The 'Volume-safe Dialysis Duration' KPI

This blog post was made by Dr. John Agar on April 24, 2014.
The 'Volume-safe Dialysis Duration' KPI

The following blog explores some simple, utterly naïve and probably crazy thoughts I have had about the development of a 'volume' Key Performance Indicator (KPI) for the day-to-day clinical management of dialysis patients. Dialysis has had a 'solute' KPI for 2+ decades – Kt/V urea – and more of this in a moment, but no simple, easy-to-apply marker for volume status currently exists.

Like a dialysis Don Quixote, I have long tilted against the windmill of Kt/V urea. It has been, in my view, the single greatest 'furphy' ever visited upon dialysis ... NB: if you are unfamiliar with the term 'furphy', you can find it explained at: http://en.wikipedia.org/wiki/Furphy or at http://www.onlymelbourne.com.au/melbourne_details.php?id=10424#.U030f1WSxBk

Again, in my view, generations of nephrologists have been incorrectly sold the lie that urea is in some way a good measure of 'adequacy'. This is despite the fact that urea transport and diffusion kinetics bear little or no relationship to the kinetics of most metabolic wastes. While urea moves very rapidly down a concentration gradient, many of the more important 'toxins' move very slowly down time-dependent gradients.

This has led nephrologists—especially in the US—to be 'furphied' into believing that once a certain level of urea clearance has been reached, it is then OK to "turn off the machine and wheel the next victim in". Well, that is just plainly wrong. I have spent the last decade and a half fighting the almost un-fightable misconception that Kt/V urea is the be-all and end-all of good dialysis. Clearly, it is not, but the belief in the US-demanded dialysis KPI of a Kt/V of 1.3 as the measure of adequacy...indeed the only measure of adequacy has become so ingrained that it has excluded all other rational thought.

Enough of my solute hobbyhorse. Let us push solute clearance to the side for the moment. I have been thinking about a simple way to devise a useful volume KPI so, let us think about 'volume'.

By volume, I mean circulating blood volume and the effect that a dialysis treatment has upon it. This is not the same as dry weight. It is vital that what follows is separated from the concept of determining dry weight. That is a different argument. My suggested volume KPI is only about the next upcoming dialysis treatment, and in this particular patient.

The measurement of the impact of any one dialysis treatment seems often confused with the measurement of dry weight; the assessment of the latter including the evaluation of all manner of the useful and the not-so-useful. As regards dry weight, there are supporters of a variety of bio-impedance options, of IVC ultrasound, of isotope dilution, of BNP, etc., but none have (yet) reached acceptance as an easy bedside application, nor do any show promise of providing an immediate, pre-dialysis, practical and cost neutral application for day-to-day use in each and every patient in each and every dialysis unit. Are dry weight assessment techniques important? Yes. But, are they useful for a daily treatment KPI? Probably not!

A useful 'volume' KPI needs to be utterly simple, easily applied, applicable pre-dialysis and have clear and interpretable meaning for both staff and patient.

I have followed Chris McIntyre's work on organ stun closely – and it is very nice work indeed! The simple concept of 'perfusion stunning' has provided excellent evidence that there is a rate of intravascular volume depletion that is risks tissue hypo-perfusion and target organ stun.

While his first work described myocardial stun as a result of reduced coronary perfusion during dialysis, his group has now shown similar data supporting cerebral stun through reduced carotid and/or vertebral perfusion, and episodic AKI and the loss of residual renal function through reduced residual renal tissue perfusion during dialysis. Indeed, the list of at-risk tissues is, potentially, as long as is organ number. This made me think about a simple, bedside, pre-dialysis measure that might provide a workable, useful volume KPI.

I have coned down onto two concepts:

(1) The plasma refill rate (PRR) is the most 'rubbery' of numbers, as so many factors impact its calculation. However, the few who have attempted to quantify a mean average PRR for a mean average patient—if there one—have zeroed in on a mean maximum PRR of between 5 and 6 ml/kg/hr(1,2). The concept of the plasma refill rate simply says if removal of fluid from the plasma volume (e.g. by dialysis) exceeds the capacity of the extracellular fluid (ECF) – to refill and replace the vascular volume [see earlier blog on 'the waterfall concept'] then the intravascular volume must contract by the difference between the removal and refill rates.

If, for arguments sake, the PRR is 'rounded out' to ~5ml/kg/hr ... and our clinical experience with extended hour vs. centre-based dialysis suggests that this figure is about right, then, in the non-existent 'average' person, intravascular volume contraction will likely occur if the rate of volume removal during dialysis exceeds 5ml/kg/hr.

Some may say that it is naïve, very naïve, to use one figure (like 5ml/kg/hr) for the PRR of all. It is clear that factors like weight, size, gender, capillary permeability, albumin level, inflammatory status, cardiovascular competency, and nutritional status (among others) will all impact on the PRR—hence my previous comment that this is a very 'rubbery' number. But, to be fair, these same factors also impact on bio-impedance, isotope dilution and all the other commonly touted, complex and costly ways to assess volume status and/or dry weight. So, for now, let us just hang onto that number.

(2) The 'stun' factor stems from the work done by Chris McIntyre and his group around organ perfusion and tissue oxygenation(3,4). This work adds beautiful symmetry to the volume 'story', as it suggests that stun mechanisms are increasingly likely to occur if fluid is removed from the intravascular volume at a rate >10ml/kg/hr, and are almost certain to occur at volume removal rates >13ml/kg/hr.

Taking a simplistic view...and I am a very simplistic guy...two magic numbers emerge!

(a) Volume contraction will occur in dialysis if fluid is removed at >5ml/kg/hr.

(b) Organ stunning is risked in dialysis if fluid is removed at >2 x the PRR = >10 ml/kg/hr.

These are two very easy-to-remember numbers, despite the fact that they are underpinned by two highly complex (and debatable) mechanisms.

Now, blend (1) and (2) into a volume KPI:

My simplistic solution to the issue of volume is to extend the dialysis treatment, at least and until the dialysis ultrafiltration rate is less than the lower risk level identified for organ stun: i.e., <10ml/kg/hr.

Though clearly a patient should continue to contribute to volume control, it is neither wise not productive to provoke conflict through imposing unrealistic and commonly unachievable at-home, inter-dialytic intake fluid restrictions, especially when the dialysis itself is often primarily to blame for post-dialysis thirst.

Post dialysis thirst—and the resultant excessive fluid gain that follows before the next dialysis—is commonly the direct result of imposing intra-dialytic UF rates that so rapidly contract the vascular volume during dialysis that post-dialysis thirst is irresistible and excessive inter-dialytic weight gain is unavoidable. This is not the patient at fault. It is we who are at fault.

It is we who have prescribed a brutally fast contraction of vascular volume by scripting an unrealistic time frame for volume removal. Dialysis treatment time must be extended such that the target weight (read fluid) loss is achieved at a removal rate no greater than 10ml/kg/hr. Chris McIntyre's risk stratification marker for myocardial (and other tissue) stun.

The necessary duration for any particular dialysis treatment can be easily predicted before the start of that treatment. (1) the pre-dialysis weight is known. (2) the target post dialysis weight is known, noting that this target weight is not necessarily the same as the ideal dry weight. By in-building a maximum intra-dialytic UFR of no greater than 10 ml/kg/hr, it is simple to calculate, pre-dialysis, (3) how long any one particular treatment time will need to be.

If dialysis sessional duration is used as the single variable KPI to judge safe volume removal, sessional lengthening (or shortening) would then be dictated by a pre-dialysis calculation of the time required for that treatment only to achieve the target post-dialysis weight.

This would avert most of the volume and perfusion-related symptoms of dialysis, i.e., the majority of patient-reported symptoms. Hypotensive episodes, nausea and vomiting from splanchnic hypo-perfusion, cramp, and dialysis fatigue would all abate. Prolonged post-dialysis recovery time would disappear. Patients would rapidly learn and understand the value of time in their dialysis program. Patients would rapidly learn that dialysis duration directly relates directly to weight gain—a relationship that would help reinforce inter-dialytic volume management. Above all, the risks associated with key organ hypo-perfusion would be minimized.

The pre-dialysis weight is measured and known. The target post-dialysis weight is set and known, pre-dialysis. The volume that must be ultra-filtered is therefore also known, even if an accurate true dry weight is rarely known. It is then dead simple to calculate the required length of a dialysis run to ensure that the UFR for that treatment does not exceed 10ml/kg/hr.

In our unit, we are now collecting prospective data prospectively which will allow the calculation of: (1) the number of patients where dialysis duration would have been lengthened under these guidelines: (2) by what duration.

In addition, we will be able to examine (3) the staffing, rostering and global economic impact of the changes needed should we wish to ensure a 95% compliance of individual and collective dialysis times to a maximum per treatment UFR of <10ml/kg/hr. 'Smart' rostering may then allow the grouping of patients who regularly require longer sessions.

Finally, some patients may qualify for shorter treatment runs—judged on volume criteria alone. Here, solute criteria would play a clear, but secondary, duration role. To strengthen the interplay between solute and volume factors, there is a clear need for a better solute clearance KPI than Kt/V urea; one that considers time-dependant solute clearance, not just small molecular diffusive clearance. Convective therapies (especially HDF) may play an important role here...but that is another story.

A useful spin-off may be that patients—and dialysis professionals—come to better understand the duration inadequacy of most current dialysis programs, with a longer-term benefit to patient symptom relief and reduced stun-related morbidity and mortality.

A simple, simplistic, yet effective Volume-safe Dialysis Duration formula is likely to save many more lives, and make dialysis far more tolerable for far more dialysis patients, than Kt/V urea ever has or will!

Now, for the Volume-safe Dialysis Duration (VsDD) formula:

Volume-Safe Dialysis Duration (VsDD) =

  • VOLUME TO REMOVE (mLs)

  • 10 x PRE-DIALYSIS WEIGHT (Kg)
  • Example # 1
  • Weight gain = 2.65 Kg
  • Volume to remove = 2650 mL
  • Pre-dialysis Weight = 56.75 Kg
  • VsDD = 2650/10 x 56.75 = 2650/567.5 = 4.66 hrs
  • Example # 2
  • Weight gain = 5.2 Kg
  • Volume to remove = 5200 mL
  • Pre-dialysis Weight = 117 Kg
  • VsDD = 5200/10 x 117 = 5200/1170 = 4.44 hrs
  • Example # 3
  • Weight gain = 3.3 Kg
  • Volume to remove = 3300 mL
  • Pre-dialysis Weight = 54.25 Kg
  • VsDD = 3300/10 x 54.25 = 3300/542.5 = 6.08 hrs
  • Example # 4
  • Weight gain = 2.25 Kg
  • Volume to remove = 2250 mL
  • Pre-dialysis Weight = 41.3 Kg
  • VsDD = 2250/10 x 41.3 = 2250/413 = 5.45 hrs
  • Example # 5
  • Weight gain = 0.8 Kg
  • Volume to remove = 800 mL
  • Pre-dialysis Weight = 68.5 Kg
  • VsDD = 800/10 x 68.5 = 800/685 = 1.16 hrs.

NB: in the last example, Kt/V (or, in time, a better measure of solute clearance) would then take over as the duration-defining KPI.

In all circumstances, dialysis duration would be determined by a combination of solute clearance (currently Kt/V or URR – though better solute clearance KPIs are badly needed) with dialysis continuing until both solute and volume KPI data points have been achieved.

Finally:

If additional fluid needs removal beyond a simple return to the pre-dialysis weight, i.e., if a sequential 'drying down' is required over several dialysis runs, then the additional volume to remove (ml) at each sequential dialysis session is simply added to the numerator.

  • Example # 6 [using the same parameters as for Example # 1]:
  • Weight gain = 2.65 kg
  • Volume to remove = 2650 ml
  • Add extra 'dry-down' volume of 250 ml
  • Total volume to remove = 2650 + 250 = 2900 ml
  • Pre-dialysis Weight = 56.75 kg
  • VsDD = 2650 + 250/10 x 56.75= 2900/567.5 = 5.10 hrs

Try it out for yourself using the calculator here.

References:

  1. Kim KE et al. TSAIO. 1970: 16:508
  2. Chaigon M et al. Hypertension. 1981: 3:327-332
  3. McIntyre C W et al. CJASN. 2008: 3:19-26
  4. Burton J O et al. CJASN. 2009: 4:914-920

Comments

  • Lenore

    May 09, 2014 2:09 PM

    Reduction in dialysis time/ increase in kidney function and urine output.
    Coagulation options not available to center. Citrusate ? Discouraged as too complicated
    Did not contest - felt I did not want to ask techs do do something new and not in routine.
    I will discuss other options with dr
    Thank you. Get best info on this dite - feel dialysis centers should teach patients more about process. Still trying to learn. Lenore
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  • Lenore

    May 08, 2014 1:50 PM

    Dr Agar. Thank you for your response.
    I was told that there were no alternatives available for coagulation. I understand what you are saying about time on dialysis. Ii am doing in center dialysis. I tried nocturnal-didn't work, then 3,days 3 hrs- miserable. I then went to 4 days 2hrs 45 min for 4 days and still having difficulties. Since I dropped the time I am feeling great. I agree it is totally opposite everything I have read. Even at 2:45. I felt like I was jumping out of my skin-maybe something else is bothering me-allergic.?
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    • John Agar

      May 09, 2014 3:57 AM

      Lenore ...

      While it is not my intent to convert this blog page into an advice column ... there are other vehicles for that ... the advice you apparently received that there are no alternatives to heparin in HD, if that is what was said, is simply incorrect.

      There are a number! Apart from standard unfractionated heparin (heparin sodium), most would now routinely use low molecular weight heparin (LMWH) as the anticoagulant of choice. In patients with sensitivity to heparin or who have formed anti-heparin antibodies and a low platelet count (heparin-induced thrombocytopenia syndrome or HITS) sufficient to force an alternative option in anti-coagulation, there are many choices available.

      Direct thrombin inhibitors and heparinoids can be used. We have a couple of patients with similar stories to yours and, in them, use danaparoid sodium (marketed in Australia, at least, as 'Orgaran' and given as a 750 IU/0.6ml bolus at the start of dialysis).

      Regional anti-coagulation is also used in these circumstances with either prostanoids, nafamostat (NB: there is a discussion of nafamostat at my HDC message board

      ... see http://forums.homedialysis.org/threads/2414-Heparin-Alternatives

      Citrate is also an option - either by infusion, or by the use of citrated dialysate, the latter of which I have also discussed at my HDC message board

      see... http://forums.homedialysis.org/threads/3344-Citrate-Dialysate

      I know other discussions of anti-coagulation have occurred within the body of discussion at the message board site but as the discussions are commonly titled from the question title chosen by the initial questioner, they sometimes don't accurately reflect the true topic under discussion. This is unfortunately an uncorrected weakness of our message board system and makes it difficult, sometimes, to pin-point all relevant discussions

      If your nephrologist needs to find an update on anticoagulation in intermittent HD, he/she could do no better than to read Andrew Davenport's review of HD anticoagulation options in Nature Reviews Nephrology: 2011. July 5: 7(9): 499-508.
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  • Judith Alexander-squires

    May 07, 2014 7:09 PM

    It is amazing that you should document this since we are also working on a CQI project involving fluid.
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    • Dori Schatell

      May 09, 2014 2:23 PM

      Hi Judith--that's fascinating! Where are you located? Can you share any information about what your CQI project is?
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    • John Agar

      May 07, 2014 10:45 PM

      That's interesting ... I hope you will let me and others know what your line of research entails.

      A regulatory index for volume is the single greatest elephant in the dialysis room. Solute clearance (as followed by Kt/V or PRU - for what they are worth) pretty much takes care of itself with modern dialysis techniques,as long as dialysis duration is sufficient (which, sadly, it all too often still isnt) ... but then I have railed against short dialysis on behalf of solute clearance too often already.

      It is astounding we still have no easy, real-time, practical, bedside, no cost, every-patient-every-dialysis measure that guides our management of volume.

      Blood volume monitors (BVM), Body composition monitors (BCM) ... whatever you like to dream up ... all are expensive, none yet provide sufficiently reliable data, all are cumbersome and time consuming.

      To my simplistic mind, none of these (and other) techniques offer a no cost, pre-dialysis marker for volume vs. duration ... I repeat, VOLUME vs DURATION ... and the simplified version of my VsDD proposal does. It seems to tick all the prequisite boxes I outlined above.

      Let us all know what you are doing.

      Meantime, we will continue to potter around with my VsDD concept until we can hang some flesh on its bones.
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  • Lenore

    May 07, 2014 3:46 PM

    I cannot use heparin. They were giving me a saline flush every 1/2 hour in addition to 500 rinse back at end of dialysis. My Weight gain was well controlled -- usually between 1 and 1.4. I was having terrible symptoms. Everyone said the amount of saline was not important. I disagreed. If you put. It in my body, you still have to take it out. I finally convinced my doc to go. 4 days for 2 hours, 15 minutes. I can then run easily with no heparin and no saline,flushes. Felt so much better immediately. Can you comment.
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    • John Agar

      May 07, 2014 11:04 PM

      Lenore ...

      My comment might surprise you ... for it is not so much targeting

      (1) the saline flush and saline load issue (though that deserves separate comment - see below)

      nor ...

      (2) the maybe tried (but if not, why not tried) alternative on-dialysis anti-coagulation options, of which there are many. That, too, is a different issue.

      No ... my jaw-dropping moment when reading your post was the 4 days a week x 2 hr + 15 minute regimen you are on. In my humble opinion, that is minimalistic dialysis taken to the ridiculous extreme, especially when your post implies that you had to persuade your nephrologist to alter your dialysis to that regimen ... suggesting to me that you may have been getting even shorter dialysis prior to that change .

      The shorter regimen you describe may alleviate the need for heparin, saline flushing and the rest but, hey, that's not a good long term trade simply to solve anti-coagulation problems ... at least not in my book.

      You are getting a measly 9 hours of dialysis a week!

      I have written much, here and elsewhere, about the pivotal importance of dialysis duration, dialysis frequency, and total weekly membrane contact time (MCT). I don't intend to repeat it here. Maybe Dori can direct you to any one of the multitude of responses I have previously given to others on this topic. But, 9 hours a week? ... eeek!

      I would direct you (and others back to the seminal paper written by Belding Scribner (the father of modern haemodialysis) and Dmitri Oreopoulos (a doyen of modern peritoneal dialysis) = available at http://www.therenalnetwork.org/qi/resources/HDP.pdf

      Plug your numbers into the HDP and see where your dialysis regimen lies! Just for your interest, you score an HDP of 35.2. If you put Scribner and Oreopoulos up against any nephrologist in the world ... the result would be, then, now and forever, a slam dunk for the 'greats'.

      I rest my case!
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  • Dr. O.

    Apr 24, 2014 4:16 PM

    You nailed it again Dr. Agar. Great information.
    Too bad in the US most nephrologists dont get it.
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