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Incidence of Sodium Polystyrene Sulfonate-associated Colonic Necrosis

      To the Editor:
      Harel et al
      • Harel Z.
      • Harel S.
      • Shah P.S.
      • Wald R.
      • Perl J.
      • Bell C.M.
      Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review.
      systematically describe 58 patients with sodium polystyrene sulfonate (SPS)-associated gastrointestinal events. The majority of events (76%) involved the colon, and one third resulted in death. Their evaluation is rigorous and detailed. However, as they indicate in their discussion, the case series model is inherently limited by selection and publication bias, and the lack of a “denominator…to calculate attributable risk.”
      Recently, a retrospective cohort study investigated SPS-associated colonic necrosis in 123,391 adult inpatients over 9 years at a single tertiary care center.
      • Watson M.A.
      • Baer T.P.
      • Nguyen A.
      • et al.
      Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study.
      The outcome was tissue-confirmed ischemic colitis/colonic necrosis, considered SPS-associated if SPS had been prescribed ≤30 days before tissue accession. The 9-year cumulative incidence of colonic necrosis was 0.14% (95% confidence interval [CI], 0.03%-0.40%) in those prescribed SPS, vs 0.07% (95% CI, 0.05-0.08%) in those not prescribed SPS (relative risk 2.10; 95% CI, 0.68-6.48; P = .2).
      Thus, inpatient SPS administration was not significantly associated with an increased relative risk of colonic necrosis, and the colonic necrosis incidence rate was not greater than reported in a recent prospective observational study.
      • Montoro M.A.
      • Brandt L.J.
      • Santolaria S.
      • et al.
      Workgroup for the Study of Ischaemic Colitis of the Spanish Gastroenterological Association (GTECIE-AEG). Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).
      It is not clear that there are indeed “safer, potentially more effective” alternatives to SPS for the management of mild to moderate, non-life-threatening hyperkalemia. No hyperkalemia therapy has been thoroughly studied for safety and efficacy in such a setting, and all potential options (SPS, loop diuretics, and dialysis initiation) are associated with side effects.
      • Watson M.
      • Abbott K.C.
      • Yuan C.M.
      Damned if you do, damned if you don't: potassium binding resins in hyperkalemia.
      The documented rarity of SPS-associated colonic necrosis should be taken into account when considering practice guidelines for management of hyperkalemia, and SPS should remain an option for hyperkalemia management, especially when an excretory modality is required.

      References

        • Harel Z.
        • Harel S.
        • Shah P.S.
        • Wald R.
        • Perl J.
        • Bell C.M.
        Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review.
        Am J Med. 2013; 126: 264.e9-264.e24
        • Watson M.A.
        • Baer T.P.
        • Nguyen A.
        • et al.
        Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study.
        Am J Kidney Dis. 2012; 60: 409-416
        • Montoro M.A.
        • Brandt L.J.
        • Santolaria S.
        • et al.
        Workgroup for the Study of Ischaemic Colitis of the Spanish Gastroenterological Association (GTECIE-AEG). Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).
        Scand J Gastroenterol. 2011; 46: 236-246
        • Watson M.
        • Abbott K.C.
        • Yuan C.M.
        Damned if you do, damned if you don't: potassium binding resins in hyperkalemia.
        Clin J Am Soc Nephrol. 2010; 5: 1723-1726

      Linked Article

      • Gastrointestinal Adverse Events with Sodium Polystyrene Sulfonate (Kayexalate) Use: A Systematic Review
        The American Journal of MedicineVol. 126Issue 3
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          Sodium polystyrene sulfonate (Kayexalate; Sanofi-Aventis, Paris, France) is a cation-exchange resin routinely used in the management of hyperkalemia. However, its use has been associated with colonic necrosis and other fatal gastrointestinal adverse events. Although the addition of sorbitol to sodium polystyrene sulfonate preparations was previously believed to be the cause of gastrointestinal injury, recent reports have suggested that sodium polystyrene sulfonate itself may be toxic. Our objective was to systematically review case reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use.
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      • The Reply
        The American Journal of MedicineVol. 126Issue 9
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          We appreciate the feedback from Yuan et al about our systematic review.1 They note our inability to calculate the attributable risk of sodium polystyrene sulfonate–associated gastrointestinal injury because of the lack of a denominator and highlight the single-center study2 of sodium polystyrene sulfonate–associated colonic necrosis. In that study, Watson et al2 found a 9-year cumulative incidence of colonic necrosis of 0.14% in those prescribed sodium polystyrene sulfonate. Although this number may seem low, extrapolating this finding to the 5,000,000 doses of sodium polystyrene sulfonate given each year in the United States would yield 7000 cases of colonic necrosis per year.
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