RENAL REPLACEMENT THERAPYBY DR LEE JUNE LYNGSupervisor: DR ZIHNI

OUTLINE INTRODUCTIONINITIATION OF THERAPYPRINCIPLE OF RRT RRT TECHNIQUES AND ITS INDICATION PROS AND CONSCOMPLICATIONS OCCURS IN CRRTCOMPARISON BTW IHD AND CRRT

INTRODUCTION When ARF is severe, resolution may take several days or weeks During this time, the kidneys cannot maintain homeostasis of fluid, K+ , metabolic acid and waste products in which some may respond to medical measure and some may not.Those who are not responsive to medical measure, acute renal replacement therapy (ARRT) is vital.

Too many questions?

Initiation of Therapy

RIFLE CriteriaLevel of injuryOutcome measures

RIFLE correlated with prognosisLimitations:Serum Cr were strong predictors of ICU mortality but not UO criteriaChange in Serum Cr not directly correlate with changes in GFRBaseline CR is necessary to calculate the change

From RIFLE to AKINSerum CreatinineIncrease SCr 24.6mmol/L2-3 foldsor urine outputPatients receiving RRT are Stage 3 regardless of urine outputStage 1Stage 2Stage 3

The Acute Kidney Injury Network Classification ( AKIN)

Modification of the RIFLE criteria by Acute Kidney Injury NetworkBoth diagnostic and staging systemDiagnostic criteriaabrupt in onset within 48 hrsAbsolute increase in serum Cr >=0.3mg/dL or 26.4 mmol/L or % increase of Cr >=50% or oliguric for >=6 hrsAfter volume status optimised and urinary tract obstruction excludedStaging systemRIFLE Loss and ESRF are removed

Indication for RRTOliguria 30mmol/lK+ >6.5mmol/l or rapidly risingPulmonary edema unresponsive to diureticsMetabolic acidosis ph40 degreeUremic complicationOverdose with dialyzable toxin (eg: lithium)

Dose and intensity of RRTThe dose of dialysis which is currently defined as derivation of fractional urea clearance during a single dialysis treatment and is governed by patient size, residual kidney function, daily protein intake, degree of catabolism and anabolism, and presence of co-morbid conditionsEfficiency of RRT: Kt/VdK clearance of urea in ml/mint is time of treatment in minVd urea distribution volume in liter

Target n RRTCurrent targets include:Reduction of urea >65-70%Kt/Vd is above 1.3CRRT at urea clearance of 35 40l/day

PRINCIPLE OF RRT

PRINCIPLE OF RRTDIFFUSION (HEMODIALYSIS)CONVECTION (HEMOFILTRATION)ULTRAFILTRATION(ALL THERAPIES)DIFFUSION AND CONVECTION (HEMODIAFILTRATION)

DIFFUSION is the movement of solutes from a higher to a lower solute concentration area.Efficient in removing small molecules (

Dialysis (....diffusion)Solutes flow down an electrochemical gradient, across a membrane.Solute removal is proportional to dialysate flow rateDialysate flows counter-current to blood

Dialysate is the fluid that is pumped into the filter canister, surrounding the hollow fibersThe concentration of solutes in the dialysis fluid determines diffusion gradientsThe removal of surplus solutes from the blood is achieved by infusing dialysate fluid that contains a lower solute concentration than the serum concentration Eg: in renal failure, K+ is often high . Thus, may start with low K+ in the dialysate. Thus, there will be diffusion from high concentration (pts blood) to the low concentration(dialysate) in order to remove K+ fr pts blood.

DialysateEg: in renal failure, HCO3 is low. So, HCO3 is added to dialysate to facilitate diffusion from high concentration( dialysate) to low concentration(pts blood)

DialysateThe main composition are sodium chloride, sodium bicarbonate or sodium acetate, calcium chloride, potassium chloride, and magnesium chlorideThus, it is used to replace electrolytes

Electrolyte Composition of dialysate

CONVECTIONIs a one-way movement of solutes through a semi-permeable membrane with a water flow. Sometimes it is referred to as solvent drag. (Water movement drags solute across membrane)Efficient in removing larger and smaller molecules The faster the substitution flow rate, the higher the clearanceThe ultrafiltratecontaining the solute should be replaced by substitution solutionsMain principle for hemofiltration

Convection

ULTRAFILTRATIONIs the movement of fluid through a semi-permeable membrane along a pressure gradientThe ultrafiltration rate depends on the pressure applied to the filter, inside and outside the fibersIt removes fluid

Principles of CRRT clearanceSmall molecules easily pass through a membrane driven by diffusion and convection.Middle and large size molecules are cleared primarily by convection. Semi-permeable membrane remove solutes with a molecular weight of up to 50,000 Daltons.Plasma proteins or substances highly proteinbound will not be cleared. 306100135

RRT techniques

MAJOR RRT TECHNIQUESINTRACORPOREALPERITONEAL DIALYSISEXTRACORPOREALCONVENTIONAL IHDSLOW LOW EFFICIENCY DIALYSIS (SLED)CRRTCVVH ( continuous veno-venous hemofiltration)CVVHD ( cont veno-venous hemodialysis)CVVHDF ( cont veno-venous hemodiafiltration)SCUF (slow cont ultrafiltration)

Major Renal Replacement Techniques

Anatomy of a Hemofilterblood inblood outdialysateindialysateoutOutside the Fiber (effluent)Inside the Fiber (blood)Cross Sectionhollow fiber membrane

Membrane types and characteristicsHemofilter membrane are composed of:High flux materialSynthetic/biocompatible materialStructural design is characterized by: High fluid removal Molecular cut-off weight of 30,000-50,000 Daltons.The blood flows in one direction and the dialysate flows in the opposite

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Semi-permeable MembraneThe semi-permeable membrane provides: An interface between the blood and dialysate compartment.Biocompatibility minimizes:Severe patient reactions Decreases the complement activation 306100135

CVVH

INTERMITTENT HEMODIALYSIS

INTERMITTENT HEMODIALYSISTechnically similar to what ESRF pt on chronic HD undergo in the community dialysis centres.Uses high dialysate flows (300-400ml/min) and short period of time ( 3-4 hrs)

IHDMedical requirements and indication:Hemodynamically stable ( no more than 1 vasopressor agent at low doses preferably)Vascular access: AVF or temporary dual lumen veno-venous dialysis catheterRelative C/I in high ICP as IHD may increase brain water content ( cerebral edema)

Intermittent Therapies - PRO

Intermittent Therapies - CON

SLED

SLEDMore gentle form / hybrid technology of IHDLower Qb (150-200ml/min) and lower Qd (100-300ml/min)

SLEDIndication:Recent ACS , AMI and severe cardiac failure with low vent ejection fractionUnstable BP requiring at most one vasopressor agentAs a prelude to IHD following recovery from major critical illness during CRRT was utilizedRecent worsening in overall condition resulting in IHD being poorly tolerated and pt become frankly hypotensive but still maintain SBP>100 with low dose of a single inotropes

SLED : Hybrid therapy

CONTINUOUS RENAL REPLACEMENT THERAPY

CRRTPreferred dialytic modality in critically ill, hypercatabolic pt with unstable circulatory state ( with high doses of multiple vasopressor)

TYPES OF CRRT THERAPYSLOW CONTINUOUS ULTRAFILTRATION ( SCUF)CONTINUOUS VENO VENOUS HEMOFILTRATION (CVVH)CONTINUOUS VENO VENOUS HEMODIALYSIS (CVVHD)CONTINUOUS VENO VENOUS HEMODIALYSIS (CVVHDF)

CRRTIndications:Hemodynamically instability requiring 1or more inotropes at high doses and/or failure to tolerate IHD or SLEDCatabolic state:CRRT provides more optimal biochemical and metabolic control than IHD/SLED

Continuous Therapies - PRO

Continuous Therapies - CON

SCUF(slow cont ultrafiltration)This type of CRRT remove fluid only without the need for replacement fluids known as substitution solutions. This can help prevent or treat fluid overload in cases when waste products don't need to be removed, or the pH levels don't need to be corrected.

SCUF

CVVHMost popular removes large volumes of fluids and waste from the patient. It then uses replacement fluids (also known as a substitution solution), which are devoid of toxins, to maintain electrolyte and acid base balance.Dialysate is not used

Replacement fluidsIs used to replace any water that is removed during hemofiltration. Thus, it is able to prevent hypovolemia Any fluid removed during hemofiltration is given back to maintain a net neutral fluid balanceReplacement fluid must be sterile intravenous fluids with concentrations of electrolytes similar to plasma.

CVVH

CVVHPrescription based on Prisma CRRT machine algorithm:Qb: 150-220ml/minA higher blood flow rate is needed if more intensive CVVH is performedUFR(ultrafiltration rate) : >35ml/kg/hPredilution 1/3Postdilution 2/3

Predilution of the blood prior to its entry in the dialyzer with replacement fluid can lead to decreased requirement of anticoagulation and also by maintaining the concentration gradientPostdilution means that the replacement fluid is returned to the blood after the filterPostdilution concentrates the blood in the filter, enhancing clearance.

CVVHDThis type of therapy primarily uses diffusion along with a cleansing fluid known as a dialysate solution to boost the removal of waste productsContinuous diffusive dialysisMostly small molecules are removed

CVVHD

CVVHDFWith CVVHDF, large volumes of fluids and waste are removed from the patient. Cleansing fluids (dialysate solution) and replacement fluids (substitution solution) are used to replace the dirty plasma with clean fluid. This allows for the removal of large volumes of toxin-filled plasma, while still maintaining electrolyte balance.

CVVHDFRemoval of small molecules by diffusion through the addition of dialysate solution.

Removal of middle to large molecules by convection through the addition of replacement solution.

CVVHDF

SCUFCVVHCVVHDCVVHDFSolute removalminimalconvectionDiffusion + convectionDiffusion + convectionH20 removal UltrafiltrationUltrafiltration Ultrafiltration Ultrafiltration Replacement fluid ( to replace H2o)No yesnoYes Dialysate (to replace e- eg: ca, HCO3nonoyesyesAdvantage Reduce volume overloadVolume and salute removalLess susceptible to e- disorder d/t dialysate replacementCan treat both volume overload + azotemiaLess susceptible to e- disorder d/t dialysate replacementAllow mech to increase convection solute removal while performing HDUseful for volume expanded pt with high solute load

disadvantageNot much solute clearanceSlow bl flow rate prone to get system thrombosisVulnerable for e- disorder d/t large infusion of replacement fluid

Vascular AccessA veno-venous double lumen hemodialysis catheter or two single lumen venous hemodialysis catheters may be used.306100135

Access LocationInternal Jugular VeinPrimary site of choice due to lower associated risk of complication and simplicity of catheter insertion. Femoral VeinPatient immobilized, the femoral vein is optimal and constitutes the easiest site for insertion. Subclavian VeinThe least preferred site given its higher risk of pneumo/hemothorax and its association with central venous stenosis.306100135

Choosing the right catheterThe length of the catheter chosen will depend upon the site used Size of the catheter is important in the pediatric population. The following are suggested guidelines for the different sites:RIJ= 15 cm FrenchLIJ= 20 cm FrenchFemoral= 25 cm French306100135

COMPLICATIONS

ComplicationsVascular access Vascular spasm(initial BFR too high)Movement of catheter against vessel wall Improper length of hemodialysis catheter insertedFluid volume deficitExcessive fluid removal without appropriate fluid replenishment

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ComplicationsHypotension Intravascular volume depletionUnderlying cardiac dysfunctionElectrolyte imbalances High ultrafiltration rates (high clearance) Inadequate replenishment of electrolytes by intravenous infusion, Inadequate replenishment of bicarbonate loss during CRRT

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ComplicationsAcid/base imbalanceBlood loss Ineffective anticoagulation therapyClotting of hemofilter Inadvertent disconnection in the CRRT system Hemorrhage due to over-anticoagulation Blood filter leaks

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ComplicationsAir embolus Leaks or faulty connections in tubing Line separation.Cardiac arrest Hypotension/hypertensionAir embolismCirculatory overloadArrhythmias306100135

OTHER ISSUES

Other issuesHypothermia CoagulationBlood loss during CRRTNutritional supportChanges in medications dosage in RRT

1)HYPOTHERMIA IN CRRTHypothermiaCausesPatients blood in extracorporeal circuit at room temperatureAdministration of large volumes of room temperature fluids (replacement and dialysate)Signs and SymptomsHemodynamic instabilityChilling, shiveringSkin pallor, coolness and cyanosisTreatmentWarming blanket306100135

2)COAGULATION IN CRRTBlood contact to circuit tubing in CRRT leading to activation of coagulation cascadeResult in clotting of filter or circuitEven the most biocompatible membranes gradually occluded by fibrin microthrombi

COAGULATION IN CRRTFactors leading to clot formationPoor or low flow rates through the dialyser circuit which is affected by vascular assessAreas of stagnant blood particularly where pumps join the circuitAir blood interfaces as in bubble traps ( the 1st sign of clotting usually occurs in the bubble trap and not the dialyzer)HCT plays a significant role in clotting of dialysis circuit and is exacerbated by high filtration ratesMembrane material: till now, no membrane material is currently available that binds heparin permanently

COAGULATION IN CRRTAnticoagulant therapy to prevent dialyzer clot formationMost CRRT machines incorporate a pump that can infuse heparin into the dialyzer circuit b4 the blood pump is startedDoses btw 200 800 units per hourOther anticoagulant:LMWH, prostacyclin and sodium citrate

COAGULATION IN CRRTIf bleeding risk is high, the safest approach is no anticoagulant at all Thus, saline flushing is used .100ml of N/S is flushed thru the filter every hour to prevent clotting of dialysis circuit

3) Minimizing blood loss during CRRTCRRT blood circuits can contain up to 250ml blood So, when CRRT is halted, effort must be made to return as much blood as possible to the patientBy perfusing blood circuit with saline

4)Nutritional support RRT can cause additional protein losses CVVH 10 15g/day IHD : 6- 8 g/day Recommended protein supplement CVVH: 1.1 2.5g/kg/day IHD: 1.1 1.2 g/kg/day

5)Changes in common ICU medications in RRT

CRRT VS. INTERMITTENT RENAL REPLACEMENT THERAPY

-By a group of expert from ADQI ( Acute Dialysis Quality Initiative ) to propsoed graded definition of RIFLE criteria in 2002-RIFLE correlated with prognosis in a number of studies-Limitation:--Serum Cr were strong predictors of ICU mortality but not UO criteria, remember to use the least favorable RIFLE strata--Change in Serum Cr not directly correlate with changes in GFR--Baseline CR is necessary to calculate the change

**-Modification of the RIFLE criteria by Acute Kidney Injury Network-Both diagnostic and staging system-Diagnostic criteria--abrupt in onset within 48 hrs--Absolute increase in serum Cr >=0.3mg/dL or 26.4 mmol/L or % increase of Cr >=50% or oliguric for >=6 hrs--After volume status optimised and urinary tract obstruction excluded-Staging system--RIFLE Loss and ESRD removed**Back to the basic CRRT transport principles: the combination of diffusion and convection allow small molecules to easily pass through the membrane, and middle and large molecules to be driven across the filter by convection. The semi-permeable membrane allows removal of solutes with a molecular weight of up to 50,000 Daltons. Keep in mind that anything that is protein-bound will not be cleared.**Membrane types and characteristics are other important technical considerations. Hemofilters are composed of a membrane that consists of high flux material (porous). The membrane material is usually synthetic, but very biocompatible to the patient. Here are a few examples of high-flux membrane material: Polysulfone (PS)Polyamide (PA)Polyacrylonitrile ( PAN) AN69 The structural design of a high flux membrane is characterized by high fluid removal and typically has a molecular cut-off weight of 55,000 Daltons.

*The hemofilter contains a semi-permeable membrane that provides an interface between the blood and dialysate compartment. This interface creates a barrier so that the blood and dialysate never come in contact with each. Biocompatibility is an important feature, because the membranes chemical properties minimize bloods reaction I.e. thrombocytes and/or complement activation and immune system response (allergic reaction). ***Chemistry control such as very effective in control hyperkalemia, ureamia, and rapid control in acidosis***The use of both diffusion and convection transport mechanism create a therapy called hemodiafiltration. This specific therapy combines dialysate solution to create diffusive clearance of small molecules, and replacement solution to create convective clearance of middle to large molecules.*A patient will need a veno-venous double lumen catheter or two single lumen venous hemodialysis catheter. One side of the lumen will deliver blood from the patient to the filter, and the other lumen will return the blood back from the filter to the patient. *There are three access locations that are used some may be preferred over others. Internal jugular vein is the primary choice due to the simplicity of catheter insertion. Femoral vein is a great access when a patient is immobilized, and is also considered an easy site for insertion. Subclavin is the least preferred and often used if no other sites are available. A Subclavin has a high risk of pnemo/hemothorax and is associated with central stenosis.*Choosing the right catheter is another important aspect to be considered.. The catheter length will depend on the site used. Pediatric of course will need to be assessed for an appropriate size catheter. *A common complication encountered during CRRT is vascular access. There are many reasons why a catheter may not be functioning properly during CRRT treatment. Here are only a few reasons a catheter may not be functioning:Vascular spasm caused by initial BFR being to high. The easiest way to remedy this complication is to decrease the blood flow rate. Catheters proximal or distal port opening move against the vessel wall impeding blood flow. This can sometimes be alleviated by repositioning the patient, or having the doctor reposition the catheter.Improper placement, or length of of the catheter.

Fluid volume deficit may also occur during CRRT if the patients I/O status is not monitored closely and regularly. A fluid volume deficit may lead to hypotension and compromise patient safety.*Intravascular volume depletion (fluid volume deficit) can lead to hypotension. It is important to monitor I/O data to make sure the patient is hemodynamically stable. If hypotension occurs during treatment, the patient fluid removal should be decreased and sometimes placed at zero. A full assessment of the reasons for the hypotension should be addressed: loss of blood, increased urinary output, or fluid status has normalized.

Patient electrolytes can become imbalanced for many reasons. A goal of CRRT is to balance electrolytes, however sometimes high ultrafiltration rates can disturb the delicate balance of electrolytes, therefore it is important to monitor and replenish electrolytes and bicarbonate. It is recommended the nurse and MD monitor lab values closely and regularly, with the MD making adjustments to dialysate or replacement solution accordingly. *Just as with electrolyte imbalance, acid/base balance is another aspect to monitor closely. The physician and the nurse must identify whether acid/base imbalance is due to renal dysfunction or due to respiratory compromise.

Blood loss during CRRT can and will occur due to ineffective anticoagulation therapy causing the hemofilter to clot. Once the filter is clotted the blood is not returned to the patient. Keep in mind when a system clots the patient can loss anywhere from 93 cc to 189 cc depending on the hemofilter set. Other reasons for blood loss could be due to over-anticoagulation so clotting parameters should be monitored closely. Inadvertent disconnection in the CRRT system could potentially happen if the connection between the catheter and set is not tight.

*All CRRT monitors on the market have an air detector so if by chance air enter the circuit the air detector would detect the air causing the treatment to be suspended. Leaks/faulty connections, or line separation could potentially happen after the air detector allowing air to enter the patient. In this case the nurse would initiate interventions of positioning the patient on their left side or in Trendelenburg position.As we have discussed, CRRT treats a variety of conditions from fluid overload to electrolyte imbalance, which could inadvertently cause cardiac arrhythmias. Monitoring cardiac status is important at all times to avoid cardiac arrest. Other reasons for cardiac arrest maybe hemolysis, air embolism, circulatory overload and arrhythmias.*The patients blood is exposed to room temperature as it circulates through the extracorporeal circuit. Additionally, fluids (replacement fluid and/or dialysate) infused at room temperature may be administered, often in volumes of 2-4 liters per hour. As a result, the patient may show signs and symptoms of decreased body temperature. As you know, this can be reflected in the patient by hemodynamic instability, chilling and shaking, as well as skin pallor, coolness, and cyanosis.*