CVVHDF What?! Renal Replacement Therapy Simplified…

Acute renal failure (ARF) is a new onset of the partial or complete reduction of normal kidney function which is characterised by the inability to remove excess water and metabolic wastes from the body. Continuous Renal Replacement Therapy (CRRT) is often indicated in ARF as well as some other conditions, with the decision to commence CRRT on a patient based on the following: 

  • Azotaemia which is defined as abnormally high levels of nitrogen containing compounds in the blood, such as urea and creatinine
    • CRRT usually warranted if urea is more than 30 and/or creatinine is more than 300
  • Fluid overload
    • Oliguria defined as less than 400 mL in 24 hours
    • Anuria defined as less than 100 mL in 24 hours
  • Refractory metabolic acidosis
    • CRRT usually warranted if pH is less than 7.2 despite concurrent medical management
  • Refractory hyperkalaemia
    • CRRT usually warranted if potassium is more than 6 mmol/L despite concurrent medical management
  • Refractory dysnatremia
    • CRRT usually warranted if sodium is more than 160 mmol/L or less then 115 mmol/L despite concurrent medical management
  • Drug overdose with water soluble toxins
  • Refractory hyperthermia despite concurrent medical management
  • Sepsis to aid in the removal of cytokines, septic mediators and bradykinins

kidney-failureCRRT provides a slow, continuous removal of fluid and metabolic wastes over a 24 hour period that mimics the physiological process of the kidneys. It utilises a semi-permeable membrane known as a filter to allow water and certain molecules to pass through the membrane as filtrate, while larger molecules remain behind within the blood. The underlying principles of how CRRT works are as follows:

Ultrafiltration refers to the movement of water through a semi-permeable membrane caused by a pressure gradient. This means water is moved from an area of higher  pressure to an area of lower pressure and can be achieved by a positive pressure on one side pushing the water through the membrane, or by a negative pressure on the other side pulling the water through the membrane. The higher the pressure differential, the higher the rate of ultrafiltration. The lower the pressure differential, the lower the rate of ultrafiltration. This concept is analogous with a drip coffee maker in that one side of the paper filter (semi-permeable membrane) has coffee granules mixed with water (molecules within blood). The coffee granules remain on one side of the filters while the water (ultrafiltrate) drips into the pot below secondary to gravity pressure.

CRRT convectionHowever, the water that drips through the filter does not come out the other side as pure water. It carries along with it the flavour molecules, caffeine and other substances that make it coffee. This is referred to as convection or the “solvent drag” and  is defined as the movement of solutes through a semi-permeable membrane secondary to the force exerted by water against the membrane. This known as hydrostatic pressure. Convection is able to move very large molecules if the flow of water through the membrane is fast enough, as the increased flow rate increases hydrostatic pressure against the filter thereby allowing more molecules, as well as larger molecules, to be carried through to the other side. To better understand this phenomenon, compare a quiet stream (low flow) to a raging river (high flow). The stream could never shift a boulder (large molecule), but the raging river could easily drag a boulder downstream. The same concept applies to convection; the faster the flow through the membrane, the larger the molecules that can be transported across the membrane.CRRT hydrostatic pressureDiffusion refers to the movement of solutes through a semi-permeable membrane caused by a concentration gradient. This means that solutes are moved from an area of higher  concentration to an area of lower concentration and occurs until the solute concentration on both sides are equal. This concept is analogous with adding drops of food colouring into a container. The food colouring will initially be concentrated in one area but eventually, the food colouring will diffuse evenly throughout the water.

CRRT diffusionIn CRRT, blood is both taken and returned to the patient from the same venous site through an invasive catheter known as a  VASCATH. The red access port is utilised to take blood from the patient and run it through the haemofilter, while the blue return port is utilised to return filtered blood to the patient. Depending on the mode, there may also be dialysate and replacement fluids added to the therapy. VASCATH CRRTDialysate fluids are infused on the outside of the hollow fibres that contain blood within the filter. It is run countercurrent to the direction of the blood flow in order to allow for a greater diffusion gradient across a semi permeable membrane, thereby increasing the effectiveness of solute removal. The dialysate does not cross the filter barrier into the bloodstream thereby meaning that if 1 litre of dialysate was administered per hour, 1 litre of dialysate will drain into the effluent bag. Dialysate fluids are usually buffered with bicarbonate, as bicarbonate levels are usually low in renal failure. It lacks in the active metabolites that treatment aims to remove such as creatinine and urea. Most of the electrolytes in the dialysate are equal to normal serum concentration, in order to maintain a normal serum electrolyte level for the patient during treatment. Potassium is the only electrolyte that may need to be added to certain brands of dialysate solution, depending on the aim of patient therapy.

Replacement fluids are infused through the filter into the patient’s bloodstream to simply replace the fluid that is lost through the ultrafiltrate. The rate of replacement fluid can be programmed via the pre blood pump stream and/or the replacement stream. This is all dependent on whether the replacement fluid is to be delivered either before (pre-dilution) or after (post-dilution) the filter. If pre-dilution is required, the majority of the rate programmed will be allocated to the pre blood pump stream. It is important to understand that the replacement stream can be programmed as either pre or post, and this indicates whether the fluid rate allocated to the replacement stream will enter the filter circuit before or after the actual filter. Therefore, some units will deliver their pre-dilution by programming the majority of the fluid rate via the replacement stream set as pre. If post dilution is required, the majority of the rate programmed will be allocated to the replacement stream.

continuous venovenous hemodiafiltrationThere are various CRRT modes that have been developed based on the principles of ultrafiltration, hydrostatic pressure, convection and/or diffusion. Each mode achieves a different outcome through the removal of solutes and/or fluids which will be most beneficial to the patient. The image above will help with the solidification of these modes and principles for you.

Slow continuous ultrafiltration (SCUF) uses the principle of ultrafiltration to remove excess fluid from the fluid overloaded patient. For this reason, the fluid removed is generally not replaced. Blood is simply taken from the patient, is pumped through the filter allowing ultrafiltration to take place and is then returned to the patient.

Continuous veno-venous haemofiltration (CVVH)
uses the principles of ultrafiltration, hydrostatic pressure and convection to remove both fluid and solutes from the patient. Due to the large loss of fluid that occurs in this mode, the patient will require a replacement fluid to be programmed within the filter. The filter ensures that the amount programmed as the replacement fluid rate is the amount of fluid that is loss during haemofiltration, to ensure that the patient keeps an even balance. This replacement fluid can be programmed to enter the filter either before (pre) or after (post) the filter.

Continuous veno-venous haemodialysis (CVVHD) uses the principle of diffusion to remove solutes from the patient. Where blood flows in one direction through the filter, a dialysate fluid flows on the other side of the filter membrane in the opposite direction of the blood. This is known as a “counter-current” flow and ensures that the highest diffusive gradient is achieved. There are no replacement fluids administered via the filter in this mode.

Continuous veno-venous haemodiafiltration (CVVHDF) uses the principles of both haemofiltration and haemodialysis, as described above. As this mode enable the ultimate removal and replacement of solutes and fluids within the blood, it is the most common mode chosen for CRRT. It is recommended that this mode is always selected, even if the clinician would like to run only haemofiltration or only dialysis. This is because the other modes can be achieved within this mode through the programming of dialysate and/or replacement fluids. However, this mode cannot be achieved in the other modes unless the whole filter is re-started.

Using the image above, have a look at the Prismaflex machine that is commonly used for CRRT to try and put all the pieces together. It can be navigated in the following way:

Navigating the Prismaflex CRRT

There are various pressures associated with the Prismaflex during CRRT. Access pressures are typically negative as the blood has to be pulled from the patient. Filter pressures and return pressures are typically positive as blood has to be pushed through the filter and to the patient, respectively. The filter pressures will begin to rise as the filer pores clog as more pressure is required to get blood through the filter. Effluent pressures and Transmembrane pressures (TMP) can be either positive or negative, depending on whether fluid is being pushed or pulled from the blood compartment to the fluid compartment. The effluent pressure will become more negative as the filter pores clog while the TMP will become more positive as the filter pores clog.

It is important to understand that access, return, filter and effluent pressures are true readings generated by the Prismaflex. The TMP is merely value calculated from some of these pressures according to the following equation:


Therefore, a persistent and gradual rise in TMP usually indicates that the filter is starting to clot. This will usually occur with a concurrent gradual rise in the filter pressure, with a gradual drop in the effluent pressure. If the clinician observes this trend occurring and the TMP is starting to exceed +300 mmHg, it may be worthwhile considering electively stopping treatment with that filter set and connecting a new set. This allows the clinician to return the blood in the set back to the patient, rather than wasting the volume of blood in the filter set when the filter clots completely. If there is a sudden rise in TMP with a concurrent sudden rise in return pressure, chances are that there is a kink in the return line that can be fixed with some simple troubleshooting.


  • Bellomo, R., Ricci, Z., & Ronco, C. (2001). Continuous renal replacement therapy in critically ill patients. Nephrology, Dialysis, Transplantation, 16(5), 67-72. Retrieved from CINAHL database.
  • Gambro. (2011). Gambro Prismaflex Operators Manual.
  • Life in the Fast Lane. (2015). Continuous replacement therapy circuits. Retrieved from:
  • London Health Sciences Centre. (2015). Principles of continuous renal replacement therapy (CRRT). Retrieved from:
  • Porth, C. M. (2011). Essentials of pathophysiology: Concepts of altered health states (3rd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins.
  • RENAL Replacement Therapy Study Investigators. (2009). Intensity of continuous renal-replacement therapy in critically ill patient. The New England Journal of Medicine, 361(17), 1627-1638. doi: 10.1056/NEJMoa0902413

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3 thoughts on “CVVHDF What?! Renal Replacement Therapy Simplified…

  1. Hi Joanne,

    Thank you for the awesome post! Couple of questions…
    1) If replacement is through PBP, how does it potentially change the way solutes are removed since the composition of the fluids going into the filter will be alter by the PBP solution?
    2) What situations warrant a pre filter? I normally see replacements being ordered as post..
    3) Can you elaborate on what is typically removed through convection and by diffusion?
    Thanks lots! #refusetobeaglofifiedbagchanger

    Liked by 1 person

    • Questions 1 and 2: To answer these questions, you have to understand the pros and cons between having a pre-dilution and post-dilution replacement.

      The biggest advantage that pre-dilution has is increasing filter life by decreasing the clotting potential of the blood within the filter. It does this by altering the haematocrit of the blood. If you did not have any pre-dilution (PBP) running, the haematocrit of the blood upon entry into the filter is normal at approximately 35 – 45%. That means that by the time the blood reaches the end of the filter and ultrafiltration has occurred, the haematocrit is a much higher percentage indicating that the blood is less viscous (or thicker). Thick blood has a habit of clotting more than more viscous blood. By adding a pre-dilution (PBP), you are effectively reducing the haematocrit prior to the blood entering the filter and therefore allowing a normal haematocrit with normal viscosity by the time the blood exits the filter. Consider a drink such as milo and let’s say we’re using a straw to drink it. The less water/milk you mix with the milo, the thicker it is and the more it is going to get trapped within the straw. The more water/milk you mix with the milo, the thinner it is and the easier it is going to get through the straw. The same analogy applies for the disadvantage with pre-dilution, in that the more dilute something is, the less you get of it. By using pre-dilution, you dilute the concentration gradient across the filter thereby reducing solute clearance.

      Post-dilution has the exact opposite advantages and disadvantages. The advantage is that it increases solute clearance due to an increased concentration gradient within the blood running through the filter. The disadvantage is that thicker blood clots more and you could reduce filter longevity. So the question of when pre or post dilution is warranted comes down to this: would you prefer a filter that runs for longer that has a slightly lesser potential for solute clearance (which you could combat by increasing flow rates), or would you prefer a filter that has more stop/start time with a higher potential for solute clearance while running?

      Question 3: In terms of solutes, convection tends to do better removing medium to larger sized molecules than diffusion. The image below will hopefully make it clearer for you:


      In terms of what is classified as small, medium or large:


      Hope this answers your questions. #HappyToHelpTheRevolutionAgainstGlorifiedBagChangers


      Liked by 1 person

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