Slide 1

Ok thank you very much Ray. On behalf of my colleagues Ali Basci and Francesco Pizzarelli I’ll give you a short summary on the guidelines on haemodynamic instability.

Slide 2

I’ll do so in order to make it a little bit livelier from a pathophysiological point of view.  Because there’s no single parameter which contributes solely to dialysis hypotension but it starts of course all with a decline of blood volume due to the ultrafiltration leading to a reduction of venous return, a reduction of ventricular filling and in the end a reduction in cardiac output and blood pressure. However, there are several compensatory mechanisms normally during a decline in blood volume which may maintain blood pressure and that is why an increase in systemic vascular resistance by constriction of your resistance vessels and by venoconstriction which mobilises haemodynamically inactive blood through the large veins into the heart. Moreover, during a decline in ventricular filling your heart rate increases and also your cardiac contractility increases in order to maintain your blood pressure. As I’ll show you, there are several factors related to the dialysis treatment which can interfere with these normal haemodynamic responses. But first about the decline in blood volume and of course, the most important factor influencing the decline in blood volume is the ultrafiltration. On many dialysis monitors there are smart methods available to modulate the ultrafiltration during dialysis and there are several profiles, I’ll show you some of them later, which can be used in an attempt to reduce IDH.

Slide 3

I’ll come now to the first guideline which may sound a little bit enigmatic in a way because it says pulsed ultrafiltration profiles should not be used for the prevention of IDH. Of course, you may ask yourself but ok what about the other ultrafiltration profiles and as I’ll show you, there is actually conflicting evidence about these other profiles which precluded us from making firm recommendations.

Slide 4

But first why would we want to do ultrafiltration profiling? Actually this is also based on pathophysiology. At the beginning of dialysis a patient is assumed to be over hydrated and your interstitial tissues are well hydrated and pressure’s relatively high. So when you remove plasma water by means of ultrafiltration and your interstitial tissues are well hydrated, you get a movement of blood from the interstitium into the intravascular space and as you can see on the right part of the slide, you have actually very little decline in blood volume because the plasma water which has been removed is being refilled. However, if your interstitial volume is very fluid depleted as when the patient is under hydrated, you will not get any refill anymore from the interstitial tissues into the intravascular space and your blood volume will decline rapidly.

Slide 5

Here’s where especially a linear decrease in profile might be helpful because here at the start of dialysis the patient is still over hydrated and you apply a high ultrafiltration rate and at the end of dialysis the patient’s under hydrated and you apply low or zero ultrafiltration rates and actually in one study in the AJKD of 2000 this approach would appear to be of help. You see here this is a standard treatment, this is the profile treatment and you see there’s a reduction in IDH. Whereas, with the use of these alternating profiles, alternating very rapid ultrafiltration rates, zero ultrafiltration rates which are actually detrimental in the prevention of IDH. These are actually I should clarify this solely ultrafiltration profiles to show there’s no sodium profile in these profiles which were described in this study.

Slide 6

However, the linear decrease in ultrafiltration profile which worked so well in the study of Donauer did not work at all in another recently reported randomised study from Korea in which you can see no difference in the incidence of IDH during the control, between the control treatment and the ultrafiltration profile whereas, other manoeuvres which I’ll discuss later were of help.

Slide 7

There’s also a very easy way actually to module your ultrafiltration and to decrease your ultrafiltration rate and that’s by simply increasing dialysis time and that’s through the following guidelines that recommend an increase in dialysis frequency or a prolongation in dialysis time in patients with frequent episodes of IDH, so these patients should not be dialysed for too short periods of time. Based on several studies of which one randomised study published in NDT in 1996 in which there was a reduction in IDH when the treatment time was prolonged from 4-5 hours.

Slide 8

Also recent data from the DOPPS showed that in patients who were treated with high ultrafiltration rates the risk of IDH was increased by 30% which was significant and even which is quite interesting of course that all cause mortality was even also significantly increased in patients with high ultrafiltration rates. But of course, this is observational data and you cannot deduce a real causal relationship from this but it’s quite interesting of course.

Slide 9

Now, about dialysate sodium and sodium profiling. This is always quite a controversial issue. There’s no doubt and this is also acknowledged by the working groups that sodium profiles and high sodium dialysate are a effective in reducing IDH but as I’ll show you, we dare not recommend them because they have also an increased risk of side effects so there’s a price to pay when you use sodium profiling or high dialysate sodium.

Slide 10

But first why do they work? They work actually because high dialysate sodium increases the tonicity of the plasma water compartment by influx from the dialysate into the plasma water which attracts a volume from the intracellular through the interstitial space. So it maintains blood volume better compared to low sodium dialysis in which there’s an outward movement of water from the intravascular space into the intracellular compartments.

Slide 11

Here is one of the many studies which show the efficacy of sodium profiling in the prevention of IDH. This is from KI 2001. Here again the standard treatment on the left part and here the sodium profiles and high sodium dialysis which were associated with 50% risk reduction in IDH. So it would seem quite nice. But also please note and I’ll discuss this later that there was no difference between the sodium profile and cool dialysis treatment.

Slide 12

Now about side effects and I have one slide on this. This is a slide from Korea from a group who did quite some work on sodium profiling and what it shows, maybe at the back of the hall you cannot see quite clearly, but that there is a linear relation between the mean dialysate sodium concentration of the dialysate and interdialytic weight gain. The same holds true for 24-hour blood pressure measurements and mean dialysate sodium. So yes, sodium profiles are effective certainly at least in the short-term. There aren’t really long term studies on sodium profiling but they have a price to pay and that’s why we didn’t recommend them routinely.

Slide 13

Now moving on from the blood volume part to the vascular reactivity part. As I’ve already told you, normally during a decline in blood volume we have several compensatory mechanisms which maintain both systemic vascular resistance by means of constriction of the resistance vessels, the arteries and the arterioles and by means of constriction of the venous system which mobilises blood from the peripheral tissues back into the heart. This normal vascular response which in very healthy people can tolerate up to a decline in blood volume of 20 % is not maintained during dialysis.

Slide 14

There’s actually an interesting phenomenon which may contribute to this insufficient response and that’s an increase in core temperature, as you can see here in the bottom part of the slide, during standard dialysate temperatures and here you can see that the dialysate temperature can even increase by 0.5 to 1°C during a dialysis session.

Slide 15

This can have actually pronounced haemodynamic effects, why? It’s because of the following. Instead of the normal vascular response which you would expect from a haemodynamic point of view due to the decline in blood volume your increase in core temperature leads to vasodilation of the skin blood vessels in the veins and in the peripheral arteries. This counteracts the thermal response, counteracts the normal vascular response to a decline in blood volume, actually kind of a small heat stroke you could call it. Also NO seems to be involved I will not go into further detail but sufficiently to say that the thermal effects during dialysis may interfere with the normal vascular response to hypovolemia.

Slide 16

But luckily it’s quite easy to modulate the thermal response and that’s why simply reducing the dialysate temperature and that’s what this guideline is about supported also by a lot of evidence that we advocate to reduce dialysate temperature or use isothermic treatments, I won’t discuss these further but you can read it in the guidelines, that they should be prescribed in order to prevent IDH in susceptible patients but also in order to prevent shivering which is an important side effect, you should not really go too low and certainly should not go below 35 °C.
So what we advise is to go in consecutive sessions to go lower until your effect is reached. So when your effect is reached with 36.5°C, you should not go any lower.

Slide 17

Here is a result of a metanalysis which shows actually that in nearly all studies in which cool dialysis was applied you have a reduction in IDH which amounts up to a 3-fold reduction in the odds for IDH.

Slide 18

What about convective techniques then? Because they also are quite effective in reducing IDH. Actually, it’s very interesting that during convective techniques also thermal factors appear to play a role. This is the temperature in the venous line of the extracorporeal circuit. This is haemodialysis and you see that during online haemodiafiltration even if you use the same temperature of the infusion fluid and the dialysate you get a decline in temperature in the extracorporeal circuit and this is likely because of additional heat loss through the infusion lines. So haemodiafiltration techniques, there are many reasons why you would want to prescribe them and haemodynamic instability can be one of them but it’s actually in this regard that it may be seen as a possible alternative to cool dialysis. I’ll show you one.

Slide 19

Here you see the haemodynamic instability during standard haemodialysis in black compared to online haemodiafiltration. You see there’s a great reduction in IDH with online HDF. However, in this study the authors modelled the online HDF for the thermal effects and reached the same effects as during haemodialysis. Both of the thermal effects I must say reversely during haemodialysis to obtain the same thermal effects compared to haemodiafiltration and what you can see is there is absolutely no difference in haemodynamic instability between anymore between both techniques. So yes convective techniques work and there can be many reasons to prescribe them, one of them is haemodynamic instability but you cannot really expect more haemodynamic reduction in haemodynamic instability compared to cool dialysis that’s what we wanted to make clear by this guideline.

Slide 20

So in order to wrap up the haemodynamic effects with cool dialysis or convective techniques you prevent the increase in core temperature leading to a normal vascular reactivity and less risk of IDH.

Slide 21

I’ll come now to my last part of the talk and this is about the cardiac contractility and the adverse controversial effects of dialysate calcium. Why is this so important? Because the contractility of the cardiac smooth muscle cells is depending upon calcium influx and normally when your stroke intraventricular filling declines, your cardiac contractility should increase in order to maintain your cardiac output.

Slide 22

This is a little bit, of course, a compromise this guideline and it states that the use of a dialysate calcium of 1.50 mmol/l should be considered in patients with frequent episodes of IDH. So how do we come to 1.50? That’s actually because we certainly recognise that the K/DOQI a dialysate concentration of calcium of 1.25 is advocated and this is quite ok of course in haemodynamic unstable patients but there is a subset of patients especially with systolic dysfunction who are very sensitive for a decline in ionised calcium during dialysis, this you can see here on this slide in which patients treated with a low calcium dialysate of 1.25 had quite a significant reduction in blood pressure, whereas this was maintained during high calcium dialysate these were all patients with systolic dysfunction but we really could not advocate high calcium dialysate because what you get is quite a positive calcium balance and an increase in ionised calcium during dialysis which is, of course, an unwanted effect in view of all the data on calcium deposits in vascular walls and in the heart.

Slide 23

So, there are actually some data on 1.5, less compared to 1.75 but what is important is that the calcium balance in general is kind of neutral during a dialysate calcium concentration of 1.5 mmol/l due to the removal by ultrafiltration. This you can see here, this is the concentration of fresh dialysate compared to spent dialysate, no difference between both, between the incoming and out coming dialysate and here you see the negative calcium values with a dialysate calcium concentration of 1.25. So you see there’s actually kind of a compromise between the unwanted effects of calcium loading with 1.75 and the beneficial haemodynamic effects of somewhat higher dialysate calcium.

Slide 24

So I come now to my conclusions. We divided the recommendations into simple first line approaches such as dietary counselling, sodium restriction leading to reduction in intradialytic weight gain and thus reducing the risk of hypertension, refraining from food intake during dialysis leading to splanchnic vasodilation, use of bicarbonate as dialysis buffer because of the vasodilating and cardiac depressant effect of acetate. I discussed about a dialysate temperature and your dosing time of antihypertensive agents and dry weight should be checked.

Slide 25

In a second line approach I won’t go through them all but I talked about the reduction in dialysate temperature, the prolongation of dialysis time and the calcium in the dialysate. Here’s where I would like to leave it. I thank you very much for your attention.

Slide 26

Chairman: Thank you Jeroen for this excellent presentation. We have 5 minutes for questions. Are there any questions? Perhaps I could ask, at the beginning you showed these quite discrepant results by doing the same manoeuvres where some appeared to be protective for haemodynamic instability and some not, whether there are local or could be local differences related to genetics or environment or dietetics or whatsoever?

Dr Kooman: Yes, that’s different, at least with cool dialysis there might be because the protective effect of cool dialysis in some studies depends upon the pre-dialytic core temperature. Patients with uraemia often have lower pre-dialytic core temperature and the lower your core temperature is, the more your increase in core temperature during standard dialysis and especially these patients might have more benefit of let’s say cooling down the dialysate but as a whole actually in most studies this difference was not made so that’s why we recommend it actually for the whole group. With regards to ultrafiltration profiles it’s different to explain these discrepant results actually. It might be due of course to the volume state of the patient as the patient is already under hydrated at the start of dialysis for instance. Your ultrafiltration profile will not really help quite a lot in a way. But in these studies there was not really a control for let’s say volume statues by means of objective techniques. So you can’t really make sure that this was the case.

Chairman: Ok another question? If not thank you Jereon and we’ll move to the second presenter.