Continous RenalReplacement Therapy Basic Principles and Definitions By Dr. Marwa Ahmad Assistant lecturer Anesthesia and Intensive care departement Sohag university
What is the CRRTIs an extracorporeal blood purificationtherapy 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 continuousrenal replacement techniques isto dialyse patients in a morephysiologic way, slowly, over 24. hours, 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. extracorporeal solute or fluid removalA variety of renal replacement therapies areencompassed within the term CRRT. Commonto all forms of CRRT is an extracorporeal circuitconnected to the patient via an arterial or venous.access catheter, or both
All CRRT circuits include a hemofilterwith a semipermeable membrane.By connecting the hemofilter to thepatient’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 molecularweight of up to approximately 20,000Da
Traditional intermittent hemodialysisoften causes hemodynamic instability.in the critically illContinuous renal replacement therapy(CRRT) was developed in the 1980s inan effort to provide artificial kidneysupport to patients who could not.tolerate traditional hemodialysis
The earliest forms of CRRT used arterialand venous access and depended onthe patient’s mean arterial pressure to. push blood through the filterThis technique was rarely successful forpatients in shock – those who needed. the continuous therapy the most
In response to this shortcoming, thecurrent techniques of veno-venous. CRRT were developedMost CRRT delivered today uses veno-venous access and an external bloodpump to maintain adequate flow.through the filter
Difference between CRRT and conventional Dialysistwo major dialysis techniques:conventional intermittenthaemodialysis (IHD) and continuous(.renal replacement therapy (CRRTOne difference between these two:options is fairly evident the time during which they are applied.
CRRT is, in theory, appliedcontinuously, whereas IHD, just likechronic haemodialysis, is applied foronly a few hours during the day.
Because of the short treatment time,IHD needs to deliver highly efficient.therapy for toxin and fluid removalIn contrast, CRRT modalities are mostlyrather low-efficiency techniques, andtherapy needs to be continuous in. order to be adequate
Differencesi) IHD is mostly performed as a mainly)diffusive therapy across a low-fluxdialysis membrane, with a highdialysate flow, which necessitates on-line dialysate production, a water-treatment module and a 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 IHDneeds the nursing and technicalexpertise of a dialysis team, whereasCRRT is technically less demanding.
Based on these differences, it mustunfortunately be admitted that thechoice between CRRT and IHD is oftenreduced to a question of whether theintensivist or nephrologist isresponsible for the treatment of ARF inthe ICU.
:Conventional renal dialysisWith renal failure of any cause, thereare many physiologic derangements.Homeostasis of water and minerals(sodium, potassium, chloride,calcium, phosphorus, magnesium,sulfate), and excretion of the dailymetabolic load of fixed hydrogen ions.is no longer possible
Toxic end-products of nitrogenmetabolism (urea, creatinine, uricacid, among others) accumulate in.blood and tissueFinally, the kidneys are no longer ableto function as endocrine organs in theproduction of erythropoietin and 1,25(.dihydroxycholecalciferol (calcitriol
Dialysis procedures remove nitrogenousend-products of catabolism and beginthe correction of the salt, water, andacid-base derangements associated.with renal failure
Renal function should not be estimated from measurements of blood urea or creatinine alone. Cockcroft and Gaultequation or reciprocal creatinine plots should not be used when the GFR is <30 mL/min or to determine the needfor 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 dialysisDialysis works on the principles of thediffusion 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 ofmaterial that contains holes of various sizes,or pores.
Smaller solutes and fluid pass through themembrane, but the membrane blocks thepassage of larger substances (for example, redblood cells, large proteins).This replicates the filtering process that takesplace in the kidneys, when the blood entersthe kidneys and the larger substances areseparated from the smaller ones in theglomerulus.
The need to CRRTWhen comparing continuous renal replacementtherapy (CRRT) with intermittent therapy, it is wise toremember that the very reason for the developmentand introduction of CRRT into clinical practice in thelate 1970s and early 1980s was to compensate forthe clear inadequacies of conventional intermittenthemodialysis (IHD) in the treatment of critically illpatients with multi-organ failure.If there had not been serious problems withconventional IHD, CRRT would not be the subject fordiscussion.
Critically ill patients requiring renalreplacement therapies cannot tolerate rapidfluid and electrolyte shifts without significant.hemodynamic compromiseEven if these hypotensive episodes are brief,they may result in further damage to thekidney. Multiple hypotensive episodes havebeen 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 thesepatients, 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 illpatient with renal dysfunction and/or fluidvolume excess by providing slow, continuousremoval of toxins and fluids.By removing fluids continuously over a 24Hour 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.
CRRT is indicated in any patient who meetscriteria for hemodialysis therapy but cannottolerate intermittent dialysis due tohemodynamic instability.CRRT is better tolerated by hemodynamicallyunstable patients because fluid volume,electrolytes and pH are adjusted slowly andsteadily over a 24 hour period rather than a3– 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” indicationsSo-called nonrenal indications for RRTare to remove various dialyzablesubstances from the blood.These substances include drugs,poisons, contrast agents, and cytokines.
Drug and toxin removalContinuous 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 andthe 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 perunit of time compared to intermittenthemodialysis (IHD) but CRRT has a distinctadvantage in hemodynamically unstablepatients 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 beused as adjuvant therapy with IHD orhemoperfusion.
Contrast agentsall 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 ithas begun prior to or in conjunction withcontrast administration.
CytokinesMany 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 ofcytokines in patients without renalfailure.
Contra 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 replacement therapyRenal 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 renalreplacement therapies.
Semipermeable MembranesSemipermeable membranes are thebasis of all blood purification therapies.They allow water and some solutes topass through the membrane, whilecellular components and other solutesremain behind.
The water and solutes that passthrough the membrane are calledultrafiltrate.The membrane and its housing arereferred to as the filter.
UltrafiltrationUltrafiltration refers to the passage of waterthrough a membrane under a pressuregradient.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 uponthe 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.
ConvectionConvection is the movement of solutesthrough a membrane by the force of water.Convection is sometimes called “solvent drag”.Convection is able to move very largemolecules if the flow of water throughthe membrane is fast enough.
In CRRT this property is maximized by usingreplacement fluids.Replacement fluids are crystalloid fluids administeredat a fast rate just before or just after the bloodenters the filter.The increased fluid flow rate across the filter allowsmore molecules to be carried through to the otherside.
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.
AdsorptionAdsorption 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.
DiffusionDiffusion is the movement of a solute across a membrane via a concentration gradient.For diffusion to occur, another fluid must flow onthe 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 oflower 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 overtime the coloring spreads (diffuses) evenly throughout the water.
Vascular Access and the Extracorporeal CircuitThere are two options for vascular access for CRRT, venovenous and arteriovenous.Venovenous access is by far the most commonlyused in the modern ICU.
Fluids Used in CRRTDialysateDialysate is any fluid used on the bopposite side ofthe filter from the blood during bloodpurification.Dialysate is a crystalloid solution containing various amounts ofelectrolytes, glucose, buffers and other solutes. The most commonconcentrations 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 thatIf 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 asreplacement fluid. Sometimes an additive will be added to the replacement fluid bag to aid in correction of electrolyteor acid-base balance.
Anticoagulation & CRRTAnticoagulation 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 ifsome form of anticoagulation is used.
(Slow Continuous Ultrafiltration (SCUFTo 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 thebloodstream. 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, butthis defeats the purpose of continuous therapy. Fluid removal ratesare typically closer to 100 mL/hour.
Continuous Veno-venous (Hemofiltration (CVVHTo perform CVVH, the patient is placed on the CRRT machine and blood is run through thefilter with a replacement fluid added either before orafter 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 netzero 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 (CVVHDTo 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 iseffective 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 fluidremoved from the patient plus the dialysate.
Continuous Veno-venous (Hemodiafiltration (CVVHDFTo 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 bagequals the fluid removed from the patient plus thedialysate and the replacement fluid.
Prescription of CRRTA typical prescription for a 75kg patient requiring CRRT for an AKI would be as follows:Anticoagulation: Unfractionated Heparin: 5,000 IU bolus followed by a pre-filter infusion at 500 IU.hr.-1 Aim to anticoagulate filter but ensure APTTR<2
Fluid balance over 24 hours: Aim for an even balance if the patient is euvolaemic Aim for the appropriate negative balance if the patient is fluid overloaded (<1500ml/24hrs)Type of Replacement fluid/Dialysate: Use solutions without potassium if serum potassium is high but switch to potassium containing solutions as serum potassium normalises Use a bicarbonate-based buffer rather than a lactate-based buffer if there are concerns about lactate metabolism or if serum lactate>8mmol.l.-1 [Note- An intravenous bicarbonate infusion may be required if a lactate-based buffer is used]
Exchange rate/treatment dose: 1500ml.hr.-1 (75kg x 20ml.kg.-1hr-1) The treatment dose is usually prescribed as an hourly “exchange rate” which is the desired hourly flow rate adjusted for the patient`s weight In the case of CVVH, the exchange rate simply represents the ultrafiltration rate whereas in CVVHDF it represents a combination of the ultrafiltration rate and the dialysate flow rate In CVVHDF, the ratio of ultrafiltration to dialysate flow is often set at 1:1 but it can be altered to put the emphasis on either the dialysis or filtration component
Complications of CRRTBleedingHypothermiaElectrolyte ImbalancesAcid-Base ImbalancesInfectionAppropriate Dosing of Medications