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Introduction

What is renal replacement therapy?

  • Renal replacement therapy (RRT) describes techniques used to purify the blood and achieve the solute and fluid homeostasis usually produced by the kidney
  • Continuous renal replacement therapy (CRRT) describes treatments which are applied for prolonged periods at a time (usually >24 hours)

How can modes of renal replacement be classified?

Modality of Fluid and Solute Removal
  • Hemofiltration
  • Haemodialysis
  • Hemodiafiltration
Continuous vs. Intermittent Modality
  • Intermittent:
    • Intermittent haemodialysis (IHD)
    • Slow low-efficiency dialysis (SLED)
    • Extended daily dialysis (EDD)
  • Continuous:
    • Continuous venovenous hemofiltration (CVVH)
    • Continuous venovenous haemodialysis (CVVHD)
    • Continuous venovenous hemodiafiltration (CVVHDF)
    • Slow continuous ultrafiltration
    • Peritoneal dialysis (PD)
Source of Pressure Gradient
  • Arteriovenous
  • Venovenous - requires an external pump

Mechanisms

What are the mechanisms used for fluid and solute removal in renal replacement, and how are they defined?

Definition
Diffusion
The transport of solute across a semi-permeable membrane, down a concentration gradient
Ultrafiltration
The passage of fluid across a semi-permeable membrane due to a hydrostatic pressure
Convection
The transport of a solute across a semi-permeable membrane along with solvent (by "solvent drag")

What are the characteristics of molecules cleared by RRT?

  • Small volume of distribution (<1L/kg)
  • Low degree of protein-binding
  • High water solubility
  • Low molecular weight:
    • Only smaller molecules (up to 500 Da) are cleared by hemodialysis
    • Up to a maximum 40 kDa can be cleared by hemofiltration
  • Low endogenous clearance (<4 ml/min/kg)
  • Extraction ratio exceeding endogenous elimination

What factors influence the clearance of a substance from plasma?

  • Membrane properties:
    • Surface area of membrane
    • Hydraulic permeability
    • Pore size
    • Charge
  • Pressure gradients: hydrostatic, colloid, osmotic
  • Solute properties: size, charge, concentration

Modality Principles

What are the modalities of RRT?

Mechanisms
Haemodialysis
  • Clearance of solutes via diffusion down a concentration gradient
  • A counter-current flow of a solution containing various electrolytes on the opposite side of membrane to blood allows diffusion to occur
  • No fluid is added to the filtrate after diffusion
  • Rate of solute clearance determined by:
    • Concentration gradient between plasma and dialysate
    • Particle size, ionic charge and protein binding
    • Membrane pores, thickness and surface area
Haemofiltration
  • Clearance of solutes via convection driven by hydrostatic pressure
  • Filtrate removal is balanced by the addition of a solution to maintain volume
  • Does not significantly change the concentration of serum electrolytes and waste products unless a replacement fluid is infused into the blood, effectively diluting out those solutes the physician wishes to remove
  • Rate of filtrate and solute removal determined by:
    • Blood flow
    • Transmembrane pressure gradient
    • Membrane coefficient (pore size/permeability)
Haemodiafiltration (Combined)
  • Clearance of solute via convection and diffusion
  • Countercurrent dialysate is used in addition to hydrostatic pressure
  • Fluid replacement is required to maintain plasma volumes

How does the modality effect solute clearance?

Size
Examples
Removal
Small Molecules
<500 Da
  • Urea
  • Creatinine
  • Potassium
  • Oxalate
  • Uric acid
  • Better cleared by diffusion (Haemodialysis)
  • Rate of clearance increased by:
    • Increasing speed of dialysis fluid flow
Middle Molecules
500 - 60,000 Da
Albumin is 66 kDa (Not a middle molecule!)
  • Interleukins
  • Cytokines
  • B2 -microglobulin
  • ANP
  • TNF
  • Light chains
  • Better cleared by convection (Hemofiltration)
  • Dialysis clearance increased by:
    • Increased dialysis time
    • Increased membrane pore size
    • Increased membrane surface area
Protein-Bound Molecules
Variable
  • Homocysteine
  • Hippuric acid
  • Phenol
  • Difficult to remove via RRT
  • Clearance improved by:
    • Increased time and flow
    • Absorbent technology
    • Albumin dialysis

Modality Choice

Which factors influence the choice of modality that should be used?

Solutes to be Removed from the Plasma
  • Hemofiltration is better at removing middle molecules
  • Hemodialysis better at removing small molecules
Patient`s Cardiovascular and Neurological Status
  • CRRT causes less rapid fluid shifts and is the preferred option if there is any degree of cardiovascular instability
  • CRRT may be associated with better cerebral perfusion in patients with an acute brain injury or fulminant hepatic failure
Availability of Resources
  • CRRT is more labour intensive and more expensive than IHD
  • Availability of equipment may dictate the form of RRT.
Clinician`s Experience
  • It is wise to use a form of RRT that is familiar to all the staff involved
Other Specific Clinical Considerations
  • Convective modes of RRT may be beneficial if the patient has septic shock
  • CRRT can aid feeding regimes by improving fluid management

What are the advantages and disadvantages of different RRT modalities?

Advantages
Disadvantages
Requirement
Intermittent Haemodialysis
  • Efficient and intensive technique
  • Allows for down-time for interventions
  • Can be performed overnight
  • Staff required for a shorter time
  • Lower costs
  • May cause haemodynamic instability with rapid fluid removal
  • Relative need for anticoagulation
  • Potential for disequilibrium
  • Need for expensive machinery
  • Need for personnel
  • Venous access
  • Anticoagulation
  • Skilled staff
  • Expensive equipment
Continuous RRT
  • Provides better haemodynamic stability
  • Efficient solute removal and electrolyte balance with continuous removal
  • Round-the-clock maintenance of volume status
  • Nutrition and medication given while volume status maintained
  • User-friendly machines
  • Patient immobilisation
  • Need for prolonged anticoagulation
  • Nursing staff intensive
  • Expensive machinery
  • Risk of hypothermia
  • Round the clock skilled nursing staff
  • Venous access
  • Anticoagulation
  • Complex equipment
Peritoneal Dialysis
  • Better haemodynamic stability than haemodialysis
  • No need for anticoagulation
  • Slow correction of volume and electrolyte disorders
  • Many nurses unfamiliar with methods
  • Risks of leaks and peritoneal infection
  • Peritoneal catheter
  • Sterile peritoneal solutions
  • Trained staff

Which modality is better for critically unwell patients?

  • There is no evidence that the use of either continuous or intermittent therapies have a survival benefit in critical illness
  • Continuous modalities have been Several benefits have been proposed from the use of continuous modalities:
    • Improved haemodynamic stability and lower rates of therapy-induced hypotension – due to slower and more predictable rates of fluid removal and solute flux
    • Increased clearance with continuous modes to aid with the resolution of uraemia and electrolyte imbalance
    • Better tolerated in patients with raised intracranial pressure or hepatic encephalopathy due to less rapid shift in solute concentration and preservation of cerebral perfusion
    • Better clearance of inflammatory mediators
  • Given this international guidance favours the use of continuous therapies in critical illness
    • KDIGO guidance recommends continuous therapies in ‘haemodynamically unstable patients’ or those with ‘raised ICP, brain injury or other forms of brain oedema.’
    • Surviving sepsis guidance recommends continuous therapies in ‘haemodynamically unstable septic patients

Specialist Modalities

What is SCUF?

  • Provision ultrafiltration to remove excess fluid – mainly at the end of a dialysis session
  • It is useful solely for fluid removal and does not alter the patient’s biochemistry

What are hybrid therapies?

  • Hybrid therapies refer to a collective of recently developed therapies which includes:
    • SLED / EDD – Slow Low-Efficiency Daily Dialysis / Extended Daily Dialysis
    • SCD – Sustained Continuous Dialysis
  • Most therapies delivered via conventional dialysis machines over a more extended period than usual IHD
  • Hybrid therapies benefit from being intermittent, but also are associated with
    less haemodynamic and osmotic disturbance than intermittent HD, and good solute control

What is SLED?

  • SLED is an intermittent therapy typically delivered over 6-12 hours
  • It typically uses lower blood and dialysate flow rates using conventional dialysis machines
  • The advantaged of SLED are:
    • Improved haemodynamic stability
    • High solute clearance
    • Removes the need for expensive CRRT machines and customized solutions
    • Allows for diagnostic and therapeutic procedures

Circuit Anatomy & Performance

What are the key components required to perform renal replacement therapy?

Basic anatomy of the continuous renal replacement therapy circuit

How do the circuits differ for each modality of continuous RRT?

Haemodialysis
Haemofiltration
Haemodiafiltration
SCUF

Dose & Efficacy

Which variables, that influence its function, are controlled through the renal replacement circuit?

Fluid flows occuring through the basic renal replacement therapy circuit
Blood Flow Rate
Blood Flow Rate
Qb
  • The rate of blood flow from the patient towards the filter
  • Blood flow rates are typically slower than in intermittent dialysis, ranging from 150-200mL/min
Ultrafiltrate Rate
Ultrafiltrate Rate
Quf
  • The rate at which ultrafiltrate is produced by hydrostatic pressure across the membrane during convective therapies
  • It is influenced by the blood flow rate and the filtration fraction
Dialysate Flow Rate
Dialysate Flow Rate
Qd
  • The flow rate of dialysis fluid in dialytic therapies
  • Standard flow rates range from 8-50 mL/min
Effluent Rate
(Dose)
Effluent Rate
(Dose)
Qef
  • The effluent flow rate is the equivalent to ultrafiltration rate Quf in continuous haemofiltration, Qd in continuous haemodialysis, and both Quf & Qd in continuous hemodiafiltration
  • It is analogous to the ‘dose’ in continuous therapies
  • Dosing is weight-based and is typically prescribed at a dose ranging from 20 mL/kg/hr to 35 mL/kg/hr
Substitution Fluid Rate
Substitution Fluid Rate
Qs
  • Techniques in which produce a volume of ultrafiltrate require replacement of this fluid with a substitute fluid to prevent significant loss of volume.
  • The rate of substitution fluid describes the rate at which this replacement fluid is added to the plasma
Net Ultrafiltrate Rate
Net Ultrafiltrate Rate
Qnet
  • Represents the overall rate of fluid removal
  • It is the difference between the total effluent removed (Qef) minus the volume of replacement therapy
  • The fluid removal rate can be tailored by the machine to meet the total removal goal of the patient

What determines the clearance in CRRT?

  • Clearance describes the volume of blood that is cleared of a substance per unit of time
  • The determinant of clearance in CRRT depends upon the mechanisms that are being utilised
    • In continuous haemofiltration:
      • A volume of ultrafiltrate is produced following the passage of the pressurised plasma over the membrane
      • Clearance is of a solute determined by the:
        • Rate at which ultrafiltrate is produced (Quf)
        • Sieving coefficient of the filter membranes (determined by the ratio of solute concentrations in the ultrafiltrate)
      • Most small molecules have a sieving coefficient of 1, meaning they pass freely through the membrane (though this is less true of middle molecules)
      • Therefore, the clearance is analogous to the ultrafiltrate production rate (Quf)
    • In continuous haemodialysis:
      • The concentration gradient across the membrane determines clearance
      •  The gradient is affected by the dialysate flow rate (Qd) and the blood flow rate (Qb)
      • Qd is much slower than Qb, and the dialysate becomes fully saturated.
      • Therefore, the dialysate rate (Qd) becomes the rate-limiting factor for solute removal and is analogous to clearance
    • Overall consequently, clearance is equivalent to the combination of the ultrafiltration rate (Quf) and dialysate (Qd), which is termed the effluent rate (Qef)
    • This is often discussed in terms of the ‘dose’ of a continuous replacement therapy which is given

How is the effluent rate determined?

  • In ultrafiltration, the effluent rate is determined by the flow of plasma into the membrane and the fraction of this which is filtered out as effluent (known as the filtration fraction)
  • To maintain a constant effluent rate:
    • At low blood flows a large filtration fraction is required
    • At high flows, a small filtration fraction can be used
  • The renal replacement circuits have inbuilt algorithms to deliver a desired effluent flow rate based upon the blood flow from the patient

What effect do changes in the blood flow rate have?

  • Normal filter blood flows range between 50-200mL/min
  • Choosing the appropriate flow is a trade-off between the advantages and disadvantages of high and low flows:
Advantages
Disadvantages
High Blood Flows
  • A lower filtration fraction required thus reducing the risk of filter clotting
  • Easier to match ultrafiltration rates and therefore fluid removal targets
  • Increased risk of haemodynamic instability
  • Increased risk of hypothermia or haemolysis
  • Requires well-functioning access to prevent high suction pressures developing
  • Increased risk of filter clotting due to high filtration fractions
  • More challenging to meet fluid removal targets
Low Blood Flows
  • Reduced haemodynamic instability
  • Reduced risk of filter related complications
  • Lower suction pressures needed to achieve flow rates
  • Increased risk of filter clotting due to high filtration fractions
  • More challenging to meet fluid removal targets

What effect do changes in the filtration fraction have?

  • The filtration fraction is a measure of haemoconcentration in the filter
  • It is defined by the ratio between volume removed by convection per volume of plasma flow
  • If the ratio is too high, the filter tends to clot – more concentrated blood is ‘stickier’ and more likely to coagulate
  • Generally aiming to keep the filtration ratio below 25-30% will prevent clotting in the filter.

Membranes

What are the properties of the membrane that impact the function?

Biocompatibility
  • The rate of blood flow from the patient towards the filter
  • Blood flow rates are typically slower than in intermittent dialysis, ranging from 150-200mL/min
Flux
  • The rate at which ultrafiltrate is produced by hydrostatic pressure across the membrane during convective therapies
  • It is influenced by the blood flow rate and the filtration fraction
Adsorption
  • The flow rate of dialysis fluid in dialytic therapies
  • Standard flow rates range from 8-50 mL/min
Thickness
  • The effluent flow rate is the equivalent to ultrafiltration rate Quf in continuous haemofiltration, Qd in continuous haemodialysis, and both Quf & Qd in continuous hemodiafiltration
  • It is analogous to the ‘dose’ in continuous therapies
  • Dosing is weight-based and is typically prescribed at a dose ranging from 20 mL/kg/hr to 35 mL/kg/hr
Surface area
  • Techniques in which produce a volume of ultrafiltrate require replacement of this fluid with a substitute fluid to prevent significant loss of volume.
  • The rate of substitution fluid describes the rate at which this replacement fluid is added to the plasma
Material
  • Represents the overall rate of fluid removal
  • It is the difference between the total effluent removed (Qef) minus the volume of replacement therapy
  • The fluid removal rate can be tailored by the machine to meet the total removal goal of the patient

Which membranes are used in CRRT?

  • There is no conclusive evidence that any specific membranes improve the outcome
  • In practice, most filters used for CRRT are:
    • Synthetic, high-flux membranes
    • Surface area of 0.6–1.2m2
    • Pore size allowing the passage of molecules up to 50,000 Daltons
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Author

The Guidewire
Trainee in ICM & Anaesthesia

Reviewer

The Guidewire
Trainee in ICM & Anaesthesia

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