This remains a mystery to me. As I’ve noted we do an 8 hour nocturnal run on a 2008K (regular, not home) at UF rates from 50 to 150 or so, TMP of 10-20 and always hit our dry weight target +/- 0.1 kg with never a TMP alarm. I did note, as Pierre suggested, that Fresenius instructions include, “A minimum ultrafiltration rate of 300 mL/hr during dialysis traetment is recommended with Hemoflow High Flux dialysers.”
Mel
First, please let me apologize in advance for what will be a long winded explanation! This is truly a complicated issue, and is not well understood even by many professionals.
The minimum UF rate of 300 ml/hr is something that came about when the dialysis industry converted from “conventional” dialyzers to" high flux" dialyzer in the late 80’ to early 90’s. Because high flux dialyzers are much more porous, there was a concern that dialysate contaminated with bacteria or endotoxin could be pushed into the blood if the dialysate pressure was higher than the blood side pressure.
If you can open the attachment I added to the post, the next part will be easier to understand. Also please note that these numbers are not exact, and will be different for every patient and dialyzer, they are just and example to help explain the concerns.
As blood goes through a dialyzer, the pressure decreases. This means that if your venous pressure is 150 mmHg, then the pressure at the arterial end of the dialyzer is approximately 250 mmHg, and the average blood compartment pressure is 200 mmHg. As dialysate goes through the dialyzer, its pressure decreases as well, but not as much as blood because it is a thinner fluid. If the UF on the machine is off, or set to 0, than the TMP is zero as well. This means that the average dialysate compartment pressure would have to be 200 mmHg to equal the blood compartment pressure. So to maintain an average pressure of 200, the dialysate would enter the dialyzer at 225 mmHg, and exit at 175 mmHg.
Blood and dialysate run in opposite directions in the dialyzer. In this case on the venous end of the dialyzer the pressure on the blood side is 150 mmHg, and the dialysate is 225 mmHg. Fluid will move from a higher pressure to a lower pressure, so dialysate is moving into the blood stream (this is called backfiltration) at the venous end of the dialyzer. On the arterial end, the dialysate pressure is 175 and the blood pressure is 250, so fluid is moving from the blood compartment into the dialysate. With the UF rate (and TMP) at zero, the amount of fluid entering the blood will be equal to the amount being removed, so the is no change inpatient weight.
When many dialysis professionals realized that backfiltration was occurring they were very concerned. The dialysis manufacturers came up with a recommendation of setting a minimum UF of 300 ml/hr to prevent it from happening. His made sense to most of us, and we adopted this as policy and went on with performing high flux dialysis.
In reality, a minimum UF of 300 makes very little difference. In the above example, if the patient was on an F80 dialyzer with a KUF of 60 ml/mmHg/hr the TMP would be 5 mmHg. There would then have to be an average dialysate pressure of 195 mmHg. On the venous end, the pressure would be 220, but the blood side would still be 150, and fluid would still move from the dialysate to the blood. To prevent backfiltration, you would have to have enough TMP to reduce the dialysate pressure on the venous end to the same as the blood side pressure, in this case it would be 150 mmHg. That would make the average dialysate pressure 125 mmHg. With the average blood side pressure at 200 the TMP is 75. That would mean that the UF rate would have to be at least 4500 ml/hr to prevent backfiltration. The reality is that backfiltration occurs during every high flux dialysis treatment. There have never been any problems associated with it, and we have done millions and millions of treatments.
TMP monitors on current dialysis machines are there to monitor gross changes in pressure due to a malfunction of the UF system. They are not precise as far as the display goes: often you have an actual TMP of 5-10 mmHg, and most TMP monitors move in increments of 20 mmHg. They do serve the purpose for which they were intended, but it can be frustrating when you get a lot of TMP alarms. (that is another longwinded explanation!)
I hope this helps!
Curt
Curt,
This is very helpful and very clear – thank you! Several questions occur to me:
While great emphasis is placed on water purity strict aseptic measures are not observed with acid or bicarbonate. If backfiltration is occuring (and it must be applying your analysis to our numbers) what is preventing pyrogens from the acid/bicarb route from contaminating the blood? I recognize that there is a large quantity difference between water used and acid/bicarb used in formulating dialysate, but this seems like a weak answer. Molecular size seems similarly weak as one of the arguments for lengthy dialysis is that the middle molecules will be removed given a long enough time.
Since only low UF rates are required with nocturnal dialysis and since treatment time probably far exceeds what is required for toxic molecule removal would we be better off to go back to low-flux dialysers?
I assume the original concern of nephrologists over the consequences of backfiltration with high flux dialysers must have been dispelled by careful research. Are you aware of the supporting studies?
Mel
Mel,
The water system is carfully monitored for bacteria contamination, and so is the dialysate, which is the water mixed with the concentrates. Standards for dialysate purtiy are developed by the Association for the Advancement of Medical Instrumentation (AAMI). The standard for dialysate has recently been lowered from 2,000 Colony Forming Units (CFU) to 200 CFU/ml. They also define three levels of dialysate: Conventional dialysate which is normally used has 200CFU as a limit (with an action level of 50 CFU/ml); Ultapure dialysate is 0.1 CFU/ml, and dialysate for infusion has a limit of <1 CFU per 1,000 liters (This is what the Aksys PHD makes so it can do those flushes).
Most uses are at the 200 CFU standard, and AAMI reviewed data to show that this is safe even with their knowledge and understanding of how much backfiltration happens in a high flux dialyzer.
There is no need to monitor bacteria in acid concentrate, because it has a pH of about 2, and is incapable of growing bacteria. Bicarb mixing systems are monitored along with the water system, and some facilities culture the bicarb solution as well. AAMI did not set a standard for bicarb because it is essentially monitored be the dialysate.
It is not possible for bacteria to cross an intact dialysis membrane, It would be sort of like trying to stuff a bowling ball through your 15 ga fistula needle! Endotoxin can theoretically get through because they are broken peices of cell walls. In reality, they would tend to adhere to the membrane instead. If there is a high level of endotixin present they can actually cause harm by passing chemical messages to the blood without even crossing the membrane.
All in all, you do not need to be too concerend about bacteria contamination with a well maintained and monitored water treatment system that gets disinfected regularly, along with the dialysis machine.
The reason long dialysis treatments work so well on middle molecules is not so much the dialyzer membrane, but the human membranes. During your treatment, molecules must “dialyze” out of your cells to get into the blood stream. The larger the molecule, the longer it takes. That is why phosphorus levels are so much better with Nocturnal dialysis.
To your question on going back to a low flux dialyzer I would say, emphatically, no. High Flux dialyzers remove a much wider range of molecules, are usually more bio-compatible, and patient outcomes have been much better since we started using them. Larger molecules are removed primarily by convection in a dialyzer, which means they flow along with the water when it crosses the membrane. It is becauseof the fluid moving back and forth in the dialyzer that they remove as many large molcules as they do. I know that if I was on dialysis, I would use a high flux dialyzer.
The concern of nephrologist was dispelled primarily by realizing that millions of treatments had been performed without a problem. There were many studies showing no problems with high flux dialyzers before they were intoduced, but it was a couple of years later that people started understanding that backfiltration was occuring. The reference list in the AAMI guidelines lists several articles published on the subject. With the understanding of the risk associated with backfiltration also came the understanding of the benefits of the improved convective clearances it causes as well.
Curt
This explanation of minimum dialysate flow rates from Jim Curtis is the clearest I’ve seen. There is an unfortunate word similarity that is leading to confusion on other HDC threads on this topic: Backfiltration and Backflushing. One is good and one either doesn’t matter or can be bad.
Backfiltration is the suspect one. Backfiltration is what is being spoken of in the above post by Curt. The fear was generated by this 1989 paper:Dialysate contamination and back filtration may limit the use of high-flux dialysis membranes. I think this study was the fist to talk about backfiltration. Click for the PubMed abstract.
Using a high recovery medium, we found that 53% of the centers had bacterial counts above the Association for the Advancement of Medical Instruments standard in water (20% cfu/ml) and 35% above the standard in dialysate (2,100 cfu/ml).
So whether or not backfiltration is a problem may depend if your water quality is up to standards. There have been more recent studies that have linked water purity to chronic inflammation, backfiltration would be the connection.
Backflushing is good. A backflush is when injectable quality dialysate is forced through the F-80 artificial kidney and into the blood. I think only the Aksys PHD machine offers the benefits of backflushing. I have my backflush interval set at 15 minutes and my backflush volume set at 150ml. This results in 600 ml of fluid being added to the circuit and to the hourly UF goal. By increasing the UF goal the backflushing increase the movement of solutes across the membrane through the process of convection. With the backflushing one should have a greater clearance of middle molecules than without the backflushing due to convection.
The backflush is one reason I think a minute/hour/run on the PHD delivers the most clinically effective minute/hour/run available.
If we are not Uf’ing, the UF is set at 100ml/hr to prevent backfiltration.
I know many programs have minimum filtration rates but Curt makes a solid case that these minimums aren’t actually preventing transfer of endotoxins from the dialysate circuit to the blood circuit.
Here is an interesting article from 1999
Progress in dialysis technology—clinical benefit vs increased complexity and risk. Report on the Dialysis Opinion Symposium at the ERA–EDTA Congress, 7 June 1998
At a conference the authors surveyed the attendees, close to 2500 responses were collected, the majority from European nephrologists. One question was:
Volume control is a feature of modern dialysis machines that allows predictable weight loss. However, in most haemodialysis procedures it also involves some backfiltration of dialysis fluid. When standard dialysis fluid is used what is your opinion about such uncontrolled backfiltration?
Nearly 60% said it should be avoided while less than 20% thought it was not a problem.
Another question asked for ones opinion of ultra pure dialysate. The vast majority felt ultra pure dialysate was good or important while only about 5% thought ultra pure dialysate was unnecessary.
In the first unit I was at I had three reactions in a row. I am on dialysis for toxin removal only, and remain so till this day five years after the start of dialysis. My uf rate is 500 per 3 1/4 hr. tx… I learned in the beginning when staff was remiss in figuring it out that if the tmp did not go out of bounds I would not become ill on tx… even though I had a very low uf… Bumping up the DFR had an effect on keeping the tmps in check. I suffered a pyrogenic reaction (along with the pts on both sides of me) at the first unit. I was told by my neph. it was a pyrogenic reaction but staff was tightlipped, however they replaced disenfection unit that weekend. I often read that nowadays these things don’t happen, but alas they do. I’ve learned to keep an eye on the machine, particularly the tmp… Many of the pts. in the unit I’m at have lower ufs. I’m planning on doing home hemo with the Nxstage machine so am curious about such things as the low uf I use… I’m happy about the fact that with this particular machine dialysite is prepackaged. Lin.
We do the minimum UF rate to make sure we are still removing wastes if we dont need fluid removal.
A:
We do the minimum UF rate to make sure we are still removing wastes if we dont need fluid removal.
What does the UF have to do with removing wastes?
Because if you have the UF turned off, the fluid flow can backfiltrate, meaning the flow of fluid against the blood is affected. Without the fluid flowing steadily past the blood along the length of the dialyser, you cant adequately remove waste. This is just the policy of our unit. There is some debate on this topic.
Amba:
Because if you have the UF turned off, the fluid flow can backfiltrate, meaning the flow of fluid against the blood is affected. Without the fluid flowing steadily past the blood along the length of the dialyser, you cant adequately remove waste. This is just the policy of our unit. There is some debate on this topic.
You’re saying it affects clearance…does anyone know how much it affects clearance and does it harm patients in any other way? Because if there is a problem we were never told before and they have been turning the UF completely off for all the years we have been on dialysis.
Ok, I’ll take a stab at it…
Ultrafiltration, ie. removal of water, is accomplished by pressure from the blood side to the dialysate side in the dialyzer. This is what is called TMP, or transmembrane pressure. The greater the UF rate, the more the TMP, all other things being equal.
Removal of “toxins”, including potassium, phosphorus, etc. is removed not by pressure, but by the concentration of these being lower on the dialysate side than on the blood side. “Toxins”, for want of a better word, go through the membrane to where their concentration is lower. This has nothing to do with transmembrane pressure as such.
Now, there is another factor involved. It’s called convection. This basically means that some of the toxins are carried out along with the water being removed (since they are small enough to pass through the membrane, or else dialysis wouldn’t be possible). So, it’s true that the higher the UF rate, the more convection there is. But this isn’t really a predictable thing. It’s not a treatment parameter, but rather just something that happens - and if it does, it can only add a bit to the efficiency of the treatment. On the flip side, there are some physiological advantages to having a lower UF rate, so, it’s hard to say that a higher UF rate is actually desirable.
Now, a low UF may have some advantages for the body, but, it’s rare to run with UF off. This would likely cause more backfiltration of dialysate into the blood (since there would be no transmembrane pressure to prevent it), and some dialysis machines don’t even allow it. What they usually do if a patient doesn’t not need any fluid removed is to actually give saline periodically during the treatment so it can be removed (that plus the standard rinse-back amount, usually 500 ml). So, you end up with a high enough UF rate, even though you’re not reducing weight, only removing what has been added during the treatment.
Pierre
It would depend on how long the UF is turned off for Heather. Our machines have just been set recently so that it wont allow you to run with no UF dialed in. Of course if you are going flat, you can turn the UF off while you recover. It only lets you have it turned off for 5 minutes, then it will alarm. You can turn it back off if needed. As far as having no UF for the whole treatment or for a reasonable length of time, you wont know how if affects you unless you do bloods. And even then it would be hard to get an accurate result. I only first heard of this the other day when I had to turn the UF off for a couple of hours. The minimum UF rate is 100ml/hr.