Presentation on theme: "Acute Hemodialysis & CRRT in AKI"— Presentation transcript:
1 Acute Hemodialysis & CRRT in AKI Paweena Susantitaphong,MD,MS1-31Physician Staff , Division of Nephrology, Department of Medicine,King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok2 International Society of Nephrology (ISN) fellowship3Adjunct Instructor of Tufts University School of Medicine, Boston, USA.
2 Background DEFINITION Acute Renal Failure Acute Kidney Injury An abrupt (within 48h) reduction in kidney functionCurrently defined as an absolute increase in sCr ofeither ≥ 0.3 mg/dl or a percentage increase of ≥ 50%or a reduction in Urine Output (documented oliguriaof < 0.5 cc/kg per h for > 6 h)Crit Care 2007;11:R31
3 Staging of AKI : KDIGO Stage Serum creatinine Urine output 1 1.5–1.9 times baseline OR ≥ 0.3 mg/dl(≥ 26.5 mmol/l) increase< 0.5 ml/kg/h for –12 hours22.0–2.9 times baseline< 0.5 ml/kg/h for ≥12 hours33.0 times baseline OR Increase in serum creatinine to ≥ 4.0 mg/dl (≥353.6 μmol/l)OR Initiation of renal replacement therapy OR, In patients < 18 years, decrease in eGFR to < 35 ml/min per 1.73 m2< 0.3 ml/kg/h for ≥ 24 hoursOR Anuria for ≥12 hours
4 World Incidence of Acute Kidney Injury : A Meta-AnalysisSusantitaphong P, et al. CJASN 2013, June 6
11 Acute Kidney Injury Associates with Increased Long-Term Mortality Lafrance JP ,et al. J Am Soc Nephrol 2010;21 :345-52
12 Renal Replacement Therapy Timing of initiationearly VS late
13 Indications in Renal Failure 1. Uremiaimpaired nutritionN/Vpoor appetitegastritis with UGIB, ileus, colitisAltered mental statusPericarditis (urgent indication)Bleeding from platelet dysfunction (urgent indication)
14 Indications 2. Refractory or progressive fluid overload 3. Uncontrollable hyperkalemia4. Severe metabolic acidosis esp. oliguria5. Steady worsening of renal functionBUN > mg/dl
15 Outcome of Early vs. Late RRT in AKI AuthorsYearDesignNPre-RRT BUNSurvival benefitMode of RRTEarlyLateParsons et al1961Retro33>200+HDFischer et al1966162~150Kleinknecht1972500<93>163Conger1975Pro1870150Gillum et al19863460100Gettings et al1999<60>60CRRTBouman et al200210647105CVVHDemirkilic et al200461CVVHDElahi et al64Liu et al2006243<76>76HD and CRRTThe 3 retrospective observational studies from the 1960s through the early 1970s compared ‘early’ hemodialysis, as defined by BUN from <93 mg/dl to 150 mg/dl, to ‘late’ hemodialysis, as defined by BUN levels of 163 mg/dl to > 200 mg/dl. These studies all demonstrated improved survival with earlier hemodialysis.Later, there were two small prospective clinical trials. In the first trial studied in 18 patients. Early ,BUN at <70 mg/dl, and late dialysis, BUN 150 mg/dl. Survival was significant higher in the early treatment group.The second study, 34 patients. Mortality was higher in the late dialyzed group; however, given the small sample size, this difference was not statistically significant.The next study is a retrospective study in post-traumatic AKI patients. Significant benefit favor the early group.Bouman randomized 106 critically ill patients with AKI to three groups: No significant differences in survival were observed between early and late dialysis. In addition, as a result of the small sample size.Next 2 retrospective showed the benefit of early dialysis
16 a historic control group). Timing of renal replacement therapy initiation inacute renal failure: a meta-analysisSeabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BLWe identified 23 studies (5 randomized or quasi-randomized controlled trials,1 prospective and 16 retrospective comparative cohort studies, and 1 single-arm study witha historic control group).By using meta-analysis of randomized trials, early RRT was associated with anonsignificant 36% mortality risk reduction (RR, 0.64; 95% CI, 0.40 to 1.05; P = 0.08).Conversely, in cohort studies, early RRT was associated with a statistically significant28% mortality risk reduction (RR, 0.72; 95% CI, 0.64 to 0.82; P < 0.001).The overall test for heterogeneity among cohort studies was significant (P = 0.005).However, early dialysis therapy was associated more strongly withlower mortality in smaller studies (n < 100) by means of subgroup analysis.Am J Kidney Dis Aug;52(2):
17 Am J Kidney Dis. 2008 Aug;52(2):272-84. Effect of early renal replacement therapy (RRT) initiation on non-recovery of renal function in AKIAm J Kidney Dis Aug;52(2):
18 Solute level (Blood urea nitrogen, serum creatinine) Parameters that were used in studies for classifyearly and late renal replacement therapy initiation in AKIClinical symptomsSolute level (Blood urea nitrogen, serum creatinine)Interval between ICU/hospital admission and renal replacement therapy initiationDays between biochemical diagnosis of AKI and renal replacement therapy initiationSeverity of AKI (AKIN/RIFLE) classificationPrognostic scoresNumber of organ failure
19 Renal Replacement Therapy Timing of initiationearly VS lateModality of RRTIntermittent VS Continuous
20 Dialysis : ModalityIntracorporeal Vs Extracorporeal (PD vs. HD - CRRT?)
21 Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?) Dialysis : ModalityIntracorporeal Vs Extracorporeal (PD vs. HD - CRRT?)Intermittent Vs Continuous (IHD,SLED vs. CRRT?)Note IHD Intermittent HemodialysisSLED Sustained Low-Efficiency DialysisCRRT Continuous Renal Replacement Therapy
22 RRT Modalities INTERMITTENT CONTINUOUS IHD SLED/EDD CRRT SCUF CAVH CVVHCAVHDCVVHDCAVHDFCVVHDFRRTs for ARF can be classified as intermittent or continuous, based on the duration of treatment. The duration of each intermittent therapy is less than 24 hours, whereas the duration of continuous therapy is at least 24 hours.
29 Renal Replacement Therapy : Modality Continuous Renal Replacemet Therapy (CRRT)Separated system Automated systemAnd finally we have the continuous therapies call continuous renal replacement therapy that might apply with the separated system which cheaper to operate or automated system with automated machine.
30 This picture demonstrate the separated CRRT system Separated CVVH system
31 : A one-year prospective observational study , 192 critically ill patients with AKI. : Separated system CVVH with the pre-dilution. Mean CVVH dose of 34.9±2.7mL/kg/h.: The APACHEII score was 23.2±8.4 and the SOFA was 12.0±4.3.: No complications. The survival rate was 32.3%.Conclusion: Separated system CVVH is simple, safe, and efficient and could provide cheaper treatments than the integrated system. It could thus be an effective, alternative treatment for critical acute kidney injury patients when the integrated mode is unavailable
32 This picture demonstrate the automate CRRT system Automated CVVH system
33 Renal Replacement Therapy : Modality PD(24 hrs)IHD(4 hrs)SLED( 6-12 hrs)CRRTSolute removal per day++++Hemodynamic stabilitybestpoorFair-goodgoodCost person and time++Complication-Infection-high sugar-visceral traumaBP drop- Airembolism- BP dropEach treatment suit for different conditions of the patients. In theory, PD is friendly for cardiovascular instability condition but the efficacy is quite limited. Intermittent hemodialysis provide high efficiency but effect cardiovascular condition. Continuous treatment and hybrid therapy such as SLED seem to be combine the benefits of both treatment.
34 Slow continuous ultrafiltration (SCUF) Modality of CRRTSlow continuous ultrafiltration (SCUF)Continuous arteriovenous hemofiltration (CAVH)Continuous venovenous hemofiltration (CVVH)Continuous arteriovenous hemodialysis (CAVHD)Continuous venovenous hemodialysis (CVVHD)Continuous arteriovenous hemodiafiltration (CAVHDF)Continuous venovenous hemodiafiltration (CVVHDF)The terminology for calling variety of modality of CRRT comprises of C for continuous. Next is the type of vascular access that currently uses venovenous type using double lumen hemodialysis catheter.Vascular access
35 Modality of CRRT Slow continuous ultrafiltration (SCUF) Continuous venovenous hemofiltration (CVVH)Continuous venovenous hemodialysis (CVVHD)Continuous venovenous hemodiafiltration (CVVHDF)Last words describes the mode of solute clearance included three cptions: hemofiltration, hemodialysis, and hemodiafiltration.Vascular accessMechanism of Clearance
36 SCUF Slow Continuous Ultra-Filtration Arteriovenous or venovenous Measuring deviceFiltrateSlow Continuous Ultra-FiltrationArteriovenous or venovenousQUF 100 – 300 mL/dayPerform to maintain fluid balance, no significant convective clearanceNo replacement fluid
37 CVVH Continuous Veno-Venous HemoFiltration Veno-venous circuit Replace-ment fluidMeasuring deviceFiltrateContinuous Veno-Venous HemoFiltrationVeno-venous circuitHigh permeable membraneTypical UF rate 1 – 2 L/hRequires at least a blood pump (Flow > 50 ml/min) requiredReplacement fluid(pre-dilution VS post-dilution)UF rate is the major determinant of convective clearance.The UF rate is determined by the TMP, water permeability, pore size, surface area, and membrane thickness.
38 CVVHD Continuous Veno-Venous HemoDialysis High permeable membrane DialysateMeasuring deviceFiltrateContinuous Veno-Venous HemoDialysisHigh permeable membraneAt least a Blood pump and a pump for Dialysate (10-30 ml/min or L/h) requiredNo replacement fluidUF for volume control, some convective clearance at high rateThe dialysate flow rate is slower than the blood flow rate, allowing small solute to equilibrate completely between the blood and dialysate. As a result, the dialysate flow rate approximates urea and Cr clearance.
39 CVVHDF Continuous VenoVenous HemoDiaFiltration High permeable membrane DialysateReplace-ment fluidMeasuring deviceFiltrateContinuous VenoVenous HemoDiaFiltrationHigh permeable membraneUltrafiltration flow > 6 ml/min(9-12 L/day)1 pump for dialysate(10-30 ml/min or L/h))Replacement fluid
42 Mortality RCT < 0.02 NS 0.72 Meta-analysis (Relative risk) Study N Mode of RRTICU hospital mortalityP-valueHospital mortalityCommentsRCTMehta,166CRRT/IHD59.5% vs 41.5%<0.0265.5% vs 47.6%< 0.02Unexplained randomization problemsAugustine80CVVHD/IHDNA67.5% vs 70%NSUnderpowered Inadequate delivered dose of dialysisUelinger125CVVHDF/IHD34% vs 38%0.7147% vs 51%0.72Enrollment problems UnderpoweredVinsonneau36060 day mortality 32.6% vs 31.5% ,p =0.98Changes in dialysis dose UnderpoweredLins31658.1% vs 62.5%Meta-analysis (Relative risk)Tonelli ,200237>6000.96Used different types of mortalityKellum ,1,4000.93After adjustment for study quality and severity of illness, mortality was lower in CRRT patientsRabindranath,1,5501.061.01Cochrane meta-analysisPannu ,2008406,0581.1Systematic review
43 Renal recovery Study N Mode of RRT Definition of renal outcome Outcome P-valueCommentsCohortJacka ,93IHD/CRRTDialysis dependence at discharge64.3% vs 12.5%0.0003Higher severity score in CRRT group,2007422,202Requirement of chronic dialysis after 90 days16.5% vs 8.3%NAHigher long-term mortality in IHD vs CRRT ; after 10 yrs total risk of ESRD almost the same in both groupsUchino,2007431,218Dialysis dependence at hospital discharge33.8% vs 14.5%<0.0001Results remained significant in patients without prior CKDRCTMehta ,2001321661) Dialysis dependence at hospital discharge2)CKD at hospital discharge and dealth1) 7% vs 14%2) 17% vs 4%1) NS2) 0.01The percentage of CKD in baseline (≥2mg/dL) was higher in patients with IHD (NS)Augustine,20043380Discontinuation of dialysis at discharge4 pts vs 5 ptsNSSmall number of patientsUehlinger,200534125IHD/CVVHDF1) Rate of dialysis dependence2) Absence of renal recovery1) 1pt vs 1pt2) 58% vs 50%1) NA2) 0.61Similar proportions of patients with CKD at baselineVinsonneau,2006353601) Rate of renal recovery at ICU discharge2) Rate of renal recovery at hospital discharge1)90% vs 93%2) 100 vs all but 1patient1) 0.52) NANot possible to determine difference in proportion of patients with CKD in the 2 groupsMeta-analysisRabindranath,1,550number of surviving patients not requiring RRTRR=0.99Cochrane meta-analysisPannu ,2008406,058chronic dialysisRR=0.91Systematic review
45 Renal Replacement Therapy Timing of initiationearly VS lateModality of RRTIntermittent VS ContinuousDose of RRTDaily vs AD
46 Dialysis Dose Measurements The treatment dose of RRT can be defined by various aspectsEfficiencyIntensityFrequencyClinical efficacyRicci Z & Ronco C: Crit Care Clin 2005.
47 Efficiency of RRT (Clearance, K) Clearance (ml/min)Efficiency of RRT can be represented by clearance (K).K (clearance) represents only the amount of treatment per unit of time.K cannot be employed to compare various modalities differing in treatment duration.K represents an instantaneous measurement, and it correlates with the amount of solute removal at the time point of the measurement.Pisitkun et al. Contr Nephrol 2004.
48 Daily clearance (ml/day) Intensity of RRT (Kt)Daily clearance (ml/day)Intensity of RRT can be described by the product of clearance x time (Kt). Because the time is accounted, Kt is more effective than K in the comparison of various RRT modalities.24h h hPisitkun et al. Contr Nephrol 2004.
49 Weekly Clearance of RRT Weekly Clearance (ml/week) Frequency is an essential factor to further describe treatment dose in different modalities. Thus weekly clearance, intensity x frequency (Kt x treatment d/wk), is superior to Kt because it offers the comparison of different modalities in the more extensive view.24h h h h hContinuous Alt.days x7 days x3 days x7 daysPisitkun et al. Contr Nephrol 2004.
50 Effect of Delivered RRT Dose : CRRT “Effects of different doses in CVVH on outcomes of ARF”10090Overall8070605040We turn to CRRT. This is a study published by Claudio Ronco in patients randomized to CVVH at 20, 35, or 45 mL/kg/hr of ultrafiltration rate and you can see the step-up in survival from 41% to 57% and 58% with the 2 higher doses of therapy.30201020 ml/kg/hr35 ml/kg/hr45 ml/kg/hrRCT, n=425Ronco C. , et al. The LANCET 2000
51 Effect of Delivered RRT Dose : CRRT “Effects of different doses in CVVH on outcomes of ARF”10090OverallSeptic patients8070605040When looking in subgroup of septic patient. The significant improving in survival was seen only in 45 ml/kg/hr group.30201020 ml/kg/hr35 ml/kg/hr45 ml/kg/hrRCT, n=425Ronco C. , et al. The LANCET 2000
52 Effect of Delivered RRT Dose : CRRT “Effects of different doses in CRRT on outcomes of ARF”UF/Dialysis 24/18 ml/kg/hrUF/Dialysis 25/0 ml/kg/hrSimilar results were shown in this study by Saudan et al. that looked at CVVH of 25 mL/kg/hr or continuous hemodiafiltration with ultrafiltration at 24 mL/kg/hr and then the addition of dialysate flow at 18 mL/kg/hr. The higher dose resulted in better survival.RCT, n=206Saudan P, et al. Kidney Int 2006; 70:1312-7
53 Effect of Delivered RRT Dose : CRRT Then most recently, the ATN study from US patients were randomized to a strategy that used intermittent therapy in hemodynamically stable patients and either continuous therapy or hybrid therapies in unstable patients at two different dosing strata.So in the high-dose arm, the intensive arm patients received 6 days a week hemodialysis with a delivered Kt/V of 1.3 per treatment or continuous therapy at 35 mL/kg/hour or SLED on a 6 days a week basis.Less intensive arm, it was 3 times a week intermittent hemodialysis or hybrid therapy or CVVHDF at 20 mL/kg/hour.There was absolutely no difference in the outcome between the two treatment arms: intensive 53.6% and less intensive 51.5%.So, what does that tell us about dose and survival? Certainly, there is a relationship between dose and survival. If we don't dialyze patients with renal failure, we know they die. So we know that if we give no dose, there is very little survival. There appears to be a graded relationship in certain settings.Because, there were still some different in the dose of the higher dose group between each study such as the ATN study use predilution CVVHD while in Ronco trial used post dilution CVVH that was more effective.So what is the plateau point when increasing dose does not provide any further benefit still need to answer. There is actually other 2 studies that is going to answer this question . First from Australia randomized 1500 patients to either 25 or 40 mL/kg/hour of continuous therapy. And another studyRCT, n=1124
54 Effect of Delivered RRT Dose : CRRT Then most recently, the ATN study from US patients were randomized to a strategy that used intermittent therapy in hemodynamically stable patients and either continuous therapy or hybrid therapies in unstable patients at two different dosing strata.So in the high-dose arm, the intensive arm patients received 6 days a week hemodialysis with a delivered Kt/V of 1.3 per treatment or continuous therapy at 35 mL/kg/hour or SLED on a 6 days a week basis.Less intensive arm, it was 3 times a week intermittent hemodialysis or hybrid therapy or CVVHDF at 20 mL/kg/hour.There was absolutely no difference in the outcome between the two treatment arms: intensive 53.6% and less intensive 51.5%.So, what does that tell us about dose and survival? Certainly, there is a relationship between dose and survival. If we don't dialyze patients with renal failure, we know they die. So we know that if we give no dose, there is very little survival. There appears to be a graded relationship in certain settings.Because, there were still some different in the dose of the higher dose group between each study such as the ATN study use predilution CVVHD while in Ronco trial used post dilution CVVH that was more effective.So what is the plateau point when increasing dose does not provide any further benefit still need to answer. There is actually other 2 studies that is going to answer this question . First from Australia randomized 1500 patients to either 25 or 40 mL/kg/hour of continuous therapy. And another studyRCT, n= NEJM 2009
55 Effect of Dialysis Dose on Survival in Critically Ill Patients Requiring RRT 100-90-80-70-60-50-40-30-20-10-0-High RRT DoseSurvival %Critically ill patients requiring RRT were stratified for disease severity:dialysis dose did not affect outcome in patients with very high or very low scores, but correlate with survival in patients with intermediate degree of illness.Low RRT DoseSeverity of DiseasePaganini et al: Blood Purif 2001.
57 Anticoagulation Drugs Advantages Disadvantages Heparin Good anticoagulationThrombocytopenia , BleedingRegional heparinReduced bleedingComplex managementLMWHLess thrombocytopeniaBleedingCitrateLower risk for bleedingMetabolic alkalosis, Hypocalcemia, Special dialysateProstacyclineReduced bleeding riskHypotensionPoor efficacySaline flushesNo bleeding risk
58 Dose heparin for CRRT aPTT (seconds) Bolus dose Rate change Repeat aPTT< 401,000 U+200 U/hrIn 6 hrsNothing+100 U/hrIn 4 hrsNo changeStop 1/2 hr and-100 U/hr>65.0Stop 1 hr and-200 U/hr: Heparin solution is made by mixing 1 ml of 10,000 U/ml of heparin in 19 ml of normal saline fora heparin concentration of 500U/ml.: Initial bolus is 25 U/kg followed by an infusion of 5U/kg/hr.: The goal of treatment is to maintain systemic prefilter aPTT ( seconds, 1.5 times control)
64 Common complications for citrate DerangementCause and signsAdjustmentMetabolic acidosisInsufficient removal of metabolic acidsAnion gap increasesLoss of buffer substrate is higher than deliveryCitrate metabolism decreases ( decreases, total Ca/iCa increase [more than ], and anion gap Increases)Increase CRRT dose (filtrate or dialysate flow) to 35 ml/kg per hrIncrease bicarbonate replacement or Increase bicarbonate dialysate flow or give additional bicarbonate or increase citrate flow (cave accumulation)Decrease citrate delivery or stop Increase dialysate or filtrate flow, Increase bicarbonate replacement or increase bicarbonate dialysate flowMetabolic alkalosisDelivery of buffer substrate is higher than lossDecrease loss of buffer due to a decline in filtrate flowDecrease bicarbonate replacement or decrease bicarbonate dialysate flow or stop additional bicarbonate iv or decrease citrate flow (cave accumulation)Change filterIncrease filtrate flowHypocalcemiaLoss of calcium is higher than delivery ( decreases and total Ca/iCa is normal)Citrate metabolism decrease ( metabolism acidosis , total ca/iCa increase, and anion gap increases)Increase iv calcium dosedecrease or stop citrate deliveryincrease dialysate or filtrate flowincrease bicarbonate replacement orincrease bicarbonate dialysate flowHypercalcemiaDelivery of calcium is higher than lossDecrease iv calcium doseHypernatremiaDelivery of sodium is higher than lossDecreased loss of sodium due to a decline in filtrate flowRecalculate default settingsProtocol violationDecrease sodium replacementDecrease dialysate sodium contentDecrease trisodium citrate flowHyponatremiaLoss of sodium is higher than deliveryIncrease sodium replacementIncrease dialysate sodium contentIncrease trisodium citrate flow
67 Thank you Acknowledgements Ratchadapiseksompotch Research Fund for projected budgetNipro Company for dialyzerNurses and Technicians of Division of Nephrology King Chulalongkorn HospitalThank you for your attention