Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age

JAMA Intern Med. 2019 Aug 1;179(8):1025-1033. doi: 10.1001/jamainternmed.2019.0631.

Abstract

Importance: Sodium polystyrene sulfonate is commonly prescribed for the treatment of hyperkalemia. Case reports of intestinal injury after administration of sodium polystyrene sulfonate with sorbitol resulted in a US Food and Drug Administration warning and discontinuation of combined 70% sorbitol-sodium polystyrene sulfonate formulations. There are ongoing concerns about the gastrointestinal (GI) safety of sodium polystyrene sulfonate use.

Objective: To assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age.

Design, setting, and participants: Population-based, retrospective matched cohort study of eligible adults of advanced age (≥66 years) dispensed sodium polystyrene sulfonate from April 1, 2003, to September 30, 2015, in Ontario, Canada, with maximum follow-up to March 31, 2016. Initial data analysis was conducted from August 1, 2018, to October 3, 2018; revision analysis was conducted from February 25, 2019, to April 2, 2019. Cox proportional hazards regression models were used to examine the association of sodium polystyrene sulfonate use with a composite of GI adverse events compared with nonuse that was matched via a high-dimensional propensity score. Additional analyses were limited to a subpopulation with baseline laboratory values of estimated glomerular filtration rate and serum potassium level.

Exposure: Dispensed sodium polystyrene sulfonate in an outpatient setting.

Main outcomes and measures: The primary outcome was a composite of adverse GI events (hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy) within 30 days of initial sodium polystyrene sulfonate prescription.

Results: From a total of 1 853 866 eligible adults, 27 704 individuals were dispensed sodium polystyrene sulfonate (mean [SD] age, 78.5 [7.7] years; 54.7% male), and 20 020 sodium polystyrene sulfonate users were matched to 20 020 nonusers. Sodium polystyrene sulfonate use compared with nonuse was associated with a higher risk of an adverse GI event over the following 30 days (37 events [0.2%]; incidence rate, 22.97 per 1000 person-years vs 18 events [0.1%]; incidence rate, 11.01 per 1000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41). Results were consistent in additional analyses, including the subpopulation with baseline laboratory values (hazard ratio, 2.91; 95% CI, 1.38-6.12), and intestinal ischemia/thrombosis was the most common type of GI injury.

Conclusions and relevance: The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events. These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cation Exchange Resins / adverse effects*
  • Enterostomy / statistics & numerical data
  • Female
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / epidemiology
  • Hospitalization / statistics & numerical data*
  • Humans
  • Hyperkalemia / drug therapy*
  • Intestinal Perforation / chemically induced
  • Intestinal Perforation / epidemiology
  • Male
  • Mesenteric Ischemia / chemically induced*
  • Mesenteric Ischemia / epidemiology
  • Mesenteric Vascular Occlusion / chemically induced*
  • Mesenteric Vascular Occlusion / epidemiology
  • Ontario
  • Polystyrenes / adverse effects*
  • Proportional Hazards Models
  • Retrospective Studies
  • Severity of Illness Index
  • Thrombosis / chemically induced*
  • Thrombosis / epidemiology
  • Ulcer / chemically induced
  • Ulcer / epidemiology

Substances

  • Cation Exchange Resins
  • Polystyrenes
  • polystyrene sulfonic acid

Grants and funding