Question 30

With respect to continuous renal replacement therapy (CRRT) in the critically ill:

a) Draw a labelled diagram to represent the circuit for continuous veno-venous diafiltration (CVVHDF).

b) Define the following terms and briefly explain their relevance in CRRT:

i. Dialysis dose

ii. Transmembrane pressure

iii. Sieving coefficient

iv. Filtration fraction

a)
Diagram expected to be appropriately labelled and depict access and return lines, filter, dialysate, effluent and replacement fluid and include sites of pressure measurement and pumps

b)
(i)
Dialysis dose is equivalent to the effluent rate in ml/kg/hour.
Effluent rate = ultrafiltration rate for haemofiltration (CVVH)
= dialysis rate for haemodialysis (CVVHD)
= ultrafiltration rate + dialysis rate for haemodiafiltration (CVVHDF)
Dialysis doses (effluent rates) greater than 25 ml/kg/hr have not been shown to improve outcome but
it is reasonable to run at higher rates to compensate for downtime when the circuit has clotted or
been taken down to allow for patient transfer/treatment

(ii)
Transmembrane pressure (TMP) = (Filter pressure + Return pressure) / 2 –
(Effluent pressure)
High TMPs with normal return pressures indicate a problem with the filter. High TMPs with high
return pressures indicate a problem with the return line +/- the filter
Different filter membrane properties can produce different ultrafiltration rates for the same TMP.
Filters that are highly permeable to water (high flux membranes) allow more water to cross the
membrane for a given TMP.

(iii)
Sieving coefficient (SC) = Ultrafiltrate concentration / Blood concentration
SC is a measure of how effectively a substance is removed through the filter.
SC = 0 means the substance is not filtered at all e.g. protein sized molecules
SC = 1 means the substance is completely filtered e.g. urea, creatinine
SC depends on solute molecule size, protein binding and filter porousness

(iv)
Filtration fraction = Ultrafiltration rate / Blood flow rate* and should  0.25
* Strictly plasma flow rate (blood pump rate x 1 – Hct)
I.e. fraction of plasma that is removed from blood during filtration
Higher filtration fractions predispose to filter clotting through haemoconcentration.

Discussion

A diagram which could " to be appropriately labelled and depict access and return lines, filter, dialysate, effluent and replacement fluid and include sites of pressure measurement and pumps" exists on this site, and is reproduced here:

Because this diagram was not produced by Gambro or Fresenius, one should not hang their reputation on its accuracy. Also, an omission has been pointed out by the readers - blood warmers do not appear on the diagram. The position of blood warming coils on this device is in two usual places: on goes on the dialysate circuit before the dialysate pump, and the other goes on the blood circuit at the very end of the return line, after the pressure gauge.

The definitions and their relevance to CRRT:

Dialysis dose

Theoretically:

• Definition of "dose" in CRRT is volume of blood "purified."
• Measure of "dose" in CRRT: clearance rate of a representative marker solute.

Practically:

• Dialysis dose is equivalent to the effluent rate in ml/kg/hour.
• Effluent rate is the ultrafiltration rate for haemofiltration (CVVH), or the sum of ultrafiltration rate and dialysis rate for CVVHDF

Relevance to CRRT:

• Prescribed dose is the effluent rate
• No benefit in outcomes with doses in excess of 25ml/kg/hr
• Practically, higher doses may be necessary to compensate for circuit downtime

Transmembrane pressure

Definition

Transmembrane pressure (TMP) = (PF + PR) / 2 – PE

Where

PF = Filter pressure

PR = Return pressure

PE = Effluent pressure

Relevance to CRRT:

• High TMP with normal return pressure suggests there is a filter problem
• High TMP with high return pressure suggests either the filter or the return line are the problem
• At any given TMP, the actual ultrafiltration rate will vary for membranes with different permeabilities

Sieving coefficient

Definition

Sieving coefficient (SC) = Ultrafiltrate concentration / Blood concentration

Relevance to CRRT:

• The sieving coefficient of any given molecule determines the success of its removal by CVVHDF
• SC depends on numerous factors, and is different for each molecule.
• Some of its determinants include:
• Molecule size of the solute
• Protein binding of the solute
• Charge of the solute and of the filter membrane
• Size and number of pores in the filter membrane

Filtration fraction

Definition

Filtration fraction = Ultrafiltration rate / Blood flow rate

more accurately:

Filtration fraction = Ultrafiltration rate / (blood pump rate × (1 – Haematocrit))

Relevance to CRRT:

• The filtration fraction is literally the fraction of plasma which is removed from blood during haemofiltration
• The ideal filtration fraction at a haematocrit of 0.30 is around 0.25
• Anything higher than this increases the risk of filter failure due to haemoconcentration.
• A higher TMP increases the filtration fraction
• A higher blood oncotic pressure decreases the filtration fraction

References

Bellomo, Rinaldo, and Claudio Ronco. "Nomenclature for continuous renal replacement therapies." Critical Care Nephrology. Springer Netherlands, 1998. 1169-1176.

Locatelli, Francesco, et al. "Dialysis dose and frequency." Nephrology Dialysis Transplantation 20.2 (2005): 285-296.

Claure-Del Granado, Rolando, et al. "Effluent volume in continuous renal replacement therapy overestimates the delivered dose of dialysis." Clinical Journal of the American Society of Nephrology 6.3 (2011): 467-475.

Clark, William R., et al. "Dose determinants in continuous renal replacement therapy." Artificial organs 27.9 (2003): 815-820.