Continuous renal replacement therapy (CRRT)

In this discussion, CVVHDF (continuous venovenous haemodiafiltration) is the representative modality of CRRT. The "continuousness" of  CRRT makes  is a more physiologically normal method: like the normal kidney, the machine dialyses you over a 24 hr period. However, there are distinct differences between the polymer membrane and the glomerulus. Additonally, continuous renal replacement therapy  is substantially different to intermittent RRT in terms of its advantages and disadvantages. Each has some role to play in critical illness. The College of Intensive Care Medicine recognises the importance of this by frequently including questions on this issue in the final exam papers (eg. Question 19 from the second paper of 2008, Question 10 from the first paper of 2011, Question 2c from the second paper of 2001, and so forth). A brief summary of this topic can be found in the Required Reading section (Ch.3.1.2- "A comparison of renal replacement therapy modalities"); there a tabulated answer is offered. Rather than a brief summary, some sort of free-verse digression occurs here, with minimal educational value for the revising exam candidate.

Of the sources used to compile this resource, the most important was  "Critical Care Nephrology" by Ronco Bellomo and Kellum (2009). Specifically, Chapter 221 by John K. Leypoldt ("Intermittent techniques for Acute Dialysis") and Chapter 232 by Lamiere et al ("Outcome of Intermittent Dialysis in Critically Ill Patients with Acute Renal Failure").

Continuous renal replacement therapy has some characteristic features:

  • The circuit runs continuously
  • Slow blood flow rate - 100-200ml/min
  • Slow dialysate flow rate - 1000-2000 ml/hr (up to 3000, and theoretically more)
  • Sterile pre-made dialysate fluid bags are used, instead of "wall water"

The liberating absence of a clear mortality benefit

It would be important to begin this chapter with the statement that thus far there has been no consistent agreement as to whether or not CRRT has any mortality benefit in ICU patient, when compared to SLED or IHD. If one were pressed to support such a statement, one would reach for the following studies:

Why is this good? Well; in the absence of a clear mortality benefit, the intensivist is free to use whichever modality fits the physiological demands of their specific situation. There are certain haemodynamic advantages to the use of CRRT, and there are certain pragmatic advantages to the use of SLED and IHD; the absence of major mortality advantages allows us to focus on these more minor features to make a decision about which modality to use.

The advantage of physiological "normality"

The human body features a glomerulus which performs its role at a fairly constant rate, with certain protective buffers in place to ensure a regularity of function independent of blood flow rates. This organ is responsible for continuous 24 hour control of acid-base status, fluid balance and electrolyte concentration. It therefore stands to reason that any artificial organ trying to take over this role should also perform it continuously, over a 24 hour period. In this manner, one might view CRRT as a more physiologically normal therapy, more resembling true renal replacement. Of course, this is a purely theoretical consideration.

The advantage of haemodynamic stability

Haemodynamic instability in renal replacement therapy is the consequence of fluid shifts and solute shifts. The intermittently dialysed patient will have to concentrate 24-48 hours worth of renal function into a single 4-6 hour session, removing two days worth of fluid and solute all in one go. In contrast, the CRRT patient enjoys a more stable process of  fluid and solute egress.

Observe a hypothetical fluid balance graph comparing CRRT and SLED:

The constant exposure to wild changes in fluid balance is not good for anybody. Certainly, not for the patient who is already dependent on some sort of vasopressor or inotrope. The removal of a large amount of fluid from the intravascular compartment can decrease preload precipitously, resulting in greatly diminished cardiac output and increased vasopressor requirements.

Again, a hypothetical graph of noradrenaline requirements over time:

Now, this is of course a fanciful exaggeration (realistically nobody would have decided to SLED a patient who was this unstable), but it illustrates the point. This haemodynamic instability associated with intermittent techniques is more associated with conventional intermittent haemodialysis; it was perhaps somewaht unfair to use SLED in the diagram, because that "hybrid technique" is sold on the advantage of improved haemodynamic stability. Still, there is a population of critically ill patients who will not tolerate even this relatively gentle therapy.

With this information, one might begin to think that CRRT might have some sort of organ-protective effect (or conversely, that IHD has some sort of organ-damaging effect).

Decreased risk of renal injury with continuous techniques

  Bell et al (2007) have found that CRRT is associated with less chronic renal failure and IHD. This Swedish study was an audit of a large retrospective cohort (2,202 patients). The authors found that 16.8% of IHD patients went on to develop chronic "end stage" renal failure, whereas only 8.3% of the CRRT patients were affected in this way. There was no difference in 60-day mortality (illustrating that one does not die of renal failure, but with renal failure).  Similarly, a 2001 randomised controlled trial by Mehta et al found that "Chronic renal insufficiencyat death or hospital discharge was diagnosed in 17% of patients whose therapy was IHD versus only 4% of those whose initial therapy was CRRT".

One might explain this trend by assuming that the haemodynamic instability associated with IHD will subject the kidneys to cyclical ischaemic injury. Every day or two, somebody comes along and rapidly sucks out half your blood volume - of course this is going to have some effect on your renal perfusion, and if that perfusion is already marginal, the existing renal injury will be amplified.

Now, this was a study comparing the fairly brutal conventional IHD with the gentle old-fashioned CRRT. Nowadays, nobody would have IHD in the unit, with the wide availability of hybrid therapies such as SLED. This raises the question: does SLED  inherit the kidney-trashing effect of IHD? Kitchlu et al published in BMJ Nephrology in 2015, with a 158 patient prospective cohort comparing SLED to CRRT.  Persistent RRT dependence at 30 days was one of the secondary outcome measures. There was no difference found in this variable, prompting the conclusion that SLED, at least, is reasonably safe in terms of exacerbating renal injury.

The illusion of improved organ perfusion

Based on this. one might generalise and say that the patient on  CRRT would have better organ perfusion overall, given that they are not being subjected to cyclical dehydration. This notion stems from the idea that intermittent haemodialysis exposes the tissues to regular low-flow states, worsening organ system function and delaying recovery.

However, it has not always been found to be so.

For instance, a 1996 study by Van de Schueren demonstrated an increase in systemic oxygen consumption associated with IHD, as well as intestinal intramucosal acidosis. Those were eleven classical ICU patients - three AAAs, some cardiogenic shock, multi-organ-system failure with sepsis, and so forth.  In contrast, John et al (1999) exposed 20 septic shock  patients to CRRT and 10 to IHD, measuring regional splanchnic perfusion variables (such as pHi and pCO2i) and finding no difference in splanchnic perfusion between the groups. The patient group, however, was somewhat different - in contrast to the MOSF patients from the Van de Schueren study, this group was predominantly composed of pneumonia (24 of 30 patients).

Some might say that the microcirculation in sepsis is already so deranged that macrocirculatory phenomena such as dialysis fluid shifts will play no role in worsening the already crappy splanchnic perfusion. This would explain the splanchnic sensitivity to IHD in cardiogenic shock (the microcirculation should be intact).

Some might also say that these variations in splanchnic microcirculation are so subtle as to be clinically meaningless. The pragmatic intensivist would point out sarcastically that it is not in his/her routine practice to titrate therapy according to gastric mucosal-arterial Pco2 gradients. Even nerdy studies (Jacob et al, 2001) conclude that "reduction of systemic and splanchnic blood flow undetectable using traditional clinical signs". Again we are reminded that there is no mortality difference between CRRT and IHD. What point, then is there to worry about these piddling minutiae?

These disagreements between studies make it difficult to support the use of CRRT on the grounds of preserving organ perfusion. Or, rather, they make it difficult to argue in favour of continuing CRRT in a patient whose haemodynamic stability permits the use of SLED.

The minor disadvantages of CRRT

Haemodynamics and renal outcomes are the most important decision-changing points. Lesser disadvantages of CRRT also exist, and should be mentioned at least in passing.

Inefficient dialysis: CRRT uses a slower countercurrent dialysate flow rate, which may result in a slightly lower solute clearance. Not only that, but in practical terms the continuous therapy ends up interrupted during the course of a day for transport, imaging, surgical procedures, filter loss et cetera, resulting in an overall reduction of daily solute clearance.

Anticoagulation: though the blood flow rate in the circuit is not much lower than in SLED or IHD, it still tends to be a little lower. Anticoagulation is required to keep the circuit alive, which exposes the patient to all sorts of bleeding risks

Immobility: though basic nursing care including regular turns and repositioning is not inhibited by CRRT, it does confine the patient to their bed for the entire period. Not only that, but they need to keep reasonably still, because figeting and moving around on the bend will cause access issues and irritating machine alarms. The need to keep still is coupled with the need for increased sedation, and therefore longer mechanical ventilation weaning, longer ICU stay, and higher vasopressor requirements (due to the effects of sedation). Thus, the patient who would be unaffected by all this is the horribly sick patient who is already going to be heavily sedated and ventilated.

Hypothermia: The circuit is constantly exposed to ambient room temperature and the cold dialysate fluid; heat is exchanged during the course of CRRT, and the patient ends up hypothermic.

Increased nursing workload: when compared to IHD and SLED, the machine maintenance workload is greater because the apparatus is in use for longer periods, and because there is a constant need to hang new bags of dialysate and remove full bags of effluent. This internal guidelines document from The Alfred refers to the setup and maintenance of the Prismaflex circuit. It is written for bedside nurses, and reveals the insanely complex dance they must perform in the service of a CRRT patient. According to the senior ones, this is actually a lot better than it used to be. 

Increased cost: Those 5L bags of proprietary "Wonder-lyte Haemo-awesome 22H" dialysate fluid are not cheap, being sterile packaged electrolyte solution.


 "Critical Care Nephrology" by Ronco Bellomo and Kellum (2009):

Chapter 221 by John K. Leypoldt ("Intermittent techniques for Acute Dialysis")

Chapter 232 by Lamiere et al ("Outcome of Intermittent Dialysis in Critically Ill Patients with Acute Renal Failure").

The Gambro and Fresenius websites have also been an excellent source of information.

Bell, Max, et al. "Continuous renal replacement therapy is associated with less chronic renal failure than intermittent haemodialysis after acute renal failure." Intensive care medicine 33.5 (2007): 773-780.

Vinsonneau, Christophe, et al. "Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial." Lancet 368.9533 (2006): 379-385.

John, Stefan, et al. "Effects of continuous haemofiltration vs intermittent haemodialysis on systemic haemodynamics and splanchnic regional perfusion in septic shock patients: A prospective, randomized clinical trial." Nephrology Dialysis Transplantation 16.2 (2001):320-327.

Rubinger, Dvora, et al. "Predictors of haemodynamic instability and heart rate variability during haemodialysis." Nephrology Dialysis Transplantation 19.8 (2004): 2053-2060.

Kielstein, Jan T., et al. "Efficacy and cardiovascular tolerability of extended dialysis in critically ill patients: a randomized controlled study." American journal of kidney diseases 43.2 (2004): 342-349.

Mehta, Ravindra L., et al. "A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure." Kidney international 60.3 (2001): 1154-1163.

Diltoer, M., et al. "Intermittent hemodialysis in critically ill patients with multiple organ dysfunction syndrome is associated with intestinal intramucosal acidosis." Intensive care medicine 22.8 (1996): 747-751.

Jakob, Stephan M., et al. "Splanchnic perfusion during hemodialysis: evidence for marginal tissue perfusion." Critical care medicine 29.7 (2001): 1393-1398.

Kitchlu, Abhijat, et al. "Outcomes of sustained low efficiency dialysis versus continuous renal replacement therapy in critically ill adults with acute kidney injury: a cohort study." BMC nephrology 16.1 (2015): 127.

Schefold, Joerg C., et al. "The effect of continuous versus intermittent renal replacement therapy on the outcome of critically ill patients with acute renal failure (CONVINT): a prospective randomized controlled trial." Crit Care 18.1 (2014): R11.

Kellum, John A., et al. "Continuous versus intermittent renal replacement therapy: a meta-analysis." Intensive care medicine 28.1 (2002): 29-37.

Antoun, Tania Abi, and Paul M. Palevsky. "THE CLINICAL APPLICATION OF CRRT—CURRENT STATUS: Selection of Modality of Renal Replacement Therapy." Seminars in dialysis. Vol. 22. No. 2. Blackwell Publishing Ltd, 2009.

Rabindranath, K., et al. "Intermittent versus continuous renal replacement therapy for acute renal failure in adults." Cochrane Database Syst Rev 3 (2007).

Zhang, Ling, et al. "Extended Daily Dialysis Versus Continuous Renal Replacement Therapy for Acute Kidney Injury: A Meta-analysis." American Journal of Kidney Diseases (2015).

Vanholder, Raymond, W. I. M. Van Biesen, and Norbert Lameire. "What is the renal replacement method of first choice for intensive care patients?." Journal of the American Society of Nephrology 12.suppl 1 (2001): S40-S43.