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CRRT Basics Dr. Gaurav Chaudhry Head, Medical Affairs Baxter (I) Private Limited
2 Introduction • Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with substantial morbidity and risk of death • Approximately 5% to 10% of patients with AKI require renal replacement therapy (RRT) during their ICU stay1 • Mortality rates of 30% to 70%.2-4 • Over the past 2 decades, the incidence of RRT requiring AKI has increased by approximately 10% per year5 1. Tolwani A. Continuous renal-replacement therapy for acute kidney injury. N Engl J Med. 2012;367(26):2505-2514 2. Tandukar, S; Palevsky, P; Continuous Renal Replacement Therapy Who, When, Why, and How Chest 2019 Mar;155(3):626-638
Introduction • Continuous renal replacement therapy (CRRT) is commonly used to provide renal support for critically ill patients with acute kidney injury, particularly patients who are hemodynamically unstable1 • A variety of techniques that differ in their mode of solute clearance may be used1 • However, substantial uncertainty remains regarding many of the fundamental aspects of RRT management1 • As with other dialysis techniques, CRRT requires a well-functioning access, a permeable membrane, pumps to circulate blood and various solutions across the membrane with accurate fluid balancing, and pressure monitoring systems. 2 1.Tadunkar, S.; Palevsky P., Continuous Renal Replacement Therapy Who, When, Why, and How CHEST 2019; 155(3):626-638 2. Macedo, E.;Mehta R, Am J Kidney Dis. Continuous Dialysis Therapies: Core Curriculum 2016;2016;68(4):645-657
From CAVH to Veno-venous therapy Ricci Z. et al, Continuous Renal Replacement Technology: From Adaptive Technology and Early Dedicated Machines towards Flexible Multipurpose Machine Platforms. Blood Purif 2004;22:269-276.| PAST “last chance” therapy for AKI NOW a standardized, widely used form of artificial kidney support Improved technology supporting application of this therapy1  Hardware advances  Software evolution
Solute clearance and modality selection As in the glomerulus, removal of fluid and solutes in CRRT occurs through a semi-permeable membrane This concept is known as selective permeability, meaning that certain substances will cross the membrane and others will not be allowed to cross
6 References| CRRT CONVECTION DIFFUSION SCUF CVVH CVVHD CVVHDF
7 References|
8 Basic components of CRRT Baxter Confidential — Do not distribute without prior approval | CRRT Hemofilt er Vascu lar Acces s Anticoagula tion Solutio ns Blood Warm er CRRT Syste m
CRRT Treatment Modalities: Continuous Venovenous Hemodialysis (CVVHD) Rona A, Fumagalli R. Indications for Renal Replacement Therapy in the Critically Ill Patient. In: Critical Care Nephrology; 2nd ed. Philadelphia, PA: Saunders Elsevier; 2009:1328-1332 Primary Therapeutic Goal: • Safe fluid removal and solute clearance Principles Used: • Diffusion Therapy Characteristics:  Requires dialysate to drive diffusion  No replacement fluid  Used to achieve solute removal (small and medium sized molecules) and fluid balance  Blood flow variable Primary Indications: • Uremia, acid/base or electrolyte imbalance, fluid overload
Transport Mechanisms: Diffusion • Diffusion is the movement of solutes through a semi-permeable membrane from an area of higher concentration to an area of lower concentration until equilibrium has been established • In CRRT, diffusion occurs when blood flows on one side of the membrane, and dialysate solution flows counter-current on the other side • The dialysate does not mix with the blood • Efficient for removing small molecules but not large molecules • Molecular size and membrane type can affect clearances FLOW Blood Side Dialysate Side Solute FLOW
Transport Mechanisms: Diffusion • Solute transfer across the membrane occurs by movement down a concentration gradient from blood to dialysate until equilibrium has been established 1 • Lower molecular weight (< 500-1,500 Daltons) solutes (smaller circles) cross the membrane more readily than higher molecular weight solutes (larger circles)1 FLOW Blood Side Dialysate Side FLOW Solutes 1. Tandukar, Srijan et al. Continuous Renal Replacement Therapy CHEST, March 2019 Volume 155, Issue3, Pages 626–638
CRRT Treatment Modalities: Continuous Venovenous Hemodialysis (CVVHD) Blood Pump Effluent Dialysate Retur n Access Effluent Pump HEMOFILTER Dialysi s Pump
CRRT Treatment Modalities: Continuous Venovenous Hemofiltration (CVVH) Rona A, Fumagalli R. Indications for Renal Replacement Therapy in the Critically Ill Patient. In: Critical Care Nephrology; 2nd ed. Philadelphia, PA: Saunders Elsevier; 2009:1328-1332 Primary Therapeutic Goal: • Safe fluid removal and solute clearance Principles Used: • Ultrafiltration (water removal) • Convection Therapy Characteristics:  Requires replacement fluid to drive convection  No dialysate  Blood flow variable Primary Indications: • Uremia, acid/base or electrolyte imbalance, fluid overload
Transport Mechanisms: Convection Solvent Drag • Convection is the one-way movement of solutes through a semi-permeable membrane with a water flow. Sometimes it is referred to as solvent drag • Pressure difference between the blood and ultrafiltrate causes plasma water to be filtered across. • This causes solvent drag for small and large molecules across the membrane leading to removal from the blood. • The ultrafiltrate containing the solute should be replaced by substitution solutions Solvent Drag Blood Side Effluent Side FLOW Solute Replacement Solution
Transport Mechanisms: Convection Solvent Drag • Solute transfer across the membrane occurs via entrainment of solutes in the bulk flow of water during ultrafiltration1 • Higher molecular weight solutes (larger circles) and lower molecular weight (< 500-1,500 Daltons) solutes (smaller circles) are transported across the membrane with equal efficiency until the molecular radius of the solute exceeds the membrane pore size1 Solvent Drag Blood Side Effluent Side FLOW Replacement Solution Solutes 1. Tandukar, Srijan et al. Continuous Renal Replacement Therapy CHEST, March 2019 Volume 155, Issue3, Pages 626–638
CRRT Treatment Modalities: Continuous Venovenous Hemofiltration (CVVH) Blood Pump Effluent Retur n Access Effluent Pump HEMOFILTER Replacement Pre-filter Post- filter
17 CRRT Treatment Modalities: Continuous Venovenous Hemodiafiltration (CVVHDF) Reference Primary Therapeutic Goal: • Safe fluid removal and solute clearance Principles Used: • Diffusion • Convection Therapy Characteristics:  Requires dialysate to drive diffusion  Requires replacement fluid  Used to achieve solute removal (small, medium and larger sized molecules) and fluid balance  Blood flow variable Primary Indications: • Uremia, acid/base or electrolyte imbalance, fluid overload
Transport Mechanisms: Diffusion + Convection • Dialysate drives diffusion • Convective clearance across the fiber • Efficient for removing small and medium size molecular waste • Molecular size and membrane type can affect clearances FLOW Blood Side Dialysate/effluent Side FLOW Solvent Drag Solvent Drag Replacement Solution Solutes
19 CRRT Treatment Modalities: Continuous Venovenous Hemodiafiltration (CVVHDF) Reference Blood Pump Effluent Dialysate Retur n Access Effluent Pump Dialysi s Pump HEMOFILTER Pre-filter Post- filter Replacement
CRRT Treatment Modalities: Slow Continuous Ultrafiltration (SCUF) Rona A, Fumagalli R. Indications for Renal Replacement Therapy in the Critically Ill Patient. In: Critical Care Nephrology; 2nd ed. Philadelphia, PA: Saunders Elsevier; 2009:1328-1332 Description: Modality based only on slow removal of plasma water at a steady rate that does not exceed plasma-refilling Main Method of clearance: Convection Therapy Characteristics: • No dialysate or replacement fluid • Typical effluent (ultrafiltration) rate 100 to 200 mL/hr • Fluid removal only • Blood flow rate variable (not critical) Primary Indications: • Fluid overload
Transport Mechanisms: Ultrafiltration Solvent Drag • Ultrafiltration is the movement of fluid through a semi-permeable membrane along a pressure gradient • Positive pressure is generated on the blood side of the membrane and negative pressure is generated on the fluid side • This gradient, positive to negative, influences the movement of fluid from the blood side to the fluid side, resulting in a net removal of fluid from the patient • Minimal solute clearance happens by convection during ultrafiltration Solvent Drag Blood Side Effluent Side FLOW Solute
CRRT Treatment Modalities: Slow Continuous Ultrafiltration (SCUF) Blood Pump Effluent Retur n Access Effluent Pump HEMOFILTER
Transport Mechanisms: Adsorption • Adsorption is the adherence of solutes and biological matter to the surface of a membrane • High levels of adsorption can cause certain filters to clog and become ineffective • Membrane type affects adsorptive tendencies/effectiveness • Adsorption may also cause limited removal of some solutes (e.g., ß2 microglobulins) from the blood Effluent Side Blood Side Plasma Proteins Blood Cells FLOW
CRRT “general formula” + + + 20 – 25 mL/Kg/h HD SCUF HF HDF Flow  C o n v e c t i v e Diffusive UF Water  Middle MW  Low MW   Solutes  Solvent  Mode   High flux membrane  No  Replacement  Dialysis Fluids Vascular access 
26 References| Hardware/Software Devices CRRT Vascular Access Anticoagulation Quality Metrics
KDIGO recommendation for CRRT delivered dose *This recommendation is Level 1A Graded, which KDIGO defines as being supported by high-quality evidence, stating that ‘most patients should receive the recommended course of action’ Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012;2:1–138. “We recommend delivering an effluent volume of 20–25 mL/kg/h for CRRT in AKI” KDIGO recommendation, 2012*
How can the difference between prescribed and delivered dose be addressed? *This recommendation is ‘Not graded’, which KDIGO defines as “used, typically, to provide guidance based on common sense or where the topic does not allow adequate application of evidence” Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012;2:1–138. “In clinical practice, in order to achieve a delivered dose of 20–25 mL/kg/h, it is generally necessary to prescribe in the range of 25–30 mL/kg/h, and to minimize interruptions in CRRT” KDIGO, 2012 *
CRRT Dose 0 10 20 30 40 50 60 10 20 30 40 50 60 0 Kellum, J. A. and C. Ronco (2010). Nat Rev Nephrol 6(4): 191-192. Palevsky, P. M., et al. (2008). N Engl J Med 359(1): 7-20. Bellomo, R., et al. (2009). N Engl J Med 361(17): 1627-1638. CRRT Delivered dose (mL/kg/h) Survival (%) Too low Too high  RENAL trial 55.3% | 22 mL/Kg/h 55.3% | 33.4 mL/Kg/h  ATN trial 48.5% | 22 mL/Kg/h 46.4% | 35.8 mL/Kg/h floor 19 – 22 25 – 30 Goal Survival and CRRT dose
CRRT Dose Real situation Downtime Effluent based dose 0 24 12 Time (h)             2,400 100 100 1,200 400 900 6 18 CT (1h)  Surgery (3h)  System clotting (1h)  Downtime Prescribed dose  Qe Qb Quf Qr PRE Qr POS Qd 2,400 100 100 1,200 200 900 Flow (mL/h) Delivered dose             
CRRT Prescription • The KDIGO Clinical Practice Guideline recommends the following preferences for choosing a vein for insertion of a dialysis catheter in patients with AKI: Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012;2:1–138. Section 5.4.2 (Not graded): − First choice: right jugular vein (12 -15 cm) − Second choice: femoral vein (19 – 24 cm) − Third choice: left jugular vein (15 – 20 cm) − Last choice: subclavian vein with preference for the dominant side A functional vascular access is the key to a successful CRRT
Effluent dose Body weight Kg Effluent dose (mL/kg/h) 25 30 35 Bajo 30 750 900 1,050 35 875 1,050 1,225 40 1,000 1,200 1,400 45 1,125 1,350 1,575 50 1,250 1,500 1,750 55 1,375 1,650 1,925 60 1,500 1,800 2,100 65 1,625 1,950 2,275 Intermedio 70 1,750 2,100 2,450 75 1,875 2,250 2,625 80 2,000 2,400 2,800 85 2,125 2,550 2,975 90 2,250 2,700 3,150 95 2,375 2,850 3,325 Elevado 100 2,500 3,000 3,500 105 2,625 3,150 3,675 110 2,750 3,300 3,850 115 2,875 3,450 4,025 120 3,000 3,600 4,200 125 3,125 3,750 4,375 130 3,250 3,900 4,550 140 3,500 4,200 4,900 X body weight 30 2,850 Male, 95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Recommended dose for weight Low Intermediate High
Blood & plasma water flow / Blood Solid (45%) Erythrocyte Leucocytes Platelets Htc  Plasma Liquid (55%) Water Protein Others (1 – Htc) Plasma water 150 6,300 (150 x 60)x(1 – 0.3) = (9,000)x(0.7) 150 6,300 4 = 1,575 +++ HD HF SCUF HDF convective diffusive UF  Coagulation risk if UF + Qr ≥ Qp/4 Male, 95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Qb =
Male, 95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Qb = 150 mL/min Quf = 100 mL/h Molecule Water Glyoxal* Urea Metilglyoxal* Creatinine 3-desoxi-glucosone* Uric acid Nε–(carboximetil) lysine* Fructosil lysine* Pentosidina* Vitamin B 12 Complement factor C5a Complemnt factor C3a MIP-1 α ** MIP-1β** LP-10** Eotaxin** MCP-1** b 2 m globulin MIF** IL-8 ** IL-13** Myoglobin IL-3** IL-17α ** IL-2** IL-4** IFN-γ ** IL-18** IL-1Ra** IL-10** FGF-21 G-CSF Free light chain κ IL-6** HMGB-1** FGF-23 IL-1β ** Free light chain λ PAI-1 TNF-α ** Albumin IL-12 p70 ** Immunoglobulin “G” Immunoglobulin “M” MW (Da) 18 58 60 72 113 162 168 204 308 342 1,355 8,000 9,000 10,000 10,000 11,000 11,000 11,000 11,800 14,000 14,000 16,000 17,000 17,000 18,000 18,000 18,000 19,000 20,000 20,000 20,516 22,000 22,000 22,500 24,500 25,000 28,000 32,000 45,000 45,000 54,000 67,000 70,000 160,000 950,000 Low Middle Diffusion Convection Type Mechanism  500  15,000  45,000 ** (pro/anti) Inflammatory molecule * Protein bound CRRT Mode
CRRT Flows Quf = 100 mL/h 1,260 100 315 1,175 2,850 30 Qr pre = QrMAX x 0.80 = 1,260 mL/h Qr pos = QrMAX x 0.20 = 315 mL/h Qd = Qe – Quf – Qr pre – Qr pos = 1,175 mL/h Male, 95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Qb = 150 mL/min Quf = 100 mL/h QrMAX = 1,575 mL/h WATER REMOVAL ONLY (NO CLEARANCE) CONVECTIVE FLOW DIFUSIVE FLOW
CRRT Prescription: checking = (0.83x(100+1260+315)) + 1175 = 2,565 mL = Male, 95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Qb = 150 mL/min Qp = 6,300 mL/h QrMAX = 1,575 mL/h Quf = 100 mL/h Qr pre = 1,260 mL/h Qr pos = 315 mL/h Qd = 1,175 mL/h Filtration fraction (FF): 𝐹𝐷= (𝑄𝑏 ×60 )×(1 − 𝐻𝑡𝑜) (𝑄𝑏× 60)(1 − 𝐻𝑡𝑜)+(𝑄𝑟 𝑝𝑟𝑒 ) = 6300 (6300)+(1 26 0 ) =𝟎 . 𝟖𝟑 Dilution Factor (DD): Qe =(FD x (Quf + Qr pos + Qr pre )+Qd
Effect of predilution on CRRT dose CRRT Downtime 0 24 12 Time (h)          1,968 (20 mL/kg/h) 6 18 Prescribed dose   Delivered dose (26 mL/kg/h) Dilution correction  Downtime adjustment (24 – 5 = 19h)  Flow (mL/h) 2,565    CT (1h)  Surgery (3h)  System clotting (1h)  Downtime 1 + 3 + 1 = 5h 2,565 Qe Prescribed dose ≠ Delivered dose 2,850 (30 mL/kg/h) 2,850 (30 mL/kg/h) Average dose (2,486 mL/h x 19h) + (0 mL/h x 5h) 24h             150 100 1,200 315 1,175 Qb Quf Qr PRE Qr POS Qd Weight: 95 Kg, Hto 30% Dilution factor: (6,300/[6,300+1,260] = 0.83) Dose correction for dilution: 0.83 x [100+1,260+315] + 1175 = 2,565 mL/h
CRRT flows: adjustment 30 2,850 Male, 95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Qb = 150 mL/min Quf = 100 mL/h QrMAX = 1,575 mL/h 2,565 mL/h Qeadjusted [(0.83x(100+1260+315)) + 1175] 2,850 mL/h Qe unadjusted – 285 mL/h 1,175 + 285 1,460 + 1,460 mL/h
47 Thank you!
How does dialysis work? These numbers are for example only. Clinicians must use their judgment on prescribing the correct dialysate concentration.
Membrane structure The Selective Layer
oXiris: A continuous development for targeted adsorption Surface charge neutralization Charge inversion and heparin coating
Solutions Adjustment Jung SY, et al. Medicine(Baltimore). 2016;95(36):e4542. Heung M, Mueller BA. Seminars in dialysis. 2018. Normal K+ < 3.5 mEq/L K+ > 5.5 mEq/L
CRRT Solutions HCO3 - Lactate Ca2+ Mg2+ K+ Na+ Cl- PO4 2- Citrate Citric acid Glucose Replace ment/ Dialysate Need Prismasol B0 32 3 1.75 0.5 - 140 109.5 - - - - RD Acute condition Regiocit - - - - - 140 86 - 18 - - R Anticoagulant Biphozyl 22 - - 0.75 4 140 122 1 - - - RD With RCA Phoxilium1 30 - 1.25 0.6 4 140 115.9 1.2 - - - RD Normo- kalemic patients Plasma 20-32* - 1.06-1.29Ŧ 0.42-0.7ǂ 3.5-5.3 135-146 95-108 0.81- 1.45 - - <5.5 (fasting) 1. Not registered in India for commercial use
Sodium Correction
CRRT Solutions According to CRRT mode • SCUF: No solution  Quf • CVVH: Replacement  Qr pos / QPBP pre • CVVHD: Dialysis  Qd • CVVHDF: Both  Qd + Qr pos / QPBP pre According to anticoagulation • Heparin  Syringe • Citrate  QPBP pre • None
CRRT Dynamic dose Bagshaw, S. M., et al. Blood Purif. 2016;42(3): 238-247. Septic shock with CVVHDF Congestive heart failure

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DOC-20221115-WA0003 data analytics tool ..pptx

  • 1.
    CRRT Basics Dr. GauravChaudhry Head, Medical Affairs Baxter (I) Private Limited
  • 2.
    2 Introduction • Acute kidneyinjury (AKI) is a common complication in critically ill patients and is associated with substantial morbidity and risk of death • Approximately 5% to 10% of patients with AKI require renal replacement therapy (RRT) during their ICU stay1 • Mortality rates of 30% to 70%.2-4 • Over the past 2 decades, the incidence of RRT requiring AKI has increased by approximately 10% per year5 1. Tolwani A. Continuous renal-replacement therapy for acute kidney injury. N Engl J Med. 2012;367(26):2505-2514 2. Tandukar, S; Palevsky, P; Continuous Renal Replacement Therapy Who, When, Why, and How Chest 2019 Mar;155(3):626-638
  • 3.
    Introduction • Continuous renalreplacement therapy (CRRT) is commonly used to provide renal support for critically ill patients with acute kidney injury, particularly patients who are hemodynamically unstable1 • A variety of techniques that differ in their mode of solute clearance may be used1 • However, substantial uncertainty remains regarding many of the fundamental aspects of RRT management1 • As with other dialysis techniques, CRRT requires a well-functioning access, a permeable membrane, pumps to circulate blood and various solutions across the membrane with accurate fluid balancing, and pressure monitoring systems. 2 1.Tadunkar, S.; Palevsky P., Continuous Renal Replacement Therapy Who, When, Why, and How CHEST 2019; 155(3):626-638 2. Macedo, E.;Mehta R, Am J Kidney Dis. Continuous Dialysis Therapies: Core Curriculum 2016;2016;68(4):645-657
  • 4.
    From CAVH toVeno-venous therapy Ricci Z. et al, Continuous Renal Replacement Technology: From Adaptive Technology and Early Dedicated Machines towards Flexible Multipurpose Machine Platforms. Blood Purif 2004;22:269-276.| PAST “last chance” therapy for AKI NOW a standardized, widely used form of artificial kidney support Improved technology supporting application of this therapy1  Hardware advances  Software evolution
  • 5.
    Solute clearance andmodality selection As in the glomerulus, removal of fluid and solutes in CRRT occurs through a semi-permeable membrane This concept is known as selective permeability, meaning that certain substances will cross the membrane and others will not be allowed to cross
  • 6.
  • 7.
  • 8.
    8 Basic components ofCRRT Baxter Confidential — Do not distribute without prior approval | CRRT Hemofilt er Vascu lar Acces s Anticoagula tion Solutio ns Blood Warm er CRRT Syste m
  • 9.
    CRRT Treatment Modalities: ContinuousVenovenous Hemodialysis (CVVHD) Rona A, Fumagalli R. Indications for Renal Replacement Therapy in the Critically Ill Patient. In: Critical Care Nephrology; 2nd ed. Philadelphia, PA: Saunders Elsevier; 2009:1328-1332 Primary Therapeutic Goal: • Safe fluid removal and solute clearance Principles Used: • Diffusion Therapy Characteristics:  Requires dialysate to drive diffusion  No replacement fluid  Used to achieve solute removal (small and medium sized molecules) and fluid balance  Blood flow variable Primary Indications: • Uremia, acid/base or electrolyte imbalance, fluid overload
  • 10.
    Transport Mechanisms: Diffusion •Diffusion is the movement of solutes through a semi-permeable membrane from an area of higher concentration to an area of lower concentration until equilibrium has been established • In CRRT, diffusion occurs when blood flows on one side of the membrane, and dialysate solution flows counter-current on the other side • The dialysate does not mix with the blood • Efficient for removing small molecules but not large molecules • Molecular size and membrane type can affect clearances FLOW Blood Side Dialysate Side Solute FLOW
  • 11.
    Transport Mechanisms: Diffusion •Solute transfer across the membrane occurs by movement down a concentration gradient from blood to dialysate until equilibrium has been established 1 • Lower molecular weight (< 500-1,500 Daltons) solutes (smaller circles) cross the membrane more readily than higher molecular weight solutes (larger circles)1 FLOW Blood Side Dialysate Side FLOW Solutes 1. Tandukar, Srijan et al. Continuous Renal Replacement Therapy CHEST, March 2019 Volume 155, Issue3, Pages 626–638
  • 12.
    CRRT Treatment Modalities: ContinuousVenovenous Hemodialysis (CVVHD) Blood Pump Effluent Dialysate Retur n Access Effluent Pump HEMOFILTER Dialysi s Pump
  • 13.
    CRRT Treatment Modalities: ContinuousVenovenous Hemofiltration (CVVH) Rona A, Fumagalli R. Indications for Renal Replacement Therapy in the Critically Ill Patient. In: Critical Care Nephrology; 2nd ed. Philadelphia, PA: Saunders Elsevier; 2009:1328-1332 Primary Therapeutic Goal: • Safe fluid removal and solute clearance Principles Used: • Ultrafiltration (water removal) • Convection Therapy Characteristics:  Requires replacement fluid to drive convection  No dialysate  Blood flow variable Primary Indications: • Uremia, acid/base or electrolyte imbalance, fluid overload
  • 14.
    Transport Mechanisms: Convection SolventDrag • Convection is the one-way movement of solutes through a semi-permeable membrane with a water flow. Sometimes it is referred to as solvent drag • Pressure difference between the blood and ultrafiltrate causes plasma water to be filtered across. • This causes solvent drag for small and large molecules across the membrane leading to removal from the blood. • The ultrafiltrate containing the solute should be replaced by substitution solutions Solvent Drag Blood Side Effluent Side FLOW Solute Replacement Solution
  • 15.
    Transport Mechanisms: Convection SolventDrag • Solute transfer across the membrane occurs via entrainment of solutes in the bulk flow of water during ultrafiltration1 • Higher molecular weight solutes (larger circles) and lower molecular weight (< 500-1,500 Daltons) solutes (smaller circles) are transported across the membrane with equal efficiency until the molecular radius of the solute exceeds the membrane pore size1 Solvent Drag Blood Side Effluent Side FLOW Replacement Solution Solutes 1. Tandukar, Srijan et al. Continuous Renal Replacement Therapy CHEST, March 2019 Volume 155, Issue3, Pages 626–638
  • 16.
    CRRT Treatment Modalities: ContinuousVenovenous Hemofiltration (CVVH) Blood Pump Effluent Retur n Access Effluent Pump HEMOFILTER Replacement Pre-filter Post- filter
  • 17.
    17 CRRT Treatment Modalities: ContinuousVenovenous Hemodiafiltration (CVVHDF) Reference Primary Therapeutic Goal: • Safe fluid removal and solute clearance Principles Used: • Diffusion • Convection Therapy Characteristics:  Requires dialysate to drive diffusion  Requires replacement fluid  Used to achieve solute removal (small, medium and larger sized molecules) and fluid balance  Blood flow variable Primary Indications: • Uremia, acid/base or electrolyte imbalance, fluid overload
  • 18.
    Transport Mechanisms: Diffusion +Convection • Dialysate drives diffusion • Convective clearance across the fiber • Efficient for removing small and medium size molecular waste • Molecular size and membrane type can affect clearances FLOW Blood Side Dialysate/effluent Side FLOW Solvent Drag Solvent Drag Replacement Solution Solutes
  • 19.
    19 CRRT Treatment Modalities: ContinuousVenovenous Hemodiafiltration (CVVHDF) Reference Blood Pump Effluent Dialysate Retur n Access Effluent Pump Dialysi s Pump HEMOFILTER Pre-filter Post- filter Replacement
  • 20.
    CRRT Treatment Modalities: SlowContinuous Ultrafiltration (SCUF) Rona A, Fumagalli R. Indications for Renal Replacement Therapy in the Critically Ill Patient. In: Critical Care Nephrology; 2nd ed. Philadelphia, PA: Saunders Elsevier; 2009:1328-1332 Description: Modality based only on slow removal of plasma water at a steady rate that does not exceed plasma-refilling Main Method of clearance: Convection Therapy Characteristics: • No dialysate or replacement fluid • Typical effluent (ultrafiltration) rate 100 to 200 mL/hr • Fluid removal only • Blood flow rate variable (not critical) Primary Indications: • Fluid overload
  • 21.
    Transport Mechanisms: Ultrafiltration SolventDrag • Ultrafiltration is the movement of fluid through a semi-permeable membrane along a pressure gradient • Positive pressure is generated on the blood side of the membrane and negative pressure is generated on the fluid side • This gradient, positive to negative, influences the movement of fluid from the blood side to the fluid side, resulting in a net removal of fluid from the patient • Minimal solute clearance happens by convection during ultrafiltration Solvent Drag Blood Side Effluent Side FLOW Solute
  • 22.
    CRRT Treatment Modalities: SlowContinuous Ultrafiltration (SCUF) Blood Pump Effluent Retur n Access Effluent Pump HEMOFILTER
  • 23.
    Transport Mechanisms: Adsorption •Adsorption is the adherence of solutes and biological matter to the surface of a membrane • High levels of adsorption can cause certain filters to clog and become ineffective • Membrane type affects adsorptive tendencies/effectiveness • Adsorption may also cause limited removal of some solutes (e.g., ß2 microglobulins) from the blood Effluent Side Blood Side Plasma Proteins Blood Cells FLOW
  • 24.
    CRRT “general formula” ++ + 20 – 25 mL/Kg/h HD SCUF HF HDF Flow  C o n v e c t i v e Diffusive UF Water  Middle MW  Low MW   Solutes  Solvent  Mode   High flux membrane  No  Replacement  Dialysis Fluids Vascular access 
  • 25.
  • 26.
    KDIGO recommendation forCRRT delivered dose *This recommendation is Level 1A Graded, which KDIGO defines as being supported by high-quality evidence, stating that ‘most patients should receive the recommended course of action’ Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012;2:1–138. “We recommend delivering an effluent volume of 20–25 mL/kg/h for CRRT in AKI” KDIGO recommendation, 2012*
  • 27.
    How can thedifference between prescribed and delivered dose be addressed? *This recommendation is ‘Not graded’, which KDIGO defines as “used, typically, to provide guidance based on common sense or where the topic does not allow adequate application of evidence” Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012;2:1–138. “In clinical practice, in order to achieve a delivered dose of 20–25 mL/kg/h, it is generally necessary to prescribe in the range of 25–30 mL/kg/h, and to minimize interruptions in CRRT” KDIGO, 2012 *
  • 28.
    CRRT Dose 0 10 20 30 40 50 60 10 2030 40 50 60 0 Kellum, J. A. and C. Ronco (2010). Nat Rev Nephrol 6(4): 191-192. Palevsky, P. M., et al. (2008). N Engl J Med 359(1): 7-20. Bellomo, R., et al. (2009). N Engl J Med 361(17): 1627-1638. CRRT Delivered dose (mL/kg/h) Survival (%) Too low Too high  RENAL trial 55.3% | 22 mL/Kg/h 55.3% | 33.4 mL/Kg/h  ATN trial 48.5% | 22 mL/Kg/h 46.4% | 35.8 mL/Kg/h floor 19 – 22 25 – 30 Goal Survival and CRRT dose
  • 29.
    CRRT Dose Real situationDowntime Effluent based dose 0 24 12 Time (h)             2,400 100 100 1,200 400 900 6 18 CT (1h)  Surgery (3h)  System clotting (1h)  Downtime Prescribed dose  Qe Qb Quf Qr PRE Qr POS Qd 2,400 100 100 1,200 200 900 Flow (mL/h) Delivered dose             
  • 30.
    CRRT Prescription • TheKDIGO Clinical Practice Guideline recommends the following preferences for choosing a vein for insertion of a dialysis catheter in patients with AKI: Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012;2:1–138. Section 5.4.2 (Not graded): − First choice: right jugular vein (12 -15 cm) − Second choice: femoral vein (19 – 24 cm) − Third choice: left jugular vein (15 – 20 cm) − Last choice: subclavian vein with preference for the dominant side A functional vascular access is the key to a successful CRRT
  • 31.
    Effluent dose Body weightKg Effluent dose (mL/kg/h) 25 30 35 Bajo 30 750 900 1,050 35 875 1,050 1,225 40 1,000 1,200 1,400 45 1,125 1,350 1,575 50 1,250 1,500 1,750 55 1,375 1,650 1,925 60 1,500 1,800 2,100 65 1,625 1,950 2,275 Intermedio 70 1,750 2,100 2,450 75 1,875 2,250 2,625 80 2,000 2,400 2,800 85 2,125 2,550 2,975 90 2,250 2,700 3,150 95 2,375 2,850 3,325 Elevado 100 2,500 3,000 3,500 105 2,625 3,150 3,675 110 2,750 3,300 3,850 115 2,875 3,450 4,025 120 3,000 3,600 4,200 125 3,125 3,750 4,375 130 3,250 3,900 4,550 140 3,500 4,200 4,900 X body weight 30 2,850 Male, 95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Recommended dose for weight Low Intermediate High
  • 32.
    Blood & plasmawater flow / Blood Solid (45%) Erythrocyte Leucocytes Platelets Htc  Plasma Liquid (55%) Water Protein Others (1 – Htc) Plasma water 150 6,300 (150 x 60)x(1 – 0.3) = (9,000)x(0.7) 150 6,300 4 = 1,575 +++ HD HF SCUF HDF convective diffusive UF  Coagulation risk if UF + Qr ≥ Qp/4 Male, 95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Qb =
  • 33.
    Male, 95 kg,Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Qb = 150 mL/min Quf = 100 mL/h Molecule Water Glyoxal* Urea Metilglyoxal* Creatinine 3-desoxi-glucosone* Uric acid Nε–(carboximetil) lysine* Fructosil lysine* Pentosidina* Vitamin B 12 Complement factor C5a Complemnt factor C3a MIP-1 α ** MIP-1β** LP-10** Eotaxin** MCP-1** b 2 m globulin MIF** IL-8 ** IL-13** Myoglobin IL-3** IL-17α ** IL-2** IL-4** IFN-γ ** IL-18** IL-1Ra** IL-10** FGF-21 G-CSF Free light chain κ IL-6** HMGB-1** FGF-23 IL-1β ** Free light chain λ PAI-1 TNF-α ** Albumin IL-12 p70 ** Immunoglobulin “G” Immunoglobulin “M” MW (Da) 18 58 60 72 113 162 168 204 308 342 1,355 8,000 9,000 10,000 10,000 11,000 11,000 11,000 11,800 14,000 14,000 16,000 17,000 17,000 18,000 18,000 18,000 19,000 20,000 20,000 20,516 22,000 22,000 22,500 24,500 25,000 28,000 32,000 45,000 45,000 54,000 67,000 70,000 160,000 950,000 Low Middle Diffusion Convection Type Mechanism  500  15,000  45,000 ** (pro/anti) Inflammatory molecule * Protein bound CRRT Mode
  • 34.
    CRRT Flows Quf =100 mL/h 1,260 100 315 1,175 2,850 30 Qr pre = QrMAX x 0.80 = 1,260 mL/h Qr pos = QrMAX x 0.20 = 315 mL/h Qd = Qe – Quf – Qr pre – Qr pos = 1,175 mL/h Male, 95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Qb = 150 mL/min Quf = 100 mL/h QrMAX = 1,575 mL/h WATER REMOVAL ONLY (NO CLEARANCE) CONVECTIVE FLOW DIFUSIVE FLOW
  • 35.
    CRRT Prescription: checking =(0.83x(100+1260+315)) + 1175 = 2,565 mL = Male, 95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Qb = 150 mL/min Qp = 6,300 mL/h QrMAX = 1,575 mL/h Quf = 100 mL/h Qr pre = 1,260 mL/h Qr pos = 315 mL/h Qd = 1,175 mL/h Filtration fraction (FF): 𝐹𝐷= (𝑄𝑏 ×60 )×(1 − 𝐻𝑡𝑜) (𝑄𝑏× 60)(1 − 𝐻𝑡𝑜)+(𝑄𝑟 𝑝𝑟𝑒 ) = 6300 (6300)+(1 26 0 ) =𝟎 . 𝟖𝟑 Dilution Factor (DD): Qe =(FD x (Quf + Qr pos + Qr pre )+Qd
  • 36.
    Effect of predilutionon CRRT dose CRRT Downtime 0 24 12 Time (h)          1,968 (20 mL/kg/h) 6 18 Prescribed dose   Delivered dose (26 mL/kg/h) Dilution correction  Downtime adjustment (24 – 5 = 19h)  Flow (mL/h) 2,565    CT (1h)  Surgery (3h)  System clotting (1h)  Downtime 1 + 3 + 1 = 5h 2,565 Qe Prescribed dose ≠ Delivered dose 2,850 (30 mL/kg/h) 2,850 (30 mL/kg/h) Average dose (2,486 mL/h x 19h) + (0 mL/h x 5h) 24h             150 100 1,200 315 1,175 Qb Quf Qr PRE Qr POS Qd Weight: 95 Kg, Hto 30% Dilution factor: (6,300/[6,300+1,260] = 0.83) Dose correction for dilution: 0.83 x [100+1,260+315] + 1175 = 2,565 mL/h
  • 37.
    CRRT flows: adjustment 30 2,850 Male,95 kg, Htc 30% Qe = 30 mL/Kg/h, 2,850 mL/h Qb = 150 mL/min Quf = 100 mL/h QrMAX = 1,575 mL/h 2,565 mL/h Qeadjusted [(0.83x(100+1260+315)) + 1175] 2,850 mL/h Qe unadjusted – 285 mL/h 1,175 + 285 1,460 + 1,460 mL/h
  • 38.
  • 39.
    How does dialysiswork? These numbers are for example only. Clinicians must use their judgment on prescribing the correct dialysate concentration.
  • 40.
  • 41.
    oXiris: A continuousdevelopment for targeted adsorption Surface charge neutralization Charge inversion and heparin coating
  • 42.
    Solutions Adjustment Jung SY,et al. Medicine(Baltimore). 2016;95(36):e4542. Heung M, Mueller BA. Seminars in dialysis. 2018. Normal K+ < 3.5 mEq/L K+ > 5.5 mEq/L
  • 43.
    CRRT Solutions HCO3 - Lactate Ca2+ Mg2+ K+ Na+ Cl-PO4 2- Citrate Citric acid Glucose Replace ment/ Dialysate Need Prismasol B0 32 3 1.75 0.5 - 140 109.5 - - - - RD Acute condition Regiocit - - - - - 140 86 - 18 - - R Anticoagulant Biphozyl 22 - - 0.75 4 140 122 1 - - - RD With RCA Phoxilium1 30 - 1.25 0.6 4 140 115.9 1.2 - - - RD Normo- kalemic patients Plasma 20-32* - 1.06-1.29Ŧ 0.42-0.7ǂ 3.5-5.3 135-146 95-108 0.81- 1.45 - - <5.5 (fasting) 1. Not registered in India for commercial use
  • 44.
  • 45.
    CRRT Solutions According toCRRT mode • SCUF: No solution  Quf • CVVH: Replacement  Qr pos / QPBP pre • CVVHD: Dialysis  Qd • CVVHDF: Both  Qd + Qr pos / QPBP pre According to anticoagulation • Heparin  Syringe • Citrate  QPBP pre • None
  • 46.
    CRRT Dynamic dose Bagshaw,S. M., et al. Blood Purif. 2016;42(3): 238-247. Septic shock with CVVHDF Congestive heart failure

Editor's Notes

  • #27 Figure on right: Patients at risk of cerebral edema who require RRT will benefit from therapies that have less impact on osmolar shifts to maintain intracranial pressure. Figure (left) adapted with permission from Kellum, et al. Continuous Renal Replacement Therapy. New York, NY. Oxford University Press. 2010; p 58. Figure (right) adapted with permission from Davenport. Am J Kidney Dis. 2003;3:457–466.
  • #29 Reference 1. Neri M, et al. Crit Care. 2016;20:318. 2. Villa G, et al. Contrib Nephrol. 2018;194:38-50. 3. Ronco C, et al. Lancet. 2000;356:26-30. 4. Claure-Del Granado R, Mehta RL. Semin Dial. 2011;24:157-63.
  • #30 Reference Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012;2:1–138.
  • #31 Reference Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012;2:1–138.
  • #32 Reference Kellum, J. A. and C. Ronco (2010). Nat Rev Nephrol 6(4): 191-192. Palevsky, P. M., et al. (2008). N Engl J Med 359(1): 7-20. Bellomo, R., et al. (2009). N Engl J Med 361(17): 1627-1638.
  • #35 Reference Vijayan, A. (2009). Semin Dial 22(2): 133-136. Engstrom, B. I., et al. (2013). J Vasc Interv Radiol, 24(9), 1295-1302. KDIGO Clinical Practice Guideline for Acute Kidney Injury." Kidney International Supplements 2(1): 89-115.
  • #38 Reference Fealy, N., et al. (2018). Crit Care Resusc 20(1): 41-47.
  • #39 Reference Rosner, M. H., et al. (2014). Br J Anaesth 113(5): 764-771. Hoste, E. A., et al. (2014). Br J Anaesth 113(5): 740-747.
  • #40 Reference Rosner, M. H., et al. (2014). Br J Anaesth 113(5): 764-771. O'Connor, M. E. and J. R. Prowle (2015). "Fluid Overload." Crit Care Clin 31(4): 803-821.
  • #48 Review movement of molecules on the slide
  • #51 Reference Continuous Renal Replacement Therapy, (2010) Kellum, Bellomo, (pp.11-13) Ronco, New York, USA Oxford University Press Baldwin, I. Nonanticoagulation strategies to optimize circuit function in renal replacement therapy (pp.129-134) Bellomo, R & Baldwin, I. Anticoagulation (pp. 135-140) Fealy, N. Regional citrate anticoagulation (pp.141-146) In J.A. Kellum, R. Bellomo & C. Ronco (Eds) Continuous Renal Replacement Therapy, (2010) New York, USA Oxford University Press
  • #55 Reference 1. Bagshaw, S. M., et al. Blood Purif. 2016;42(3): 238-247.