| INDIVIDUALIZED RENAL REPLACEMENT THERAPY IN ARF |
| N. Lameire, Ghent, Belgium |
Chair: S. Shaldon, Fontvieille, Monaco |
C. Ronco, Vicenza, Italy |
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Prof N. Lameire
Chief Renal Division University of Ghent Ghent, Belgium
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Slide 1
Prof Lameire: Thank you. Ladies and Gentlemen good morning, Mr Chairman good morning. My task is to give you briefly an overview of the individual or indivualized renal replacement therapy in acute renal failure.
Slide 2
Before doing that let me give you my personal opinion about the management of any patients with acute renal failure, particularly the critically ill that I believe that hooking that type of patient to a dialysis machine is only one part of the management and that I think the role of the nephrologist in conjunction with the intensive care people, particularly in the critically ill patient is instrumental and that I don’t like the evolution in many units all over the world, also in Europe where the treatment and the management of acute renal failure is only in the hands of intensive care people, I think it is the collaboration between the two that is essential and there are many more things to say about management of ARF patients than the dialysis but you know that as well as I do. The indications for renal replacement therapy in critically ill patients, of course the first ones and it all started by that way, is replacing the failed renal function and we all agree that life threatening indications represent hypercholemia, acidemia, pulmonary edema, the typical uraemic complications like for example, uraemic pericarditis, we should indeed have dialysis for solute control, fluid removal and for regulation of acid-base and electrolyte status. However, under the influence of our colleagues in the intensive care unit, I learned and many of us learnt that there are other indications besides simply or simply replacing kidney function and it is helping them, were for this called by Ravi Mehta and Claudio Ronco under the name of renal support. Indeed many times we are called into the intensive care unit by the intensivists who have trouble in giving enough fluids, enough nutrition for example, because it has been calculated quite easily if you want to give enough calories and enough nutritional support to a patient in oliguria and only parenterally that with a minimum of 2.5-3 l is the absolute minimum that you can give, so often we are called to support this by additional fluid removal. Also in pure congestive heart failure we have some functional renal dysfunction we maybe called. There is some evidence that in sepsis by selecting the modality of renal replacement therapy we can manipulate the cytokines, there is still no proof that whether by removing inflammatory cytokines and anti-inflammatory cytokines we really help these patients but at least theoretically it could be helpful. We can help our oncologists during cancer chemotherapy because, as you know the Tumour Lysis Syndrome is more and more often seen with the aggressive antichemocancer therapy. We may be called to help the intensivist when the patient is in acute respiratory distress syndrome. I must tell you that at least many cases that we are called in for, for acute respiratory distress syndrome are much more often pulmonary edema and not pure acute renal distress syndrome because the patient is simply fluid overloaded, particularly when he is in oliguria and then of course, for fluid management in multi-organ failure and I think the role of the nephrologist is indeed to collaborate with the intensivist and not to be too restrictive either if they call us for advice, we should go, we should be there and help them as much as possible.
Slide 3
Now renal replacement therapies have evolved of course, on the intermittent form and the continuous forms and there has been a long debate for many years to which is best. I don’t think there is anything better. Whatever you are most familiar with and with careful monitoring your patient, I think you can use any of these modalities because it’s very rare nowadays that a patient dies in uraemia. He dies from the complications of acute renal failure, of the infections of pulmonary edema, the breathing etc. and the modality plays a role but only a minor role, we should not exaggerate the role of the renal replacement therapy as a determining prognostic factor of the patient. So the intermittent end forms of the classical ones and let me tell you right from the beginning in a critically ill patient I think we should go for daily dialysis and not consider an acute renal failure patient like we did in the past like as a chronic renal failure patient, three times a week, four hours. This in most of the cases is simply not enough. We have the intermittent forms of hemofiltration and now the new form I will dwell on in the last minute of my talk, the so-called slow extended daily dialysis, which is some modification, a combination, a hybrid form between the continuous forms and the intermittent form. We will not talk about peritoneal dialysis, not that I will exclude it and particularly in young children and babies for example, peritoneal dialysis can really be very helpful but it is rarely used in the critically ill adult patient because simply these patients are too catabolic and the clearances we can achieve are not sufficient and then we have all forms of continuous renal replacement therapy it all started with Peter Kramer on the CAVH and then it became clear that this was associated with too many complications and then we changed the access to CVVH, which is a pure continuous veno-venous hemofiltration, there is no diffusion involved it’s only convection. Then very strangely enough although this is a fantastic form of renal replacement therapy and I assume most of you are familiar with it then gradually we saw that actually besides the convection, actually people were not satisfied with the solute clearances and the fluid removal that they could achieve with these forms and they added again miraculously enough another machine and then a membrane and now the combination in most of the continuous forms is indeed with a combination of CVVH which is continuous veno-venous hemodialysis or hemodialfiltration which is the combination of diffusion, classical dialysis and convection.
Slide 4
So there are many, many forms that you can play about but actually the great, great classification is between the continuous, 24 hours a day with its advantages and disadvantages and the intermittent forms. What are these advantages? Well, I took this from a nice review a quite recently published by Doctor Fliser and Kielstein in the Current Opinion but you see here the differences, the advantages and disadvantages, you see here 3-5 hours per day, 4-7 times a week. In the critically ill I would say 7 days a week. It is more technically demanding and that is why of course, your dialysis nurses have to do this, the intensive care nurse is not able, is not technically skilled enough to do the classical intermittent hemodialysis in the intensive care unit that is of course there is a qualified dialysis staff necessary. Well the hemodynamic stability has been a long discussion whether indeed intermittent dialysis provokes more hypotensive episodes in contrast with CRRT, there is no doubt about it that there are frequent hypotensive episodes when you too aggressively ultra filter and when you start with a blood flow which is usually used in chronic renal failure patients.
Slide 5
There are some studies now showing that if you do this very gently and very slowly, particularly with the SLED technique, that actually you can avoid a lot of these hypertensive episodes.
Slide 6
The urea elimination is good, there is certainly one absolute indication for hemodialysis, this is serious hyperkalemia, that is an absolute indication you will be never be able to manage a life threatening hyperkalemia with CVVH and then the advantages are that there is on line bicarbonate dialysis production which is possible. It allows the out of unit diagnostic and therapeutic procedures. A very important topic.
Slide 7
I mean if you calculate the number of hours that the continuous forms really are applied instead of 24 hours in most of the studies they have to interrupt or be it not only for technical reasons but also because the patient needs to have CT scan has to have exploratory laparotomy etc. etc. these patients are never stable and therefore if you go for intermittent, one of the main advantages is that you can apply this for example, at night and leave enough time for all these diagnostic and therapeutic interventions.
Slide 8
There are of course, disadvantages, high machine and staff costs, labour intensive, periodic solute control with subsequent disequilibrium, all the disadvantages associated with the intermittent character. CRT normally 7 days a week, 24 hours per day, usually technically very simple although I have shown you that slowly they have been introducing end dialysate and membranes and the combination of dialysis and ultrafiltration, the operation, the monitoring is certainly, they think is simpler although it may not be as simple as that and I think the best combination is to start with the dialysis nurse, to leave the monitoring to the intensive care nurse and then have frequent contacts. Ultrafiltration is certainly slower and therefore better and I admit that there is probably an overall a maybe better hemodynamic stability.
Slide 9
The urea elimination is good although you have to respect if you do CVVH the ultrafiltration volume, I’ll come back to that to the nice study that Claudio Ronco has performed. Advantages are of course, you don’t have these swings, so it’s smooth, it’s stable and there is no need for specific infrastructure. The disadvantages are of course, the continuous anticoagulation that is required in these continuous forms and as I said the continued immobilization of the patients and don’t forget quite expensive sterile substitution solutions. Now if you go for metanalysis and I know metanalysis is a different and a difficult statistical tricky method to apply but if you do that and I remember that metanalysis has the same relation to analysis as metaphysics to physics, so it doesn’t mean that much but if you do that and these people have all done this, you see actually that overall there is no major advantage in survival or when you compare intermittent with CRRT. The last which was not included in the metanalysis, the last study here was by Paganini’s group was published quite recently in the American Journal of Kidney disease and you see again hospital mortality when they compared and they tried to match but of course, it’s not easy matching and randomising people in such a study but they tried to do that and you see that there was absolutely no difference between the continuous forms and the intermittent forms. On the other hand another study quite recently published in 2005 in Clinical Nephrology coming from Canada showed that actually although the in hospital mortality was a little bit higher in the continuous forms, when they corrected for that and when they said although it is a retrospective study that of course, there is a tendency to put the more sick patients on continuous forms, then they saw that for example, when there was multiple organ dysfunction syndrome, when they applied then intermittent forms, there the in-hospital mortality was higher than in the continuous forms. So there should be indeed individualised techniques and then another study, also very recently not included yet in the metanalysis you saw, that there was no actually statistical difference but if you restricted for the ICU population and you looked at the relative risk for death before the triage to CRT in this study versus intermittent there was clearly a tendency that CRT was indeed doing overall having better results. This was a nice study, a large number of patients and it has to be confirmed although statistically you see the one bar of relative risk is always crossed so statistically there was no difference although we cannot deny there is a tendency. Then it has been said well, due to the better preservation of the hemodynamic stability maybe the renal recovery is going to be better but again a metanalysis but only including four studies could not show again that the relative risk of non recovery or of recovery of renal function in the surviving patients of course, was not much different between intermittent and the continuous forms in this case CVVH.
Slide 10
What about hemodynamic stability? I always show the same slide and I know that I can feel that Claudio’s thinking again he’s there with the Misset study but it is as far as I know the only study that actually prospectively has looked into that about a hemodynamic tolerance. This was CVAH the older form of continuous form arterial venous hemofiltration and you see the mean arterial pressure, the maximum fall in mean arterial pressure and the percentage episodes of hypotension characterised by a drop in mean arterial pressure of more than 10 mmHg there was absolutely no difference between the CAVH and the intermittent hemodialysis despite the fact that there was also no difference in the need of adrenergic drugs.
Slide 11
In these patients dobutamine, dopamine of epinephrine it was all the same dose. So the only study that really has looked, randomised and crossed over by Misset in France looking at hemodynamic stability could not detect that. That doesn’t mean that there is no difference but at least as far as I know there is no firm evidence from the literature that it is better.
Slide 12
What about the dose? A landmark study and I don’t’ say that because he’s my Chairman but indeed has been performed by Claudio Ronco in Vicenza where they have looked at the effect of the dose of continuous renal replacement therapy, that is the volume that you ultra filter. What he could show was that indeed when you have to give at least a dose of 35 ml/kg/hour, ultrafiltration when you use CVVH in these patients and you see then a clear difference, a clear better survival in these patients. We all had the tendency in the past to give too low ultrafiltrations.
Slide 13
When he then increased the dose to 45 there was no further benefit as far as survival in the general overall ICU population where ARF was concerned but when he looked, made a SIP analysis in the septic patients and there we may come to the manipulation of the cytokines, when you indeed increase then in the septic patients to 45, then there was a clear survival benefit. And I think also in Ghent we believe that study, we always believe the studies by Claudio and we now are indeed aiming and I could recommend you if you do CVVH indeed try to achieve 35 ml/kg/hour. I must say though although it is a completely different population, these were post cardiac surgery patients it’s another population, better prognosis anyway but when they tried to apply the same system and they compared high volumes early or late start with a normal, I’d say a normal volumes they could not find a difference in Amsterdam in these post cardiac surgery patients with acute renal failures. So I would say I certainly believe there’s a dose effect but in this kind of population which is a much better population in the sense that you’re much less critically ill than the population that Claudio studied there was no such clear effect.
Slide 14
What about intermittent hemodialysis? We all are familiar with the famous Schiffl Study not unexpected I must say when I read this paper in the New England said why did I not do this study indeed not unexpected. You see that when he compared the classical alternate day hemodialysis as applied to a chronic renal failure patient to daily hemodialysis that the mortality was significantly lower and that also the resolution of acute renal failure was certainly shorter in the daily hemodialysis. The fact is though that I believe that alternate day in critically ill ARF patients is simply not enough and so what if you were to be aggressive towards Doctor Schiffl which I don’t intend to do, you could say he compared bad dialysis with good dialysis so no wonder he found that good dialysis was better.
Slide 15
What about slat? SLED is now becoming more and more popular. In fact it’s a hybrid situation, we learned from the experience of the continuous forms and the others said well intermittent has also some advantages. So you see the number of hours that the patient is on the machine in CRT it’s theoretically 24 hours, let’s say that in most of the studies it’s only 20 because of interruption for technical reasons, investigations etc. it’s very rarely 24 hours. You have then the intermittent hemodialysis which is here 4 hours but then you have the SLED, SLED is indeed where you go for 6-8 slow daily what they call extended dialysis.
Slide 16
It has some advantages because first of all it offers the choice between the advantages of a classical dialysis monitor with high efficiency, low cost and high precision of ultrafiltration in combination with the advantages of CRT, it is extended, it gives you a smooth metabolic control and probably it guarantees you a better hemodynamic stability in a modular fashion using one single type that is familiar to your dialysis unit, your nurses know it very well and you have of course, now these movable and transportable machines quite handy to use in the intensive care or in the cardiac surgery unit. With a water treatment module reverse osmosis, hemofiltration capacity and you can adjust the dialysate flow as slow as you like.
Slide 17
For example, one study, and there are now many coming, compared the hemodynamic stability during extended daily dialysis versus CVVH and you see again that there was absolutely no difference in the hemodynamic, at least in the maintenance of the arterial blood pressure with the same dose or the same amount of vasopressors used in these patients.
Slide 18
You always have to correct for that I mean hemodynamic stability can be mimicked if you give a higher dose of a vasopressor but that was controlled in this.
Slide 19
One handy machine and it’s certainly not my intention to make here publicity for a given company but we use it also and it is becoming more and more popular in Europe, is the Genius machine. This is a single path dialysis machine actually the concept is quite old. What is tricky and what is genius and that’s where the name comes from is that there is the fresh dialysate is here and the dirty, used, spent dialysate is there and there is no mixture and indeed we checked it several times for many hours, there is no mixture and this is due to differences, slight differences in temperature, slight differences in the density of that fluid and then you have one pump and so you have the same blood flow with the same dialysate flow, so you can go for six hours, 8 hours, 12 hours and the dialysate is contained in this container which is now available for 90 litres so easily you can, this is transportable, you can use this machine quite freely. There are a number of other advantages. You should read about this and ask the company to give you some explanation for that. Also what is maybe important in the maintenance of the stability, the circuit is cooling down a little bit and may provoke you a better stability.
Slide 20
This has been done here using this machine, you see there was no difference in hemodynamic stability.
Slide 21
The factors effecting please go back the choice of renal replacement therapy are patient factors, the underlying disease process, the indications for dialysis and the location of the patient and the duration of treatment that you can afford.
Slide 22
There are also technical factors the need for high urea clearance. Specific indications for CVVH are for example, hepatic failure and acute renal failure and the ease of application and your local possibilities.
Slide 23
So in treatment cost there is no doubt about it that CRT is more expensive than intermittent.
Slide 24
So I think and this is my last slide that actually there are a number of indications and in most of these indications SLEDS can be used and I think if the nephrologist wants to keep the therapy and the dialysis therapy of these critical patients enhanced the SLED modality maybe one way for helping, combining the advantages of continuous with the advantages of intermittent forms.
Thank you very much for your attention.
Chairman: Thank you Norbert.
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