Dialysis

Dialysis is the separation of particles in a liquid based on their ability to pass through a membrane.

Indications

Failure of normal renal functions, i.e.:

  • Acid
  • Electrolyte derangement
    Particularly hyperkalaemia.
  • Intoxications
  • Overload
  • Ureamia

Physical Mechanisms

Fluid and electrolytes can be removed by four different mechanisms:

  • Diffusion
    Diffusion is the spontaneous movement of substances from a higher concentration to a lower concentration, where rate of movement is proportional to the concentration gradient (as per Fick's Law).
  • Ultrafiltration
    Movement of water, as determined by Starling's Forces.
    • When a solvent passes through a membrane, the process is called osmosis. The frictional forces between solutes and water molecules will pull dissolved substances along, a process known as bulk flow or solvent drag.

Implementation

  • Haemodialysis
    Uses diffusion.
    • Blood is pumped through an extracorporeal circuit that contains a dialyser.
    • Dialysate flow is countercurrent, which maximises the gradient for diffusion.
    • Solutes move across a membrane between blood and dialysate, as per Fick's Law:
      • Concentration gradient between blood and dialysate
        • Flow rate of blood and dialysate
      • Solubility of the solute
        • Mass
        • Charge
        • Protein binding
      • Dialysis membrane permeability
        • Thickness
        • Porosity
        • Surface area
  • Haemofiltration
    Uses ultrafiltration.
    • Both a positive hydrostatic pressure in blood and a negative hydrostatic pressure in dialysate is generated, causing ultrafiltration and removal of solutes via solvent drag.
    • Elimination via bulk flow is independent of solute concentration gradients across the membrane.
    • Transport is dependent on Starling Forces:
      • The transmembrane pressure generated
        This is a function of:
        • Blood flow to the membrane
          Determines hydrostatic pressure.
        • Oncotic pressure gradient
      • Porosity of the membrane
    • Additionally, a high filtration fraction will cause excessive haemoconcentration, and clotting of the filter
    • The filtered fluid (ultrafiltrate) is discarded, and replaced with another fluid depending on the desired fluid balance.

Differences

  • Renal Replacement Therapy (RTT) can be via:
    • Peritoneal dialysis (PD)
    • Intermittent haemodialysis (IHD)
      IHD causes greater cardiovascular instability compared to CRRT as the fluid and electrolyte shifts occur more rapidly.
    • Continuous Renal Replacement Therapy (CRRT)
      • Continuous Veno-Venous Haemofiltration (CVVH)
      • Continuous Veno-Venous Haemodiafiltration (CVVHDF)

Method chosen depends desired effect:

  • Small molecules (<500 Da) and electrolytes can be removed by filtration or dialysis
  • Medium-sized molecules (500-5000 Da) are best removed by filtration
  • Low molecular weight proteins (5000-50000 Da) are removed by filtration
    This includes removal of inflammatory proteins, which may be benficial in sepsis.
  • Water is best removed by filtration

Pharmacokinetics of RRT

Pharmacokinetics are unpredictable, but are broadly affected by:

  • Drug factors
    • Free drug in plasma
      Drugs with a small proportion of free drug in plasma are (unsuprisingly) poorly removed by RRT (but may be removed via plasmapheresis). These include:
      • Highly (> 80%) protein bound substances
        Examples included phenytoin, warfarin, and many antibiotics.
        • Not that this may not apply in overdose
          Once protein binding sites are saturated, both free drug fraction and efficacy of dialysis is increased.
      • Drugs with a VD greater than 1L.kg-1
    • Size/Molecular Weight
      • Small molecules (< 500 Da) are more easily cleared by diffusive methods of RTT
      • Molecules > 15kDa are poorly dialysed
        This includes proteins, heparins, and monoclonal antibodies.
    • Volume of distribution
      Drugs with high volumes of distribution are poorly dialysed, as removal of drug from plasma only removes a small proportion of total-body drug content.
  • Dialysis factors
    • Dose/Flow rates
      Reduced flow rates will reduce clearance.
      • Conventional high-flux haemodialysis has more rapid clearance compared to lower-flux haemoperfusion or CRRT
    • Membrane permeability
    • Timing
      Drugs given between IHD or SLED sessions will not be cleared until the next session.s
  • Patient factors
    • Residual renal function
      Patients residual GFR will also affect pharmacokinetics.

An Incomplete List of Drugs

Drugs Removed on RRT Drugs not removed on RRT
Barbiturates Digoxin
Lithium TCAs
Aspirin Phenytoin
Sotalol/Atenolol Other beta-blockers
Theophylline Gliclazide
Ethylene Glycol Benzodiazepines
Methanol Warfarin
Aminoglycosides, metronidazole, carbapenems, cephalosporins, penicillins Macrolides, quinolones

References

  1. Johnson CA, Simmons WD. Dialysis of Drugs. Nephrology Pharmacy Associates.
Last updated 2018-08-30

results matching ""

    No results matching ""