Questioning Medicine: Kayexalate Therapy for Hyperkalemia
Published: Nov 6, 2014 | Updated: Nov 7, 2014
You know what God and nephrologists have in common? They are the only entities who can separate salt and water in the human body.
With the American Society of Nephrology's kidney week right around the corner, my Twitter feed is loaded with #kidneywk14 and smart comments from some of my favorite nephrologists, like Allen Nissenson, MD. I'm eager to learn, 140 characters at a time, what the modern, game changing practices these nephrology thought-leaders are going to bring to the table.
However, there is one detail that needs to be addressed, and it needs to be challenged because of its use by too many nephrologists, hospitalists, and emergency room physicians. If you have read some of our recent posts, you might think it has to do with screening. But this week, I'll spare all of you any rants on mindless screening procedures, and instead discuss a popular drug that maybe shouldn't be so popular.
Most physicians who are part of the Free Open Access Medical education (#FOAMed) movement already know what I'm about to discuss. All of the people who follow the Questioning Medicine podcast will also know the subject I am about to tackle. Yet, a large majority of physicians are still unaware of the lack of benefit and utility of Kayexalate, also known as sodium polystyrene sulfonate (SPS), for the treatment of hyperkalemia. Although "SPS" is often used as an abbreviation for sodium polystyrene sulfonate, SPS is actually a brand name for sodium polystyrene sulfonate in sorbitol,
Theoretically Kayexalate should work, and theoretically the weatherman should always be accurate. Yet, as the trials are reviewed, and the days pass, the therapy fails to reach primary endpoints without the risk of serious adverse events and mortality.
Early Research
SPS was approved as a treatment for hyperkalemia by the FDA in 1958. According to Sterns et al., drugmakers weren't required to prove the effectiveness and safety of their drugs until 1962.
Two of the early studies that investigated Kayexalate date back to 1961 in The New England Journal of Medicine. The "larger" of the two, Scherr et al., published results of using Kayexalate treatments on 32 patients at Bellevue hospital in New York City. The second study, Flinn et al., included results of the therapy on only 10 patients with severe hypouresis at Brigham Hospital in Boston.
These pioneers wrote positively of Kayexalate as a preventive treatment but also noted its ineffectiveness once the condition had developed beyond a certain point.
"The gradual drop in serum values suggested that this technique is an extremely effective form of therapy for the prophylaxis of hyperkalemia but that its action is too slow for immediate therapy when the electrocardiographic changes of potassium intoxication are advanced," Flinn and colleagues wrote.
In reading those trials, I can officially say that not only were the hairdos and outfits abysmal in 1961, but so were the studies for which we defined evidence-based medicine. With very-low-power numbers, and no control arms, these studies looked more like projects being presented at an eighth grade science fair than the hard science that should be used to shape clinical practice and drug therapies.
Even with a study as poorly done as the one by Flinn et al., the researchers note sorbitol by itself might be better than SPS. "Sorbitol alone may be an effective way of promoting dehydration in over-hydrated patients," they wrote.
Modern Studies
In a somewhat more recent study (1998) by Gruy-Kapral et al., researchers treated six chronic renal failure patients with four different single-dose resin cathartic regimens, or potassium excreting substances, such as Kayexalate, colace, and sorbitol, and also a placebo of water, on five different test days for 12 hours.
The researchers found that phenolphthalein alone resulted in an average fecal potassium output of 5.4 mEq/L, but that the addition of a resin caused an increase in insoluble potassium output and a decrease in soluble potassium output.
"Because single-dose resin-cathartic therapy produces no or only trivial reductions in serum potassium concentration, and because this therapy is unpleasant and occasionally is associated with serious complications, this study questions the wisdom of its use in the management of acute hyperkalemic episodes," Gruy-Kapral and colleagues wrote.
I know some physicians who believe that even if Kayexalate maybe of little value, it's certainly of little harm. But, this line of thought might be a little too naive. We know from animal studies that Kayexalate can result in extensive bowel necrosis (Lillemoe et al.).
In one study of humans, by McGowan et al., which reviewed 11 pathology cases of intestinal necrosis after Kayexalate therapy over the course of 9 years at a single center, four patients died. Two of the fatal cases were noncritical patients with potassium between 5.7 to 5.8 mEq/L, who developed symptoms of intestinal injury sometime between 3 and 11 days after administration of SPS. And eight of the patients with chronic necrosis had potassium less than 6.8 mEq/L.
The majority of cases of intestinal necrosis associated with sodium polystyrene sulfonate occurred when the resin was administered with sorbitol. In addition, intestinal necrosis was induced in a rat model by sorbitol alone or by sorbitol mixed with sodium polystyrene sulfonate, but not with sodium polystyrene sulfonate alone. Thus, it was presumed that sorbitol was required for the intestinal injury.
In absolute terms, it is a small number of people compared with those who have receive the drug. Yet, I would challenge that even a small risk for no statistical or clinical benefit in total body potassium is foolish when there are serious adverse events, and mortality, at stake.
Time for Change
For the naysayers or those who think that this is just another young physician spouting off, I encourage you to read and digest a piece published 4 years ago in the Journal of the American Society of Nephrology,by Sterns et al., in which they state, "we can find no convincing evidence that SPS increases fecal potassium losses in experimental animals or humans ..."
In fact, Sterns et al., also question whether Kayexalate should even be on the market. "If Kayexalate or SPS in sorbitol were presented to the FDA as new drugs with the data available today, it is doubtful that either would pass muster," the authors wrote. And, they suggest, clinicians should weigh uncontrolled studies showing benefit against uncontrolled studies showing harm.
"It would be wise to exhaust other alternatives for managing hyperkalemia before turning to these largely unproven and potentially harmful therapies," Sterns and colleagues concluded.
And in 2009, according to Sterns et al., the FDA issued a warning advising against concomitant administration of sorbitol with the powdered resin. However, many hospitals stock, and routinely administer a premixed suspension of SPS in sorbitol for the treatment of hyperkalemia.
While the use of triple X has been made inappropriate by a certain adult industry I think it's time to put the X in Kayexalate. An X for being on formulary in many hospitals, an X for its continued approval by the FDA, and an X for its use by physicians everywhere.
Thank you for reading. Your thoughts are welcome. We are always available on Twitter @MedQuestioning and @AndrewBuelt. You can also email us at questioningmedicine@gmail.com.
Andrew Buelt, DO, and Joe Weatherly, DO, are family medicine residents in St. Petersburg, Fla. Together, they co-produce the podcast Questioning Medicine, where they deconstruct issues confronting today's clinicians.
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