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Wednesday, September 26, 2012

The link between Albuterol and Potassium

It's a proven fact that beta adrenergic medicine such as epinephrine, Albuterol and Levalbuterol cause a decrease in serum levels of potassium.  I've received several questions about this including the following:
  • If I use Ventolin, do I need to be concerned about my potassium level?
  • Can Ventolin be used to lower potassium in patients with hyperkalemia?
In a quest to answer these questions I did the following research. To get started, we'll answer some of the basic questions about the beta adrenergic/ potassium relationship?

What is potassium?  

It's a mineral that is important to maintain normal function of cells.  It's also an electrolyte that plays a vital role in heart function and skeletal muscle contraction.  The effects of potassium inside the body are kept at a balance by the sodium/ potassium pump, which I describe below.  If potassium is high (hyperkalemia) it can cause muscles spasms or cramps, and this can also lead to abnormal heart rhythms and death.  I describe the importance of potassium in the link provided in the next paragraph.  

How is potassium maintained in the body?

To understand how medicines like Albuterol lower Potassium it's important to understand some of the basics of human anatomy.  To answer this question I will quote myself, "The balance of sodium and potassium:" 
Ann Crawford in her article "Balancing act:  Sodium and Potassium" in the July issue of Nursing (pp. 44-50) describes the pump as the main mechanism of moving sodium "from inside cells to the extracellular compartments, and returns potassium from the extracellular compartments into cells using adenosine triphosphate (ATP) as an energy source."

She likewise explains that electrolytes tend to move from areas of high concentrations to lower concentrations.  So the body naturally works to maintain potassium inside cells 35 times greater than outside cells so potassium has a tendency to want to get out of cells.  Likewise, sodium outside cells is kept 14 times greater than inside cells so sodium has a natural tendency to want to go into cells.

Sodium attracts water. So if sodium levels inside the cell were to get too high the cells would absorb water and would swell and ultimately explode.  Obviously this wouldn't be good.

Rene Fester Kratz in his book "Molecular & Cell Biology for Dummies" explains the pump as a protein in cellular walls and "for every round of action, the sodium potassium pump moves three sodium ions out of the cell and two potassium ions into the cell.  Thus the pump creates a higher concentration of sodium outside the cell, a higher concentration of potassium inside the cell, and a greater positive charge outside the cell.  These differences in ion concentration and electrical charge are important in the functioning or nerve and muscle cells in animals."
Why do beta adrenergics lower potassium?

According to, "Why Albuterol lowers potassium,"the following is how beta adrenergics lower potassium:
To understand how albuterol can decrease your potassium levels, you need to understand how certain hormones, known as catecholamines, affect potassium. Catecholamines, such as the hormone epinephrine and adrenaline, increase the activity of a protein known as a sodium-potassium ATPase. When this protein is activated, it pumps potassium into cells while also pumping sodium out of cells. The movement of potassium into the cells causes a decrease in the amount of potassium in the blood.
Albuterol (and Levalbuterol) is known as a beta-2 agonist. This means that it is able to bind to and mimic the effects of adrenaline on certain cells, including its ability to trigger the transport of potassium out of the blood. Consequently, taking albuterol can lower your potassium levels. This may make your muscles weak or cause muscle spasms, and it can also cause an abnormal heart rhythm. Other symptoms of hypokalemia include fatigue, constipation and the breakdown of muscle fibers.
In this way, adrenaline and beta adrenergics induce a similar effect to insulin in causing  the sodium/ potassium ATPase pump to pump more potassium into cells, and thereby reducing serum potassium levels.

Does Levalbuterol (Xopenex) have the same ability to lower potassium?  

Yes.   A 2005 report by the Emergency Medicine Residency, Grand Rapids MERC/ Michigan State University, "Nebulized levalbuterol or albuterol for lowering serum potassium," notes that Xopenex is equally capable at lowering potassium as albuterol.  

In medical emergencies, is albuterol an effective therapeutic means of lowering potassium? 

This is something that many respiratory therapists frown upon, because we find that many doctors will order one breathing treatment of 0.5cc albuterol with the intent of lowering potassium.  Past studies have concluded the therapeutic dose should be 5-20 mg of Albuterol over a 15-20 minute period.  

According to "Hyperkalemia Revisited" (Parham, Walter A, et al, Tex Heart Inst J. 2006; 33(1): 40–47), the following should be considered as the evidence:
Growing evidence suggests that there may be a role for albuterol in the treatment of patients with severe hyperkalemia. Catecholamines activate Na-K ATPase pumps through β2 receptor stimulation in a manner that is additive to the effect of insulin.(1, 2) In a study by Montoliu and coworkers, (3) 0.5 mg of intravenous albuterol was given to patients with hyperkalemia, leading to a 1-mEq/L decrease in serum potassium levels with minimal adverse effects. (4) Because there are no approved intravenous forms of β agonists available in the United States, studies have been performed to determine whether nebulized β agonists would have a similar effect on serum potassium levels. One such study found that albuterol, when given in very high doses (10–20 mg vs the normal 0.5 mg), decreased potassium levels by 0.62 to 0.98 mEq/L.45 The onset of action for inhaled albuterol was immediate and lasted for 1 to 2 hours. Although in these studies the effects varied among individuals, β2agonist administration was found to be safe and was associated with a significant decrease in serum potassium levels. Therefore, β2 agonist therapy should be considered as an adjunctive treatment for patients with severe hyperkalemia.
Emphasis added by this author.  So you can see there is mounting evidence that Albuterol can be an effective therapy for hyperkalemia, if given in therapeutic doses.

Should Albuterol be a front line therapy for hyperkalemia?

The authors of oxford journals (Kamel, S. Kamel, Charles Wei, "Controversial issues in the treatment of hyperkalemia," Nephrology Dialysis Transplantation, 2003, Vol. 18, Issue 11, pages 2215-2218) agree with the study results as mentioned in the last section. They go on to question the use of albuterol as a front line therapy for hyperkalemia:
Nonetheless, we have reservations about the use of β2 agonists as a first-line therapy in emergency treatment of hyperkalaemia. First, 20–40% of patients studied have a decline in PK of <0.5 mM and it is not possible to predict who will fail to respond. Secondly, there are safety concerns because the doses used are 4–8 times those prescribed for the treatment of acute asthma. Although no severe adverse events were reported, most of these studies were performed in stable patients. Some of these studies excluded patients on β-blockers and those with significant coronary heart disease or unstable heart rhythms. Therefore, the safety of these agents was determined in a group of patients that may not resemble the general ESRD population.
Allon and Copkney (5) examined whether the effect of nebulized β2 agonists is additive to that of insulin. There was a similar decrease in PK with insulin (0.65 mM) or albuterol (0.66 mM). There was a substantially greater fall in PK with the combined regimen (1.2 mM). The dose of intravenous regular insulin used in this study was only 10 units, and PK fell less than in studies when higher doses of insulin were used (6). Thus, it remains uncertain whether β2 agonists would have a PK-lowering effect additive to that of insulin if insulin were given at the higher doses.
So should I be worried if I use Albuterol?  

While the potassium lowering effects of albuterol are often discussed in medical circles, the effect on those of us who use albuterol on a regular basis is rarely mentioned.  In fact, recently it was posed to me by a fellow asthmatic, and I humbly responded (here) by stating that one albuterol treatment shouldn't effect potassium enough to worry about.  Yet if you take ventolin a lot, meaning you use it more than 2 puffs every 4-6 hours, then you may want to supplement your diet with potassium.  Bananas are a good source of potassium.  If you us it a lot, and you continue to have symptoms of a high potassium (heart palpitations, muscle cramps), then you should call your doctor.

Your doctor will (should) also check your serum potassium level on a regular basis, like once a year.  If your potassium levels are out of range your physician should inform you of this.  Again, however, chances are your doctor won't say anything because, so long as you're not excessively abusing the substance, your potassium level should be fine.  

We often do continuous breathing treatments in the emergency room, and I have never observed a doctor being overly concerned about potassium.  If he is he will simply supplement the patient with potassium chloride through the IV.  Yet for the general asthmatic who uses albuterol, you shouldn't have anything to be concerned about.  If you're still concerned, eat bananas. Perhaps that's why I love bananas so much.  I eat 1-3 every day.

Related links:
  1. The balance of sodium and potassium
  2. The balance of sodium and potassium part II
Further references:
  1. 1.  Greenberg A. Hyperkalemia: treatment options. Semin Nephrol 1998;18:46–57. [PubMed]
  2. 2.  Flatman JA, Clausen T. Combined effects of adrenaline and insulin on active electrogenic Na+−K+ transport in rat soleus muscle. Nature 1979;281:580–1. [PubMed]
  3. 3.  Montoliu J, Lens XM, Revert L. Potassium-lowering effect of albuterol for hyperkalemia in renal failure. Arch Intern Med 1987;147:713–7. [PubMed]
  4. 4.  Montoliu, ibid
  5. 5.  Allon, M. Copney, C., "Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients," Kidney International, 1990, 38: 869-872
  6. 6.  Blumberg A, Weidmann P, Shaw S et al, "Effect of various therapeutic approaches on plasma potassium and major regulating factors in terminal renal failure," American Journal of Medicine, 1998; 85: 507-512

1 comment:

Health News Articles said...

describes the pump as the main mechanism of moving sodium "from inside cells to the extracellular compartments, and returns potassium from the extracellular compartments into cells using adenosine triphosphate..
Health News Articles