When a patient presents with hyperkalemia, in addition to the initial steps of obtaining an EKG and treating with calcium, insulin, glucose, albuterol, and furosemide if indicated, consultants will often ask us to also administer sodium polystyrene sulfonate, more commonly known as kayexalate, pending hemodialysis. Is this management strategy supported by evidence? Reviewing the (rather sparse) literature, the short answer appears to be no.

 

Kayexalate was approved for use in 1958, four years before the FDA began requiring drug manufacturers to demonstrate efficacy as well as safety. It theoretically lowers potassium by binding cations in the GI tract and increasing GI excretion of potassium. In the best case scenario, it takes on the order of hours to begin to have an effect. Moreover, it may not have any acute effect at all; some studies have demonstrated that, when taken for multiple days, kayexalate can effectively treat mild hyperkalemia in the outpatient setting, but there is almost no data supporting the use of kayexalate in moderate or severe hyperkalemia. One study found that a single dose of kayexalate + laxative (phenolphthalein or sorbitol) given to ESRD patients did not increase stool potassium output over a 12 hour period compared to administering a laxative alone. It did not lower serum potassium by a significant amount either, though these patients were not hyperkalemic to start with.

There have also been numerous case reports of intestinal ischemia/necrosis, bezoar formation, and death associated with kayexalate, particularly when administered with sorbitol. Furthermore, because it is a general cation binder, it may decrease absorption of other medications such as lithium and thyroxine.

Patiromer is another recently FDA-approved gastrointestinal cation binders that have a higher selectivity for binding potassium than kayexalate, though again there is as yet no data on its efficacy in acute hyperkalemia. It also is not currently available at Sinai. ZS-9 is another similar drug in the pipeline, but it’s not yet been FDA approved.

 

Therefore, the next time the consulting or admitting team raises the question of giving kayexalate as an adjunctive therapy for hyperkalemia, consider bringing up its potential for significant harm and the paucity of data on its efficacy in acute hyperkalemia. If the patient is unable excrete potassium effectively through lasix, perhaps it is time for hemodialysis.

 

Special thanks to Dr. Gregory Fernandez for prompting the review of this topic.

 

References:

J Am Soc Nephrol. 2010 May;21(5):733-5. Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective?

J Am Soc Nephrol. 1998 Oct. Effect of Single Dose Resin-Cathartic Therapy on Serum Potassium Concentration in Patients with End-Stage Renal Disease.

Clin J Am Soc Nephrol. 2015 Dec 7;10(12):2136-42. Randomized Clinical Trial of Sodium Polystyrene Sulfonate for the Treatment of Mild Hyperkalemia in CKD.

Pharmacy and Therapeutics. 41(1), 43–50. Potassium-Binding Agents for the Clinical Management of Hyperkalemia.

Food and Drug Administration. 2009. Kayexalate

Emcrit – Is Kayexalate Useless?