Hearts in the Crossfire: Standard Hemodialysis Stuns Organs—But, There is Hope!
Dr. Chris McIntyre, newly moved from the UK to the shining dialysis beacon of London Ontario, Canada, became one of my favorite people on earth during his keynote address at the recent Annual Dialysis Conference (ADC)—and we’ve never even met!
In case you don’t know him either, the ADC program lists Dr. McIntyre as “Professor of Medicine, Robert Lindsay Chair of Dialysis Research and Innovation, Schulich School of Medicine and Dentistry, University of Western Ontario; Director of London Kidney Clinical Research Unit, London Health Sciences Centre, London, Ontario, Canada,” and goes on to say that he “leads a team of multidisciplinary researchers focused largely on the pathophysiology of the widespread abnormalities of cardiovascular function and body composition in CKD patients… these studies have increasingly focused on the adverse consequences resulting from dialysis therapy itself and the improvement in outcomes by the reduction of preventable harm .” (Now do you see why he is one of my new favorite people?!)
His talk was brilliant (STUNNING, actually, pardon the pun), and I truly wish it had been videotaped so CMS could see it, but sadly it wasn’t. So, read on if you’d like to make do with my notes—with apologies to Dr. McIntyre if I got anything wrong—and some of his team’s papers in PubMed.
- Circulatory stress causes most of the complications of uremia. Dr. McIntyre referred to an intradialytic “chamber of horrors,” noting that intradialytic hypotension (IDH) occurs in up to 2/3 of standard in-center hemodialysis (HD) treatments . So, those all-too-common painful cramps, headaches, and wiped-out feelings are signs of a much larger and longer-term problem…
- Patients don’t just fade away: they tend to go quickly—due to sudden cardiac death. Myocardial stunning (first mentioned in 1983 in general, and in 2006 in HD) is the mechanism for fibrosis and left ventricular hypertrophy (LVH). In effect, the heart muscle is zapped by lack of oxygen each time blood flow drops, and the muscle does not return to normal after a treatment is over.We can measure for stunning by testing blood for troponin T; higher levels correspond to more damage.  (NOTE: I would wager that this test is never done in the US outside, perhaps, of research studies—so, of course we don’t find what we don't look for…)
- So, what caused the stunning—did standard HD itself drive the process? Dr. McIntyre and his colleagues used a PET scanner DURING HD to look at patients’ hearts! In one study, seven HD patients without diabetes or significant cardiac histories were scanned before treatment, 30 minutes in, and at 220 minutes (NOTE: this was done in the UK—in the US, most don't even get 220 minutes of in-center HD!). Global blood flow to the heart muscle dropped in all patients. At 30 minutes—without ultrafiltration—it fell by 13.5+11.5%. At 220 minutes, with ultrafiltration, it fell by 26.6+13.9% (both were significant). Two patients developed new regional heart wall abnormalities—and they had less blood flow to the heart muscle than the rest.
- “The reduced blood flow was comparable to a heart attack,” emphasized Dr. McIntyre, who went on to say that, “Hemodialysis-induced stunning leads to myocardial hibernation and decreased systolic function. After stunning, patients’ blood pressure becomes less responsive. After 6 months, only a tiny fraction have normal hearts.” In a study of 30 patients who had hemodialysis-induced heart damage, just one year of dialysis led to a significant drop in left ventricular ejection fraction: their hearts pumped out 61.5+10.1% less blood. 
- But wait—it gets worse! The heart is NOT the only organ stunned by reduced blood flow during standard in-center HD. The gut is stunned, too. Apparently, Dr. McIntyre noted, each of our guts contains enough endotoxin to kill 2000 people. When endotoxin stays in the gut, it is excreted harmlessly from the body. If endotoxin leaks into the bloodstream, it triggers inflammation, or even sepsis. Papers from the team implicates circulating endotoxins as a novel factor in ESA-resistance (!!!!! I’ve never believed that higher hemoglobin levels were lethal—but inflammation certainly can be, and none of the studies ever looks at it!) and heart disease.
- The kidneys are stunned. Stunning is the likely reason for the faster loss of residual kidney function with standard in-center HD than with PD…
- The brain is stunned. Compared to people who are not on dialysis and have similar levels of arterial stiffness, those on dialysis have white matter injuries and very impaired cognitive function —including depression.
The impact of stunning is even seen in children receiving standard in-center HD.
So, Is There Hope to Avoid Damage from Stunning?
In a word: Yes.
Frankly, Dr. McIntyre’s talk would have been very depressing if he hadn’t gone one step further and described a FREE intervention that could start TODAY to help people on standard in-center HD: cool dialysate.
Using slightly cool dialysate can reduce the impact of organ stunning in a standard in-center HD setting . In a small randomized crossover trial, 10 patients who were prone to intradialytic hypotension (IDH) tested dialysate at 37°C (98.6°F) or 35°C (95°F).  Patients dialyzing with warmer fluid developed almost four times as many new heart muscle abnormalities as those dialyzing with cooler fluid. Patients tolerated the slightly cooler temperature well.
Changing the temperature did not affect the “adequacy” of dialysis. The team conducted a year-long study to follow 73 patients randomized to usual 37°C dialysate (98.6°F) vs. dialysate set to 0.5°C cooler than each person’s core body temperature (measured in the ear). Cooled dialysate made the treatments more tolerable—and completely prevented abnormal brain changes.
There are other ways to reduce the risk of intradialytic hypotension and organ stunning with standard in-center HD that Dr. McIntyre did not address in his talk—though he was involved in both of the studies below:
- Do PD. In ten patients observed on PD with echocardiogram, no stunning occurred. Heart muscle wall abnormalities were very rare. 
- Remove less water at each treatment. Dialyzing more often than the seemingly magical three days per week paid for by Medicare reduces the risk of intradialytic hypotension and myocardial stunning on echocardiogram. Though the study was small (N=46), there were trends toward lower troponin T levels, too.
If you have followed this blog, you may have seen Dr. Agar’s passionate defense of longer, gentler dialysis here, here, and here. Dialyzing more gently can avoid intradialytic hypotension—which can be so awful that some patients choose to stop dialysis and die rather than go through it again. When we can give patients back their lives while helping them avoid injury to their hearts, kidneys, guts, and brains—that is the biggest win of all.
 Bashour TT, Kabbani SS, Brewster HP, Wald SH, Hanna ES, Cheng TO. Transient Q waves and reversible cardiac failure during myocardial ischemia: electrical and mechanical stunning of the heart. Am Heart J. 1983 Oct;106(4 Pt 1):780-3
 Galetta F , Cupisti A,Franzoni F,Carpi A,Barsotti G, Santoro G. Acute effects of hemodialysis on left ventricular function evaluated by tissue Doppler imaging. Biomed Pharmacother 2006 Feb;60(2):66-70.
 McIntyre CW, Burton JO, Selby NM, Leccisotti L, Korsheed S, Baker CSR, Camici PG. Hemodialysis-Induced Cardiac Dysfunction Is Associated with an Acute Reduction in Global and Segmental Myocardial Blood Flow. Clin J Am Soc Nephrol 2008:3(1), 19–26
 Breidthardt T, Burton JO, Odudu A, Eldehni MT, Jefferies HJ, McIntyre CW. Troponin T for the Detection of Dialysis-Induced Myocardial Stunning in Hemodialysis Patients. Clin J Am Soc Nephrol 2012 7(8),1285–1292
 Dasselaar JJ, Slart RH, Knip M, Pruim J, Tio RA, McIntyre CW, de Jong PE, Franssen CF. Haemodialysis is associated with a pronounced fall in myocardial perfusion Nephrol Dial Transplant 2009 24:604–610
 Burton JO, Jefferies HJ, Selby NM, McIntyre CW. Hemodialysis-induced repetitive myocardial injury results in global and segmental reduction in systolic cardiac function. Clin J Am Soc Nephrol 2009 4(12):1925-31
 Harrison LE, Burton JO, Szeto CC, Li PK, McIntyre CW. Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance? PLoS ONE 2012 7(6):e40209
 McIntyre CW, Harrison LE, Eldehni MT, Jefferies HJ, Szeto CC, John SG, Sigrist MK, Burton JO, Hothi D, Korsheed S, Owen PJ, Lai KB, Li PK. Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. Clin J Am Soc Nephrol 2011 6(1):133-41
 Eldehni MT, McIntyre CW. Are there neurological consequences of recurrent intradialytic hypotension? Semin Dial 2012 25(3):253-6
 Hothi DK, Rees L, Marek J, Burton J, McIntyre CW. Pediatric myocardial stunning underscores the cardiac toxicity of conventional hemodialysis treatments. Clin J Am Soc Nephrol 2009 4(4):790-7
 Selby NM, Burton JO, Chesterton LJ, McIntyre CW. Dialysis-induced regional left ventricular dysfunction Is ameliorated by cooling the dialysate. 2006 Clin J Am Soc Nephrol 2006 1(6): 1216–1225
 Eldehni MT, Odudu A, McIntyre CW. Randomized Clinical Trial of Dialysate Cooling and Effects on Brain White Matter. J Am Soc Nephrol. 2014 Sep 18. [Epub ahead of print].
 Selby NM, McIntyre CW. Peritoneal Dialysis is not associated with myocardial stunning. Perit Dial Int 2011; 31:27-33
 Jefferies HJ, Virk B, Schiller B, Moran J, McIntyre CW. Frequent hemodialysis schedules are associated with reduced levels of dialysis-induced cardiac injury (myocardial stunning). Clin J Am Soc Nephrol 2011 6: 1326–1332