Slaying the Water Dragon

Setting a Maximum Ultrafiltration Rate (UFR_max)

I must sound like a scratched CD, but I really hardly give a toss about solute clearance.

Why? Well, modern dialysers, bio-compatible and smart membranes, flow delivery systems (except, perhaps, some of the lower dialysate flow systems currently popular in some jurisdictions), and an increase in optimal access all combine to ensure that all water-soluble or membrane-permeable solutes are adequately removed, though, to be sure, protein-bound solutes do remain a challenge to be met. And, importantly, the currently used solute Key Performance Indicator (KPI), Kt/V_urea, won’t help us with these.

So…as current solute clearance techniques do as well as is currently technically possible, the value (and relevance) of solute markers like Kt/V_urea or PRU is diminished to a “been there, done that” level. But, while I am an avowed critic of Kt/V_urea, I am also a realist and recognize that until a more inclusive marker for solute clearance can be found—and we should start looking—Kt/V_urea will remain with us for the medium term.

But…

The beast that must be stalked and slain…the dialysis dragon that demands defeat…is not solute—and it never really has been.

While there are clearly traps and problems hidden within the laboratory, the real beast is not biochemistry. The beast that matters, the one that kills, is fluid, and, the most difficult dialysis dilemma is, and has always been FLUID REMOVAL.

I have blogged a number of times at this site about fluid ^{(1, 2, 3)}. I have returned, again and again, to speak about fluid removal at ADC meetings stretching back over a decade.

We desperately need…no, our patients desperately need…a maximum safe rate for fluid removal. They need this as a dialysis KPI far more than they need Kt/V_urea.

It is true – Kt/V_urea did serve a purpose once upon a time. It did ensure and enshrine a KPI for “adequate” small solute clearance. But, hey, we need to move on now. We need to grapple with the beast that really matters, the one that drowns hearts, lungs and minds: the water dragon.

Chris McIntyre’s team have defined the battlefield for us ^{(4, 5, 6)}, and the battlefield is “organ stun”…be that myocardial stun, cerebral stun, gut stun, indeed “any tissue stun”. Stun is the term McIntyre has coined to describe the end-organ functional result of an acute fall in tissue perfusion pressure. This is the dragon-in-waiting that lurks beneath any dialysis session where rapid and aggressive fluid removal is administered.

Organ stun is not rocket science. In fact, it is a very simple concept. The rate at which the circulating blood volume can be restored/replenished from tissue fluid stores (the plasma refill rate) is rate limited: it is about 400 ml/hour in the average person. So, if the rate of removal of fluid from the circulation (e.g. by dialysis) is faster than the rate that tissue fluid can refill the circulation, blood volume contraction must result.

If the blood volume contracts rapidly, tissue perfusion (read: oxygen supply) will fall, rapidly. In effect, all body tissues and organs will be affected, whether heart, brain, gut, muscle, or residual kidney tissue, and as the perfusion pressure falls, the oxygen supply to that tissue will acutely diminish.

This leads to a functional consequence for each and every tissue: heart, brain, gut, muscle, or residual kidney tissue. The tissue (or organ) thus deprived of sufficient oxygen then functions (performs) less well, or, more importantly, suffers permanent hypoxic (low oxygen) damage. This is especially so if the injury is repetitive, happening again and again, as it does 3 times each week in the dialysis patient!

To prevent this, the rate of fluid removal must be reduced to a rate below a safe maximum removal rate. Let us call this safe maximum rate the “maximum ultrafiltration rate” (or UFR_max). Do we already have data that tells us the removal rate that threatens organ perfusion? Well…yes, we do.

The UFR_max would appear, from accumulated data, to lie somewhere in the range of 10-13 ml/kg of body weight/hour. In simple terms, remove fluid at a rate above 13 ml/kg/hour, and organ damage is almost certain. Keep fluid removal rates below 10 ml/kg/hour, and adequate organ oxygenation appears both safe and assured. For fluid removal rates between 10 and 13 ml/kg/hour, the potential for damage rapidly escalates, especially where pre-existing organ damage has already occurred. This is a stark feature of the graph (below) published in Kidney International in 2011 by Jennifer Flythe ⁽⁷⁾. It is worth taking a look at this graph. It isn't hard to get the message.

So, if setting a UFR_max, where should that maximum rate be set?

My view is strongly toward maximum safety, not maximum risk. With maximum safety at <10, and maximum risk being >13, I know where my KPI preference lies! Where is yours?

I think there should be a new KPI for UFR_max. I argue strongly for this view in a “Personal Viewpoint” paper that will shortly appear in the April, 2015 edition of Hemodialysis International⁽⁸⁾.

The UFR_max is simple to calculate—and can be done BEFORE a dialysis session begins. Assuming the rate of removal is to be no more than 10 ml/kg/hour then, knowing the amount of fluid that has to be removed, it is simple to calculate the duration required for the upcoming session.

I believe that each and every dialysis treatment should satisfy TWO requirements, or

dialysis KPI’s:

1. A solute KPI = a Kt/V_urea of 1.3 (or PRU of 70%)
2. A fluid KPI = a UFR_max of <10 ml/kg/hour

Each and every dialysis session should be continued until both KPI’s have been satisfied.

While initially throwing up a number of logistic problems for providers, there are ways to solve these, some of which I outline in the HDI paper. But, in the end, what matters most is patient safety and survival, and we are not currently ensuring that safety, or maximizing that survival.

Surely we can overcome the temporary disturbance to our dialysis unit equilibrium and delivery practices that a UFR_max might bring.

We have prospectively gathered data from our own service and intend to present this data this year. It suggests that a duration KPI governed by UFR_max can be introduced with only a little imagination and without too much service “pain”.

We owe it to our patients to make this happen.

References

1. http://www.homedialysis.org/news-and-research/blog/44-volume-safe-dialysis-duration-kpi
2. http://www.homedialysis.org/news-and-research/blog/27-dialysis-waterfall-forget-urea
3. http://www.homedialysis.org/news-and-research/blog/29-dialysis-waterfall-part-2
4. McIntyre CW, Burton JO, Selby S. Haemodialysis induced cardiac dysfunction is associated with an acute reduction in global and segmental myocardial blood flow. CJASN. 2008: 3:19–26
5. McIntyre CW. Recurrent circulatory stress: the dark side of dialysis. Semin. Dial. 2010 Sep-Oct; 23(5): 449-51
6. Eldehni MT, McIntyre CW. Are there neurological consequences of recurrent intradialytic hypotension? Semin Dial. 2012: 25(3): 253-256.
7. Flythe JE, Kimmel SE, Brunelli SM. Rapid fluid removal during dialysis is associated with cardiovascular morbidity and mortality. Kidney Int. 2011: 79(2): 250-257. Online here:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091945