How to prescribe sodium polystyrene sulfonate (SPS) for hyperkalemia?

How to Prescribe Sodium Polystyrene Sulfonate for Hyperkalemia

Sodium polystyrene sulfonate (SPS) should be prescribed at 15-60 g orally daily (typically 15 g one to four times daily) or 30-50 g rectally every 6 hours for non-emergent hyperkalemia, but newer agents like patiromer or sodium zirconium cyclosilicate are preferred when available due to SPS's significant safety concerns including fatal intestinal necrosis. 1, 2

Critical Safety Warning

Do not use SPS as emergency treatment for life-threatening hyperkalemia due to its delayed and variable onset of action (hours to days). 2, 1 The FDA explicitly contraindicates SPS in patients with obstructive bowel disease, neonates with reduced gut motility, and those with hypersensitivity to polystyrene sulfonate resins. 2

Serious Gastrointestinal Risks

• Fatal intestinal necrosis, ischemic colitis, perforation, and bleeding have been reported with SPS, with an overall mortality rate of 33% in some series. 1
• Never administer SPS with sorbitol - the majority of serious gastrointestinal adverse events occurred with concomitant sorbitol use. 2
• Avoid in patients with constipation history, inflammatory bowel disease, ischemic colitis, vascular intestinal atherosclerosis, previous bowel resection, or those who haven't had a bowel movement post-surgery. 2
• Discontinue immediately if constipation develops. 2

Dosing Regimens

Oral Administration

• Standard dose: 15 g orally 1-4 times daily (total daily dose 15-60 g) 2, 1
• Suspend each dose in 3-4 mL of liquid per gram of resin (water or syrup). 2
• Administer with patient in upright position. 2
• Separate from other oral medications by at least 3 hours (6 hours in gastroparesis) due to nonselective binding that can reduce absorption of other drugs. 2, 1
• Prepare suspension fresh and use within 24 hours; do not heat. 2

Rectal Administration

• Dose: 30-50 g every 6 hours as retention enema 2, 1
• Insert large French 28 rubber tube 20 cm into rectum with tip in sigmoid colon. 2
• Administer as warm emulsion in 100 mL aqueous vehicle, flush with 50-100 mL fluid. 2
• Retain as long as possible, then cleanse with non-sodium containing solution (up to 2 liters). 2
• Avoid rectal route in neutropenic patients. 1

Expected Efficacy

Potassium Reduction

• 15 g oral dose reduces potassium by approximately 0.39-0.51 mEq/L 3, 4
• 30 g oral dose reduces potassium by approximately 0.58-0.69 mEq/L 3, 5, 4
• 60 g oral dose reduces potassium by approximately 0.91 mEq/L 3
• 30 g rectal dose reduces potassium by only 0.22 mEq/L 3
• Onset occurs over 14-16 hours, with peak effect within 24 hours. 6

Clinical Trial Data

The only randomized controlled trial showed 30 g daily for 7 days reduced potassium by 1.25 mEq/L versus 0.21 mEq/L with placebo (mean difference -1.04 mEq/L, P<0.001) in outpatients with CKD and mild hyperkalemia (5.0-5.9 mEq/L). 1, 5

Monitoring Requirements

Electrolyte Monitoring

• Monitor serum potassium, calcium, and magnesium regularly - SPS nonselectively binds these cations, causing hypocalcemia and hypomagnesemia. 1
• Check potassium 6-24 hours after dose to assess response. 6
• Verify elevated potassium with second sample to rule out pseudohyperkalemia from hemolysis. 1

Cardiac Monitoring

• Monitor ECG and cardiac rhythm closely, especially if potassium >7.0-7.5 mEq/L or QRS widening present. 1

Common Adverse Effects

• Gastrointestinal disorders: constipation (8%), diarrhea, nausea, vomiting, gastric irritation 1
• Hypomagnesemia, hypocalcemia, hypokalemia 1
• Systemic alkalosis 1
• High sodium load: 1500 mg sodium per 15 g dose 1

When to Use Alternative Agents

Newer potassium binders (patiromer or sodium zirconium cyclosilicate) are preferred for chronic hyperkalemia management because they have no reported cases of fatal gastrointestinal injury, faster onset (1-7 hours), and allow continuation of RAAS inhibitor therapy. 1

Specific Clinical Scenarios Favoring Alternatives

• Patients requiring chronic potassium management 1
• Patients on maximum-tolerated RAAS inhibitor doses with potassium 5.0-6.5 mEq/L 1
• Patients with gastrointestinal risk factors 1, 2
• When faster onset needed (though still not for emergencies) 1

Practical Algorithm

For mild hyperkalemia (5.0-5.9 mEq/L):

• Use 30-60 g oral SPS as single daily dose if newer agents unavailable 3, 5
• 60 g dose most effective with minimal hypokalemia risk 3

For moderate hyperkalemia (6.0-6.5 mEq/L):

• Consider alternatives to SPS given limited efficacy 1
• If using SPS, prescribe 60 g orally 3

For severe hyperkalemia (>6.5 mEq/L):

• Do not use SPS - use emergency measures (insulin/glucose, calcium, beta-agonists, dialysis) 1, 2