Annual Dialysis Conference 2010: The Take Home Message of Myocardial Stunning

By Peter Laird, MD

The most important lesson that I have learned from this years Annual Dialysis Conference 2010 is that of myocardial stunning related to current conventional dialysis practices, especially as seen in America. Although the debate over the need or lack of need for further randomized and controlled trials once again stole the headlines of this conference, the issue of myocardial stunning may be the trump card that brings into practice more frequent and less violent dialysis sessions long before the debate on RCTs is settled.

Myocardial stunning is an unexplained phenomenon related to reversible ischemia in the heart or more simply put, inadequate blood flow to the heart tissues that does not result in permanent damage.  Dr. Charles Chazot presented a late afternoon discussion on how high ultrafiltration rates negatively impact cardiovascular outcomes by inducing intradialytic hypotension that the leads to reversible ischemia and myocardial stunning.  An ultrafiltration rate higher than 10-12ml/hr/kg is associated with higher mortality, higher rates of intradialytic hypotension and higher rates of myocardial stunning. High Ultrafiltration rates on HD: Do they impact cardio-vascular outcome? Do they impact cardio-vascular outcome? Charles Chazot, MD, NephroCare Tassin, France:

• A high UF rate is frequent, reported in 15-20% of HD patients
• A high UF rate -above 10-12ml/hr/kg-is associated with overall mortality in HD patients
• A high UF rate is associated with an increased rate of patients with cardiovascular complications present with higher UF rate
• A high UF is associated with cardiac stunning and potential long-term cardiac damage and increased mortality
• A high UF rate is associated with an increased rate of intradialytic hypotension but the association between IDH and increased mortality is not confirmed

Perhaps the most alarming news at the ADC is that this is an important phenomenon in pediatric dialysis patients as well.  American dialysis practices largely ignore the simple physiologic parameter of plasma refill rates with ultrafiltration rates often exceeding this by a large factor leading to intradialytic hypotension and reversible cardiac ischemia/cardiac stunning.  Treatment times greater than or equal to 240 minutes have significantly lower episodes of intradialytic hypotension with average American treatment times falling short of this parameter according to DOPPS, Longer treatment time and slower ultrafiltration in hemodialysis: associations with reduced mortality in the DOPPS:

Europe and Japan had significantly longer (P < 0.0001) average TT than the US (232 and 244 min vs 211 in DOPPS I; 235 and 240 min vs 221 in DOPPS II). Kt/V increased concomitantly with TT in all three regions with the largest absolute difference observed in Japan. TT > 240 min was independently associated with significantly lower relative risk (RR) of mortality (RR = 0.81; P = 0.0005). Every 30 min longer on HD was associated with a 7% lower RR of mortality (RR = 0.93; P < 0.0001). . . UFR > 10 ml/h/kg was associated with higher odds of intradialytic hypotension (odds ratio = 1.30; P = 0.045) and a higher risk of mortality (RR = 1.09; P = 0.02).

The HEMO study is a RCT that allegedly proved that higher intensity dialysis did not have any survival benefit, but it did not take into account ultrafiltration rates as an independent survival factor. Understanding the importance of reversible myocardial ischemia and myocardial stunning and how they relate as a prognostic factor in the incidence of sudden cardiac death of dialysis patients may turn out to be the most important survival factor in this longstanding debate. Dose of dialysis, convection and haemodialysis patients outcome—what the HEMO study doesn't tell us: the European viewpoint:

Body water volume
In the HEMO study, urea clearance was normalized by urea distribution volume. The use of Kt/V as a measure of outcome has been criticized since V independently predicts mortality when used as a surrogate for body mass and nutritional status. This could represent a drawback in the HEMO study design. However, among the HEMO study participants body water volume after dialysis did not significantly differ in any of the four arms. Therefore, from a practical point of view, this problem does not exist for the interpretation of the study results.

The solution to myocardial stunning is found in increased treatment times and frequency with concomitant reductions in ultrafiltration rates. Correlating ultrafiltration rates to plasma refill rates may turn out to be the single most important survival paradigm in dialysis treatments. Attempts to use sodium profiling to increase plasma refill rates has failed due to elevated salt loads from profiling leading to increased incidence of LVH which is also associated with increased cardiovascular death rates in dialysis patients.

The rest of the world already embraces the concept of slow and gentle dialysis with lower ultrafiltration rates, yet the American nephrology community is still waiting for a RCT to dictate practice patterns. Reversible myocardial ischemia leading to myocardial stunning renders conventional American incenter rapid ultrafiltration rates in randomized controlled studies unethical in my opinion. If the usual therapy control group therapy is unethical, then the entire RCT is likewise unethical. Myocardial stunning in dialysis patients may become the final trump card in the frequent dialysis debate once its prevalence and adverse affects become well known. For me, that was the take home message of the Annual Dialysis Conference 2010.

Comments

[Linda Gromko, MD]

With my husband in the CCU, I learned about CRRT: Continuous Renal Replacement Therapy. This sounds to me to be an extension of the concept of "nocturnal" dialysis. CRRT is very gentle dialysis done round-the-clock in the most fragile of patients. Sepsis is an example where CRRT is used. If "slow and gentle" is suitable for the most tenuous of patients, who are the ESRD patients who truly can withstand more aggressive therapies, e.g. three times a week in center?

[Zach]

Peter,

Is your definition of slow and gentle dialysis 4-5 hour treatment times, three days a week?

[Peter Laird, MD]

The DOPPS study above noted that the break off point was at 240 minutes with significantly better outcomes over this 4 hour time period as well as ultrafiltration rates less than 10ml/hr/kg. It is quite likely that if nephrologists set dialysis dosages based on these two factors alone, outcomes in America would start to look like those of Europe and Japan. I believe that the fix is much easier to accomplish than thought. Of course fistula usage vs catheter use and several other factors are involved in these outcomes as well. But the American style of short, fast and violent dialysis sessions is deadly according to the data above.

[Dori Schatell]

Peter, that same DOPPS paper (with Rajiv Saran as the lead author) also showed that each additional 30 minutes of treatment reduced the relative risk of death by 7%, pointing to the value of 8-hour long treatments.

But it's not the "American nephrology community" that is waiting for an RCT to change their practice. It's CMS. To me, the most remarkable thing about the ADC meeting was the pretty much unanimous agreement that MORE DIALYSIS IS BETTER--but CMS refuses to accept anything less than RCTs, which will never be powered to examine survival because it would take 16,000 patients to do so, and the FHN studies were barely able to get a few hundred.

But permit me to share a few (non-original) observations:
1). NO RCTs were done to demonstrate the superiority of 3x/week short treatments in the first place, and if they were started today, they would never get past the FDA.

2). It is not always possible (or necessary) to do an RCT. Cigarette smoking was PROVED by the U.S. Surgeon General to cause cancer in 1964 without a single RCT. It is not possible to randomly assign several thousand people to smoke for 30 or 40 years and then see what happens. It's not possible to randomly assign people to dialysis options, either.

3). NO RCT has ever been done of transplant, yet the community (and CMS) universally acknowledge that it has better survival than standard HD. Of course it does--it offers more renal replacement therapy!

Clearly logic is not the strongest suit of CMS. Or, it's all about $$$ and not about improving patient outcomes.

[Peter Laird, MD]

Dear Dori, thank you once again for making possible my participation in the ADC this year. It was an incredible one day experience for me and I wish I was able to take in more. I am already looking at Phoenix for next year which is only a seven hour drive from our house in CA.

I concur that the CMS is the biggest barrier to optimal dialysis strategies in America but they do not stand alone in this. Having dialyzed in 7 units in 6 different states, there is a great disparity in treatment paradigms between those units that I have personally experienced. Bill is fond of stating that dialysis survival is dependent on your zip code and in that he is correct.

The worst was when I spent 6 weeks in Cape Cod where my mother lives with a nephrologist that refused to honor my prescription with a larger artificial kidney to keep my usual clearances. He did not allow this for any of his patients as a stated policy. I felt completely terrible during my entire visit. His decision was completely based on making money for his own pocket since Kaiser pays well to these units when we travel. An extra two dollars per session would not have impacted upon the dialysis budget in his unit to any more than $40.00 for the entire month. My clearance dropped by 15% yet he was happy with a spKt/V of 1.22 and would not adjust it despite telling him I didn't feel well.

http://www.billpeckham.com/from_the_sharp_end_of_the/2008/09/the-red-eye-shu.html

In fact, the short, fast and violent American style sessions are based on cranking out the Kt/V over 1.2 or 1.4 in the shortest period of time to meet the CMS requirements and get to the next patient. Survival differences between Japan and America are not based on patient characteristics as Dr. Blagg noted in a prior article:

http://www.billpeckham.com/from_the_sharp_end_of_the/2008/09/differences-in.html

Fortunately, I have also been in several units where patient outcomes are tied into physician compensation and in those units, the high flux artificial kidney that met my goals was always used as well as attention to several other parameters that matter in survival.

All of these issues are at the discretion of the individual nephrologist, yet many choose to max their own pocket income instead of maximizing their patient outcomes. CMS is complicit with this and has promoted regulations that incentivize this behavior, yet is still the individual nephrologist that makes the actual dialysis prescription.

It is still possible even with current CMS funding to provide home dialysis which is only a fraction of what it is in Australia for instance and make lots of money for the dialysis unit. Yet many of the nephrologists that I have talked to are quite unlearned in many aspects of home dialysis and many are fearful to have patients at home where they cannot intervene in a timely manner if something does go wrong. This is just my own anecdotal experience when discussing home dialysis with those that prior to my current nephrologist were handling my care.

The issue of requiring an RCT is absolutely a red herring and that is why I believe showing that the usual approach to American dialysis with short, fast and violent sessions is dangerous with objective evidence of "mini heart attacks" in those patients with frequent episodes of intradialytic hypotension caused by ignoring the simple relationship between plasma refill rates and ultrafiltration rates.

Having gone through the tasks of presenting to nephrologists during my training and the attention to details that is quite unique to their specialty, I am appalled by the complete disregard of plasma refill rates by many and the reliance on treatment options of this iatrogenic condition. When the ultrafiltration rate exceed by a large factor the plasma refill rates, the patient will become hypotensive especially if they already have underlying cardiovascular conditions which may in fact be iatrogenic as well.

I had an interaction with the late Nathan Hellman of the Renal Fellow Network last year on a post that he did on intradialytic hypotension and its remedies which including sodium modeling which arguably could be part of the cycle leading to intradialytic hypotension with the added salt load from this procedure leading to excessive interdialytic weight gains.

http://www.billpeckham.com/from_the_sharp_end_of_the/2009/01/treatment-options-for-intradialytic-hypotension.html

http://www.billpeckham.com/from_the_sharp_end_of_the/2009/02/treatment.html

Yet that fact remains that this has been a much overlooked aspect of dialysis care in America and not in Australia where it is one of the key considerations in dialysis prescriptions. Longer dialysis times, lower blood pump speeds, lower ultrafiltration rates are a simple fix to a seeming complex problem that is already standard in dialysis prescriptions in Australia, Europe and Japan.

As a fellow physician, we are to do no harm to our patients. There is only one specialist who can prescribe dialysis care in America and that is nephrologists. My discussion of intradialytic hypotension and the responses to my criticism of the post on the Renal Fellow Network last year readily shows the different approach to dialysis in America from that of Australia with replies from someone like Dr. John Agar on the same issue.

http://www.uremicfrost.com/2009/02/interdialytic-weight-gain.html

http://www.homedialysis.org/files/pdf/resources/tom/200712.pdf

I can't get around the fact that there is a quite different philosophy of dialysis in America that although it is evolving, I don't believe it has completely arrived even though those that attend the ADC do accept this different philosophy more so than many of their colleagues. Hopefully this core group of influential nephrologists at the ADC will have more influence over their colleagues in the general community. I cannot get around the fact that in a true medico-legal and fiduciary sense, American nephrologists are accountable for the last place American survival rate. To blame our patients for the bad outcomes is to continue putting our head in the sand.

The knowledge of myocardial stunning associated with intradialytic hypotension implies directly that this is an iatrogenic condition amenable to correction by simply noting the basic relationship between plasma refill rates and ultrafiltration rates. It is that simple.

[Sidharth Sethi]

Thanks Peter for telling us about the Pediatric point of view of the meeting. I had been waiting to hear more pediatric aspects from the meeting. Next time you attend a meeting, do remember that there is a pediatric nephrologist's community, waiting to learn more

[Peter Laird, MD]

Dear Sidharth,

Thank you for your comment. I would have liked to have heard all of the lectures at the conference, but I was only able to go for one day this year. I did read over almost all of the handouts that are available and that is where I found the information on the pediatric myocardial stunning. I must confess that our personal experience is in adult optimal dialysis issues, but if we can in the future take note of these issues, we will certainly do our best to do so.

Thank you again,

Peter