5/5/2010

Objectives: Renal Replacement • Review the concepts of different Therapies (RRT) for the modalities of RRT Non-Nephrologist • Examine the necessaryyp components involved in RRT • Examine the indications for RRT

Kevin Harned, MD • Review particular caveats to specific University of Kentucky Medical Center treatment modalities Division of Nephrology, Bone & Mineral Metabolism

November 3, 2009

3 physiologic principles of Physiology: RRT: • Diffusion: Process of movement of •Diffusion molecules across an area due to differences in concentration gradients – Moves from high-to-low concentration until •Convection the concentrations for both areas are equal – Adequate for clearing small molecules (<1kDa) •Adsorption – Na, K, Ca, Creatinine, Urea, Gentamicin

Physiology: Physiology:

• Convection: Using suction to physically • Adsorption: Binding of substances to pull water across a membrane, and with the surface of the filter/membrane the fluid shift anyygthing else that can “fit” – More a factor of electrical charge of the through the membrane’s pores as it substance, organic vs inorganic (as in rides with the water (aka “Solvent drag”) removal by charcoal filters) – Think of the white-water rafter being “pulled” downstream by the river – Better for of middle molecular weight molecules (up to 60kDa) – Vancomycin, cytokines (IL-1, IL-8, etc)

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Physiology: Terminology: • Peritoneal dialysis (PD) • Adsorption: Binding of substances to • Intermittent Hemodialysis (IHD) the surface of the filter/membrane • Continuous Renal Replacement Therapies (CRRT) – More a factor of electrical charge of the – Continuous veno-venous hemofiltration (()CVVH) substance, organic vs inorganic (as in – Continuous veno-venous hemodialysis (CVVHD) removal by charcoal filters) – Continuous veno-venous hemodiafiltration (CVVHDF) – Sustained, low-efficiency daily hemodialysis (SLEDD) – High-volume hemofiltration (HVHF) • Slow continuous (SCUF) • “Liver Dialysis” − Molecular Adsorption Recirculating System (MARS) Courtesy of WR Clark, CRRT 2007 Symposium − “Prometheus” (Not in the United States)

PD: PD:

• Diffusion >>> Convection • Can be performed via manual exchanges • Uses peritoneum as a semi-permeable or automated cycler machine at night membrane for exchange • 3 Glucose concentrations: • Fluid infused into abdominal cavity via PD catheter • 15%1.5% •2.5% • Solute clearance is a factor of: • 4.25% • Volume of fluid infused (usually 2-3L) • The higher the Glucose concentration, the more • Time allowed to dwell (factor of the properties of water will be removed from the pt d/t higher the peritoneum) osmolality of the PD fluid compared to the plasma • % of Glucose in fluid (convective component) • Fluid removal solely dependent upon % of Glucose in fluid

Typical PD Rx (manual): Typical PD Rx (cycler):

• Volume = 2.5L • Volume = 2.5L • Time = Dwell x 3hrs • Time = 1hr 40min fill/dwell; 20min drain • # of exchanges = 3 • Length of tx = 7PM – 7AM • Need 9-12hrs of RRT to be sufficient • Fluid = 1.5% Dianeal • Fluid = 1.5% Dianeal

2 5/5/2010

PD: PD:

• D/t logistics of placing PD catheter, as well • Not good candidates if: as its efficiency limitation, PD is not ideal • Morbidly obese (insufficient dose) for the Acute Kidney Injury (AKI) pt • Multiple abdominal surgeries (scarring of requiring RRT peritoneum) • Better if slowly progressed to ESRD • Pt is blind (can’t care for catheter = infxn) • Good candidates if: • Pt has ascites (regardless of etiology) • High-fxn’ing pt (allows them to keep their independence) • Still has residual kidney fxn • Pt’s w/ CHF (fluid shifts are more gentle)

PD: IHD:

• Complications • Diffusion >>> Convection –PD inadequacy •Ingredients • Peritoneal membrane eventually develops • Vascular Access properties that make clearance inadequate •Bldiilood circuit • Usually d/t numerous episodes of peritonitis • Filter w/ semipermeable membrane – Peritonitis • Dialysate fluid circuit • Approx 1 infxn/15 months • Diffusive component – Encapsulating Peritoneal sclerosis • Ultrafiltrate circuit = fluid removed •<1% of PD pt’s • Convective component • Bowel obstruction, hemorrhagic ascites • Anticoagulation • Mortality 30-50%

IHD: Vascular Access IHD: Blood circuit

• Temporary dialysis catheter (Uldall, •BFR= Blood Flow Rate Quinton, Vascath) – Target = 300 – 500ml/min • Tunneled dialysis catheter (Cannon, •PA= Arterial port pressure Palindrome, Decathalon) – This is a negative # measured inside the lines of the RRT circuit that represents the amount of suction • Native arterio-venous fistulas (AVF’s) required to physically pull the blood from the patient • Synthetic and native arterio-venous grafts – Goal -75 to -250mmHg (AVG’s) •PV= Venous port pressure – This is a positive # measured inside the lines of the RRT circuit that represents the amount of pressure required to PUSH the blood back to the patient – Goal 100 to 250mmHg

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IHD: Blood circuit IHD: Blood circuit

• PA alarms ONLY when it is too low (<-250) • PV alarms typically when it is too high – ALWAYS represents an ACCESS problem (>250) • Improper needle placement (AVF/AVG) – ACCESS problem • Insufficient arterial inflow of blood into the • Improper needle placement (AVF/AVG) access (AVF/AVG) • Outflow stenosis (AVG >> AVF) – Venous anastomosis (AVG) • Kink in dialysis catheter – Draining vein (needle stick sites, proximal swing segment • Catheter sucking against interior wall of of transposed brachial-basilic AVF’s, Cephalic Arch, central vein venous stenosis) • Kink in dialysis catheter • Clot at tip of catheter acting as a one-way • Clot inside lumen of tip of catheter obstructing valve outflow – Thrombosis of Venous Drip chamber

Caveat to monitoring the IHD: Filter pressures • Each pressure is measured via a line connected to the machine that is screened through a Dialysis discoid filter where the line attaches to the Fluid machine pppump – If these filters get wet (with fluid or blood), they will not be able to permit the air pressure to transmit across properly – Consequently, the machine will give you false readings

IHD: Dialysate circuit IHD: Dialysate circuit

• DFR = Dialysate Flow Rate • Solutes we can control: – Target = 500-750ml/min – Metabolic acidosis – Provides the DIFFUSION component for solute –K+ clearance – Ca2+ – NO EFFECT ON VOLUME STATUS OF PT –Uremia –Na (somewhat) – Phos (somewhat)

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IHD: Filter IHD: Ultrafiltrate circuit

• UF = Actual volume removal – Requires CONVECTION to physically pull the fluid from the pt’s blood across the membrane O O O O – Nothing selectively removes just water! 2 2 2 2 H H H H O O O O

• Small amount of clearance simply d/t solvent drag 2 2 2 2 H H – Amount of UF entirely dependent on H intravascular volume status of pt and his/her O O O O blood pressure 2 2 2 2 H H H H P OH O O O 2 2 2 2 H – The volume of fluid removed is what leads to U u H H H hypotension, not the actual BFR F m p

Continuous Renal Replacement IHD: Anticoagulation Therapies (CRRT) • Heparin = #1 type used worldwide • Continuous veno-venous hemofiltration – Bolus only (CVVH) – Bolus + infusion • Continuous veno-venous hemodialysis – Infusion only (CVVHD) – “Tight” Heparin • Continuous veno-venous hemodiafiltration (CVVHDF) • No anticoagulation • High-volume hemofiltration (HVHF) • Sustained, low-efficiency daily • If already anticoagulated for another hemodialysis (SLEDD) reason, nothing additional is given.

CVVH: CVVH:

• All CONVECTION • Replacement Fluid Rate/Substitution Fluid • Blood flow rates 150-400ml/min Rate • Uses a higher fluid removal rate than required – Clearance of solutes by solute drag tt“li”to restore “euvolemia” – Machi ne PULLS thi s vol ume and gi ves thi s – Pull 2-6 LITERS from the patient/hr volume back • Requires use of replacement fluid to prevent – No is lost/gained patient from becoming hypotensive – Target = 35ml/kg/hr – Most machines BOTH REMOVE AND REPLACE this volume, so the net fluid loss is ZERO •UF – Extra fluid that is NOT replaced, leading to • Net fluid loss = (RFOUT + UF) - RFIN actual water-loss

5 5/5/2010

CVVH: Filter CVVH:

• Blood flow rates 150-400ml/min • Uses a higher fluid removal rate than O O O O

required to restore “euvolemia” 2 2 2 2 H H H H O O O O

– Pull 2-6 LITERS from the patient/hr 2 2 2 2 H H • Requires use of replacement fluid to H

prevent patient from becoming O O O O P 2 2 2 2 H H H H OH O O O

hypotensive 2 2 2 2 H u H H H m * • Net fluid loss = Total UF rate - Replacement fluid rate p Palevsky, PM; “Continuous Renal Replacement Therapies.” ASN Board Review Course—August 2001. HDCN online symposium.

CVVHD: CVVHD:

• Diffusion >>> Convection (just like IHD) • Blood flow rate 150-400ml/min • Blood flow rate 150-400ml/min • Solute removal dependent on diffusion across • Solute removal dependent on diffusion across membrane w/ dialysate memb/diltbrane w/ dialysate – Dialysate is counter-current to blood flow in order to maximize concentration gradients across entire length of the – Dialysate is counter-current to blood flow in order to filter maximize concentration gradients across entire length of the – Usually on the order of 1.5-3L/hr filter – Usually on the order of 1.5-3L/hr • UF set only at rate that pt hemodynamically • UF set only at rate that pt hemodynamically can withstand, w/ goal of restoring can withstand, w/ goal of restoring “euvolemia” (0-150ml/hr) “euvolemia” (0-150ml/hr) Palevsky,• PM; Net“Continuous fluid Renal loss Replacement = UF Therapies.” rate ASN Board Review Course—August 2001. HDCN online symposium.

CVVHDF: CVVHDF:

• Diffusion > Convection • Blood flow rate 150-400ml/min • Blood flow rate 150-400ml/min • Utilize dialysate for diffusion • Utilize dialysate for diffusion clfllllllearance of small molecules along clearance of small molecules along w/ high-UF rates for convection to w/ high-UF rates for convection to remove “middle molecules” remove “middle molecules” – Like CVVH, requires the use of – Like CVVH, requires the use of replacement fluid

replacement fluid Palevsky, PM; “Continuous Renal Replacement Therapies.” ASN Board Review Course—August 2001. HDCN online symposium.

6 5/5/2010

HVHF: SLEDD:

• Simply put is CVVH, but instead of • Actually is IHD, except the tx is continued 35ml/kg/hr, target Substitution Fluid Rate for 8-20hrs instead of 3-4hrs, and fluid is is >60ml/kg/hr. pulled more gingerly • Cheaper – Don’t have to buy new machine – Ran by Dialysis Nurse • No evidence that SLEDD is any better OR worse than IHD or CRRT

Molecular Adsorption Recirculating SCUF: System (MARS):

• Think of it as CVVH, but w/ convection SO • Often called “liver dialysis” LOW that really there is NO SOLUTE • Use hemofilter similar to RRT, but then CLEARANCE the ultrafiltrate is then further dialyzed in a second filter, followed by contact • The HYDROSTATIC pressure of the blood w/ several adsorption columns, then going through the filter is what “pushes” the UF out, with a small amount of returned to the patient convection to pull a little extra fluid. – UF 50-300ml/hr

CRRT: Vascular Access CRRT: Anticoagulation

• Temporary dialysis catheter • Essential to keep the circuit from – Uldall, Quinton, etc thrombosing • Tunneled dialysis catheter – Unless patient extremely coagulopathic – Cannon, Tessio, etc • 2 main areas of thrombosis • Native AVF or AVG –Venous chamber – Rarely used since this would require – Filter needles to remain in the access constantly • Risk of infection and damage to the access

7 5/5/2010

Anticoagulation strategies: Heparin: • Heparin infusion • Therapeutic on coumadin/warfarin • Can try to use “just enough” to “thin” • Coagulopathy from various reasons the circuit or fully anticoagulate the –Sepsis patient – Liver failure –Xigris • Important to check APTT for monitoring • Argatroban (as in HIT) • Can add-in volume of heparin to the UF •Citrate so that extra volume is removed as well • If using Heparin or citrate, best to administer • Should be placed pre-blood pump to Pre-blood pump make certain blood is anticoagulated – “Blood-air interface” = thrombogenic (for the filter before it reaches the filter

Citrate: Citrate:

• “The Principle” • “The Principle” – Ionized Ca (ie, free Calcium) is – Ionized Ca (ie, free Calcium) is Ca required in multiple steps of the required in multiple steps of the coagulation cascade to form the final Ca coagulation cascade to form the final stable thrombus stable thrombus

Ca

Ca

Complications of Citrate: Theory of citrate: • Hypocalcemia or hypercalcemia • Metabolic alkalosis • Use an agent on the “arterial side” (coming from the patient) of the CRRT circuit to bind the – 1 molecule citrate metabolized via liver, majority of ionized calcium so that very little is skeletal muscle and renal cortex into 3 available for the coagulation cascade molecules of HCO3 (less metabolism in liver – Citrate LOVES to complex w/ Calcium iiimpairment) • Note that some of the [agent+Ca] chelate will be removed via the filter • Hypernatremia • Add back elemental Ca on the “venous side” – Most protocols call for tri-sodium citrate, thus (going to the patient) of the CRRT circuit to yielding the extra Na load replenish Ca stores for normal coagulation properties inside the patient’s body, as well as • Citrate toxicity for all the other biochemical reactions requiring – Increased total Ca, decreased Ionized Ca, Ca widening (d/t citric acid in serum)

8 5/5/2010

5 Indications: Volume overload:

• Volume overload not sufficiently • Fluid MUST be INTRAVASCULAR responding to diuretics • We CANNOT quickly remove 3rd-spaced •Hyperkalemia fluid: • Metabolic acidosis refractory to – Pleural effusions bicarbonate replacement –Ascites •Uremia – Pericardial effusions • Intoxications (Ethylene glycol, Lithium) – Generalized Anisarca • Possible w/ Albumin vs other oncotic agent priming and prolonged, repeated treatments

Volume overload: Hyperkalemia:

• Not responding to IV diuretics •If serum K+ <6.5, can try medical tx – Diuril 500mg IV, then Lasix 120mg IV x 1 alone –Lasix vs Bumex gtt – Kayexalate 30-60g PO/PT q2’ until has •Increasing O requirements BM’s 2 • EXCEPT: If possible ileus, bowel ischemia, etc • Worsening CHF as Kayexalate can promote bowel perforation • Elevated CVP/PCWP – Insulin 10units SQ + 1amp D50 – Albuterol neb (continuous) – 1 amp bicarb (only if acidodic) – Ca gluconate/chloride (only if EKG ∆’s)

Hyperkalemia: Metabolic acidosis:

• If serum K+ > 6.5, initiate medical tx • If serum pH < 7.2, consider IV buffering

but still call Renal for possible emergent – D5W + 3amps NaHCO3 @ 0.5-1ml/kg/hr dialysis – Tris hydroxymethyl aminomethane (THAM) • mL of 0.3M THAM = wt (kg) x BD (mEq/L) x 1.1 • EXCEPT: – Anuria –Uremia

• Lactate = ‘potential bicarb’, so correct the underlying problem (if possible)

9 5/5/2010

Uremia: Intoxications:

• Usually do not have sx’s until BUN >100 • Clearance ability is highly dependent –MS ∆’s upon: – Itching – Size of molecule – Anorexia – % of protein binding –N/V – Volume of distribution in the body – Pericarditis w/ pericardial rub •Water-soluble – Fast redistribution from peripheral compartments into the blood

Intoxications: Size of Intoxications: Protein Binding Molecules • We can only remove the free-drug • Diffusion – limited to ~ 1kDa – Must be < 80% protein bound – Methanol • Alcohols – Ethylene glycol •Aminoglycosides – Lithium •Li – > 80% protein bound •Arsenic • Convection – up to ~ 60kDa depending • CCB’s on properties of the filter •Diazepam • Phenytoin • Adsorption – up to 40 or 60kDa • Salicylate •TCA’s

Intoxications: Volume of Intoxications: Hemoperfusion Distribution • Uses circuit similar to RRT, but instead of a • Vd = Apparent volume into which the drug dialysis filter there is an adsorbent-containing is distributed at equilibrium cartridge – < 1 L/kg Vd ideal for clearance by RRT – Activated charcoal OR – Resin • Alcohols • Salicylates • BFR 250-400ml/min •Li • Clearance of the toxin totally dependent upon • Theophylline the affinity for the charcoal/resin for the •Atenolol substance •Aminoglycosides – NO Diffusion and NO Convection – > 1 L/kg include Digoxin, CCB’s, -Blockers, – NOT limited to size, water-solubility or protein binding TCA’s, Quinine – Clearance continues until the cartridge is saturated • Approximately 6-8hrs

10 5/5/2010

Intoxications: Hemoperfusion Intoxications: Hemoperfusion

• Charcoal HP binds substances irreversibly • Resin HP is reversible

• HP is the preferred method when the toxin is: – Lipid soluble – Highly protein bound

• Most common use is for Theophylline

Intoxications: Hemoperfusion

• Prone to biocompatability problems: – Thrombocytopenia (drop by 30%) – Leukopenia (drop by 10%) d/t: • Activation of complement – Reduction of fibrinogen and fibronectin d/t adsorption to charcoal –Hypothermia – Hypocalcemia (charcoal) –Hypoglycemia

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