HemoDoc, From Doctor to Patient

The Kjellstrand Lecture: The Deadly Delay - Part III: The Killer Weekend

By Peter Laird, MD

The NEJM recently published a widely acclaimed study on the elevated death rates of 32,065 hemodialysis patients on Monday and Tuesday after the long "killer weekend." This is considered one of the most important medical studies in the field of nephrology in 2011. The Renal Fellow Network does an annual survey on the most important clinical developments each year and then publishes the results in a top ten posting. This year, the NEJM elevated mortality with the long interdialytic interval article was rated as the third most important study in 2011. (here)

Long Interdialytic Interval and Mortality among Patients Receiving Hemodialysis

BACKGROUND: Patients with end-stage renal disease requiring dialysis have limited tolerance of metabolic and volume-related deviations from normal ranges; in addition, the prevalence of cardiovascular disease is high among such patients. Given these problems, we hypothesized that a long interdialytic interval is associated with adverse events in patients receiving hemodialysis.

CONCLUSIONS: The long (2-day) interdialytic interval is a time of heightened risk among patients receiving hemodialysis. (Funded by the National Institutes of Health.)

However, these were not new and groundbreaking results. The issue of increased deaths with the long interdialytic interval is a well known phenomenon that has been ignored by nephrology for more than a decade. A.J. Bleyer et al, studied the records of 375,482 dialysis patient deaths in the USRDS from 1977 to 1997, a twenty year study period. This study showed direct evidence of an increased risk of death from hemodialyis after the long interdialytic interval which was not found in PD patients.  PD patients deaths are evenly distributed  among each day of the week. Likewise, non cardiac deaths in hemodialysis patients are not elevated on Monday or Tuesday.

Sudden and cardiac death rates in hemodialysis patients

The results from the entire USRDS database indicated a nonrandom distribution of cardiac deaths for HD patients. Figures 1 and 2 demonstrate that although cardiac and noncardiac deaths for PD patients are rather evenly distributed throughout the week, cardiac deaths in HD patients occur most frequently on Monday, with the next most common day of death being Tuesday. In addition, noncardiac deaths for HD patients are evenly distributed throughout the week.

Data from the CMAS were then used to identify the most likely dialysis schedule. MWF HD patients were much more likely to die a cardiac death on Monday than other days of the week. Wednesday and Friday—the other dialysis days—were the next most common days of cardiac death. Deaths from noncardiac causes were evenly distributed. Patients on a TTS dialysis schedule were more likely to die from a cardiac cause on Tuesday than other days, although these changes were not as prominent.

A second study by Karnik, et al in 2001 confirmed these results among a study group of more than 77,000 patients.

Cardiac arrest and sudden death in dialysis units.

BACKGROUND: For patients with end-stage renal disease and their providers, dialysis unit-based cardiac arrest is the most feared complication of hemodialysis. However, relatively little is known regarding its frequency or epidemiology, or whether a fraction of these events could be prevented.

METHODS: To explore clinical correlates of dialysis unit-based cardiac arrest, 400 reported arrests over a nine-month period from October 1998 through June 1999 were reviewed in detail. Clinical characteristics of patients who suffered cardiac arrest were compared with a nationally representative cohort of> 77,000 hemodialysis patients dialyzed at Fresenius Medical Care North America-affiliated facilities.

In my opinion, the most astounding revelation of the NEJM long interdialytic article of 2011 is that there has not been any change in therapy since two much larger studies were published over a decade prior to its publication showing exactly the same results. Mortality among American dialysis patients has flatlined for over twenty years as more and more patients flatline more often on Monday and Tuesday from preventable cardiac deaths.  It has puzzled me greatly why this NEJM article made such headline news around the world and fostered surveys declaring this "news" the third most important clinical study of 2011 when in many ways, it was inferior to the prior studies in terms of patient numbers and years of study.

Perhaps we will never know the impetus behind this study and the inordinate attention it received, but we do know that in the year of the bundle going into effect, this study has led many to recommend PD more often instead of looking at alternative HD modalities such as every other day dialysis and daily dialysis. The cost differential for PD vs daily HD points to PD as the most "cost effective" therapies if only considering clinic expenses alone. However, if you consider survival and total patient expenditures including hospitalization and pharmaceuticals, daily HD is the most cost effective and best survival strategy for dialysis patients with PD having equal survival to in-center conventional hemodialysis. (here)

Dr Kjellstrand calculated the number of lives in the last ten years from 2001 to 2011 that could have been saved from what we knew then on the long dialysis weekend excessive deaths. During the time that the FHN study was conceived, planned, implemented and reported, over 10,400 lives a year could have been saved instead of waiting ten years for the publication of the FHN and the long interdialytic weekend mortality studies, both in the NEJM. Sadly, despite all of these studies on the long killer weekend, the best that the academic nephrologists can recommend with confidence to America is that we need to study this issue further before making a commitment to more frequent hemodialysis schedules. How many more years will we see over 10,000 patients needlessly lose their lives year after year after year. This is now a ten year debate that has yet to see any action to eliminate to date. When will we end the killer weekend?

Slides courtesy of Dr. Carl Kjellstrand.

The Kjellstrand Lecture: The Deadly Delay - Part II: Potassium and Fluid Balance

By Peter Laird, MD

In Dr. Kjellstrand's Annual Dialysis Conference lecture in 2009, he focussed on two of the most important basic physiology lessons for those prescribing dialysis is the fluctuation and "unphysiology" of potassium levels and  volume status. Prior to dialysis, most hemodialysis patients have potassium levels higher than 5.0 and after dialysis, especially if a 1K bath is used, the serum potassium levels may fall below 3.0 leaving the patient always above or below the normal range for potassium levels. Daily dialysis eliminates the high and low fluctuation of potassium levels keeping levels between 3.5 - 4.8 at all times. 

A recent article in the Journal of the American Medical Association on potassium fluctutions in heart attack patients treated with infusions of intravenous potassium to keep the levels above 4.0 experience more episodes of cardiac arrhythmias and death when the levels of potassium were higher than 4.5 and lower than 3.5 in a U-shaped outcomes profile:

Serum potassium levels and mortality in acute myocardial infarction

RESULTS: There was a U-shaped relationship between mean postadmission serum potassium level and in-hospital mortality that persisted after multivariable adjustment. Compared with the reference group of 3.5 to less than 4.0 mEq/L (mortality rate, 4.8%; 95% CI, 4.4%-5.2%), mortality was comparable for mean postadmission potassium of 4.0 to less than 4.5 mEq/L (5.0%; 95% CI, 4.7%-5.3%), multivariable-adjusted odds ratio (OR), 1.19 (95% CI, 1.04-1.36). Mortality was twice as great for potassium of 4.5 to less than 5.0 mEq/L (10.0%; 95% CI, 9.1%-10.9%; multivariable-adjusted OR, 1.99; 95% CI, 1.68-2.36), and even greater for higher potassium strata. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. In contrast, rates of ventricular fibrillation or cardiac arrest were higher only among patients with potassium levels of less than 3.0 mEq/L and at levels of 5.0 mEq/L or greater.

CONCLUSION: Among inpatients with AMI, the lowest mortality was observed in those with postadmission serum potassium levels between 3.5 and <4.5 mEq/L compared with those who had higher or lower potassium levels.

If we extrapolate these results to the hemodialysis setting, it shows just how dangerous potassium fluctuations are in patients with myocardial ischemia (insuficient blood flow and oxygen delievery to the heart tissues). Lest some would criticize this as a different population than the dialysis population, I would remind the readers that dialysis patients have a very high prevalence of myocardial ischemia during each dialysis session. (here, here and here).

Likewise, patients experience constant difficulties managing fluid balance with thrice weekly dialysis protocols, especially following the "killer" dialysis weekend. Nephrologists have adopted a variety of methods to avoid intradialytic hypotension (low blood pressure while undergoing dialysis) but most reviews do not acknowledge the simple physiology of depleting the cardiovascular compartment (heart and vessels) and the slower replenishment of fluid back into the blood vessels from edematous "3rd space" tissues that most patients recognize as swelling in their legs but instead focus on various treatment options except for the most important, increasing time or frequency of dialysis to prevent hypotension in the first place. With only 5 liters of blood and plasma in the the blood vessels, patients undergoing dialysis with 4 liters taken off by ultrafiltration will always experience various symptoms of cardiovascular collapse if taken off too rapidly. The rate limiting step is how fast, or more aptly, how slowly these fluids in the swollen tissues return to the blood system.  Dr. John Agar has an excellent overview of fluid and solute shifts during dialysis on Home Dialysis Central. (here and here)

With daily dialysis, patients do not experience the wide variations in fluid balance and because they keep the extreme elevations seen in thrice weekly conventional in-center dialysis to a minimum, these patients do not experience many of the "common" or "expected" symptoms associated with dialysis including low blood pressure, severe cramping, nausea and vomiting and passing out.  Dr Scribner believed in sodium restriction as the primary method of controlling blood pressure by controlling the volume status. However, daily dialysis lessons the burdens of severe fluid restrictions for patients enhancing the quality of life. 

All of these factors are described in an extensive body of literature describing potassium and fluid balances with daily vs thrice weekly schedules. Paradoxically, the medical specialty most established on the principles of basic physiology is also the specialty that dismisses this knowledge during the practice of dialysis. Daily dialysis is the only modality that aligns with the physiology of the normal state. Standard dialysis does not restore the "interior milieu" to normal at any time. Daily dialysis on the other hand does restore this balance to more physiologic fluctuations and eliminates the extremes of change that cause much of the morbidity and mortality associated with dialysis. By avoiding these highs and lows, dialysis patients are at less risk of many of the symptoms and complications associated with dialysis therapy. The FHN studies did not contribute new evidence to what has been known for over 40 years already.  Knowing physiology is the first step in understanding optimal dialysis.

Slides by permission from Dr. Carl Kjellstrand.

Should Dialysis Patients Take Statins to lower Heart Risk?

By Peter Laird, MD

The debate over cholesterol management of dialysis patients is filled with divergent data from several studies. Some studies actually indicate an increased rate of survival with higher cholesterol levels, but these outcomes are clouded by the effect that malnutrition/inflammation has on mortality. In this case, the findings of elevated cholesterol and higher survival are more likely a secondary measure of poor nutrition and higher death rates from the malnutrition/inflammation connection:

Association Between Cholesterol Level and Mortality in Dialysis Patients: Role of Inflammation and Malnutrition

Conclusions The inverse association of total cholesterol level with mortality in dialysis patients is likely due to the cholesterol-lowering effect of systemic inflammation and malnutrition, not to a protective effect of high cholesterol concentrations. These findings support treatment of hypercholesterolemia in this population. 

However, further randomized and controlled studies found no benefits to dialysis patients with statin therapy. The 4D trial was a double blind, placebo controlled RCT evaluating 1255 patient on dialysis that also had Type II diabetes. After four years comparing Artovastin (lipitor) to placebo, there was no difference in mortality even though there were fewer cardiac events due to a higher than expected number of cerebrovascular events. In 2009, many nephrologist believed that the AURORA trial, the second major clinical trial of statins in dialysis patients, settled the issue for good when it likewise found no survival benefit in dialysis patients:

AUROROA Trial Results

A total of 804 patients had a major cardiovascular event during the followup period, of which 396 were in the rosuvastatin group and 408 were in the placebo group (9.2 and 9.5 events per 100 person-years of followup respectively). There was no significant effect of treatment with rosuvastatin on the primary combined endpoint (HR 0.96; 95% CI 0.84 to 1.11; p = 0.59). There was also no significant effect of treatment with rosuvastatin on the individual components of the primary endpoint. A summary of the AURORA trial results can be found in the Table. The lack of effect of rosuvastatin on the primary endpoint was consistent among all subgroups including those with diabetes, high LDL-C level, elevated hsCRP, hypertension and preexisting CVD. The lack of effect of rosuvastatin on the primary endpoint was also not influenced by overall time on hemodialysis.

The latest study evaluating cholesterol lowering in patients with chronic kidney disease to include dialysis patients is the SHARP trial.  It is the first study showing any benefit to cholesterol lowering in this population. Granted, patients not yet on dialysis had a greater benefit than those on dialysis, the results remain provocative.

The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomized placebo-controlled trial

After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0·2%] vs 5 [0·1%]). There was no evidence of excess risks of hepatitis (21 [0·5%] vs 18 [0·4%]), gallstones (106 [2·3%] vs 106 [2·3%]), or cancer (438 [9·4%] vs 439 [9·5%], p=0·89) and there was no significant excess of death from any non-vascular cause (668 [14·4%] vs 612 [13·2%], p=0·13).

Interpretation

Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease.

One of the difficulties of studying the cardiovascular benefits of statins in dialysis patients is that most cardiac events in dialysis patients appear to from a different mechanism of action than plaque rupture and thrombosis leading to acute coronary syndrome and myocardial infarction.

High ultrafiltration rates, short dialysis treatment times, mineral-bone disorders, rapid electrolyte shifts and underlying LVH are all factors leading to myocardial stunning, hybernation and myocardial ischemia during the dialysis procedure. These confounding cardiac factors have never been controlled and eliminated in dialysis patients who have a significantly higher risk of sudden cardiac death. The results of the SHARP trial showing significant benefits in CKD patients not on dialysis should not lead to dismissing the use of statins in dialysis patients from studies not designed to eliminate these other factors. Instead, there is no reason physiologically for an improved clinical outcome especially in daily, home dialysis patients who are at lower risk of LVH, rapid electrolyte shifts and myocardial ischemia than those that are in-center patients.

Before eliminating statin therapy from dialysis patients as many nephrologists now advocate, any further studies should consider Dr. Kjellstrand's Unphysiology theory leading to testing statins in the most stable dialysis population, home dialysis patients on daily, nocturnal dialysis. These patients have documented reversal of LVH and significantly lower mortality than standard in-center patients that the prior cholesterol studies have used as their study population. For myself, I personally believe that statin therapy is just as important in dialysis patients as in any other patient at risk for acute cardiovascular outcomes. It may be the large number of confounding factors leading by a different path to cardiovascular deaths that confounds any benefit of statin therapy. If we are to answer this question definitively, designing a trial in well nourished patients at lower risk of cardiovascular outcomes in the first place might significantly highlight the need not only for statins but optimal dialysis as well.

Troubling Study on Hemodynamic Consequences of Altering Potassium Levels in Dialysate

By Peter Laird, MD

One of the greatest challenges to improving outcomes in hemodialysis patients is reducing the incidence of sudden cardiac death. In fact, more hemodialysis patients die as the result of sudden cardiac death from arrhythmia's than they do from actual myocardial infarctions (heart attacks). Hemodialysis patients also present with different symptoms during a myocardial infarction than those without renal disease and dialysis therapy with less complaints of chest pain and higher risk of cardiac arrest while hospitalized. Yet, the underlying pathophysiology of this observed increased risk of sudden cardiac death remains largely unstudied to date.

In addition to sudden cardiac death, many dialysis patients are at high risk of intradialytic hypotension (IHD) during hemodialysis itself. Elevated ultrafiltration rates higher than 10 ml/h/kg significantly increase the risk of IHD as well as congestive heart failure in the long run. Myocardial ischemia during hemodialysis leads to long standing myocardial stunning and hybernation, all of which predispose patients to increased frequency of hemodynamically significant episodes of IHD, especially in those patients with known congestive heart failure and myocardial fibrosis with left ventricular enlargement (LVH). Any studies evaluating the hemodynamic effects of differing dialysis modalities should include baseline characteristics and intradialytic cardiovascular parameters to ensure the safety of the intervention.  In addition, these types of studies should not include any patients at high risk for poor cardiovascular outcomes.

The study in question evaluated differing potassium levels on hemodialysis patients by testing blood pressure responses and peripheral vascular resistance in three separate dialysis solutions, one point below, one point above and normal potassium dialysate levels. However, the authors did not monitor for myocardial ischemia during the different sessions, nor did they exclude those elderly patients with known risks of sudden cardiac death from underlying LVH.

Haemodynamic consequences of changing potassium concentrations in haemodialysis fluids

Results. Comparing K-1 and K+1, differences were found within the tertiles regarding systolic (+5.3, +6.6, +2.3 mmHg, p<0.05, <0.05, ns) and mean blood pressure (+4.3, +6.4, -0.5 mmHg, p<0.01, <0.01, ns), as well as peripheral resistance (+212, +253, -4 dyne.sec.cm-5, p<0.05, <0.05, ns). The stroke volume showed a non-statistically-significant inverse trend (-3.1, -5.2, -0.2 ml). 18 hypotension episodes were recorded during the course of the study. 72% with K-1, 11% with K and 17% with K+1 (p<0.01 for comparison K-1 vs. K and K-1 vs. K+1). 

Conclusions. A rapid decrease in the concentration of serum potassium during the initial stage of the dialysis obtained by reducing the concentration of potassium in the dialysate translated into a decrease of systolic and mean blood pressure mediated by a decrease in peripheral resistance. The risk of intra-dialysis hypotension inversely correlates to the potassium concentration in the dialysate. 

Unfortunately, despite the well documented occurrence risk of low potassium, none of these high risk elderly patients with a high prevalence of known ischemic cardiomyopathy had any cardiac monitoring for ST depression during dialysis, nor did they follow these patients for hypoxia which low potassium baths are likewise documented causing. In addition, myocardial ischemia and myocardial stunning are likewise induced by low potassium dialysate levels yet the authors once again did not measure these parameters as well. In such, this elderly group of patients with known ischemic  cardiomyopathy in my opinion were placed at great risk by this experimental protocol which I am sure would be approved in and United States university setting.

Lastly, because the experimental parameters measured were of the most fundamental and in essence primitive clinical sophistication, the conclusions of this experiment on causation of the results observed are essentially nonexistent since many different clinical scenarios can account for the observed results.  The authors so noted in their discussion some of these short fallings on their data:

However, if we take into account the experimental data obtained from animals besides the typical metabolic circumstances of kidney failure that requires dialysis, it is surprising to observe the haemodynamic pattern that is traced and which, contrary to expectations, shows a hypertensive effect for acute decrease in serum potassium. In fact, the experimental hypokalaemia model demonstrates a vasoconstriction and an increase in myocardial contractility [11-13]. The difference between the theoretical and the observed pattern could be due to the method employed to evaluate peripheral resistance (indirect, non-invasive measurements using beat-to-beat in our case) and the metabolic circumstances of dialysis with sharp variations in other factors that together can modify haemodynamics (calcaemia, osmolarity, acid-base balance, temperature), as well as concomitant counterregulatory phenomena, particularly the sympathetic and renin- angiotensin systems. The fact that hypokalaemia sensitizes myocardium to hypoxic related dysfunction [26] together with the selection for the study of an elderly population (mean age 70.3 years) with a high incidence of ischemic cardiomyopathy (10 out of 24 subjects) could have influenced the incidence of intra-dialytic hypotensions and the results. Moreover two other reasons could potentially explain a blood pressure reduction related to acute potassium decrease in the dialysis population: hypokalaemia may exacerbate autonomic dysfunction while intra-dialytic potassium loss accounts for a decrease in total osmoles [7].  

Regardless of the pathophysiological explanations of the haemodynamic consequences, the results are potentially relevant in that (i) dialysate potassium concentration could theoretically be modulable in a profile, as proposed for other electrolytes like sodium and bicarbonate and (ii) more attention could be paid to controlling the potassium balance with alternative measures (diet, chelating agents, avoidance of medications which inhibits the renin-angiotensin system if unnecessary [27] and possibly prescription of mineralocorticoids [28]). 

Thus, the authors in this ill advised and poorly executed study advance proposed clinical solutions to the resultant observations even though they have not elucidated the underlying pathophysiology of the data observed.  The ethical prohibition against experimentation that places patients at risk were not applied to this study with elderly patients, nearly half of which with known ischemic cardiomyopathy. In addition, they had no documented electrocardiographic monitory and oxygen saturation accompanied the simply blood pressure results. Nor did the authors evaluate any of these patients for regional wall motion abnormalities during the differing potassium levels.  A simple measure of cardiac enzymes could have substituted for the more expensive cardiac imaging. In addition, the authors did not comment on the measured levels of potassium in the patients. It is already known that giving a 3 K bath to dialysis patients with a potassium level higher than 5.6 is dangerous with 17% of the hypotensive episodes noted in the high potassium groups:

Prevention of Sudden Cardiac Death in Dialysis Patients: A Nephrologist's Perspective

Notably, the inappropriate use of a high-potassium dialysate (Greater than or equal to 3 mEq/L) in patients with a serum potassium greater than 5.6 mEq/L was associated with an increased risk of death.24 

I am thus confounded by the lack of effective safety measures utilized, the known high risk interventions in high risk patients with ischemic cardiomyopathy, the lack of defined pathophysiologic etiology of the data observed by virtue of only basic hemodynamic monitoring of the peripheral blood pressure alone all draws attention to how poorly designed this study truly is that also adds little to the discussion of intradialytic hypotension in dialysis patients due to variable potassium levels.

Unfortunately, hemodialysis patients benefit little from all of the experiments performed to date even when marked benefits are discovered, the American nephrology community in general chooses to simply ignore those findings such as the FHN and more frequent hemodialysis. However, evaluating this study reveals the cavalier approach that these researchers undertook in placing elderly, high cardiovascular risk patients to the known cardiovascular stressors with the not unexpected results obtained of increased intradialytic hypotension. In a word, I am appalled. The fact that this study not only survived ethical evaluation by a committee before it commenced and peer review prior to publication should cause great concern among dialysis patients due to the number of cardiovascular risks placed upon these patients with no safeguards. The most pertinent question is what if any cautions did the researchers advise these patients during the informed consent for the experiment? This is one of the most troubling experiments I have ever encountered.

Nature Reviews Nephrology Ignores the FHN LVH Outcomes

By Peter Laird, MD

Since entering into the dialysis advocacy forums nearly three years ago through an invitation by Bill Peckham (DSEN) and Dori Schatell (HDC), the evidence of overwhelming American nephrology negativity towards optimal dialysis strategies is striking.  Dori and Bill first revealed to me basic dialysis studies over the last five decades which lists hundreds of studies with positive outcomes for more frequent and longer duration dialysis with no negative studies to date. Yet the American academic nephrology community continues to denigrate and ignore these fundamental results stating that they have not yet been proven by a randomized and controlled trial.  

The latest example of academic bias in my opinion by Nature Reviews Nephrology and Medscape shows overt bias against optimal dialysis by completely ignoring the Frequent Hemodialysis Network Trial Group's positive LVH results of frequent hemodialysis dosage while at the same time encouraging automated defibrillators and implantable cardioverter-defibrillator based on theoretical decision analysis models and personal opinion, not actual RCT evidence:

Sudden Cardiac Death in Chronic Kidney Disease: Epidemiology and Prevention

Dialysis dose

Higher dialysis dose may control volume overload, improve the uremic milieu, diminish levels of inflammatory markers and reduce LVH and LV dilation, thereby reducing the risk of sudden cardiac death. . .

. . . However, daily hemodialysis could potentially reduce cardiovascular events or mortality. Although no randomized trials with hard clinical end points have been undertaken, Culleton et al. have demonstrated improvement in LV mass index in those randomly allocated to daily dialysis compared to conventional dialysis.76

In conclusion, currently there are insufficient data to make any recommendations about increasing dialysis dose to reduce the risk of sudden cardiac death in patients with ESRD. . . 

Conclusions

CKD is a risk factor for sudden cardiac death. The rate of sudden cardiac death is very high in patients undergoing dialysis. Cardiomyopathy and ischemic heart disease predispose to conduction abnormalities and arrythmogenesis, which can be exacerbated by electrolyte shifts, sympathetic overactivity, and baroreflex abnormalities. Inflammatory markers and diabetes are predictors of sudden death. Cardiac arrests in dialysis units occur in 7 per 100,000 hemodialysis sessions and are associated with the underutilization of automated external defibrillators. Survival following cardiac arrest is very poor. The decision to implant a cardioverter-defibrillator should be influenced by age and CKD stage.

The authors of this review further ignored the implications of these RCT findings by Culleton in the paper they did review, but failed to relate that reduction of LVH by daily, nocturnal dialysis in turn reduces sudden cardiac death directly.

JAMA Reports

Nighttime, Home Dialysis Appears Beneficial for Kidney Failure Patients

Bruce Culleton, M.D., M.Sc. 
University of Calgary 

AUDIO:
“This new type of dialysis reduces the negative effects of kidney disease on the heart and in doing so, we believe this reduces the risk for future heart attack, heart failure and sudden death.”

The basis of the encouraged usage by the authors to utilize implantable cardioverter-defibrillator is based on a decision analysis (a theoretical computer generated outcomes study) while they concurrently ignored the FHN RCT results.  The authors also advocate increasing access to automated external defibrillators in the dialysis setting even though they admittedly relate that this recommendation is not based on any data, just personal opinion:

Automated external defibrillators

Although data do not exist to support a survival benefit of AED placement in dialysis centers, it seems reasonable to provide AEDs for use in patients who want resuscitation if they arrest.

The evidence of American academic bias towards more frequent and longer duration dialysis is not in the least mitigated by the directed dialysis industry support fostering this biased view.  Indeed, in this article that completely overlooks the FHN, the required financial disclosure and associations reveals a possible incentive behind the recommendations of the authors for defibrillator devices even without any data to support that conclusion:

1. Drs. Wood and Ellenbogen report participation in device-related clinical research supported by grants from Medtronic, Guidant, St. Jude Medical, and Cameron Health. Dr. Ellenbogen reports having received honoria from Medtronic, Guidant, and St. Jude Medical.

The relationship between "impartial" scientific researchers and those that impart research grants runs deep in modern American medicine breeding an incestuous relationship between the medical industry and their researchers.  Sadly, many clinicians in their busy daily practice do not often have the time to thoroughly review the literature in enough detail to critically analyze the strengths and weaknesses of individual studies and reports, review articles especially.  Instead, it is often the title alone that will create a lasting impression of an alleged benefit or lack there of that is in fact misleading at best.  

The only solution to this attack on the integrity of current medical studies in my opinion is for the reader of the journals to actively critique openly all evidence of academic bias in our journals. Ultimately, the final arbiter must be the clinicians utilizing these evidence based results themselves. The medical blogosphere is the best place to do this since peer review and editorial oversight does not prevent publication of what in my opinion are biased articles as the one in question above. 

New CPR Technique Boosts Survival

By Peter Laird, MD

Hands-Only CPR is the latest update on the life saving procedure used for over four decades called cardio-pulmonary-resuscitation of CPR for short. Out of hospital CPR performed by non-medical personnel is often hampered by responders who don't want to give mouth to mouth resucitation when performing CPR.  The good news not only for repsonders but victims of sudden cardiac death is that the mouth to mouth part of CPR is no longer required or recommended with the new Hands-Only CPR method:

 

A newly published article in the Lancet shows a remarkable 53% increased survival with an alternative method for professional responders using two hand held devices.

New CPR Technique for our-of-hospital Cardiac Arrest Increases Survival by 53%

The new technique uses two devices simultaneously to increase circulation. One is a handheld device that attaches with a small suction cup to the patient's chest. After each compression, the suction cup allows the chest to be lifted up, stimulating blood flow. The second device, called an impedance threshold device, attaches to the patient's airway using a facial mask or breathing tube. When the chest lifts upward, the impedance threshold device prevents air from rushing into the lungs. That creates a vacuum inside the chest and helps refill the heart after each compression. Researchers found in each compression-decompression cycle, the heart and brain receive nearly three times more blood flow when compared with standard CPR.

For initial bystander response, the Hands-only CPR is a lifesaving bridge waiting for the EMT's/Paramedics to respond. It will be interesting to see if the devices noted in the Lancet article translate into real life practices that confirm the degree of response found in this article.  Improving intial response outcomes gives the doctors in the Emergency Room much more to work with than the usual dead on arrival cardiac arrest victims.   Applying the combination of Hands-Only CPR with these simple devices will give many victims of sudden cardiac arrest the chance to recover completely as I have seen in only a handful of patients from my own practice. 

Early Initiation of Dialysis Increases Mortality Risk

By Peter Laird, MD

Gary Peterson of RenalWeb listed an important confirmatory study from the Canadian Medical Association Journal on the timing of dialysis initiation and remaining residual renal function.  This is the second major study looking at the issue of early initiation of dialysis that not only shows no benefit, but actual harm may occur with this strategy. The IDEAL study recently published in the NEJM revealed no benefit of early dialysis.  The CMAJ article available in full .pdf delves into some of the putative reasons why those with preserved renal function at onset of dialysis may actually be at higher risk.  Ultrafiltration practices may be at the center of this debate:

Association between estimated glomerular filtration rate at initiation of dialysis and mortality

A nonsignificant increase in cardiovascular deaths in the early-initiation group was observed in both this study and the IDEAL trial. Sudden cardiac death is the most common cause of death among patients undergoing hemodialysis,and some researchers have suggested that sudden cardiac death may be precipitated by the dialysis procedure itself. Patients with higher residual renal function have less intradialytic weight gain because clearance is preserved, and they may be at greater risk for hypotension because of ultrafiltration from the dialysis. The increased risk of hypotension with its attendant effect on cardiac ischemia, combined with myocardial stunning, could contribute to increased mortality among patients with initiation of dialysis at higher levels of estimated glomerular filtration rate. Consistent with this hypothesis, Termorshuizen and coworkers found that excess ultrafiltration in relation to intra-dialytic weight gain was associated with increased mortality. 

Sadly, I have read on IHD several patients complaining that their dialysis techs and nurses ignore their complaints that the ultrafiltration rates are too excessive and instead simply brand them as difficult patients.  Yet the evidence mounts that excessive ultrafiltration rates are deadly causing myocardial ischemia (lack of oxygen and blood flow to the heart) leading to scarring of the heart called fibrosis. The precise cause of the the increased mortality associated with early initiation remains unproven and the discussion above at this point is speculative.  The take home message is that the clinical presentation is a stronger indicator of the need for dialysis initiation than simply an arbitrary GFR level. 

The FHN defined optimal dialysis strategy as more frequent and longer duration, yet again, the mechanics of dialysis and ultrafiltration rates, potassium levels in dialysate, blood pump speed, ultra-pure dialysate, avoiding reuse all are areas of further research with much evidence to date that we need to modify our dialysis practices to avoid what appear to be iatrogenic complications of dialysis. It is time to enter into a period of reevaluating optimal dialysis practices and implementing the best survival strategies for the benefit of all needing this life saving renal replacement alternative.