Potassium
Too much of a good thing?
by Dr. Greg Curnew, MD and Jeffrey Lee
Vol.20, No.05, August 2012

If any of your patients have suffered from an acute myocardial infarction (AMI) lately, you’ll know it’s essential to closely monitor their serum potassium levels to forestall post-MI arrhythmias. A recent large observational study, however, suggests that the current recommendation for maintaining a serum potassium level between 4.0-5.0 mmol/L may not produce the best mortality benefit.1

AMIs are multifactorial events that cause myocardial damage and trigger adrenergic activity, which subsequently drives potassium into cells and leads to deficiencies in serum K+.2 Several studies have shown a relationship between hypokalemic states (< 3.5 mmol/L) and the occurrence of ventricular arrhythmias in patients with an AMI.3,4,5 As a result, AMI patients are monitored closely through frequent blood tests and receive supplement potassium to reduce the risk of subsequent myocardial infarctions and arrhythmias.

Mortality and serum K+ levels

A recent observational study by Goyal et al that included 38,689 patients found a U-shaped relationship between in-hospital mortality and admission/mean post-admission serum potassium levels. The lowest risk was found in patients with levels between 3.5-< 4.0 mmol/L, who had a comparable mortality risk to patients with levels between 4.0-< 4.5 mmol/L. However, the mortality risk was found to be twice as high in the 4.5-< 5.0 mmol/L group and even higher in patients with severe hyperkalemia (> 5.0 mmol/L) and hypokalemia (< 3.5 mmol/L).1

In other words, the risk of mortality can be reduced with a serum potassium level maintained between 3.5-4.5 mmol/L, but the benefits disappear quickly when levels are under- or over-compensated.

Ventricular arrhythmias/cardiac arrest and serum K+ levels

Goyal’s study also examined the incidence of ventricular flutter, ventricular fibrillation, or cardiac arrest while in-hospital. In contrast to the relationship serum K+ levels had with mortality, a relatively flat relationship with serum potassium levels was produced with these events. Rates were lowest across a broad range of serum potassium levels (3.0-< 5.0 mmol). But these event rates increased for much lower and higher potassium levels (< 3.0 mmol/L and > 5.0 mmol/L, respectively).1

Lack of strong evidence

The optimal serum potassium levels that would produce the most benefit in this setting have yet to be determined. Currently, we lack randomized control trials to base guidelines on and many of today’s recommendations are sourced from old (>20 years), small and underpowered studies.1

Furthermore, rapid advances in cardiac pharmaceuticals and changes in AMI routine care standards, such as the use of beta-blockers, over the last few decades have changed the natural history and prognosis of AMI for the better. So it’s possible that the current guidelines (with respect to serum potassium levels) based on historic data may not be applicable to AMI patients in the current era.

Table 1 Potassium content in food

Potassium and diet

It’s well known that consuming too much sodium leads to vascular disaese, but recent studies have found that potassium is equally important in its prevention. Nowadays, most Canadians consume too much sodium and not enough potassium. The recommended amount of daily sodium and potassium intake is 1,500-2,300 mg and 4,600 mg, respectively. Statistics from Health Canada showed that most adults consume 3,400 mg of sodium and 2,600-3,400 mg of potassium daily. An observational study has found that higher potassium intake is associated with a decreased stroke risk. Another observational study found that modifying diet by adding potassium and magnesium, while reducing sodium, results in a decrease in systolic blood pressure.

Potassium can be incorporated in the diet quite easily. Some sources of potassium can be found in Table 1, and other good sources include cod, lentils, broccoli, celery, green beans, carrots, low-fat yogurt, kiwi, oranges and strawberries.

For those who require potassium supplementation, the Ontario Drug Benefit plan covers prescriptions for K-10 and PMS-Potassium Chloride, which both provide 1.33 mEq/ml. These supplements, though, are only available in liquid form. Pill supplements are available at pharmacies as Slow-K and Apo-K. Both products contain 8 mEq of potassium per pill and cost approximately $20.49 and $13.99 for 100 pills, respectively. Interestingly, 1.5 bananas contains approximately the same amount of potassium as 2 Slow-K pills. And every inch of a banana is said to contain 1 mEq of potassium.

Dual renin blockade

Blocking the renin-angiotensin system has its benefits; however, dual blockade of the system should be avoided. The ON-TARGET trial studied treatment with either an ACE-inhib­itor, ARB, or the combination of both in patients at risk for vascular disease and demonstrated that combination therapy added no significant clinical benefit, aside from a reduction in proteinuria. Instead, there was a significant increase incidence of renal failure, need for dialysis, and hyperkalemia. Hyperkalemia can be deadly as the PEARL-HF study found there was a 10-fold increased risk of death one day after a potassium level > 5.5 mmol/L was achieved. Furthermore, the recent ALTITUDE trial was stopped prematurely because of increased stroke deaths, hyperkalemia, and need for dialysis after diabetic patients with renal insufficiency were treated with a combination of ACE-inhibitor or ARB with a renin-blocker (aliskiren).

How much K is OK?

Goyal et al’s study provides new and updated evidence that, unlike older studies, has more power and a robust population size to clarify the association between outcomes and serum potassium levels. In light of this new study, it’s still clear that having severe hypokalemia (< 3.5 mmol/L) and severe hyperkalemia (> 5.0 mmol/L) is dangerous as it puts patients in a pro-arrhythmia state. But the new evidence challenges the current AMI guidelines of maintaining serum potassium levels between 4.0-5.0 mmol/L. It suggests that a safer range can be found between 3.5-4.5 mmol/L, and that a patient with a serum potassium level between 4.5-5.0 mmol/L carries a higher risk of mortality.

This doesn’t serve as a guide to ideal potassium consumption in healthy people. Potassium is an important electrolyte that can have multiple consequences on health outcomes. The potassium content of vegetables appears to be vascular protective. Eating whole foods rich in potassium has shown by various studies to lower blood pressure and help prevent strokes. Is it possible that some with very high potassium diets are getting too much of a good thing? We just don’t have the data to answer that question.

References

1. Goyal A et al. JAMA 2012;307(2):157-64.

2. Singh RB et al. Biomed Pharmacother 58 Suppl 1:S111-5.

3. Su J et al. Am J Emerg Med 2011 Oct 27; PMID: 22035586.

4. Madias JE et al. Chest 118(4):904-13.

5. Gheeraert PJ et al. Eur Heart J 27(21):2499-510.

Gregory P. Curnew, MD, FRCPC is Associate Professor at McMaster University in Hamilton, ON, and Director of the Coronary Care Unit at Hamilton General Hospital.
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