Potassium Bindings Agents

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Sodium polysterene sulfonate resin (SPS)

SPS is an ion-exchange resin that exchanges sodium for ammonium, calcium, magnesium, and K+, and is targeted to enhance K+ elimination through the feces. Hypokalemic effect is produced by binding with potassium secreted into the colon.

It is given orally and timing may take up to 10 hours. To accelerate, a rectal route of administration is considered but the effects may be significantly lowered because of the decreased amount of time the resin stays in the colon.

To avoid adverse effects such as bowel obstruction, induction of bowel movement by cathartic such as sorbitol may be as if given with the resin. However, this may cause intestinal necrosis whether given orally or by retention enema.

1. SPS

• Mechanism of Action: Binds K+ in colon
• Dose: Intraoral, 15-60g in 20% sorbitol; Intrarectal, 30-60g in 20% sorbitol
• Pharmacokinetics:
  • Onset of Action: 1-3 hours
  • Duration of Effect: Varies
• Contraindications: Patients with abnormal GI transit, acutely ill patientsdue to adverse side effects
• Adverse Effects: Bowel obstruction, digestive perforation, hypocalcemia, hypomagnesemia, edema, high blood pressure
• Pearls: Oral route is preferred due to longer GI transit time, but if needed, accelerate administration through rectal route but with significantly lowered effects; Sorbitol may cause bowel necrosis and intestinal perforation; K+ removed from the body: 0.5-1 mEq/g resin

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Patiromer

This acts in a similar manner as SPS, assisting with fecal K+ excretion in exchange for calcium at the distal colon. As the medication moves through the bowel, it exchanges calcium with hydrogen ions, and when these acidic groups dissociate, K+ binds with ammonium and magnesium. Unlike SPS, it does not swell when exposed to water.

2. Patiromer 

• Mechanism of Action: Ca2+-K+ cation exchange resin
• Dose: Intraoral, 4.2-16.8 g once or twice daily
• Pharmacokinetics:
  • Onset of Action: 7-48 hours
  • Duration of Effect: 12-24 hours
• Contraindications: Patients with abnormal GI transit
• Adverse Effects: Hypomagnesemia – most common, and constipation
• Pearls: Not been clinically tested in the emergency setting; K+ removed from the body: Mean 0.75 mEq/g resin

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Sodium Zirconium Cyclosilicate (ZS-9)

ZS-9 is a nonabsorbable selective cation exchanger, but unlike patiromer, it is not a polymer. It binds more than nine times the amount of K+ compared with SPS and it allows excretion of K+ by exchange with sodium and hydrogen throughout the GI tract.

3. Sodium Zirconium Cyclosilicate

• Mechanism of Action: Preferentially binds K+ throughout GI tract
• Dose: Intraoral, 10g up to three times daily
• Pharmacokinetics:
  • Onset of Action: 1-6 hours
  • Duration of Effect: 4-12 hours
• Contraindications: Patients with abnormal GI transit
• Adverse Effects: Minor GI symptoms (UTI), edema, increased sodium levels
• Pearls: Not recommended for acute management of of hyperkalemia due to delayed onset of action; K+ removed from the body: 0.7 mEq/L per 10g dose

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Overview of Evidence

Author, year	Design/ sample size	Intervention & Comparison	Outcome
Lepage 2015	Randomized control trial (n=33)	Placebo vs sodium polystyrene sulfonate 30g orally daily x 7 days	Sodium polystyrene sulfonate reduced K greater than placebo (mean difference -1.04 mEq/L) Average treatment duration 6.9 days Trend toward higher rates of electrolyte disturbances and increased GI side effects in treatment group
Fishbane 2019*	Randomized, double blind, placebo controlled trial (n=196)	Placebo vs sodium zirconium cyclosilicate 5g daily on non-dialysis days (max 15g over 4 week increments)	41.2% of patients in sodium zirconium cyclosilicate vs 1.0% of placebo were treatment respondersRescue therapy to reduce hyperkalemia during treatment period required by 2.1% sodium zirconium cyclosilicate vs 5.1% placebo Sodium zirconium cyclosilicate required more than 3 hemodialysis treatments after the interdialytic interval before a reduction in K without rescue therapy
Zannad 2015**	Randomized, double blind, placebo controlled trial (n=258)	Randomized to sodium zirconium cyclosilicate 5g, 10g, or 15g or placebo: 1 time/day x 28 days	Sodium zirconium cyclosilicate reduced aldosterone by -31%, -30%, and -30% in the 5g, 10g, and 15g groups, respectively compared to 14% increase in placebo group Similar results to HARMONIZE trial with median time to serum K normalization of 2 hours
Scherr 1961	Retrospective review (n=32)	Sodium-cycle sulfonic polystyrene cation-exchange resin administered orally or by rectum in divided doses totaling 10g-60g per day	23 patients showed a decrease in K of at least 0.4 mEq/L in the first 24 hours K change associated with reversion of normal EKG in every case 2 patients required additional therapy with sodium bicarbonate, glucose, and insulin Constipation occasionally encountered and controlled with enemas or cathartics
Gruy-Kapral 1998	Prospective controlled trial (n=6)	Single-dose resin-cathartic vs placebo	No reduction in serum potassium concentrations at 12 hours
Kosiborod 2014*	Randomized, double blind, placebo controlled trial (n=258)	Zirconium cyclosilicate 5g, 10g, 15g, or placebo daily x 28 days	Median time to normalization was 2.2 hours 84% of patients achieved normokalemia by 24 hours and 98% by 48 hours
Peacock 2020	Phase 2 trial (n=70)	Zirconium cyclosilicate 10g TID or placebo	Patients treated with SZC experienced a 0.13 mEq/L greater drop in potassium, but this was not statistically significant.Trend towards more patients treated with SZC achieving a potassium below 6 mE/LNon-significant trend towards patients treated with SZC being less likely to require additional therapies for hyperkalemia (16% vs. 31%)
Ash*** 2015	Phase 2 trial (n=54)	Zirconium cyclosilicate 0.3g, 5g, 10g, or placebo TID	At hour 2, Zirconium cyclosilicate 10 g reduced potassium by 0.13 mE/L compared to 0.02 mEq/L of placebo.At hour 8, Zirconium cyclosilicate 10 g reduced potassium by 0.37 mEq/L compared to 0.24 mEq/L of placebo.
Packham 2015	Phase 3 trial (n=753)	Zirconium cyclosilicate 1.25g, 2.5g, 5g, 10g, or placebo	Over the first four hours, SZC reduces potassium by an average of ~0.2 mEq/L compared to placebo.With repeated dosing over the first 24 hours, SZC reduces the potassium by an average of 0.4 mEq/L.