HemoDoc, From Doctor to Patient

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.

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. 

The Holiday Heart Syndrome

By Peter Laird, MD

The holidays are a time that we associate with rest from work and gathering together with friends and family over food and drink watching football games and eating too much. With Thanksgiving, Christmas and New Years, doctors who work in the hospital will spend many of those same holidays taking care of patients who have not only eaten too much, but also have drank excessively to the point that they actually develop life threatening arrhythmias such as atrial fibrillation and supraventricular tachycardias from the acute alcohol intoxication.   Holidays for doctors and healthcare workers is not a time of rest with ED's filled with many otherwise healthy people presenting with the so called holiday heart syndrome first coined in 1978 by Ettinger, et al. 

Alcohol and rhythm disturbance: the holiday heart syndrome.

The association between alcohol use and rhythm disturbances, particularly supraventricular tachyarrhythmias in apparently healthy people is called "holiday heart syndrome". The syndrome was first described in persons with heavy alcohol consumption, who typically presented at weekends or after holidays, but it may also occur in patients who usually drink little or no alcohol. The most common rhythm disorder is atrial fibrillation, which usually converts to normal sinus rhythm within 24 hours. The incidence of the holiday heart syndrome depends on the drinking habits of the studied population. The holiday heart syndrome should be considered particularly as a diagnosis in patients without overt heart disease presenting with new onset atrial fibrillation. Though recurrences occur, the clinical course is benign and specific antiarrhythmic therapy is usually not warranted.

So while you are sitting at the table over all of the upcoming holidays, if you can't remember to be kind to your heart and keep all alcoholic intake in moderation, do it to be kind to the doctor who will take care of you when you present with a rapid heart rate, shortness of breath, dizziness and a pounding sensation in your chest.  I am sure that the kind hearted doctor caring for you in that situation would much rather be home with his own family and friends enjoying the dinner awaiting him as well.

Happy holidays and stay healthy.