This chapter is related to the aims of Section H3(ii) from the 2023 CICM Primary Syllabus, which expects the exam candidate to "understand the pharmacology of renal replacement fluid". It is of course unclear what the college might have meant by this learning objective (were the trainees supposed to describe the principles of renal replacement fluid?). Interpreted generously one could accept that the general thrust is towards explaining what the dialysate and replacement fluid contain, what the purpose of these constituents is, and what are the consequences of modifying their composition would be.
- Dialysate is the fluid medium used to exchange solutes with the blood in a dialysis filter
- Replacement fluid is the fluid used to dilute the post-filter blood in haemofiltration, restoring volume and buffering the blood as it returns to the patient.
- In CRRT, these fluids are usually supplied as 5000ml bags, pre-packed and sterilised.
- The composition of these fluids is close to the composition of extracellular fluid
- The major difference is that these fluids are usually free from potassium and phosphate
- Most often the buffer used is bicarbonate, but lactate acetate and citrate are other options.
- Other major characteristics expected of dialysate and replacement fluid are that they are sterile and warmed to body temeperature.
The book chapter by Aucella et al is probably one of the better resources for this topic; it is found around p. 287 of Ronco Bellomo and Kellum's Acute Kidney Injury (2007). Another excellent reference is the chapter by Davensport (2001). Unless otherwise referenced, these were the two main resources used to create this summary chapter. Additionally, Richard Veech (1988) offers an excellent historical note which describes the development of dialysis fluids in terms of the complications they caused, and how these influenced the changes in composition of commercially available products.
Dialysate is the fluid which is infused into the filter; by convention everything that comes out of the filter is called effluent, even though it might be essentially unchanged in its composition. The medical dictionaries define dialysate variably. There is an official ADQI definition:
"A solution of variable composition designed to facilitate diffusion of solutes into the ultrafiltrate-dialysate compartment of the hemofilter or hemodialyzer."
Replacement fluid is the fluid which is used to restore volume, buffer base and a normal haematocrit to the post-filter blood in haemofiltration and haemodiafiltration. The use of replacement fluid is what defines haemofiltration as a distinct modality from SCUF. The difference between ultrafiltration rate and replacement fluid rate is the total fluid removal rate. ADQI define replacement fluid as follows:
"Replacement (substitution) fluid: A solution of variable composition, often physiologic, used to replace large volumes of ultrafiltrate during hemofiltration or hemodiafiltration. Replacement fluid may be given as predilution or postdilution."
In the design of dialysate solutions, only a few basic characteristics are expected of the product:
These matters make it seem as if there is a significant amount of engineering required in the design of these fluids. That is not the case. For example, when Kramer et al (1977) were performing pioneering CAVH to remove fluid from heart failure patients, they used unmodified Ringer's lactate as replacement fluid, straight off the shelf. In these early years and more recently in resource-poor environments people had used peritoneal dialysis fluid as dialysate (as a source of large and readily available volumes of sterile fluid). This is obviously not idea, as the high concentration of dextrose in such makeshift dialysate produces haemodynamic and metabolic disturbances (Celik et al, 2009).
Generally, modern dialysate contains:
Both phosphate and potassium are usually elevated in renal failure, which is why these fluids usually do not contain any potassium or phosphate. Potassium is conventionally added to the bags of dialysate (say, 20mmol per every 5L bag). Phosphate is usually replaced in some way while the patient is on dialysis.
Buffer is the alkaline component of dialysis fluids. The role and influence of buffers in dialysis is significantly dependent on the technique of dialysis which is used. The following diagram illustrates how this works.
In nongraphical form:
There being no THAM in dialysate solutions available on the market currently, the choice of buffers in dialysate is limited to:
Acetate seemed like a good choice for an easily metabolised buffer base. Unfortunately, about 35-45 mmol of buffer is required. At such doses, acetate acts as a vasodilator. Bradley et al (1988) were able to demonstrate that the MAP of patients being dialysed with acetate drops more than with other buffers.
Bicarbonate seems like a natural choice, given that this is the normal buffer of the extracellular fluid. However, it's presented a bit of a challenge. It does not have the same shelf life (being prone to bacterial colonisation) and it tends to react with calcium and magnesium, producing insoluble precipitates. It was the first buffer used for "bath" dialysis in rotating drum dialysers, but because of the aforementioned problems it was superceded by acetate in the mid-1960s. Ultimately, with the advent of better mixing equipment, bicarbonate again became a valid choice for intermitten haemodialysis (i.e. ultraclean water has bicarbonate added too it at the point of use).
Lactate has long been used as a buffer for peritoneal dialysis fluids and because these were some of the first dialysate fluids it became a dialysis buffer. Lactate is usually added to the bags as a racemic mixture (its cheaper than separating the enantiomers). Of these enantiomers, L-lactate is well behaved and metabolised by all normal livers, whereas D-lactate is an unnatural product which is broken down slowly by skeletal muscle. Ergo, in peritoneal and haemodialysis with racemic lactate buffer, D-lactate may accumulate.
Nothing is also a valid option. in buffer-free dialysate, there is no buffer in the actual fluid - instead, bicarbonate is infused post-filter according to whatever serum concentration you would prefer to generate.
Citrate given as a part of pre-blood-pump predilution fluid can be viewed as a buffer, insofar as it is an anion the metabolism of which contributes to the total increase of the strong ion difference. However, it is usually present in very small concentrations only (usually no more than 3 mmol/L, all that is required to chelate the calcium in the blood) and so its role in alkalinising the patient is probably minor, relative to other buffers.
Generally speaking, today's dialysate solutions use mainly lactate or bicarbonate buffer. Bicarbonate is probably the preferred option, Given that it appears to be better tolerated haemodynamically than lactate (Barenbrock et al, 2000). Bicarbonate dialysate is generally of a physiologic pH, whereas lactate buffered fluid is usually acidic. This means the lactated dialysate is less likely to harbour bacteria.