Determing scrip for noctunral txs on NxStage

Dear Dr. Laird,

I have not been able to find any info on how to set scrips for nocturnal txs on NxStage. I read that your scrip uses a FF of 45. I don’t know anyone who has an FF this high. Wondering how you decided your scrip and if there is an acceptable FF range? And can you give me any insight on selecting nocturnal scrips?

Dear Jane,

Thank you for your question. I will answer the second question but defer the issue of nocturnal prescriptions to Dr. Agar since I am not a nephrologist and I don’t actually do nocturnal dialysis myself. Dr. Agar on the other hand has many years of experience with nocturnal dialysis and I am sure he can give you parameters of nocturnal dialysis that you can discuss with your medical team.

As far as the second question of how I selected my FF of 45%, it all goes back to the dialysate flow curves that the NxStage system is based on. Low flow dialysate utilizes the dialysate more efficiently than high flow where it plateaus and further increases in the dialysate dosage and flow rates results in only modest increased clearances. However, at the other end of the curve, an increase in dialysate flow rates results in higher clearances until it also begins to hit the early plateau above a dialysate flow rate of 200 ml/min. I simply reverse engineered my FF based on maximizing the dialysate flow rates as close to the 200 ml/min target.

American dialysis centers use a formula of BFR X 1.5-2.0 to determine dialysate flow rates. Thus, many patients with a BLR of 400 ml/min will have a dialysate flow rate of 600 ml/min. I personally found the 2:1 ratio better for my own clearances so I ran incenter at a BFR of 400 with a dialysate flow rate of 800. In the same terms as NxStage uses, this would be an FF of 150-200%.

For example, with my 40L NxStage prescription and an FF of 45%, BFR of 370 ml/min, my dialysate flow rate is 166.5 ml/min, well below the target range of 200 ml/min to maintain the efficiency of the dialysate since it is a low volume, low flow system. Yet at the same time, I have been able to double my dialysate dosage from 20 to 40L and increase my Kt/V by 86%, from 0.5 to 0.93. This indicates that the FF I am using is not compromising the efficiency of the system, it thus maximizes my clearances in the time frame. Dr. Agar is completely correct that time is one of the most important factors, but in my opinion, the NxStage has too limited a volume of dialysate. Just my own personal take on these issues.

Now, the usual 20L prescription with a BFR of 450 and FF of 35% results in a dialysate flow rate of 157.5 ml/min which is nearly identical to my dialysate flow rate on a higher FF, yet the clearances in my case were 86% lower at 20L. For myself, the key to understanding the NxStage prescription in short daily dialysis is all about the dialysate flow rate, not the actual FF. I have yet to find an objective, evidence based review of optimal FF’s but I can tell you the optimal NxStage dialysate flow rate is between the range of 100 to 200 ml/min. NxStage for teaching purposes substitutes the simplified FF as their measure instead of the more complex dialysate flow rate. The machine calculates the dialysate flow rate off of the FF. All of the NxStage literature that I have read to date is based on dialysate flow rates, but patients are taught FF as their measure.

Nocturnal dialysis on NxStage has quite different parameters than my short daily dialysis. Time is expanded to 6-8 hours and a heparin pump is mandatory. Blood flow rates are greatly reduced and dialysate dosages are usually 40 to 60L although some people dialyze on lower dosages due to different reasons. The dialysate flow rates are quite low in the nocturnal NxStage prescriptions which does maximize the efficiency of the dialysate used. I give up a small amount of the efficiency factor but nearly double the clearances in my short daily regimen. Once again, understanding the relationship between blood flow rates and dialysate rates and where the efficiencies lie is how you will understand what the best FF really is. It is not really a question of what is the best FF, but instead, in my opinion, what is the optimal dialysate flow rate for your own dialysis prescription.

As noted many times before, I do not have sufficient personal, hands-on experience with the NxStage machine to offer sensible and sound comment on dialysis prescriptions for this machine. There are NxStage users groups with, I believe, better resources for advising on the NxStage than I can offer … though I am pleased to see Peter Laird has already given a detailed response to your question as a NxStage user himself.

NB: at this point let me take you back to the 7th post at this site … now many posts back on ‘Page 1’ … where you asked me … ‘What factors determine optimal nocturnal dialysis?’. The answers I gave there - and to a raft of follow-up questions you asked over a number of following posts in the same thread in response to my initial answer - also deal with a number of the issues I again answer here. Can I suggest you return to that post and re-read some of the answers I gave there … as they will add to what follows here.

However, I can certainly offer some further general remarks about dialysis prescription … though you need to be aware that these are made from my experience with single-pass dialysis equipment. Remember that there are more than 400,000 dialysis patients in the US alone and of these, I think only between 3000 and 4000 (~1%) use NxStage. As such, the comments I make here, while not all applicable directly to the NxStage user, are likely of some interest to the vast majority of dialysis patients who do not use single pass equipment, either in their facility or in the home.

While the dialysis prescription depends on a number of factors, chief among these is that dialysis is being offered to the individual and should be tailored for the individual and , wherever possible, individualised, patient by patient, and not blanket-prescribed. Unfortunately, the latter is all too often the fall back position adopted in facility care.

The capacity to individualise the prescription is, in my view, one of the key benefits and advantages of home dialysis.

No one prescription can thus be given. It is for you to work with your team, within some broad guidelines, to find the best prescription that suits you. Not one that suits others, but one that suits you.

That said, you can immediately deduce that, especially in the case of the home patient, there is not and should not be any one single prescription mantra.

Each home patient is an individual. Each home prescription should therefore be ‘teased’ and ‘tweeked’ and ‘massaged’ to achieve the best dialysis outcome possible for that one patient.

  1. Water … the importance of the quality of the water used to create the final dialysis solution that, separated only by a membrane thinner than a human hair comes into contact with the patients’ blood, has had far too little attention paid to it. In Europe in particular, but increasingly here in Australia too … and in many other countries around the world … the European standard for dialysis water has been (or is being) adopted.

What is the difference? … well, heaps!

The US still adopts the AAMI standard for water quality while we (and others) are moving to use the EDTNA/ERCA … see …

NB: My apologies … there is a much more readable pdf version of this document but I was unable to make the pdf link work.

In essence, the following biological differences exist between the two standards. There are differences in the biochemical standards, too, but I will not explore those here. (1) For bacteriological accepted ‘counts’ in the water the AAMI = 200 colony forming units/ml of water vs the European = 100 (maximum levels) and 50 with 25 respectively as ‘action’ levels. (2) For endotoxin levels, the European levels are even more stringent. Here, the AAMI = 2 endotoxin units/ml vs European = 0.25 (a factor of 8 x more stringent) with ‘action levels being set at AAMI = I EU/ml and European = 0.03 EU/ml (a factor for ‘action’ of >30 x more stringent for the European standards).

Why does this matter? … well, we know that many/most/all dialysis patients suffer from a degree of chronic inflammation … some do so more than others … and while there are many potential contributors to this state of chronic inflammation, poor water quality is a key factor - some might say the key factor.

So … Step 1 = prescribe a system that ensures highest possible quality (preferably ultra-pure) for water. Now … NxStage is actually good at that! It’s not perfect - no system yet is - but its way better than most single pass systems.

Is that part of the prescription? … I hear you ask? Yes … I think so!

  1. Membrane … though there are a number of dialyser membranes available, most now use membranes with (relatively) low bio-reactivity … ie: these are what are known as bio-compatible membranes.

Australia abandoned, outlawed and banned the reuse of dialysers back in about ’92 or ’93 … or about then. While many other countries have done the same, re-use remains common in the US.

The benefits of re-use include, primarily, (1) cost reduction and (2) supposedly and truthfully, prevention of the 1st use syndrome. Back in the ‘80s and early ‘90s, this was a condition sometimes seen when a dialyser was used for the 1st time and where a reaction was caused by exposure of the blood to a new dialysis membrane. However, the newer synthetics from which membranes are now made are far more bio-compatible than the older cellulosic membranes used ‘back then’ and, to be frank, the only possible reason now to re-use is to cut dialysis costs … of importance in a ‘for-profit’ dialysis system.

However, re-use also exposes the dialyser (and, in due course, the patient) to a range of ‘sterilising’ chemicals … and if residues of these remain after rinsing (as they do), then this is a further stimulus for inflammation and risk.

In Australia, we now most commonly use high flux synthetic bio-compatible membranes with 49% of our national use being polysulphone-helixone high flux and a further 25% being polyamix high flux. High flux membranes are more efficient at removing high(er) molecular weight toxins – eg: b2microglubulin and homocysteine (among others) … and their use has now become standard practice. But, the higher the flux (read porosity) = the higher the risk of back-contamination of the patient from water impurities (see 1 above). So, high flux means that either European water standards or an added layer of water protection (Dia-safes) … or, better, both must be ensured … the latter (the Dia-safes) being changed at a minimum every 3rd month. We should ensure that both are a part of the routine dialysis prescription.

Then there is the surface area of the membrane: some (bigger) patients need far higher surface area dialysis than little® people do. Broadly, we try to tailor the surface area (m2) to the patients’ size and again, in Australia, the mean membrane surface area lies between 1.8 and 2.1 square metres.

So … Step 2 = don’t re-use, use high flux membranes against water prepared to European water standards and with dialysers prescribed to a surface area in broad step with the surface area of the patient.

Is that part of the prescription? … I hear you ask? Yes … I think so!

  1. [B]Blood Flow Rate /B … I have written here before on my feelings about Qb. I will not repeat in detail … it can be found among answers to prior questions … but in principle, I am not a fan of ‘flogging the fistula’ with a high Qb. I am suspicious of the negative affect a ‘high suck pressure’ has on the endothelial surface and on the venous wall at the arterial end of the fistula (or, for that matter, the endothelium and/or the vessel wall opposite the suck-hole of a catheter) … just as I am suspicious of the effect that turbulence may have on the endothelium and vessel wall in the region of the venous needle (AVF) or venous return port (catheter). I maintain … why run 400-450 if 300-325 will do?

Do I know, for a fact, that this matters … sadly, no! There is very little sound research into this key question … and I suspect I am too old, too grey and too past it to solve the concern. Others should … no, they must!

Our mean Qb in Australia lies between 300-325 ml/min. Our nocturnal patients run their Qb at 75-100 ml/min or so less than that. Why flog the vessels when you don’t need to? I just can’t see the point … unless its to sustain short hour fast, bazooka (my term) dialysis.

So … Step 3 = don’t flog the vessel unless you have to – and with nocturnal long, slow (and especially if also frequent) dialysis regimens, you don’t have to. Subliminal is good. Gentle is good. “Wham-bam-thank-you-ma’am” dialysis just isn’t good dialysis … well, not in my book. Ok … these are my personal views … but I plan to stick to them.

  1. Dialysate Flow Rate (Qd) … here I run into trouble. You are a NxStage user … I am not. You use a pre-formed dialysate at (for me) a very low flow or Qd … I do not. I am profligate with water … though our work in dialysis water conservation is now a matter of public record … while you are not.

OK … I know that the NxStage uses its dialysate more efficiently – that’s the main reason why it manages to provide adequate dialysis at such a low Qd. It doesn’t mean that I necessarily like it nor agree with it. And, there isn’t a lot of data on this significant area of divergence and difference to really know the answer.

In the original Uldall/Pierratos design of modern nocturnal home haemodialysis (NHHD), a dialysate flow rate of 100 ml/min was used. Remember that this was in a single pass dialysis system. It was then shown by Uldall + Pierratos that PO4 and other solute clearances significantly rose when the Qd was raised to 300 ml/min.

A Qd of 300 ml/min x 8hrs treatment x 6 treatments/week effectively generated an eGFR of ~40-45 ml/min (high level CKD3) whereas a Qd of 100 ml/min yielded an eGFR equivalent of only a little more than ½ that (CKD4). Remember, though, that conventional dialysis generates an effective eGFR of 12-15 ml/min (deep CKD5) … and pretty much anything has to be better than that!

In the majority model for NHHD across Australia … an alternate night regimen of NHHD x 8-9 hrs … the model adopted by Peter Kerr at Monash in Melbourne and by Carmel Hawley at Princess Alexandra in Brisbane … NB: we (in Geelong) still encourage 4-5 (mean 5.2) nights/week … a Qd of 500 ml/min in the general rule.

Note … even though I state ‘general’ rule … it is a model still subject to patient-by-patient variation.

However, to change Qd (unlike for other dialysis settings) a single pass machine must be ‘modified’ by the technicians to run at any given setting. Qd isn’t something that can be simply or easily ‘switched’. So, Qd is, in effect, the least ‘modifiable’ variable.

A limiting factor, in our experience … again, remembering that we use single pass dialysis and not on-line dialysate generation as with the System One option in NxStage … is water volume. The higher the dialysate flow rate, the more water is used for the treatment cycle. As our patients pay their own power and water bills (albeit, there is now a government subsidy in several states - though not all - that pays between $1200 and $1500 of the utility costs and which adequately covers these costs), limiting the Qd in high frequency NHHD seems justified … it generates an excellent eGFR equivalent yet does not over-pump the water flows. As some regional or remote NHHD patients depend on rainfall (scarce in our part of the world) for their water, limiting the Qd to 300 ml/min (given an eGFR equivalent of 40-45 ml/min) seems a fair trade between affordability and a still excellent clearance.

So … Step 4 = consider Qd (remembering the technical switching that is needed to alter it) and consider the program time and frequency. Variation between 300 – 500 in an NHHD program of a minimum exposure of alternate nights per week seems a reasonable approach to me.

  1. [B]Heparin[/B] ... in most patients, we use ~1000u hr of conventional sodium heparin administered via a heparin pump. We have had no issues with the use of standard heparin. If there is clotting of fibres ... we adjust up as need be - say, to 1250/hr.

So … Step 5 = start at 1000 units per hour sodium heparin and adjust as need be.

  1.  [B]Phosphate[/B] ... this is so individual as to be beyond the scope of this answer to advise. It demonstrates the difficulty of answering a question such as yours that seeks a specific guideline for what is in fact a highly variable requirement.

In alternate night regimens, enough PO4 is (commonly) removed to allow for both freedom of PO4 intake and the cessation of PO4 binders… yet not so much is (usually) removed as to require PO4 replacement. But … this is a variable feast. No two patients are the same and each must be individualised.

In more frequent regimens (like the one we favour), PO4 removal is so efficient that PO4 must (commonly … but not always) be added back to the dialysate in the form of Fleet enema pack … Fleet being, in effect, sodium phosphate. But the amount needed varies quite a bit … from none to ~40 ml/dialysis treatment. The mean? … well, we start at 25 ml and var up or down depending on the pre- and post- dialysis PO4 … aiming to get the pre-dialysis PO4 to around the upper end of the normal range and the post- PO4 to a little below the lower limit of the normal range (understanding and knowing that there is quite a rapid PO4 rebound post dialysis).

So … Step 6 = know thy regimen, know thy patient and know thy numbers! It is so variable, so indiviudal, that nly your team - on the spot and with the numbers - can advise.

  1. Hours and Frequency … I hardly have to answer this! You know my views here. I like long, slow, frequent regimens. Full-stop!

My own preference to get the best dialysis I can for a patient yet not let dialysis dominate (even the night time) is between 4 and 5 nights/week … though preferable 5 … (NB: I have slipped back from favouring 6 nights/week out of sympathy for ensuring dialysis ‘time-off’ – but my team haven’t – so we argue this point to- and fro- on a regular basis).

Frequency and sessional length (and access method) introduce the next points … 6 and 7 … but as for 5?

So … Step 7 = long sessions of 8-9 hrs (always) over as often as the patient ‘can’ or will … within the bounds of common sense and capability.

  1.  [B]Access issues[/B] ... I don't want to get into this area in this post other than to say that I am an AVF doc. No other access is suitable unless there is no choice or the AVF is temporarily out of action. 

Regarding puncture method … I am still in favour of the button-hole method for many (but by no means all) patients. i think we are learning (slowly) who may or may not be suited to buttons. It is still far from an exact science and overnight and longer and more frequent needle-in-vessel dwell time may be (very) important as may skin type, the presence or absence of diabetes … along with other risk factors as well.

This is far to (a) complex and (b) unknown to sensibly discuss here … so I will leave it well alone.

So … Step 8 = AVF access +/- button or ladder (science unknown).

  1. ? Mupirocin (or similar) … Sessional length and sessional frequency raise issues with access safety – not, in our hands, any risk of leakage or disconnection … this hasn’t been a problem … but in-fistula needle dwell time and (especially with buttonholing) the risks of infection.

This has led us to adopt … as per the paper just published by Nesrallah and Pierratos in CJASN … the use of routine mupirocin to the button site after haemostasis and between dialysis sessions.

But … that is a different story!

Finally, you have asked some questions which (I think) go to some specifics about the NxStage (FF, litres etc) as it applies and impacts on you and your treatment and which I feel I cannot fairly answer. I actually think its not fair to ask Peter either.

While Peter Laird is a NxStage co-user, he is a dialysis patient and is not a part of your treating team (as neither am I). We need to be cautious about giving specific advice … and specifics pertaining to individuals are not wise for any of us to get too far into on an internet site.

Sites such as this are intended to provide over-arching, general information and not patient-specific, treatment-altering, or treatment-impacting advice. That must be for your treating team and is a matter for you to discuss with your treating team

Back to the generalities … I think that deals with most of the prescription issues. While I am sure I have left important bits out … it’s a start.

Hope that answers some of the questions … especially for others who may want to understand some of the overall principles that guide treatment selection.

John Agar

Dear Dr. Agar,

Thank you for addressing some lingering issues for us.

It was your Nocturnal Home Haemodialysis web site that encouraged us to request and pursue nocturnal home hemo. Your posts helped us, with our team, work out many of the details and a good starting script.

We’re still very new to nocturnal. The difference already in mental and physical well being for us both, dialysor and care partner, is nothing short of remarkable. You surely touch thousands with ESRD, but we wanted to acknowledge how much it has meant to us. We fondly refer to you as our “Aussie Doctor”.

With Gratitude,

Boris and Kathleen Kostyszyn
Florida, USA