Kamalanathan Sambandam, MD Associate Professor of Medicine

Kamalanathan Sambandam, MD Associate Professor of Medicine
Continuous Renal Replacement Therapy Simulator ASN Innovations in Kidney Education Kamalanathan Sambandam, MD Associate Professor of Medicine Tamim Hamdi, MD Assistant Professor of Medicine Division of Nephrology University of Texas Southwestern Medical School START

Instructions 1 Use various radio buttons to navigate through the learning tool. Forward/ Back Attention sign Click to uncover key points Click again to hide Home Information !

Select cases that illustrate CRRT concepts
Instructions 2: Cases Select cases that illustrate CRRT concepts

Choose playground to start CRRT simulator
Instructions 3: Cases Choose playground to start CRRT simulator

Instructions 4: The Simulator
Toggle between CRRT modes by selecting these buttons

Adjust the CRRT flow rates by modifying fields in green

Hit RUN to execute simulation and calculate clearance data

View more on CRRT concepts by selecting these buttons

Let’s Begin!

Prescribing CRRT: Summary
Select mode of CRRT: SCUF SLED CVVHD CVVHF CVVHDF Choose CRRT dialyzer membrane Select type of anticoagulation: None Heparin Citrate Choose your substitution fluids Choose CRRT dose Select Qb, Qd, Qr (pre-filter vs post-filter) accordingly [see next slide] Re-evaluate based on clinical course M-100 = 0.9m2, M-150 = 1.5m2

Prescribing CRRT: QB/QR/QD
Define dose required: At least 20mL/kg/hr Effluent Flow (QD + QR) Increase according to the metabolic needs of your patient In order to maximize small molecule clearance, minimize cost, and minimize filter clotting: For continuous hemodialysis, QB ≥ X QD For Post-filter continuous hemofiltration, QB ≥ 5 X QR For Pre-filter continuous hemofiltration, QB ≥ 6 X QR For CVVHD with QD 2000mL/hr (33mL/min) → QB ≥ 83ml/min For Post-filter CVVHF with QR 2000mL/hr (33mL/min) → QB ≥ 165ml/min For Pre-filter CVVHDF with QR 1000mL/hr (17mL/min) & QD 1500mL/hr (25mL/min) → QB ≥ 100mL/min (i.e. the larger of 17 X 6 = 100 or 25 X 2.5 = 63) Prismaflex Pump Ranges: Blood Pump: mL/min Dialysis and Replacement Fluid Pumps: 0-8L/hr (0-133mL/min) If pressure alarms allow, increase QB (usually QB = mL/min) to reduce Filtration Fraction and lessen clotting.

Choose Your Adventure Case 1- Early vs Late CRRT Initiation
Case 2- Clearance and Blood Flow Case 3- Dosing for “Routine” CRRT Case 4- Severe Hyperkalemia & Acidosis Case 5- Rhabdomyolysis Case 6- Frequent Therapy Downtime Case 7- Hypercalcemia with Nml iCa PLAYGROUND

Case 1- Early vs Late CRRT Initiation
A 28 year old female presents with altered mental status and high spiking fevers. She continues to deteriorate such that by hospital day 3 she has developed diffuse erythroderma , shock, respiratory failure, and AKI. The diagnosis of staphlococcal toxic shock is made. Nephrology is consulted on day 4 when oliguria ensues. By this time, a third pressor is added for BP support. BP 98/52 on norepinephrine, vasopressin, epinephrine SaO2 = 93% on 40% FIO2. CXR with vascular redistribution. K = 4.5, HCO3 = 19, BUN 82, Cr = 4.9, lactate 3.8mmol/L, pH 7.34 UOP = 5mL/hr (yesterday 900mL/24hr) What is the next step? Start CRRT now or wait for an “absolute indication” for renal replacement therapy?

Case 2- Clearance and Blood Flow
A 38 year old female who overdosed on acetaminophen has fulminant hepatic failure and oliguric AKI. She has been maintained on CRRT for the last 2 days. Her current clinical status is summarized as follows: BP 101/52 on norepinephrine. SaO2 = 92% on 60% FIO2. K = 5.1, HCO3 = 16, BUN 66, Cr = 3.1 UOP = 3mL/hr Current CRRT Rx: Pre-filter CVVHDF, Qb = 100mL/min, Qr = Qd = 1000L/hr The ICU team asks you if you can correct her hyperkalemia and acidosis by raising Qb to 160mL/min to increase her CRRT dose. How is CRRT dose defined? Will increasing Qb to 160mL/min improve the metabolic derangements?

Case 3- Dosing “Routine” CRRT
A 58 year old man develops AKI after undergoing emergent CABG after STEMI. Nephrology is consulted 3d later for evaluation for RRT. BP 103/54 on dopamine drip SaO2 = 96% on 2L NC. No pulm congestion. K = 6.1, HCO3 = 17, BUN 110, Cr = 4.7, HCT 30% UOP = 5mL/hr Wt = 52 Kg “Routine” orders for post filter CVVHDF are placed: Qb = 100 mL/min, Qd = Qr = 1000 mL/hr Is this an appropriate starting CRRT dose?

Choose Your Simulation:
PLAYGROUND Choose Your Simulation: CVVHF- pre CVVHD CVVHDF- pre CVVHF- post CVVHDF- post

Case 4- Severe Hyperkalemia & Acidosis
A 65 year old man presents with AKI and a type A aortic dissection extending to the mesenteric vessels and renal arteries. He is taken for emergent surgery and intra-operative CRRT is requested. BP 103/54 on epinephrine and vasopressin drips SaO2 = 99% on 100% FIO2. K = 8.0, HCO3 = 6, BUN 110, Cr = 4.7, lactate 18, HCT 30% UOP = 0mL/hr Wt = 70 Kg Should you use a hypertonic bicarbonate substitution fluid to correct this severe acidosis? What CRRT prescription will you employ?

Case 5- Rhabdomyolysis A 40 year old man is found down and brought to ED. Urine drug screen is cocaine positive. He is oliguric. Nephrology is consulted for management. BP 92/44 on dopamine drip SaO2 = 92% on 40% FIO2. CXR suggests aspiration. K = 6.6, HCO3 = 20, BUN 110, Cr = 3.5, HCT 30% CK is 55,000 UOP = 5mL/hr Wt = 100 Kg What CRRT modality would you employ?

Case 6- Frequent Therapy Downtime
A 35 year old man with AIDS presents with shock and respiratory failure from disseminated histoplasmosisis. He is placed on amphotericin and develops oliguric AKI 4 days later. Nephrology is consulted for management. Postfilter CVVHDF is initiated with no anticoagulation. Over the next several days CRRT treatment is repeatedly stopped for a variety of alarms. How would you manage each alarm? “Cannot detect access/return” “Access pressure rising” or “Access too negative” “Filter is clotting”

Case 7- Hypercalcemia with Nml iCa
A 78 year old female with presents with pneumococcal pneumonia and MSOF. On hospital day 3, nephrology is consulted for the development of oliguric AKI and post-filter CVVHDF is initiated with citrate anticoagulation. She is 45kg and CRRT is started at an effluent dose of 20mL/kg/hr. Over the next 2 days she develops high total calcium with normal ionized calcium and a high anion gap. What is the cause of these derangements? How would you manage this?

Qr Qb CVVH-pre CVVH-post CVVHD CVVHDF-pre CVVHDF-post
CRRT Dose RCTs Qb & diffusion mL/hr Qb Qb & convection mL/min Filtration fraction BUN1 = 110 mL/min Anticoagulation HCT1 = 30% Pressures BUN3= Severe ↓HCO3 BUN2= HCT2= Filtration Fraction (%) Urea Clearance (mL/min) Effluent Saturation (%) (Qr + UF) / Qb X 100 % EUN (Qr + UF) / BUN1 EUN / BUN1 X 100 % EUN

Qr Qb CVVH-pre CVVH-post CVVHD CVVHDF-pre CVVHDF-post
CRRT Dose RCTs mL/hr Qb & diffusion mL/min Qb Qb & convection Filtration fraction mL/min Anticoagulation BUN1 = 110 HCT1 = 30% Pressures Severe ↓HCO3 BUN3 HCT3 = HCT2 BUN2 Net Filtration Fraction (%) Urea Clearance (mL/min) Effluent Saturation (%) UF / Qb X 100 % EUN (Qr + UF) / BUN1 EUN / BUN1 X 100 % EUN

Qb Qd CVVH-pre CVVH-post CVVHD CVVHDF-pre CVVHDF-post
CRRT Dose RCTs Qb & diffusion Qb Qb & convection Filtration fraction BUN1 = 110 mL/min Anticoagulation BUN2 < BUN1 HCT1 = 30% HCT3 = 30% Pressures Severe ↓HCO3 Qd mL/hr mL/min Filtration Fraction (%) Urea Clearance (mL/min) Effluent Saturation (%) UF / Qb X 100 % EUN (Qd + UF) / BUN1 EUN / BUN1 X 100 % EUN

Qr Qb Qd CVVH-pre CVVH-post CVVHD CVVHDF-pre CVVHDF-post
CRRT Dose RCTs mL/hr Qb & diffusion mL/min Qb Qb & convection Filtration fraction mL/min Anticoagulation BUN1 = 110 HCT1 = 30% BUN3 < BUN2 Pressures Severe ↓HCO3 HCT3 = BUN2 Qd HCT2 mL/hr mL/min Net Filtration Fraction (%) Urea Clearance (mL/min) Effluent Saturation (%) UF / Qb X 100 % EUN (Qd + Qr + UF) / BUN1 EUN / BUN1 X 100 % EUN

Qr Qb Qd CVVH-pre CVVH-post CVVHD CVVHDF-pre CVVHDF-post
CRRT Dose RCTs mL/hr Qb & diffusion Qb mL/min Qb & convection mL/min Filtration fraction Anticoagulation Pressures BUN1 = 110 HCT1 = 30% HCT3 Severe ↓HCO3 BUN2 < BUN1 BUN3 < BUN2 HCT2 Qd mL/hr mL/min Filtration Fraction (%) Urea Clearance (mL/min) Effluent Saturation (%) (Qr + UF) / Qb X 100 % EUN (Qd + Qr + UF) / BUN1 EUN / BUN1 X 100 % EUN

CRRT Dose: Effluent Flow vs Clearance
CRRT dose can be expressed as Effluent Flow or Clearance Effluent Flow: The sum of the rate of dialysate and replacement fluid that is spent per unit time Often standardized to body weight (as mL/kg/hr) For 70kg patient with Qd = Qr = 1000mL/hr, Total Effluent Flow = ( ) / 70 = 29mL/kg/hr Advantages: Simple to calculate Usual means of calculating dose in CRRT trials Disadvantage: Does not account for loss of clearance for less efficient CRRT prescriptions (ie. Pre-filter hemofiltration or low Qb : effluent flow ratios)

Theoretical volume that is completely cleared of a substance per unit time For kidney: [Y]u X Vu where [Y]u and [Y]p are urinary and plasma concentrations [Y]p of Y respectively, and Vu is urinary flow • • Cly = • • Cly X [Y]p • [Y]u X Vu

Theoretical volume that is completely cleared of a substance per unit time For CRRT: [Y]e X Ve where [Y]e and [Y]p are effluent and plasma concentrations [Y]p of Y respectively, and Ve is effluent flow • • Cly = Advantage Accurately describes solute removal rate Disadvantage Must know the solute’s transport characteristics for the filter or measure its concentration [Y]e in the effluent • [Y]e X Ve • Cly X [Y]p

If Qb ≥ 6 X Qr and ≥ 2-2.5 X Qd then EUN ≈ BUN
CRRT Clearance Qr Qb BUN ! Qd EUN If Qb ≥ 6 X Qr and ≥ X Qd then EUN ≈ BUN [Y]e X V [Y]p • EUN X (Qr + Qd + UF) BUN • Cly = = • ClBUN ≈ (Qr + Qd + UF)

Effect of QB on Convective Clearance
Post Filter Mode 14% 18% 25% 31 % 40% Pre Filter Mode Efficiency  15% 5 X Qr 6 X Qr

Effect of QB on Diffusive Clearance
6% 12% 21% Efficiency  15% 2-2.5 X Qd Relton, Greenberg, Palevsky. ASIAO Leypoldt, et al. ASIAO

CASE 2: Clearance and Blood Flow
CRRT and Blood Flow CASE 2: Clearance and Blood Flow AUTHOR’S OPINION CRRT dose may be expressed as effluent flow or clearance. Although effluent flow is the more common and easier means to express dose, it does not capture the loss of efficiency that may occur with less ideal Qb/Qd/Qr combinations. When Qb ≥ X Qd and 6 X Qr, effluent flow and clearance are approximately equivalent for expressing small molecule removal. In this case, increasing Qb from 100mL/min to 160mL/min when Qd = Qr = 1000mL/hr will have little effect on increasing CRRT dose since clearance is already approaching total effluent flow at the lower blood flow.

CRRT Dosing CRRT dose is most commonly expressed as effluent flow adjusted for body weight: CVVH: Dose = QR (mL/kg/hr) CVVHD: Dose = QD (mL/kg/hr) CVVHDF: Dose = QR + QD (mL/kg/hr) For 52kg patient with QR = 1000mL/hr, QD = 1000 mL/hr, Dose = 38mL/kg/hr Randomized Trials in CRRT Dosing: Study N Interventions Population Risk of Death ARF Duration Renal Recovery Ronco 2000 425 20 vs 35 vs 45mL/kg/hr 75% post surgical, 12% septic 59% vs 43% vs 42% (p <0.002) No effect Bouman 2002 106 24- 36L/d vs 72L/d (20 vs 48mL/kg/hr) 58% post CV surgery, 100% resp failure, 100% inotrope or pressors Saudan 2006 206 CVVHF 25mL/kg/hr vs CVVHDF 42mL/kg/hr 60% septic 61% vs 41% (p =0.03) Tolwani 2008 200 20 vs 35mL/kg/hr 54% septic, 77.5% resp failure Palevsky (ARF Trial Network) 2008 1124 20 vs 35mL/kg/hr AND 3X/wk IHD vs 6X/wk IHD 63% septic, 80.6% resp failure Bellomo (RENAL) 2009 1508 25 vs 40mL/kg/hr 49.4% septic, 73.9% resp failure Joannes-Boyau 2013 140 35 vs 70mL/kg/hr 100% septic, 97% resp failure

CASE 3: Dosing “Routine” CRRT
CRRT Dosing CASE 3: Dosing “Routine” CRRT AUTHOR’S OPINION In the absence of profound electrolyte derangements requiring more rapid correction, the standard starting dose of CRRT should be an effluent dose of 20ml/kg/hr of actual body weight. Avoiding over-dosing limits CRRT complications such as hypothermia and hypophosphatemia and minimizes cost without an adverse affect on patient outcomes. Increase dose as determined by the metabolic need of the patient. For this 52kg patient, I would reduce total effluent flow to 52kg X 20mL/kg/hr = 1040mL/hr, equivalent to Qr and Qd each 520ml/hr.

CRRT Dosing CRRT dose is most commonly expressed as dialysate and/or replacement fluid flows adjusted for body weight instead of clearance: CVVH: Dose = QR (mL/kg/hr) CVVHD: Dose = QD (mL/kg/hr) CVVHDF: Dose = QR + QD (mL/kg/hr) For 52kg patient with QR = 1000mL/hr, QD = 1000 mL/hr, Dose = 38mL/kg/hr Randomized Trials in CRRT Dosing: Study N Interventions Population Risk of Death ARF Duration Renal Recovery Ronco 2000 425 20 vs 35 vs 45mL/kg/hr 75% post surgical, 12% septic 59% vs 43% vs 42% (p <0.002) No effect Bouman 2002 106 24- 36L/d vs 72L/d (20 vs 48mL/kg/hr) 58% post CV surgery, 100% resp failure, 100% inotrope or pressors Saudan 2006 206 CVVHF 25mL/kg/hr vs CVVHDF 42mL/kg/hr 60% septic 61% vs 41% (p =0.03) Tolwani 2008 200 20 vs 35mL/kg/hr 54% septic, 77.5% resp failure Palevsky (ARF Trial Network) 2008 1124 20 vs 35mL/kg/hr AND 3X/wk IHD vs 6X/wk IHD 63% septic, 80.6% resp failure Bellomo (RENAL) 2009 1508 25 vs 40mL/kg/hr 49.4% septic, 73.9% resp failure Joannes-Boyau 2013 140 35 vs 70mL/kg/hr 100% septic, 97% resp failure

Effect of QB on Convective Clearance
Post Filter Mode 14% 18% 25% 31 % 40% Pre Filter Mode Efficiency  15% 5 X Qr 6 X Qr

Effect of QB on Diffusive Clearance
6% 12% 21% Efficiency  15% 2-2.5 X Qd Relton, Greenberg, Palevsky. ASIAO Leypoldt, et al. ASIAO

Click the Kidney (left) or CRRT Filter (right) to elucidate
Filtration Fraction The Filtration Fraction (FF) represents the proportion of delivered solvent that is filtered across the membrane. The same principle applies to the kidney and the CRRT filter. Click the Kidney (left) or CRRT Filter (right) to elucidate Renal plasma flow (RPF) GFR FF = GFR / RPF

Filtration Fraction The Filtration Fraction (FF) represents the proportion of delivered solvent that is filtered across the membrane. The same principle applies to the kidney and the CRRT filter. Click the Kidney (left) or CRRT Filter (right) to elucidate A CVVHD CVVHF Post-filter CVVHF Pre-filter The FF will = 0 if no UF is prescribed. Qd + UF Qb UF Qd **FF should be kept < 20% to limit clotting** Technically, the denominator should be corrected for HCT [i.e Qb(1-Hct)] but this is unnecessarily complex for the purpose of estimating clotting risk. FF = UF / Qb !

Filtration Fraction The Filtration Fraction (FF) represents the proportion of delivered solvent that is filtered across the membrane. The same principle applies to the kidney and the CRRT filter. Click the Kidney (left) or CRRT Filter (right) to elucidate A CVVHD CVVHF Post-filter CVVHF Pre-filter Qr Qr + UF Qb UF Qr + UF is the flow of blood water traversing the membrane. Blood will become hemocon-centrated in the filter, increasing clotting risk, until diluted again by post-filter replacement fluid. Qr **FF should be kept < 20% to limit clotting** Technically, the denominator should be corrected for HCT [i.e Qb(1-Hct)] but this is unnecessarily complex for the purpose of estimating clotting risk. FF = (Qr + UF) / Qb !

Filtration Fraction The Filtration Fraction (FF) represents the proportion of delivered solvent that is filtered across the membrane. The same principle applies to the kidney and the CRRT filter. Click the Kidney (left) or CRRT Filter (right) to elucidate A AAA MAA AAAa 44441 44441 CVVHD CVVHF Post-filter CVVHF Pre-filter Qr Qr + UF Qb UF Qr + UF is the flow of blood water traversing the membrane. However, this blood water has been pre-diluted by pre-filter Qr. Assuming UF = 0, there is no net hemoconcentration in the filter, limiting filter clotting. Qr **FF should be kept < 20% to limit clotting** As calculated by the CRRT machine, FF = (Qr + UF) / Qb. However since Qr does not contribute to net hemoconcentration, NET FF is calculated here ignoring Qr. Technically, the denominator should be corrected for HCT [i.e Qb(1-Hct)] but this is unnecessarily complex for the purpose of estimating clotting risk. ! NET FF = UF / Qb !

Filtration Fraction The Filtration Fraction (FF) represents the proportion of delivered solvent that is filtered across the membrane. The same principle applies to the kidney and the CRRT filter. Click the Kidney (left) or CRRT Filter (right) to elucidate Renal plasma flow (RPF) GFR If one were to be a purist, for CRRT one should convert FF = GFR / RPF

Press “Attention signs” for more info
CRRT Circuit Pressures Qr PAccess ! PReturn ! “Access pressure” alarms for >50-70 mmHg pressure ∆ from operating point Qb “Return pressure” alarms for >50-70 mmHg pressure ∆ from operating point Qd PFilter Press “Attention signs” for more info ! “Filter pressure” alarm occurs at >450 mmHg. “TMP alarm occurs at >300 mmHg. “Filter clotting” alarm occurs if TMP or Pressure Drop increases 100 mmHg above baseline. Qd +UF (PF + PR) 2 TMP = – PE Pressure Drop = PF - PR EUN !

CASE 6: Frequent Pressure Alarms
CRRT Circuit Pressures CASE 6: Frequent Pressure Alarms AUTHOR’S OPINION “Cannot detect access/return” Access pressure is too low signifying possible disconnection of line from access. Verify line is connected. If so, increase Qb to increase access pressure against a fixed resistance. In general this will not affect clearance if previously presented rules for minimum Qb followed. “Access pressure rising” or “Access too negative” Signifies catheter is clotting, is kinked, or is against a vessel wall or Qb is too high. Decrease Qb. May need to shift greater proportion of effluent flow to dialysate to maintain clearance, following the rule of Qb ≥6 X Qr and ≥2.5 X Qd. May need catheter repositioning, exchange, or thrombolysis. “Filter is clotting” Decrease Qb while maintaining Qb ≥6 X Qr and ≥2.5 X Qd. Consider decreasing ultrafiltration rate or transition more effluent from replacement fluid to dialysate. This will decrease the TMP since less fluid is pulled across the filter. Consider changing filter and intensifying anticoagulation.

Press “Attention signs” for more info
CRRT Circuit Pressures Qr PAccess ! PReturn ! “Access pressure” alarms for >50-70 mmHg pressure ∆ from operating point Qb “Return pressure” alarms for >50-70 mmHg pressure ∆ from operating point Qd PFilter Press “Attention signs” for more info ! “Filter pressure” alarm occurs at >450 mmHg. “TMP alarm occurs at >300 mmHg. “Filter clotting” alarm occurs if TMP or Pressure Drop increases 100 mmHg above baseline. Qd +UF (PF + PR) 2 TMP = – PE Pressure Drop = PF - PR EUN !

Anticoagulation in CRRT
Low Qb and extended treatments necessitate anticoagulation. Options for anticoagulation: Systemic anticoagulation (for use when hemorrhage risk is small)- Heparin Direct thrombin inhibitor Activated protein C Regional anticoagulation (for use when systemic anticoagulation is contraindicated)- Citrate + Calcium Heparin + Protamine Frequent saline flushes through circuit

Citrate Anticoagulation
ACD-A contains 112.9 mmol/L citrate, mmol/L glucose, mmol/L Na, and mmol/L H+ ! QACD-A = 2.5-3% of Qb (eg. for Qb = 100mL/min QACD-A = 150 mL/hr) Qr QCaCl2 iCa = 1.3mg/dL (0.33mmol/L) iCa = 4.8mg/dL (1.2mmol/L) Qb iCa ≤ 1.3 mg/dL 0.33mmol/L) Qd CaCitrate (4-6mmol/L) Disadvantages of Citrate Anticoagulation - More expensive than heparin - Risks of severe ↑ or ↓Ca with breaks in therapy if calcium drip is either not stopped with downtime or not restarted. - NaCitrate ACD-A solution may cause hypernatremia - Metabolic alkalosis from metabolized citrate - Citrate may accumulate with hepatic insufficiency (↑ total Ca with nml or ↓ ionized Ca and ↑ anion gap)

CASE 7: Hypercalcemia with normal iCa
Citrate Anticoagulation CASE 7: Hypercalcemia with normal iCa AUTHOR’S OPINION This case has the classic features of citrate toxicity from the administration of more citrate than can be cleared by CRRT and hepatic conversion to bicarbonate: High total calcium and low ionized calcium are due to the preponderance of calcium circulating complexed with albumin and citrate. Elevated anion gap occurs because the accumulating CaCitrate- carries a negative charge Correct by reducing the rate of citrate and calcium infusion or changing to heparin anticoagulation. The blood flow rate may be decreased if Qb >2.5 X Qd or >6 X Qr to assist with the reduction in citrate since the citrate infusion rate is usually set at 2.5-3% of Qb. Consider increasing CRRT dose since 10-50% of the administered citrate is removed by CRRT.

ACD-A contains 112.9 mmol/L citrate, mmol/L glucose, mmol/L Na, and mmol/L H+ ! QACD-A = 2.5-3% of Qb (eg. for Qb = 100mL/min QACD-A = 150 mL/hr) Qr QCaCl2 iCa = 1.3mg/dL (0.33mmol/L) iCa = 4.8mg/dL (1.2mmol/L) Qb iCa ≤ 1.3 mg/dL 0.33mmol/L) Qd CaCitrate (4-6mmol/L) Possible Interventions for Citrate Toxicity - Reduce QACD-A and calcium infusion (can be guided by circuit iCa sampled distal to ACD-A inflow) - Increase CRRT dose (CRRT removes 10-50% of administered citrate, especially with diffusion) - Change to heparin anticoagulation

Timing of Initiation of RRT
Start RRT early in the course of critical illness AKI or wait until absolute indications ensue? Early Start Pros: Avoidance of emergent electrolyte abnormalities Avoidance of marked hypervolemia Simplify management of non-renal disturbances Allows initiation in controlled setting/time Early Start Cons: ↑ Dialysis catheter days Dialysis of some that will recover prior to absolute indication for RRT

When to start RRT: Existing Evidence Study Method (N) Population Early RRT Late RRT Risk of Death Gettings 1999 Retrospective, single center (100) Post-traumatic pts receiving CVVH BUN <60 BUN >60 80% vs 61% (p = 0.041) favoring early start Bouman 2002 Prospective, randomized, controlled, two centers (106) Pts receiving CRRT and mechanical ventilation ↓UOP X 6hrs, CrCl <20 X 3hrs BUN >112, K >6.5, or severe pulm edema No effect Demirkilic 2004 Retrospective, single center (61) Post CV surgery pts receiving CVVHDF UOP <100mL in 8hrs Creat >5 or K >5.5 23.5% vs 55.5% (p = 0.016) favoring early start Liu (PICARD) 2006 Prospective, observational, multicenter (243) ICU pts receiving any form of RRT BUN <76 BUN >76 Adjusted RR 1.85 ( ) favoring early start Bagshaw (BEST) 2009 Prospective, observational multicenter (1238) Multiple definitions (urea, creat, time) Various (see next) PICARD = Program to Improve Care in Acute Renal Disease BEST = Beginning and Ending Supportive Therapy for the Kidney

Bagshaw SM, et al. J Crit Care

CASE 1: Early vs Late RRT AUTHOR’S OPINION When it is determined that RRT will be inevitably required, start RRT early rather than waiting until urgent indications ensue. Initiate CRRT now.

Severe Acidosis Employ high dose CRRT with standard substitution fluids or use hypertonic bicarbonate substitution fluid to correct severe acidosis? High dose CRRT: Pros: Removes more strong acid while also providing more bicarbonate buffer (i.e. the anion gap closes) Cons: More hypothermia and hypophosphatemia May require more citrate if higher blood flow is required Requires more frequent substitution fluid bag changes by nursing Higher flows may be limited by high filter or access pressures Hypertonic bicarbonate substitution fluids: Relatively low blood and effluent flows may be employed The strong acid remains (i.e. the anion gap does not improve) Theoretically could worsen intracellular acidosis as carbonic acid is formed and dehydrates to form CO2 which may move to the intracellular space Could cause hypernatremia May require additional additives in the homemade substitution fluid May require more frequent bag changes by nursing if only 1L bags are prepared by pharmacy

CASE 4: Correcting severe acidosis and hyperkalemia
AUTHOR’S OPINION When severe electrolyte derangements need correction, it is preferable to increase clearance with high dose CRRT rather than using non-standard substitution fluids with high bicarbonate content. Initiate CVVHDF with the following prescription: Qb = 250mL/min, Qd = 6000mL/hr, Qr = 2500mL/hr (total effluent = 8.5L/hr), standard substitution fluid with 0mEq/L K. Monitor K and body temperature closely. This prescription follows previously outlined rules: Qb is ≥ 2.5 X Qd and 6 X Qr (converted to mL/min). The shift of clearance to a greater proportion of hemodialysis over hemofiltration allows for a more attainable Qb.

Severe Acidosis Employ high dose CRRT with standard substitution fluids or use hypertonic bicarbonate substitution fluid to correct severe acidosis? High dose CRRT: Pros: Removes more strong acid while also providing more bicarbonate buffer (i.e. the anion gap closes) Cons: More hypothermia and hypophosphatemia May require more citrate if higher blood flow is required Requires more frequent substitution fluid bag changes by nursing Higher flows may be limited by high filter or access pressures Hypertonic bicarbonate substitution fluids: Relatively low blood and effluent flows may be employed The strong acid remains (i.e. the anion gap does not improve) Theoretically could worsen intracellular acidosis as carbonic acid is formed and dehydrates to form CO2 which may move to the intracellular space Could cause hypernatremia May require additional additives in the homemade substitution fluid May require more frequent bag changes by nursing if only 1L bags are prepared by pharmacy

Diffusion Vs Convection
Poor clearance of larger solutes Moderate clearance of larger solutes GO GO Diffusive Clearance Hemodialysis Convective Clearance Hemofiltration

CASE 5: Rhabdomyolysis AUTHOR’S OPINION
Diffusion Vs Convection CASE 5: Rhabdomyolysis AUTHOR’S OPINION Myoglobin, a 77kDa protein, has a sieving coefficient of 0.2 with CVVHF with current high flux dialyzers. This means that convective clearance is able to achieve an effluent concentration of 20% of the blood concentration. With CVVHD, effluent concentration is negligible. Albumin has a molecular weight of 66kDa but a sieving coefficient of <0.01, due to its negative charge. Initiate CVVHF at high dose with a goal to assist in clearance of myoglobin and mitigate ongoing renal injury from pigment nephropathy.

Kamalanathan Sambandam, MD Associate Professor of Medicine

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