Continuous Renal Replacement

Form of extracorporeal blood purification using a continuous circuit, providing:

This covers CRRT; a general overview and comparison of RRT modalities is provided under Overview of Renal Replacement.

Principles

Physical

Principles:

  • Ultrafiltration
    Generation of a transmembrane pressure that exceeds the oncotic pressure, resulting in net loss of water across the dialysis membrane. This is achieved by:
    • Relative pressurisation of the blood relative to the dialysate, ↑ hydrostatic pressure
      Volume cleared is proportional to the transmembrane pressure.
    • ↑ Osmolality of the dialysate, drawing water across the membrane

\(TMP = {P_{Filter} + P_{Return} \over 2} - {P_{Effluent}}\)

Where:

  • \(TMP\) = Transmembrane Pressure
  • \(P\) = Pressure
  • Convection (Solvent drag)
    Passive transport of solute particles across a semipermeable membrane along with the movement of solvent.
    • Better clearance of mid-sized molecules
  • Diffusion
    Generation of an electro-chemical gradient across the membrane.
    • Rate of diffusion is affected by:
      • Molecular weight
      • Membrane porosity
      • Blood flow rate
    • Better clearance of small molecules

Values:

  • Sieving Coefficient
    Describes how effectively a given solute is removed.
    • A high value indicates effective clearance

\(SC = {[UF] \over [Blood]}\)

Where:

  • \(SC\) = Sieving coefficient
  • \(UF\) = Ultrafiltrate
  • Filtration Fraction
    Fraction of plasma removed from blood during filtration.

\(FF = {Rate_{UF} \over Rate_{Blood}} = {Rate_{UF} \over Rate_{Blood \ Pump} \times (1 - Hct)}\)

Where:

  • \(FF\) = Filtration Fraction
  • \(UF\) = Ultrafiltrate
  • \(Hct\) = Haematocrit

Practical

  • Dose
    Effluent production in mL/kg/hr.
    • CRRT dose should generally be 20-25mL/hr
      • This typically requires a prescription of 25-30mL/hr due to interruptions
      • Higher doses are not associated with improved outcome, but do ↑ the incidence of other electrolyte abnormalities
        e.g. ↓ PO4.
      • Higher doses may be used (with little evidence) in profound metabolic derangements refractory to standard RRT
        • Rhabdomyolysis with intractable hyperkalaemia
        • Liver failure to ↑ ammonia clearance
    • Hypotension and electrolyte disturbances are more common at higher intensities (dosing) and are not associated with improved outcome
    • Composition of effluent (and therefore the nature of “dose”) varies depending on the:
      • Use of pre-filter dilution
      • Mechanism of effluent production
        • Ultrafiltration
          i.e. TMP driven.
        • Diffusion
          i.e. Dialysis flow rate driven.
    • There is no good evidence suggesting which measure of weight should be used

Note this definition of dose is peculiar to CRRT; dosing intermittent dialysis is different due to the alterations in kinetics and fluid shifts that occur.

  • Fluid removal
    Difference between:
    • Effluent production
    • Pre-filter diluent
    • Post-filter replacement

CRRT relies on the same physical principles as IHD and SLED, but as fluid shifts occur more slowly CRRT has the greatest haemodynamic stability, and is preferred in patients with:

  • Haemodynamic instability
  • ↑ ICP
  • Cerebral oedema

Types of CRRT

There are a number of technical variations of CRRT based on the physical principles used:

  • Haemofiltration (CVVH)
    No dialysate is used; effect occurs via filtration and convection.
    • Ultrafiltration results in a solute-water mix filtered across the semi-permeable membrane
    • A substitution solution is used to replace lost volume
      The difference between the ultrafiltration volume produced and the substitution solution infused is the total fluid removal.
  • Haemodialysis (CVVHD)
    Counter-current delivery of dialysis solution, without generation of a transmembrane pressure.
    • Clearance is almost entirely by diffusion
  • Haemodiafiltration (CVVHDF)
    Combination of the above, using both:
    • Counter-current dialysis solution
      Solute clearance by diffusion.
    • Ultrafiltration
      Additional substitution solution used to replace lost volume.

Indications

Indications for CRRT include:

CRRT may be initiated in ICU based on anticipation of reaching these thresholds, or on a series of composite features that individually do not meet the threshold.

A mnemonic for the major causes is:

  • Aacidosis
  • Electrolyte
  • Intoxication
  • Overload (fluid)
  • Uraemia
  • Acidosis
  • Electrolyte disorders
    • Hyperkalaemia
      Thresholds vary, but consider if K+ >6.5mmol/L or rapidly ↑.
    • Hyponatraemia <110mmol/L
    • Hypernatraemia >160mmol/L
  • Toxins
  • Refractory fluid overload
  • Uraemia
    • Urea >35-40mmol/L
    • Uraemic complications
      • Pericarditis
      • Encephalopathy
  • Other
    • Hyperthermia >40°C

A short, but mostly-adequate exam list of dialysable toxins includes:

  • Alcohols
    • Ethanol
    • Methanol
    • Ethylene glycol
  • Anticonvulsants
    • Lithium
    • Valproate
    • Phenytoin
    • Phenobarbital

Contraindications

Equipment

Vascular Access

Vascath:

  • Uncuffed, non-tunneled catheter
  • Preferentially sited in:
    • Right IJV
    • Femoral vein
    • Left IJV
    • Dominant SCV
      Risk of central vein stenosis with SCV insertion.
    • Non-dominant SCV
  • Positioned at the junction of the SCV and RA
    • Risk of atrial erosion if in too far
    • Risk of central vein stenosis if abutting SVC

Tunneled dialysis catheter:

  • Medium-term dialysis line
  • Usually sited in RIJ

Solutions

Substitution:

  • Balanced crystalloid solutions used to replace water and solute
    Include:
    • Pre-filter dilution
      Mixed with blood prior to the haemofilter.
      • ↓ Effective solute clearance
      • ↓ Filter clotting, due to ↓ haematocrit
      • Required if using a citrated solution, as this is where the anticoagulant is kept
    • Post-filter replacement
      Mixed with blood after the haemofilter, generally in the bubble trap.
      • Restores water and solute
      • May be the same solution as the pre-filter diluent

Pure post-filter replacement with no pre-filter dilution is the most efficient method for solute clearance, but has a high risk of filter clotting due to the ↑ haematocrit. In general, the haematocrit should be kept <50% in the filter to minimise the risk of clotting and maximise filter lifespan.

Dialysate:

  • Crystalloid solution
  • Buffered with:
    • Citrate
      Used when the circuit is anticoagulated with citrate and calcium.
    • Bicarbonate
      Requires reconstitution due to instability of bicarbonate in solution.
      • Shock
      • Hepatic failure
      • Lactic acidosis
    • Lactate
      Generally superseded by bicarbonate buffers.

Anticoagulation

Anticoagulation is frequently used to prevent clotting of the filter and circuit, but must be balanced against risks of bleeding. In general, circuit anticoagulation is recommended when patient is:

  • Not coagulopathic
  • Not systemically anticoagulated

Acceptable filter life is ~24 hours.

Comparison of Anticoagulation Techniques
Technique Method Advantages Disadvantages
No anticoagulant
  • Used in patients with endogenous coagulopathy or other contraindication
  • ↓ Filter life
Heparin alone
  • Low dose
    Heparin <500 units/hr.
  • Medium dose
    Heparin 500-1000 units/hr.
  • Easy, cheap, familiar, available
  • Minimal effect on systemic coagulation
  • Therapeutic heparinisation can be used if systemic anticoagulation is indicated (e.g. PE)
  • HITTS
  • Heparin resistance
Regional anticoagulation with citrate Citrate given into the access line and reversed with calcium given into the return line.
  • Regional anticoagulation reduces systemic haemorrhage
  • Longer filter life
  • ↓ Transfusion and major bleeding compared to UFH
  • Special dialysate required
  • Citrate toxicity (especially hepatic failure, shock)
    Metabolic acidosis, hypocalcaemia, widening total calcium:ionised calcium.
Regional anticoagulation with heparin/protamine Heparin into access line and reversed with protamine at a fixed ratio into the return line.
  • Easy, cheap, familiar, available
  • Reversible
  • Can be monitored
  • Short half-life
  • HITTS
  • Heparin resistance
  • Narrow TI
  • Unpredictable kinetics
Systemic low-molecular weight heparin
  • Predictable kinetics
  • Does not require monitoring
  • Less HITTS
  • May accumulate in renal failure
  • Requires anti-Xa for monitoring
  • Incompletely reversed with protamine
  • More expensive

Responding to Filter Clotting

  • Evaluate for mechanical causes
    Cannula:
    • Position
    • Flow rates
    • Kinking
  • Check anticoagulation efficacy
  • Consider ↑ or change of anticoagulation

Complications

  • Vascular access
  • Haemodynamic instability
    More pronounced with more aggressive dialysis modes (particularly IHD.

Key Studies

  • RENAL (2009)
    • ~1,500 Australasian ICU patients requiring CRRT
    • Multi-centre (35) RCT
    • 90% power for 8.5% ARR in mortality from control group mortality of 60%
      This was described as a “conservative” effect.
    • High-intensity (40mL/kg/hr) vs. low-intensity (25mL/kg/hr) CRRT
      • High-intensity received an average of 33.4mL/kg/hr
      • Low-intensity received an average of 22mL/kg/hr
    • No change in mortality (44.7% vs. 44.7%)
    • Significantly ↑ hypophosphataemia in high-intensity group

References

  1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1–138.
  2. Bersten, A. D., & Handy, J. M. (2018). Oh’s Intensive Care Manual. Elsevier Gezondheidszorg.
  3. Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients. New England Journal of Medicine. 2009 Oct 22;361(17):1627–38.
  4. Gemmell L, Docking R, Black E. Renal replacement therapy in critical care. BJA Education. 2017;17(3):88-93. doi:10.1093/bjaed/mkw070