嚴(yán)重膿毒癥與mods邱海波

1、CRRT Severe sepsis and MODS,邱海波東南大學(xué)附屬中大醫(yī)院ICU東南大學(xué)急診與危重醫(yī)學(xué)研究所,1. CRRT vs IRRT2. Early vs late CRRT 3. High vs normal flow4.Possible ways to increase mediators clearance,Current opinion in CRRT,Mode of RRT differenc

2、es among continents,Bellomo, et al. 2019,Understanding 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 Apri

3、l 1,2019, and March 31, 20192 ICU in Canada.N=261,CRRT對(duì)ARF腎功能恢復(fù)的影響－CRRT促進(jìn)腎功能恢復(fù),Crit Care Med 2019; 31:449 –455,IHD vs CRRT,ICU RRTn=116,RRT for overdosen=7,Pre-existing CRFn=16,ICU RRT for ARF/MOFn=66,Initial CRRT

4、n=66,Initial IHDn=28,Jacka MJ, Ivancinova X, Gibney RTN. Can J Anaesth 2019;52:327-332,,,,,,Munns et al觀察危重急性腎衰竭患者 IHD CRRTCCr下降25%7%尿量下降50%10%鈉排泄分?jǐn)?shù)下降46%12%腎功能下降的原因: IHD平均動(dòng)脈壓下降

5、，導(dǎo)致腎臟低灌注，加重腎臟缺血性損傷，延遲急性腎衰竭腎功能的恢復(fù),為什么CRRT促進(jìn)腎功能恢復(fù)?,,160 pats with ARF: Daily vs every-other-day IHDMean ultrafiltration volumeDaily: 1.2 ± 0.5 L Every-other-day: 3.5 ± 0.3 L (P <0.001).Hypotension occurr

6、ed in Daily: 5 ± 2% Every-other-day: 25 ± 5% (P < 0.001)Time to recovery of renal function Daily: 9 ± 2 days Every-other-day:16 ± 6 Days P = 0.001,N Engl J Med 2019; 346:305-310,為什么CRRT有助于

7、腎臟功能的恢復(fù)？？,Effect of RRT dose on recovery of renal function?,P = NS,Ronco C et al. Effects of different doses in CVVH on outcomes of ARF:A prospective RCT,,,Lancet 2000; 356: 26 -30,CRRT vs IRRTon return of renal funct

8、ionOn mortality,Mortality:Which is better CRRT or IHD?,Swzrtz. RD. Comparing continuous HF with HD in patients with severe ARF Am J Kidney 2019; 34: 424 - 432Mehti. RL. Collaborative Group for Treatment of ARF in ICU

9、:A RCT of continuous versus IHD for ARF. Kidney Int 2019; 60: 1154 - 63Kellum JA. Continuous versus intermittent RRT. A meta-analysis. Intensive Care Med 2019; 162: 197- 202,Conclusion :There is no conclusive evidenc

10、e to support the superiority of CRRT vs IHD. Both techniques are complimentary,,CRRT vs IRRT對(duì)危重病患者的影響－CRRT可降低危重病患者病死率,Quality score 5: definitely equal,,CRRT vs IRRT對(duì)危重病患者的影響－CRRT可降低危重病患者病死率,Hospital mortality:CRRT wa

11、s 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, 2019, 28: 29-37,1. CRRT vs IRRT2. Early vs

12、late CRRT 3. High vs normal flow4.Possible ways to increase mediators clearance,Current opinion in CRRT,1989－2019：100例創(chuàng)傷后ARF早期－后期的臨界：BUN 60mg/dl兩組病人創(chuàng)傷評(píng)分、GCS、發(fā)生休克的比例、年齡、性別和創(chuàng)傷分布均無差異,早期－后期CRRT對(duì)危重病患者的影響－早期或預(yù)防性CRRT可降低ARF

13、患者病死率,Gettings LG. Intensive Care Med, 2019, 25: 805-813,早期－后期CRRT對(duì)危重病患者的影響－早期或預(yù)防性CRRT可降低ARF患者病死率,生存率－明顯差異,Gettings LG. Intensive Care Med, 2019, 25: 805-813,,OutcomeEarly start 39% survival Late start 20% survival

14、,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-v

15、olume 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, 2019,Dose and Timing of CVVH in ARF,Bouman CS, et al. Critical Care Med 2019; 30:22

16、05-2211,,,,,,,,,,74.3%,,,,68.8%,,,,75.0%,,,,,,,,0%,20%,40%,60%,80%,100%,28-Day Survival,,,,,,LV-Late,LV-Early,HV-Early,Treatment Group,n=35SOFA10.3±2.8,n=36SOFA10.6±1.9,n=35SOFA10.1±2.2,1. CRRT v

17、s IRRT2. Early vs late CRRT 3. High vs normal flow4.Possible ways to increase mediators clearance,Current opinion in CRRT,High-volume hemofilitration (HVHF),Ronco C et al. Effects of different doses in CVVH on outcom

18、es of ARF:A prospective RCT,,,Lancet 2000; 356: 26 -30,RCT of HVHF in Septic Shock,5919 ICUadmissions,Oliguric ARFN=248,Non-oliguric ARFN=130,Not randomized in studyN=142,RandomizedIn studyN-106,EHVn=35,ELVn=35,

19、LLVn=36,Hemofiltrationn=352,No hemofiltrationN=6,Bouman CS et al. Effects of early high-volume CVVH on survival and recovery of renal function in IC patients with ARF. Crit Care Med 2019; 30: 2205 (n=106),,,,,,,,,,

20、,EHV 74.3%,LLV 75%,ELV 68.8%,ELV= Early low vol hemofiltration=1-1.5 L/hrLLV= Late low vol hemofiltration=1-1.5 L/hrEHV= Early high vol hemofiltration=3-4 L/hr,Early=within 12 hours of diagnosis of septic shock,,Survi

21、val %,No difference renal recovery or 28-d mortality,160 pats with ARF: Daily vs every-other-day ID,N Engl J Med 2019; 346:305-310,Survival vs dialysis dose in IHD,CRRT: Impact on outcomes,,Severity of Disease,Survival

22、rate %,,,,,,,High Dose (CRRT),Low Dose(IHD),The Cleveland Clinic Observation,100,90,80,70,60,50,40,30,20,10,0,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,ATN (n=1260),Multi-center RCT in the USA. P

23、atients with ARF randomized to: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) CVVH

24、DF at 35 ml/kg/hr or SLED 6-times/week (target Kt/V = 1.2-1.4/session)Conventional Management Strategy: If hemodynamically stable (SOFA CVS score: 0-2) IHD 3-times/week (target Kt/V =1.2-1.4/session); If hemodynamica

25、lly 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= 1500Australia and New Zealand25 ml/kg/hr vs. 40 ml/kg/hr of CVVHDFO

26、utcome: all cause mortality at 90 daysCurrently under way,1. CRRT vs IRRT2. Early vs late CRRT 3. High vs normal flow4.Possible ways to increase mediators clearance,Current opinion in CRRT,Higher Uf volumes,,,Conve

27、ction,Grootendorst AF et al , 1992Bellomo R et al, 2019,,1,促進(jìn)介質(zhì)清除/遏制炎癥反應(yīng)的可能途徑,HVHF,HVHF: An ultrafiltration rate > 50–60 ml/kg/hrOR: 60 L/d including net ultrafiltration in continuous hemofiltration mode,目的：評(píng)估高

28、流量血濾對(duì)感染性休克患者(n-11)血流動(dòng)力學(xué)和細(xì)胞因子的影響方法：隨機(jī)cross-over試驗(yàn)，患者隨機(jī)接受8h HVHF (6L/h) (AN69濾器，1.6m2)或8h CVVH (1L/h) (AN69濾器，1.2m2)檢測指標(biāo)：血流動(dòng)力學(xué)、去甲腎上腺素需要量、血清C3a、C5a、IL-2、IL-8、IL-10和TNF的含量HVHF組與CVVH組CVP、CI、 PAWP和液體平衡無差異維持MAP>70mmH

29、g，HVHF組NE劑量顯著低于CVVHNE劑量分別降低10.5ug/min和1.0ug/min P=0.02,高流量血濾在感染性休克患者中的作用－HVHF顯著降低感染性休克NE用量,Cole L, et al. Intensive Care Med, 2019, 27: 978-986,Mean Norepinephrine Dose,Mean C3a concentration,Mean C5a concentration,E

30、ffect of HVHF on mortality,Oudemans-van Straaten Hm et al, Intens Care Med 2019;25:814-821.,*=Madrid ARF score,HV-CVVH明顯改善感染性休克預(yù)后,脈沖式高容量血液濾過 (Pulse HVHF),極高容量很難維持24h以上，而且對(duì)溶質(zhì)動(dòng)力學(xué)無明顯改進(jìn)Ranco提出了脈沖式高容量血液濾過,Seminars in Dialys

31、is, 2019, 19(1): 69-74,,,HVHF--- As salvage therapyin severe septic shock,Objectives: To evaluate the effect PHVHF (12-h) in reversing progressive refractory hypotension in pats with sshockN=20 sshock pats with NE >

32、; 0.3 μg/kg.min and and lactic acidosisResponders vs Non-R (NE and lactate levels at 6h after PHVHF),Intensive Care Med (2019) 32:713–722,Higher Uf volumes,Higher membrane cut-off,,,,,Permeability,Convection,Groo

33、tendorst AF et al , 1992Bellomo R et al, 2019,Leese T et al. 1987Berlot G et al. 2019,促進(jìn)介質(zhì)清除/遏制炎癥反應(yīng)的可能途徑,,1,,2,Efficacy of membrane pore size on morbidity and mortality in an immature swine model of Staph. Aureus induc

34、ed sepsisJames R. Matson, Crit Care Med, 26: 730-737, 2019,Cut-off100 KD,Higher Uf volumes,Higher membrane cut-off,,,,,Permeability,Convection,Grootendorst AF et al , 1992Bellomo R et al, 2019,Leese T et al. 1

35、987Berlot G et al. 2019,,1,,2,Use of sorbents in combination therapies,,,Adsorption,Ronco C et al. 1999Tetta C et al. 2019,,3,促進(jìn)介質(zhì)清除/遏制炎癥反應(yīng)的可能途徑,,Coupled plasmafiltration-adsorption, by regenerating the plasmafil

36、trate, avoids unwanted losses, avoids the contact of RBC, WBC and platelets with the sorbent, and prevents treatment induced thrombocytopenia.,,,,,,,,Hemodiafilter,,,,,,Plasmafilter,,,,,Dialysate30 ml/min,Plasmafilt

37、er,,,20 ml/min,100-200 ml/min,,CPFA: Hemodynamics and Biological Effects,,P < 0.01,NA,MAP,at 10 hours of treatment versus baseline,D- Norepinephrine Dose and D+ MAP,0,20,40,60,80,100,%,,,,,,P < 0.01,TN

38、F Prod.,Phagocytosis,D Monocyte TNF production and Phagocytic Capacity,,,P < 0.01,,,0,500,1000,1500,,,%,at 10 hours of treatment versus baseline,pg/ml,P < 0.05,CVVH + 血漿吸附對(duì)感染性休克血流動(dòng)力學(xué)的影響Hemodynamic response to

39、coupledplasmafiltration-adsorption in human septic shock,N=12 mechanically ventilated pats with septic shockIntervention: A median of 10 consecutive sessions (prescribed treatment time: 10 h/session; delivered duration

40、: 8.43±1.37 h/min) of coupled plasmafiltration-adsorption,Intensive Care Med (2019) 29:703–708,CRRT in ICU,Early CRRT: 改善創(chuàng)傷合并ARF患者的預(yù)后CRRT　vs IRRT：CRRT可能促進(jìn)腎臟功能恢復(fù)可能降低危重病人的病死率Use 45 ml/kg.min for CVVH for septic