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Acute Hemodialysis & CRRT in AKI Paweena Susantitaphong,MD,MS 1-3 1 Physician Staff, Division of Nephrology, Department of Medicine, King Chulalongkorn.

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Presentation on theme: "Acute Hemodialysis & CRRT in AKI Paweena Susantitaphong,MD,MS 1-3 1 Physician Staff, Division of Nephrology, Department of Medicine, King Chulalongkorn."— Presentation transcript:

1 Acute Hemodialysis & CRRT in AKI Paweena Susantitaphong,MD,MS Physician Staff, Division of Nephrology, Department of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 2 International Society of Nephrology (ISN) fellowship 3 Adjunct Instructor of Tufts University School of Medicine, Boston, USA.

2 DEFINITION Acute Renal Failure  Acute Kidney Injury An abrupt (within 48h) reduction in kidney function Currently defined as an absolute increase in sCr of either ≥ 0.3 mg/dl or a percentage increase of ≥ 50% or a reduction in Urine Output (documented oliguria of 6 h) Crit Care 2007;11:R31 Background

3 StageSerum creatinineUrine output 1 1.5–1.9 times baseline OR ≥ 0.3 mg/dl (≥ 26.5 mmol/l) increase < 0.5 ml/kg/h for 6–12 hours 22.0–2.9 times baseline < 0.5 ml/kg/h for ≥12 hours 33.0 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 m 2 < 0.3 ml/kg/h for ≥ 24 hours OR Anuria for ≥12 hours

4 World Incidence of Acute Kidney Injury : A Meta-Analysis Susantitaphong P, et al. CJASN 2013, June 6

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6 No. studies No. subjects 3,585,911 3,303,992 3,281,715 3,281,715 29,400,495 Susantitaphong P, et al. CJASN 2013, June 6

7 No. studies No. subjects with AKI 429,535 8,226 42,354 42,354 6,534 Susantitaphong P, et al. CJASN 2013, June 6

8 No. studies No. subjects with AKI 405,616 90,048 40,631 38,914 4,427 No. subjects without AKI 1,765,574 1,127,070 1,120,523 1,120, ,969 Susantitaphong P, et al. CJASN 2013, June 6

9 Acute Kidney Injury Increases Risk of ESRD among Elderly Ishani A,et al. J Am Soc Nephrol 2009; 20: 223–228

10 Coca SG, et al. AJKD 2010

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 initiation ◦ early VS late

13 Indications in Renal Failure 1. Uremia impaired nutrition  N/V  poor appetite  gastritis with UGIB, ileus, colitis Altered mental status Pericarditis (urgent indication) Bleeding from platelet dysfunction (urgent indication)

14 Indications 2. Refractory or progressive fluid overload 3. Uncontrollable hyperkalemia 4. Severe metabolic acidosis esp. oliguria 5. Steady worsening of renal function BUN > mg/dl

15 AuthorsYearDesignNPre-RRT BUNSurvival benefit Mode of RRT EarlyLateEarlyLate Parsons et al1961Retro >200+HD Fischer et al1966Retro162~150>200+HD Kleinknecht1972Retro500<93>163+HD Conger1975Pro HD Gillum et al1986Pro ±±HD Gettings et al1999Retro100<60>60+CRRT Bouman et al2002Pro ±±CVVH Demirkilic et al2004Retro61+CVVHD Elahi et al2004Retro64+CVVH Liu et al2006Retro243<76>76+HD and CRRT Outcome of Early vs. Late RRT in AKI

16 Timing of renal replacement therapy initiation in acute renal failure: a meta-analysis Seabra VF, Balk EM, Liangos O, Sosa MA, Cendoroglo M, Jaber BL We identified 23 studies (5 randomized or quasi-randomized controlled trials, 1 prospective and 16 retrospective comparative cohort studies, and 1 single-arm study with a historic control group). By using meta-analysis of randomized trials, early RRT was associated with a nonsignificant 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 significant 28% 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 with lower mortality in smaller studies (n < 100) by means of subgroup analysis. Am J Kidney Dis Aug;52(2):

17 Effect of early renal replacement therapy (RRT) initiation on non-recovery of renal function in AKI Am J Kidney Dis Aug;52(2):

18 Clinical symptoms Solute level (Blood urea nitrogen, serum creatinine) Interval between ICU/hospital admission and renal replacement therapy initiation Days between biochemical diagnosis of AKI and renal replacement therapy initiation Severity of AKI (AKIN/RIFLE) classification Prognostic scores Number of organ failure Parameters that were used in studies for classify early and late renal replacement therapy initiation in AKI

19 Renal Replacement Therapy Timing of initiation ◦ early VS late Modality of RRT ◦ Intermittent VS Continuous

20 Dialysis : Modality Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?)

21 Dialysis : Modality Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?) Intermittent Vs Continuous (IHD,SLED vs. CRRT?) NoteIHDIntermittent Hemodialysis SLEDSustained Low-Efficiency Dialysis CRRTContinuous Renal Replacement Therapy

22 RRT Modalities INTERMITTENTCONTINUOUS IHDSLED/EDD CRRT SCUF CAVH CVVH CAVHD CVVHD CAVHDF CVVHDF

23 Mechanism of clearance Hemodialysis = Diffusion Hemofiltration = Convection Hemodiafiltration = Diffusion + Convection

24 Diffusion t = 0 t = equilibrium Concentration gradient Molecular weight: speed & size Membrane resistance: membrane & unstir fluid layer

25 T = 0 Ultrafiltration (Convection) T = later

26 Dialysis : Modality Intermittent Hemodialysis

27 Dialysis : Modality 6-12 hrs Sustained Low-Efficiency Dialysis (SLED) Hemodialysis in ARF patient -Long duration 6-12 hrs -Dialysate flow ml/min -Critically-ill patient

28 Dialysis : Modality Continuous Renal Replacemet Therapy (CRRT)

29 Separated system Automated system Renal Replacement Therapy : Modality Continuous Renal Replacemet Therapy (CRRT)

30 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 Automated CVVH system

33 PD (24 hrs) IHD (4 hrs) SLED ( 6-12 hrs) CRRT (24 hrs) Solute removal per day ++++ Hemodynamic stability bestpoorFair-goodgood Cost person and time Complication-Infection -high sugar -visceral trauma BP drop - Air embolism - BP drop Renal Replacement Therapy : Modality

34 Slow 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) Vascular access

35 Slow continuous ultrafiltration (SCUF) Continuous venovenous hemofiltration(CVVH) Continuous venovenous hemodialysis (CVVHD) Continuous venovenous hemodiafiltration (CVVHDF) Vascular accessMechanism of Clearance

36 Measuring device Filtrate SCUF  Slow Continuous Ultra- Filtration Arteriovenous or venovenous Q UF 100 – 300 mL/day Perform to maintain fluid balance, no significant convective clearance No replacement fluid

37 Replace -ment fluid Measuring device Filtrate CVVH  Continuous Veno-Venous HemoFiltration Veno-venous circuit High permeable membrane Typical UF rate 1 – 2 L/h Requires at least a blood pump (Flow > 50 ml/min) required Replacement fluid (pre-dilution VS post-dilution)

38 CVVHD  Continuous Veno- Venous HemoDialysis High permeable membrane At least a Blood pump and a pump for Dialysate (10-30 ml/min or L/h) required No replacement fluid UF for volume control, some convective clearance at high rate Dialysate Measuring device Filtrate

39 Continuous VenoVenous HemoDiaFiltration High permeable membrane Ultrafiltration flow > 6 ml/min (9-12 L/day) 1 pump for dialysate (10-30 ml/min or L/h)) Replacement fluid Dialysate Replace -ment fluid Measuring device Filtrate CVVHDF

40 Continuous Renal Replacement Therapy Volume Control Diffusive Clearance Convective Clearance Volume Replacement SCUFYes-+No CVVHYes-+++Yes CVVHDYes++++No CVVHDFYes++ Yes

41 IHDCRRT

42 StudyNMode of RRTICU hospital mortality P-valueHospital mortality P-value Comments RCT Mehta, CRRT/IHD59.5% vs 41.5%< % vs 47.6% < 0.02 Unexplained randomization problems Augustine CVVHD/IHDNA 67.5% vs 70% NS Underpowered Inadequate delivered dose of dialysis Uelinger CVVHDF/IHD34% vs 38%0.7147% vs 51% 0.72 Enrollment problems Underpowered Vinsonneau CVVHDF/IHDNA 60 day mortality 32.6% vs 31.5%,p =0.98 Changes in dialysis dose Underpowered Lins CRRT/IHDNA 58.1% vs 62.5% NS Meta-analysis (Relative risk) Tonelli, >600CRRT/IHDNA 0.96 NS Used different types of mortality Kellum, ,400CRRT/IHDNA 0.93 NS After adjustment for study quality and severity of illness, mortality was lower in CRRT patients Rabindranath, ,550CRRT/IHD1.06NS1.01 NS Cochrane meta-analysis Pannu, ,058CRRT/IHDNA 1.1 NS Systematic review Mortality

43 StudyNMode of RRTDefinition of renal outcome OutcomeP-valueComments Cohort Jacka, IHD/CRRTDialysis dependence at discharge 64.3% vs 12.5%0.0003Higher severity score in CRRT group, ,202IHD/CRRTRequirement of chronic dialysis after 90 days 16.5% vs 8.3%NAHigher long-term mortality in IHD vs CRRT ; after 10 yrs total risk of ESRD almost the same in both groups Uchino, ,218IHD/CRRTDialysis dependence at hospital discharge 33.8% vs 14.5%<0.0001Results remained significant in patients without prior CKD RCT Mehta, IHD/CRRT1) Dialysis dependence at hospital discharge 2)CKD at hospital discharge and dealth 1) 7% vs 14% 2) 17% vs 4% 1) NS 2) 0.01 The percentage of CKD in baseline ( ≥ 2mg/dL) was higher in patients with IHD (NS) Augustine, IHD/CRRTDiscontinuation of dialysis at discharge 4 pts vs 5 ptsNSSmall number of patients Uehlinger, IHD/CVVHDF1) Rate of dialysis dependence 2) Absence of renal recovery 1) 1pt vs 1pt 2) 58% vs 50% 1) NA 2) 0.61 Similar proportions of patients with CKD at baseline Vinsonneau, IHD/CVVHDF1) Rate of renal recovery at ICU discharge 2) Rate of renal recovery at hospital discharge 1)90% vs 93% 2) 100 vs all but 1patient 1) 0.5 2) NA Not possible to determine difference in proportion of patients with CKD in the 2 groups Meta-analysis Rabindranath, ,550IHD/CRRT number of surviving patients not requiring RRT RR=0.99NS Cochrane meta-analysis Pannu, ,058IHD/CRRTchronic dialysis RR=0.91NS Systematic review Renal recovery

44 Indication for CRRT Cardiovascular failure Hypercatabolism Cerebral edema Liver failure Sepsis Adult respiratory distress syndrome Cardiopulmonary bypass Crush syndrome

45 Renal Replacement Therapy Timing of initiation ◦ early VS late Modality of RRT ◦ Intermittent VS Continuous Dose of RRT ◦ Daily vs AD

46 Dialysis Dose Measurements The treatment dose of RRT can be defined by various aspects ◦ Efficiency ◦ Intensity ◦ Frequency ◦ Clinical efficacy Ricci Z & Ronco C: Crit Care Clin 2005.

47 Efficiency of RRT (Clearance, K) Efficiency of RRT (Clearance, K) Clearance (ml/min) Pisitkun et al. Contr Nephrol 2004.

48 Intensity of RRT (Kt) Daily clearance (ml/day) 24h 8h 3h Pisitkun et al. Contr Nephrol 2004.

49 Weekly Clearance of RRT Weekly Clearance (ml/week) 24h 8h 8h 3h 3h Continuous Alt.days x7 days x3 days x7 days Pisitkun et al. Contr Nephrol 2004.

50 “Effects of different doses in CVVH on outcomes of ARF” Effect of Delivered RRT Dose : CRRT ml/kg/hr35 ml/kg/hr45 ml/kg/hr Overall Ronco C., et al. The LANCET 2000 RCT, n=425

51 Effect of Delivered RRT Dose : CRRT ml/kg/hr35 ml/kg/hr45 ml/kg/hr OverallSeptic patients “Effects of different doses in CVVH on outcomes of ARF” Ronco C., et al. The LANCET 2000 RCT, n=425

52 Saudan P, et al. Kidney Int 2006; 70: RCT, n=206 “Effects of different doses in CRRT on outcomes of ARF” UF/Dialysis 24/18 ml/kg/hr UF/Dialysis 25/0 ml/kg/hr Effect of Delivered RRT Dose : CRRT

53 RCT, n=1124

54 Effect of Delivered RRT Dose : CRRT RCT, n=1508 NEJM 2009

55 Effect of Dialysis Dose on Survival in Critically Ill Patients Requiring RRT Severity of Disease Survival % High RRT Dose Low RRT Dose Paganini et al: Blood Purif 2001.

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57 Anticoagulation DrugsAdvantagesDisadvantages HeparinGood anticoagulationThrombocytopenia, Bleeding Regional heparinReduced bleedingComplex management LMWHLess thrombocytopeniaBleeding CitrateLower risk for bleedingMetabolic alkalosis, Hypocalcemia, Special dialysate ProstacyclineReduced bleeding riskHypotension Poor efficacy Saline flushesNo bleeding riskPoor efficacy

58 aPTT (seconds)Bolus doseRate changeRepeat aPTT < 401,000 U+200 U/hrIn 6 hrs Nothing+100 U/hrIn 4 hrs NothingNo changeIn 6 hrs Nothing Stop 1/2 hr and -100 U/hr In 4 hrs >65.0NothingStop 1 hr and -200 U/hr In 4 hrs Dose heparin for CRRT : Heparin solution is made by mixing 1 ml of 10,000 U/ml of heparin in 19 ml of normal saline for a 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)

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64 DerangementCause and signsAdjustment Metabolic acidosis Insufficient removal of metabolic acids Anion gap increases Loss of buffer substrate is higher than delivery Citrate 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 hr Increase 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 flow Metabolic alkalosis Delivery of buffer substrate is higher than loss Decrease loss of buffer due to a decline in filtrate flow Decrease bicarbonate replacement or decrease bicarbonate dialysate flow or stop additional bicarbonate iv or decrease citrate flow (cave accumulation) Change filter Increase filtrate flow Hypocalcemia Loss 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 dose decrease or stop citrate delivery increase dialysate or filtrate flow increase bicarbonate replacement or increase bicarbonate dialysate flow HypercalcemiaDelivery of calcium is higher than lossDecrease iv calcium dose Hypernatremia Delivery of sodium is higher than loss Decreased loss of sodium due to a decline in filtrate flow Recalculate default settings Protocol violation -Decrease sodium replacement -Decrease dialysate sodium content -Decrease trisodium citrate flow Change filter HyponatremiaLoss of sodium is higher than deliveryRecalculate default settings Protocol violation -Increase sodium replacement -Increase dialysate sodium content -Increase trisodium citrate flow Common complications for citrate

65 : Rt internal jugular catheter : CVVH order BFR cc/min, RF (pre- dilution 1,500 cc/hr) UF -100 cc/hr (2,400 cc/day) : Dialysate solution 0.45% 900 cc, 3%NaCl 50 cc, 7.5%HCO3 50 cc KCl 3 mEq/L : 10% Calcium gluconate 180 cc/day : 50% Magnesium sulphate 2 cc iv Na +, K +, Cl -, HCO 3 -, Ca 2+, blood sugar q 6-12 hrs BUN, Cr, Mg 2+, PO 4 3- CBC,, PT/PTT q 24 hrs EXAMPLE

66 Vascular access -Bleeding -Thrombosis -Hematoma -Aneurysm formation -Hemothorax -Pneumothorax -Pericardial tamponade -Arrthymias -Air embolism -Infection Extracorporeal circuit -Air embolism -Reduced filter life -Reduced dialysis dose -Hypothermia -Bioincompatibility -Immunologic activation -Anaphylaxis Hematologic complications Need for anticoagulantion -Hypocalcemia -Metabolic alkalosis -Hypernatremia -Citrate intoxication -Bleeding Thrombocytopenia Bleeding Hemolysis Heparin-induced thrombocytopenia Electrolyte disturbances -Hypophosphatemia -Hypomagnesemia -Hypocalcemia -Hypokalemia -Hyponatremia -Hypernatremia Hemodynamic instability Volume management errors Nutritional losses -Amino acids & proteins -Poor glycemic control -Vitamin deficiencies -Trace minerals Acid-base disturbances -Metabolic acidosis -Metabolic alkalosis -Citrate-induced alkalosis & acidosis Altered drug removal Delayed renal recovery Common complications in CRRT

67 Thank you


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