In this episode, I’ll discuss the evidence for gastrointestinal cation exchangers other than sodium polystyrene sulfate in acute hyperkalemia.
In the treatment of acute hyperkalemia, IV calcium provides immediate cardioprotection and allows time for insulin to move potassium into the intracellular space and away from the heart. This is only a short term solution however, since potassium will re-equilibrate out of the intracellular space several hours after insulin is given. Another intervention is required to remove the excess potassium from the patient and provide a definitive solution to acute hyperkalemia.
Hemodialysis is an effective intervention to remove excess potassium from a patient, and although there are not universally agreed upon triggers for initiation of dialysis, it is the preferred option in severe hyperkalemia.
When dialysis is not immediately available, or if the hyperkalemia is not felt to be severe enough to justify the invasive procedure of dialysis, gastrointestinal ion exchange resins are used.
Sodium polystyrene sulfate (SPS) is the oldest and most common agent, however there is considerable controversy over its use in acute hyperkalemia.
While not common, this medication can cause intestinal necrosis, a potentially fatal complication. Certain conditions lead to a higher incidence of intestinal necrosis from SPS and should be considered absolute contraindications to use:
-Postoperative patients
-Patients with an ileus or who are receiving opioids
-Patients with a bowel obstruction
For these reasons, there is a strong desire to find an alternative to the use of sodium polystyrene sulfate for hyperkalemia.
There are two small studies that look at gastrointestinal cation exchangers other than sodium polystyrene sulfate in acute hyperkalemia. One for Sodium Zirconium Cyclosilicate and one for Patiromer.
The patiromer study was published in Academic Emergency Medicine January 2020. The study was a single-center, randomized, open-label pilot study. The authors used a convenience sample of adult patients with end-stage renal disease and a serum potassium level of ≥ 6.0 mEq/L. Patients were randomized between standard of care or one dose of 25.2 g oral patiromer plus standard of care. The primary outcome being studied was the difference in potassium between groups after 6 hours had elapsed post-treatment.
Each group contained 15 patients. At 6 hours there was a numerical decrease in potassium of 0.5 mEq/L in the patiromer group however this did not reach statistical significance. At just 2 hours post-treatment, there was a statistically significant decrease in potassium of 0.61 mEq/L. Safety outcomes were no different between groups.
The sodium zirconium cyclosilicate study was published in Academic Emergency Medicine June 2020. The study was a multicenter, randomized, double-blind, placebo-controlled study that enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10-hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum potassium from baseline until 4 hours after the start of dosing. A greater reduction in mean serum potassium from baseline occurred with SZC compared with placebo at 2 hours. The change at 4 hours was numerically in favor of SZC but the confidence interval crossed zero. A numerically lower proportion of patients in the SZC group required additional potassium-lowering therapy due to hyperkalemia at 0 to 4 hours versus placebo but the confidence interval crossed 1.
While both of these studies are small, the desire to avoid SPS and its associated side effects leads many providers to consider either patiromer or SZC when available and to otherwise manage patients with repeat doses of insulin and glucose until dialysis can be performed rather than risk the side effects of SPS.
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