2) IHD 3-times/week (target Kt/V =1.2-1.4/session); •If hemodynamically unstable (SOFA CVS score: 3-4) CVVHDF at 20 ml/kg/hr or SLED 3-times/week (target Kt/V = 1.2-1.4/session)RENAL•Multicenter RCT (centers = 35)•N= 1500•Australia and New Zealand•25 ml/kg/hr vs. 40 ml/kg/hr of CVVHDF•Outcome: all cause mortality at 90 days•Currently under way 1. CRRT vs IRRT2. Early vs late CRRT 3. High vs normal flow4.Possible ways to increase mediators clearanceCurrent opinion in CRRT Current opinion in CRRT Higher Uf volumesHigher Uf volumesConvectionGrootendorst AF et al , 1992Grootendorst AF et al , 1992Bellomo R et al, 1998Bellomo R et al, 19981 1促进介质去除促进介质去除/ /遏制炎症反响的可能途径遏制炎症反响的可能途径HVHF•HVHF: •An ultrafiltration rate > 50–60 ml/kg/hr•OR: 60 L/d including net ultrafiltration •in continuous hemofiltration modeq目的：评估高流量血滤对感染性休克患者目的：评估高流量血滤对感染性休克患者(n-11)血流动力血流动力学和细胞因子的影响学和细胞因子的影响q方法：随机方法：随机cross-over试验，患者随机承受试验，患者随机承受8h HVHF (6L/h) (AN69m2)或或8h CVVH (1L/h) (AN69m2)q检测指标：血流动力学、去甲肾上腺素需要量、血清检测指标：血流动力学、去甲肾上腺素需要量、血清C3a、、C5a、、IL-2、、IL-8、、IL-10和和TNF的含量的含量qHVHF组与组与CVVH组组CVP、、CI、、 PAWP和液体平衡无差异和液体平衡无差异q维持维持MAP>70mmHg，，HVHF组组NE剂量显著低于剂量显著低于CVVHqNEug/min高流量血滤在感染性休克患者中的作用高流量血滤在感染性休克患者中的作用－－HVHF显著降低感染性休克显著降低感染性休克NE用量用量Cole L, et al. Intensive Care Med, 2001, 27: 978-986Mean Norepinephrine DoseMean C3a concentrationMean C5a concentrationEffect of HVHF on mortalityOudemans-van Straaten Hm et al, Intens Care Med 1999;25:814-821. Oudemans-van Straaten Hm et al, Intens Care Med 1999;25:814-821. *=Madrid ARF score*=Madrid ARF scoreHV-CVVHHV-CVVH明显改善感染性休克预后明显改善感染性休克预后脉冲式高容量血液滤过脉冲式高容量血液滤过 (Pulse HVHF)•极高容量很难维持24h以上，而且对溶质动力学无明显改进•Ranco提出了脉冲式高容量血液滤过Seminars in Dialysis, 2006, 19(1): 69-746420PulseL/hHVHF--- As salvage therapyin severe septic shock•Objectives: To evaluate the effect PHVHF (12-h) in reversing progressive refractory hypotension in pats with sshock•N=20 sshock pats with NE > 0.3 μg/kg.min and and lactic acidosis•Responders vs Non-R (NE and lactate levels at 6h after PHVHF)Intensive Care Med (2006) 32:713–722Higher Uf volumesHigher Uf volumes Higher membraneHigher membrane cut-off cut-offPermeabilityConvectionGrootendorst AF et al , 1992Grootendorst AF et al , 1992Bellomo R et al, 1998Bellomo R et al, 1998Leese T et al. 1987Leese T et al. 1987Berlot G et al. 1997Berlot G et al. 1997促进介质去除促进介质去除/ /遏制炎症反响的可能途径遏制炎症反响的可能途径1 12 2Efficacy of membrane pore size on morbidity and mortality in an immature swine model of Staph. Aureus induced sepsisJames R. Matson, Crit Care Med, 26: 730-737, 1998James R. Matson, Crit Care Med, 26: 730-737, 1998 Cut-offCut-off100 KD100 KDHigher Uf volumesHigher Uf volumes Higher membraneHigher membrane cut-off cut-offPermeabilityConvectionGrootendorst AF et al , 1992Grootendorst AF et al , 1992Bellomo R et al, 1998Bellomo R et al, 1998Leese T et al. 1987Leese T et al. 1987Berlot G et al. 1997Berlot G et al. 19971 12 2 Use of sorbents inUse of sorbents in c combination therapiesombination therapiesAdsorptionRonco C Ronco C et al. 19 et al. 199999Tetta CTetta C et al. et al. 200120013 3促进介质去除促进介质去除/ /遏制炎症反响的可能途径遏制炎症反响的可能途径SorbenSorbent tCoupled plasmafiltration-adsorption, by regenerating Coupled plasmafiltration-adsorption, by regenerating the plasmafiltrate, avoids unwanted losses, avoids the the plasmafiltrate, avoids unwanted losses, avoids the contact of RBC, WBC and platelets with the sorbent, contact of RBC, WBC and platelets with the sorbent, and prevents treatment induced thrombocytopenia. and prevents treatment induced thrombocytopenia. HemodiafilterHemodiafilterPlasmafilterPlasmafilter DialysateDialysate30 ml/min30 ml/minPlasmafilterPlasmafilter20 ml/min20 ml/min100-200 ml/min100-200 ml/minCPFA: Hemodynamics and Biological EffectsNANAMAPMAPat 10 hours of treatment versus baselineat 10 hours of treatment versus baselineD D- - Norepinephrine Dose Norepinephrine Dose and and D D+ + MAPMAP 0 0 2020 4040 6060 8080100100%%TNF Prod.TNF Prod. PhagocytosisPhagocytosisD D Monocyte TNF production Monocyte TNF production and Phagocytic Capacityand Phagocytic Capacity 0 0 2020 4040 6060 80801001000 0 50500 0 1001000 0 1501500 0%%at 10 hours of treatment versus baselineat 10 hours of treatment versus baseline pg/mlpg/ml5 5CVVH + CVVH + 血浆吸附对感染性休克血流动力学的影响血浆吸附对感染性休克血流动力学的影响Hemodynamic response to coupledHemodynamic response to coupledplasmafiltration-adsorption in human septic shockplasmafiltration-adsorption in human septic shock•N=12 mechanically ventilated pats with septic shock•Intervention: A median of 10 consecutive sessions (prescribed treatment time: 10 h/session; delivered duration: 8.43±1.37 h/min) of coupled plasmafiltration-adsorptionIntensive Care Med (2003) 29:703–708CRRT in ICUCRRT in ICU•Early CRRT: 改善创伤合并改善创伤合并ARF患者的预后患者的预后•CRRT　　vs IRRT：：–CRRT可能促进肾脏功能恢复可能促进肾脏功能恢复–可能降低危重病人的病死率可能降低危重病人的病死率•Use 45 ml/kg.min for CVVH for septic shock pats•WWay to increase mediators clearance:ay to increase mediators clearance:–PHVHF vs CPFAPHVHF vs CPFAThanks for you attention知识回忆知识回忆Knowledge Knowledge ReviewReview祝您成功！。