Continous Renal Continous Renal Replacement Replacement

TherapyTherapyBasic Principles and DefinitionsBasic Principles and Definitions

By By Dr. Marwa AhmadDr. Marwa AhmadAssistant lecturerAssistant lecturer

Anesthesia and Intensive care Anesthesia and Intensive care departementdepartement

Sohag university Sohag university

What is the CRRTWhat is the CRRT

Is an extracorporeal blood purification therapy intended to substitute forimpaired renal function over anextended period of time and applied foror aimed at being applied for 24 hours aday.

The concept behind continuous The concept behind continuous renal replacement techniques is renal replacement techniques is to dialyse patients in a more to dialyse patients in a more physiologic way, slowly, over 24 physiologic way, slowly, over 24 hours, just like the kidneyhours, just like the kidney . .

Intensive care patients are particularly suited to these techniques as they

are, by definition, bed bound, and, when acutely sick, intolerant of the fluid swings associated with IHD.

CRRT refers to any continuous mode of CRRT refers to any continuous mode of extracorporeal solute or fluid removalextracorporeal solute or fluid removal . .

A variety of renal replacement therapies A variety of renal replacement therapies are encompassed within the term are encompassed within the term CRRTCRRT. . Common to all forms of CRRT is Common to all forms of CRRT is an extracorporeal circuit connected to an extracorporeal circuit connected to the patient via an arterial or venous the patient via an arterial or venous access catheter, or bothaccess catheter, or both..

All CRRT circuits include a hemofilterwith a semipermeable membrane. By connecting the hemofilter to the patient’s circulation, fluid can beremoved from the patient on the basisof the hydrostatic pressure gradientacross the filter.

The rate of fluid removal is affected byeither the patient’s arterial bloodpressure (when an arterial cannula is used) or by the pressure generated withan extracorporeal pump (for venouscannulation techniques). The ultrafiltrate is composed of water aswell as compounds with a molecular weight of up to approximately 20,000Da

Traditional intermittent hemodialysis often causes hemodynamic instability in the critically ill.

Continuous renal replacement therapy (CRRT) was developed in the 1980s in an effort to provide artificial kidney support to patients who could not tolerate traditional hemodialysis.

The earliest forms of CRRT used arterial and venous access and depended on the patient’s mean arterial pressure to push blood through the filter .

This technique was rarely successful for patients in shock – those who needed the continuous therapy the most .

In response to this shortcoming, the current techniques of veno-venous CRRT were developed .

Most CRRT delivered today uses veno-venous access and an external blood pump to maintain adequate flow through the filter.

Difference between CRRT Difference between CRRT and conventional Dialysisand conventional Dialysis

two major dialysis techniquestwo major dialysis techniques: : conventional intermittent conventional intermittent haemodialysis haemodialysis ((IHDIHD) ) and continuous and continuous renal replacement therapy renal replacement therapy ((CRRTCRRT))..

One difference between these two One difference between these two options is fairly evidentoptions is fairly evident:: the time during which they are the time during which they are

appliedapplied. .

CRRT is, in theory, appliedcontinuously, whereas IHD, just like chronic haemodialysis, is applied for

only a few hours during the day.

Because of the short treatment time, Because of the short treatment time, IHD needs to deliver highly efficient IHD needs to deliver highly efficient therapy for toxin and fluid removaltherapy for toxin and fluid removal..In contrast, CRRT modalities are In contrast, CRRT modalities are mostly rather lowmostly rather low--efficiency efficiency techniques, and therapy needs to be techniques, and therapy needs to be continuous in order to be adequatecontinuous in order to be adequate . .

DifferencesDifferences

((ii ) )IHD is mostly performed as a mainly IHD is mostly performed as a mainly diffusive therapy across a lowdiffusive therapy across a low--flux dialysis flux dialysis membrane, with a high dialysate flow, membrane, with a high dialysate flow, which necessitates onwhich necessitates on--line dialysate line dialysate production, a waterproduction, a water--treatment module and treatment module and

a dialysis monitora dialysis monitor . .

(ii) In contrast, CRRT is performedmostly as convective therapy across ahigh-flux membrane, and usingindustry-prepared substitution fluid inbags.

(iii) It is clear that the application of IHD

needs the nursing and technical expertise of a dialysis team, whereas CRRT is technically less demanding.

Based on these differences, it must unfortunately be admitted that the choice between CRRT and IHD is often reduced to a question of whether theintensivist or nephrologist isresponsible for the treatment of ARF inthe ICU.

Conventional renal dialysisConventional renal dialysis::With renal failure of any cause, there are many physiologic derangements. Homeostasis of water and minerals (sodium, potassium, chloride, calcium, phosphorus, magnesium, sulfate), and excretion of the daily metabolic load of fixed hydrogen ions is no longer possible.

Toxic end-products of nitrogen metabolism (urea, creatinine, uric acid, among others) accumulate in blood and tissue.

Finally, the kidneys are no longer able to function as endocrine organs in the production of erythropoietin and 1,25 dihydroxycholecalciferol (calcitriol).

Dialysis procedures remove nitrogenous end-products of catabolism and begin the correction of the salt, water, and acid-base derangements associated with renal failure.

Renal function should not be estimated from measurements of blood urea or creatinine alone. Cockcroft and Gault equation or reciprocal creatinine plots should not be used when the GFR is <30 mL/min or to determine the need for dialysis.

Indications of dialysis in acute renal failure (ARF)

•Severe fluid overload•Refractory hypertension•Uncontrollable hyperkalemia•Nausea, vomiting, poor appetite, gastritis with hemorrhage•Lethargy, malaise, somnolence, stupor, coma, delirium, asterixis, tremor, seizures,•Pericarditis (risk of hemorrhage or tamponade)•bleeding diathesis (epistaxis, gastrointestinal (GI) bleeding and etc.•Severe metabolic acidosis•Blood urea nitrogen (BUN) > 70 – 100 mg/dl

Indications of dialysis in chronic renal failure (CRF)

• Pericarditis.• Fluid overload or pulmonary edema refractory to

diuretics.• Accelerated hypertension poorly responsive to

antihypertensives.• Progressive uremic encephalopathy or

neuropathy such as confusion, asterixis, myoclonus, wrist or foot drop, seizures.

• Bleeding diathesis attributable to uremia.

Principle of dialysis

Dialysis works on the principles of the diffusion of solutes and ultrafiltration of fluidacross a semi-permeable membrane.Diffusion describes a property of substancesin water. Substances in water tend to movefrom an area of high concentration to an

areaof low concentration.

Blood flows by one side of a semi-permeablemembrane, and a dialysate, or specialdialysis fluid, flows by the opposite side. A semipermeable membrane is a thin layer

of material that contains holes of various sizes,or pores.

Smaller solutes and fluid pass through the Smaller solutes and fluid pass through the membrane, but the membrane blocks themembrane, but the membrane blocks thepassage of larger substances (for example, redpassage of larger substances (for example, redblood cells, large proteins). blood cells, large proteins). This replicates the filtering process that takesThis replicates the filtering process that takesplace in the kidneys, when the blood entersplace in the kidneys, when the blood entersthe kidneys and the larger substances arethe kidneys and the larger substances areseparated from the smaller ones in theseparated from the smaller ones in theglomerulus.glomerulus.

The need to CRRTWhen comparing continuous renal replacement therapy (CRRT) with intermittent therapy, it is wise toremember that the very reason for the development and introduction of CRRT into clinical practice in thelate 1970s and early 1980s was to compensate for the clear inadequacies of conventional intermittent hemodialysis (IHD) in the treatment of critically illpatients with multi-organ failure. If there had not been serious problems with conventional IHD, CRRT would not be the subject fordiscussion.

Critically ill patients requiring renal

replacement therapies cannot tolerate rapidfluid and electrolyte shifts without significant hemodynamic compromise.

Even if these hypotensive episodes are brief, they may result in further damage to the kidney. Multiple hypotensive episodes have been shown to slow recovery from acute renal failure in the critically ill.

The critically ill patient is also susceptible toprotein calorie malnutrition due to theMarked catabolism that accompanies criticalillness.In order to provide adequate protein to these patients, large amounts of fluids and protein must beadministered, either enterally or parenterally.Intermittent hemodialysis (IHD) requires thatpatients’ protein and fluid intake be limited betweentreatments to prevent toxic levels of nitrogen andfluid overload.

CRRT addresses the needs of the critically ill patient with renal dysfunction and/or fluidvolume excess by providing slow,

continuous removal of toxins and fluids. By removing fluids continuously over a 24 Hour period, CRRT mimics the native kidney.

Hemodynamic stability is improved, andmultiple hypotensive episodes aresignificantly reduced.Because there is no buildup of toxins andfluids,patients receiving CRRT can receive asmuch protein and fluid as needed to achieveoptimal nutrition.

Indications of Indications of CRRTCRRT

CRRT is indicated in any patient who meetscriteria for hemodialysis therapy but cannottolerate intermittent dialysis due to hemodynamic instability.CRRT is better tolerated by hemodynamically unstable patients because fluid volume,electrolytes and pH are adjusted slowly andsteadily over a 24 hour period rather than a 3– 4 hour period.This pattern more closely mimics the native kidney and prevents abrupt shifts in fluid,electrolyte and acid-base balance.

Indications for renal replacement therapy (RRT) fall into two broad categories, so-called “renal” (i.e., to specifically address theconsequences of renal failure) and “nonrenal” (without necessitating renal failure). Although the distinction is not always precise,it is a reasonably easy way to categorizeindications for RRT.

Renal indications

• Volume overload (e.g., pulmonary edema)

• Azotemia with uremic symptoms• Hyperkalemia (>6.0 mmol/L)• Metabolic acidosis (pH < 7.2) due to

renal failure

“Nonrenal” indications

So-called nonrenal indications for RRTare to remove various dialyzablesubstances from the blood. These substances include drugs,poisons, contrast agents, and

cytokines.

Drug and toxin removal

Continuous renal replacement therapy (CRRT) may be effective in removingsubstances with higher degrees of proteinbinding and is sometimes used to removesubstances with very long plasma half-lives.Techniques such as sorbent hemoperfusionmay also be used for this indication.

In general, the size of the molecule and

the degree of protein bindingdetermines the degree to which thesubstance can be removed (smaller, nonprotein bound substances areeasiest to remove).

The role of CRRT in the management of acutepoisonings is not well established.There is relatively lower drug clearance per unit of time compared to intermittenthemodialysis (IHD) but CRRT has a distinctadvantage in hemodynamically unstable patients who are unable to tolerate the rapidsolute and fluid losses associated with IHD oreven other techniques such ashemoperfusion.

CRRT may also be effective for the slow, continuous removal of substances with largevolumes of distribution, a high degree oftissue binding, or for substances that areprone to “rebound phenomenon” (e.g., lithium, procainamide, and methotrexate). In such cases, CRRT may even be used as adjuvant therapy with IHD orhemoperfusion.

Contrast agents

all radio-contrast agents are nephrotoxic andCRRT is being advocated by some experts tohelp prevent so-called contrast nephropathy.Standard IHD has been shown to removeradio-contrast agents but does not appear toprevent contrast nephropathy. Despite less efficiency in removing contrast, CRRT has been shown to result in lesscontrast nephropathy, particularly when it has begun prior to or in conjunction with contrast administration.

Cytokines

Many endogenous mediators of sepsis can beremoved using continuous venovenoushemofiltration (CVVH) or continuous veno-venous hemodiafiltration(CVVHDF) (dialysis isnot able to remove these mediators).This observation has prompted manyinvestigators to attempt to use CVVH as anadjunctive therapy in sepsis.

While it remains controversial as towhether CVVH offers additional benefitin patients with renal failure and

sepsis,available evidence does not support arole of CVVH for the removal of cytokines in patients without renal failure.

Contra indications of CRRTContra indications of CRRT

•Advance directives indicating the patient does not desire dialysis, or

that the patient does not desire life- sustaining therapy.• Patient or family refusal of therapy.• Inability to establish vascular access.

Principles of renal Principles of renal replacement replacement therapytherapy

Renal replacement always uses asemipermeable membrane to achieve bloodpurification. It can be intermittent or continuous, and can

involveany of 4 major transport mechanisms: diffusion,convection, adsorption and ultrafiltration.The focus of this packet is continuous renal replacement therapies.

Semipermeable Membranes

Semipermeable membranes are the basis of all blood purification therapies.They allow water and some solutes topass through the membrane, whilecellular components and other solutes remain behind.

The water and solutes that passthrough the membrane are calledultrafiltrate.The membrane and its housing arereferred to as the filter.

Ultrafiltration

Ultrafiltration refers to the passage of water through a membrane under a pressure gradient.Pressures that drive ultrafiltration can bepositive, that is the pressure pushes fluidthrough the filter.They can also be negative, there may besuction applied that pulls the fluid to theother side of the filter.

The rate of ultrafiltration will depend upon the pressures applied to the filter and on therate at which the blood passes through thefilter.Higher pressures and faster flows increasethe rate of ultrafiltration. Lower pressures and slower flows decreasethe rate of ultrafiltration.

Convection

Convection is the movement of solutes

through a membrane by the force of water.

Convection is sometimes called “solvent drag”.

Convection is able to move very large

molecules if the flow of water through

the membrane is fast enough.

In CRRT this property is maximized by using

replacement fluids.

Replacement fluids are crystalloid fluids administered

at a fast rate just before or just after the blood

enters the filter.

The increased fluid flow rate across the filter allows

more molecules to be carried through to the other

side.

To better understand this phenomenon, think of a quiet stream as compared to a raging river. The stream could never shift a boulder, but thepowerful raging river could easily drag a boulderdownstream. So it is with convection; the faster theflow through the membrane, the larger the

moleculesthat can be transported.

Adsorption

Adsorption is the removal of solutes from the bloodbecause they cling to the membrane. Think of an air filter. As the air passes through it,impurities cling to the filter itself. Eventually theimpurities will clog the filter and it will need to bechanged. The same is true in blood purification. High levels ofadsorption can cause filters to clog and becomeineffective.

Diffusion

Diffusion is the movement of a solute across a

membrane via a concentration gradient. For diffusion to occur, another fluid must

flow on the opposite side of the membrane. In

bloodpurification this fluid is called dialysate.

When solutes diffuse across a membrane they alwaysshift from an area of higher concentration to an area of lower concentration until the solute concentration on

both sides of the membrane is equal. To understand

diffusion, think of adding drops of food coloring to a bathtub.

Initially the coloring appears as a dense cloud, but over

time the coloring spreads (diffuses) evenly throughout the

water.

Vascular Access and the Extracorporeal Circuit

There are two options for vascular access for

CRRT, venovenous and arteriovenous. Venovenous access is by far the most

commonly used in the modern ICU.

Fluids Used in CRRTDialysateDialysate is any fluid used on the bopposite side ofthe filter from the blood during blood purification.Dialysate is a crystalloid solution containing various amounts

ofelectrolytes, glucose, buffers and other solutes. The most

common concentrations of these solutes are equal to normal plasma

levels. The concentration of solutes will be ordered by the physician

based on the needs of the patient.Typical dialysate flow rates are between 600 – 1800 mL/hour.

Replacement FluidsAs stated earlier, replacement fluids are used to

increase theamount of convective solute removal in CRRT. It is

very important to understand that despite their name, Replacement fluids do not replace anything. Many professionals new to CRRT mistakenly believe

that If replacement fluids are added to the therapy, fluid removal rates are decreased or eliminated.

This is not the case. Fluid removal rates are calculated independently of replacement fluid

rates.The most common replacement fluid is 0.9%Normal Saline. Other crystalloid solutions may also be used as replacement fluid. Sometimes an additive will be

added to the replacement fluid bag to aid in correction of

electrolyte or acid-base balance.

Anticoagulation & CRRT

Anticoagulation is needed in CRRT because theclotting cascades are activated when the bloodtouches the non-endothelial surfaces of the

tubing and filter. CRRT can be run withoutanticoagulation, but filters last much longer if some form of anticoagulation is used.

Types of CRRT Therapy

CRRT encompasses several therapeutic modalities:

• Slow Continuous Ultrafiltration (SCUF)• Continuous VenoVenous Hemofiltration

(CVVH)• Continuous VenoVenous HemoDialysis

(CVVHD)• Continuous VenoVenous

HemoDiaFiltration (CVVHDF)

Slow Continuous Ultrafiltration (SCUF)

To perform SCUF, the patient is placed on the CRRT machine and the blood is run through

thefilter. No dialysate or replacement fluid is

used. The primary indication for SCUF is fluid overload without uremia or significant electrolyte imbalance.

SCUF therapy primarily removes water from the bloodstream. The main mechanism of water transport is ultrafiltration. Other solutes are carried off in small amounts, but usually not enough to be clinically

significant. When performing SCUF, the amount of fluid in the

effluent bag is the same as the amount removed from the patient.Fluid can be removed at a rate of up to 2 L/hour using

SCUF, but this defeats the purpose of continuous therapy. Fluid

removal rates are typically closer to 100 mL/hour.

Continuous Veno-venous Hemofiltration (CVVH)

To perform CVVH, the patient is placed on the CRRT machine and blood is run through thefilter with a replacement fluid added either before or after the filter. No dialysate is used.CVVH can be an extremely effective method of solute removal and is indicated for uremia or severe pH or electrolyte imbalance with or without fluid overload.Because CVVH removes solutes via convection, it is particularly good at removal of large molecules.

One major advantage of CVVH is that solutes can be removed in large quantities while easily maintaining a

net zero or even a positive fluid balance in the patient. This flexibility makes CVVH an ideal therapy for

patients who have severe renal impairment combined with a

need to maintain or increase fluid volume status. When performing CVVH, the amount of fluid in theeffluent bag is equal to the amount of fluid removed

fromthe patient plus the volume of replacement fluidsadministered.

Continuous Veno-venous Hemodialysis (CVVHD)

To perform CVVHD, the patient is placed on the CRRT machine and dialysate is run on theopposite side of the filter, no replacement fluid isused. CVVHD is very similar to traditional hemodialysis,

and is effective for removal of small to medium sized

molecules.Solute removal occurs primarily due to diffusion, and dialysate can be tailored to promote diffusion of

specificmolecules.

While CVVHD can be configured to allow a positive or zero fluid balance, it is more

difficult than with CVVH because the rate of solute removal is dependent upon the rate of fluid removal from the patient.When performing CVVHD the amount of fluid inthe effluent bag is equal to the amount of fluid removed from the patient plus the dialysate.

Continuous Veno-venous Hemodiafiltration

(CVVHDF)To perform CVVHDF the patient is placed on

the CRRT machine with dialysate running on theopposite side of the filter and replacement

fluid either before or after the filter. CVVHDF is the most flexible of all the

therapies, and combines the benefits of diffusion andconvection for solute removal.

The use of replacement fluid allows adequatesolute removal even with zero or positive net fluid balance for the patient. The replacement fluid rates and dialysate rates are similar to those described for CVVHD and CVVH. In CVVHDF the amount of fluid in the effluent

bag equals the fluid removed from the patient plus

thedialysate and the replacement fluid.

Prescription of CRRTPrescription of CRRT

A typical prescription for a 75kg A typical prescription for a 75kg patient requiring CRRT for an AKI patient requiring CRRT for an AKI would be as follows:would be as follows:

AnticoagulationAnticoagulation::Unfractionated Heparin: 5,000 IU bolus Unfractionated Heparin: 5,000 IU bolus

followed by a pre-filter infusion at 500 followed by a pre-filter infusion at 500 IU.hr.-1IU.hr.-1

Aim to anticoagulate filter but ensure Aim to anticoagulate filter but ensure APTTR<2APTTR<2

Fluid balance over 24 hours:Fluid balance over 24 hours:Aim for an even balance if the patient is euvolaemicAim for an even balance if the patient is euvolaemicAim for the appropriate negative balance if the Aim for the appropriate negative balance if the

patient is fluid overloaded (<1500ml/24hrs)patient is fluid overloaded (<1500ml/24hrs)

Type of Replacement fluid/Dialysate:Type of Replacement fluid/Dialysate:Use solutions without potassium if serum potassium Use solutions without potassium if serum potassium

is high but switch to potassium containing is high but switch to potassium containing solutions as serum potassium normalisessolutions as serum potassium normalises

Use a bicarbonate-based buffer rather than a Use a bicarbonate-based buffer rather than a lactate-based buffer if there are concerns about lactate-based buffer if there are concerns about lactate metabolism or if serum lactate>8mmol.l.-1 lactate metabolism or if serum lactate>8mmol.l.-1 [Note- An intravenous bicarbonate infusion may be [Note- An intravenous bicarbonate infusion may be required if a lactate-based buffer is used]required if a lactate-based buffer is used]

Exchange rate/treatment doseExchange rate/treatment dose::1500ml.hr.-1 (75kg x 20ml.kg.-1hr-1)1500ml.hr.-1 (75kg x 20ml.kg.-1hr-1)The treatment dose is usually prescribed as an The treatment dose is usually prescribed as an

hourly “exchange rate” which is the desired hourly “exchange rate” which is the desired hourly flow rate adjusted for the patient`s hourly flow rate adjusted for the patient`s weightweight

In the case of CVVH, the exchange rate simply In the case of CVVH, the exchange rate simply represents the ultrafiltration rate whereas in represents the ultrafiltration rate whereas in CVVHDF it represents a combination of the CVVHDF it represents a combination of the ultrafiltration rate and the dialysate flow rateultrafiltration rate and the dialysate flow rate

In CVVHDF, the ratio of ultrafiltration to dialysate flow In CVVHDF, the ratio of ultrafiltration to dialysate flow is often set at 1:1 but it can be altered to put the is often set at 1:1 but it can be altered to put the emphasis on either the dialysis or filtration componentemphasis on either the dialysis or filtration component

Complications of CRRT

BleedingHypothermiaElectrolyte ImbalancesAcid-Base ImbalancesInfectionAppropriate Dosing of Medications