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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 Memorial Hospital, Chulalongkorn University, Bangkok 2 International Society of Nephrology (ISN) fellowship 3 Adjunct Instructor of Tufts University School of Medicine, Boston, USA. Slide 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 Slide 3 StageSerum creatinineUrine output 1 1.51.9 times baseline OR 0.3 mg/dl ( 26.5 mmol/l) increase < 0.5 ml/kg/h for 612 hours 22.02.9 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 mol/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 Slide 4 World Incidence of Acute Kidney Injury : A Meta-Analysis Susantitaphong P, et al. CJASN 2013, June 6 Slide 5 Slide 6 No. studies 154 112 108 108 189 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 Slide 7 No. studies 110 26 25 25 31 No. subjects with AKI 429,535 8,226 42,354 42,354 6,534 Susantitaphong P, et al. CJASN 2013, June 6 Slide 8 No. studies 92 21 20 20 20 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 1,120,523 127,969 Susantitaphong P, et al. CJASN 2013, June 6 Slide 9 Acute Kidney Injury Increases Risk of ESRD among Elderly Ishani A,et al. J Am Soc Nephrol 2009; 20: 223228 Slide 10 Coca SG, et al. AJKD 2010 Slide 11 Acute Kidney Injury Associates with Increased Long-Term Mortality Lafrance JP,et al. J Am Soc Nephrol 2010;21 :345-52 Slide 12 Renal Replacement Therapy Timing of initiation early VS late Slide 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) Slide 14 Indications 2. Refractory or progressive fluid overload 3. Uncontrollable hyperkalemia 4. Severe metabolic acidosis esp. oliguria 5. Steady worsening of renal function BUN > 70-100 mg/dl Slide 15 AuthorsYearDesignNPre-RRT BUNSurvival benefit Mode of RRT EarlyLateEarlyLate Parsons et al1961Retro33120-150>200+HD Fischer et al1966Retro162~150>200+HD Kleinknecht1972Retro500163+HD Conger1975Pro1870150+HD Gillum et al1986Pro3460100HD Gettings et al1999Retro10060+CRRT Bouman et al2002Pro10647105CVVH Demirkilic et al2004Retro61+CVVHD Elahi et al2004Retro64+CVVH Liu et al2006Retro24376+HD and CRRT Outcome of Early vs. Late RRT in AKI Slide 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. 2008 Aug;52(2):272-84. Slide 17 Effect of early renal replacement therapy (RRT) initiation on non-recovery of renal function in AKI Am J Kidney Dis. 2008 Aug;52(2):272-84. Slide 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 Slide 19 Renal Replacement Therapy Timing of initiation early VS late Modality of RRT Intermittent VS Continuous Slide 20 Dialysis : Modality Intracorporeal Vs Extracorporeal (PD vs. HD - CRRT?) Slide 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 Slide 22 RRT Modalities INTERMITTENTCONTINUOUS IHDSLED/EDD CRRT SCUF CAVH CVVH CAVHD CVVHD CAVHDF CVVHDF Slide 23 Mechanism of clearance Hemodialysis = Diffusion Hemofiltration = Convection Hemodiafiltration = Diffusion + Convection Slide 24 Diffusion t = 0 t = equilibrium Concentration gradient Molecular weight: speed & size Membrane resistance: membrane & unstir fluid layer Slide 25 T = 0 Ultrafiltration (Convection) T = later Slide 26 Dialysis : Modality Intermittent Hemodialysis Slide 27 Dialysis : Modality 6-12 hrs Sustained Low-Efficiency Dialysis (SLED) Hemodialysis in ARF patient -Long duration 6-12 hrs -Dialysate flow 70-300 ml/min -Critically-ill patient Slide 28 Dialysis : Modality Continuous Renal Replacemet Therapy (CRRT) Slide 29 Separated system Automated system Renal Replacement Therapy : Modality Continuous Renal Replacemet Therapy (CRRT) Slide 30 Separated CVVH system Slide 31 : A one-year prospective observational study, 192 critically ill patients with AKI. : Separated system CVVH with the pre-dilution. Mean CVVH dose of 34.92.7mL/kg/h. : The APACHEII score was 23.28.4 and the SOFA was 12.04.3. : 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 Slide 32 Automated CVVH system Slide 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 Slide 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 Slide 35 Slow continuous ultrafiltration (SCUF) Continuous venovenous hemofiltration(CVVH) Continuous venovenous hemodialysis (CVVHD) Continuous venovenous hemodiafiltration (CVVHDF) Vascular accessMechanism of Clearance Slide 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 Slide 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) Slide 38 CVVHD Continuous Veno- Venous HemoDialysis High permeable membrane At least a Blood pump and a pump for Dialysate (10-30 ml/min or 1-2.5 L/h) required No replacement fluid UF for volume control, some convective clearance at high rate Dialysate Measuring device Filtrate Slide 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 1-2.5 L/h)) Replacement fluid Dialysate Replace -ment fluid Measuring device Filtrate CVVHDF Slide 40 Continuous Renal Replacement Therapy Volume Control Diffusive Clearance Convective Clearance Volume Replacement SCUFYes-+No CVVHYes-+++Yes CVVHDYes++++No CVVHDFYes++ Yes Slide 41 IHDCRRT Slide 42 StudyNMode of RRTICU hospital mortality P-valueHospital mortality P-value Comments RCT Mehta, 2001 32 166CRRT/IHD59.5% vs 41.5%600CRRT/IHDNA 0.96 NS Used different types of mortality Kellum, 2002 38 1,400CRRT/IHDNA 0.93 NS After adjustment for study quality and severity of illness, mortality was lower in CRRT patients Rabindranath, 2007 39 1,550CRRT/IHD1.06NS1.01 NS Cochrane meta-analysis Pannu,2008 40 6,058CRRT/IHDNA 1.1 NS Systematic review Mortality Slide 43 StudyNMode of RRTDefinition of renal outcome OutcomeP-valueComments Cohort Jacka, 2005 41 93IHD/CRRTDialysis dependence at discharge 64.3% vs 12.5%0.0003Higher severity score in CRRT group,2007 42 2,202IHD/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,2007 43 1,218IHD/CRRTDialysis dependence at hospital discharge 33.8% vs 14.5% aPTT (seconds)Bolus doseRate changeRepeat aPTT < 401,000 U+200 U/hrIn 6 hrs 40.1-45.0Nothing+100 U/hrIn 4 hrs 45.1-55.0NothingNo changeIn 6 hrs 55.1-65.0Nothing 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 (45 -55 seconds, 1.5 times control) Slide 59 Slide 60 Slide 61 Slide 62 Slide 63 Slide 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 2.1-2.5], 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 Slide 65 : Rt internal jugular catheter : CVVH order BFR 120-150 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 Slide 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 Slide 67 Thank you