Use of sodium polystyrene sulfonate for hyperkalemia

Let's start with a patient case.  A 58 year old male is sent to the hospital from his PMD for hyperkalemia.  He has a past medical history of diabetes mellitus type 2, hypertension, osteoarthritis, and obesity for which he is taking sitagliptin 100 mg daily, lisinopril 20 mg daily, atorvastatin 80 mg daily, and aspirin 81 mg daily.  Pertinent findings on arrival to the emergency department are SCr = 1.2 mg/dL (at his baseline), K+ = 5.9 mEq/L (previously 4.2), blood pressure = 152/96 mm Hg, Hb A1c = 10.8%, and a normal EKG.  Upon further questioning about his medication and supplement use, he admits to occasional ibuprofen and oxycodone use this past month for his osteoarthritis and is newly using Morton's Salt Substitute (as he's trying to avoid salt because of his uncontrolled hypertension).  What is the role of sodium polystyrene sulfonate (SPS) in this situation?

Evidence for SPS

Sodium polystyrene sulfonte (Kayexalate) is one of a small number of medications used to remove potassium from the body.  It was approved by the FDA in 1958, when evidence for effectiveness was not required for medications to be approved (this didn't occur until 1962, when the Kefauver-Harris Amendment required all drugs to have effectiveness and safety demonstrated - anything before this was grandfathered in).  At this time, other options for potassium removal were limited as hemodialysis was not readily available and loop diuretics were not approved yet (furosemide was the first one in 1966).  Evidence for efficacy is scant and consists of only a small number of uncontrolled studies including very few patients.  It is notable that in these studies, SPS was also given with low potassium diets, sodium bicarbonate, and a large volume of dextrose.

Though evidence is sparse, decades of use do support the efficacy of SPS.  There are serious risks of using SPS; however, including the risk of constipation and stool impaction.  Because of this, administration with sorbitol became routine and the most commonly used preparation of SPS suspension currently on the market does contain 33% sorbitol.  In September 2009, the FDA issued a warning for intestinal necrosis with the use of SPS (most reports also had use of sorbitol) and they recommended avoiding the combination in those without normal bowel function (eg. post-op patients that haven't had a bowel movement, those with a history of impaction, chronic constipation, inflammatory bowel disease, ischemic colitis, or previous bowel resection or obstruction).  Other gastrointestinal adverse events such as bleeding, ischemic colitis, and perforation are also reported.  The evidence has not confirmed if these risks are from the SPS, sorbitol, or the SPS/sorbitol combination.

Pharmacology

SPS is a cation-exchange resin (an insoluble polymer with a structure resembling a crystal lattice) with the potential to exchange 1 mmol potassium per gram of drug.  It carries with it a sodium content of 4.1 mmol per gram.  SPS is not absorbed and as it moves through the gastrointestinal tract, the resin binds preferentially for potassium over sodium.  How complete this exchange occurs is based on many factors including the contact time, transit time, the relative concentrations of ions, the resin capacity, and the dissociation ability of sodium.  Because of these factors, the exchange is highly variable (the 1 mmol per gram rule is a very rough estimate and the K+ still needs to be monitored carefully).  Also, the large sodium load means there is a risk of exacerbating cardiovascular disease and worsening other fluid-retaining conditions.

Onset, dosing, administration

Since the exchange activity of SPS occurs primarily in the colon, the onset of activity is not immediate (somewhere between 2-24 hours).  SPS is usually dosed 15-60 grams, one to four times per day (6 hour intervals).  It can be given with water or syrup but not with fruit juices (as these often contain additional potassium).  SPS can also be given rectally, at a dose of 30-50 grams once or twice daily.

Back to the patient case

An important part in managing hyperkalemia is identifying the etiology which includes performing a medication, supplement, and diet review.  Our patient states that he recently has been taking NSAIDs which are known to cause hyperkalemia.  Additionally, salt substitutes, though reasonable for blood pressure control, often contain large amounts of potassium instead of sodium (Morton's actually contains 610 mg or 8 mEq per 1/4 teaspoonful).  For now, all NSAIDs, his ACE inhibitor, and his salt substitute should be discontinued and a potassium restricted diet can be ordered.  Since the potassium is <6 mEq/L and there are no EKG changes, calcium is not necessary but kaliuresis is - either from loop diuretics or SPS.  SPS is not the best option for a few reasons.  His transit time could be prolonged due to gastroparesis as he does have uncontrolled diabetes and also reports the use of opioids.  Also, the large salt load of SPS is not desirable as it could exacerbate underlying cardiovascular disease.  Additionally, alternative options are available because he seems to be at his baseline renal function and will likely respond to a loop diuretic, making this the best option.

Take home points:

• Avoid SPS in those without normal bowel function and those who may be adversely affected by the large sodium content
• When using SPS, do not give additional sorbitol as it is associated with intestinal necrosis
• Make sure to discontinue and avoid all sources of potassium

References:
Kayexalate (R) [package insert]. Laval, Quebec: Sanofi-Aventis Canada Inc; 2014.
Sterns RH, Rojas M, Bernstein P, et al.  Ion-exchange resins for the treatment of hyperkalemia: Are they safe and effective?  J Am Soc Nephrol  2010;21:733-5.

photo by rosmary