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Is Sodium Polystyrene Sulfonate Truly Guilty without Sorbitol?

      To the Editor:
      The systematic review by 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.
      on gastrointestinal adverse events with sodium polystyrene sulfonate (SPS) use was of great value because these events have often been sporadically reported as case reports. However, a fundamental question as to the causality between SPS use and its adverse events should be raised. Crystals of ion-exchange resins, including SPS, can be seen on histopathological specimens; that is, when patients take ion-exchange resins, crystals can be detected microscopically as incidental findings irrespective of the etiology of perforation. Thus, a causal relationship between the drug and its adverse events should be carefully examined.
      By comparing the characteristics of patients receiving SPS with sorbitol and those receiving SPS without sorbitol, 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.
      revealed that the incidence of histopathological necrosis was significantly higher in patients receiving SPS with sorbitol than in those receiving SPS only (73% vs 41%, P = .01). Furthermore, the time of appearance of symptoms tended to be shorter in patients receiving SPS with sorbitol than in those receiving SPS only. These results probably indicate that drastic adverse events occur less frequently in patients receiving SPS without sorbitol. These results are consistent with the experiment conducted by Lillemoe et al in 1987,
      • Lillemoe K.D.
      • Romolo J.L.
      • Hamilton S.R.
      • et al.
      Intestinal necrosis due to sodium polystyrene (Kayexalate) in sorbitol enemas: clinical and experimental support for the hypothesis.
      who showed that SPS administration alone did not cause any significant pathological changes. However, colonic necrosis was observed in all rats receiving SPS and sorbitol. Thus, these findings raise a question: Is SPS without sorbitol truly guilty?
      Although 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.
      claimed that they used World Health Organization causality assessment criteria, their assessment of a causal relationship between SPS and its adverse events seem invalid, because the causality for all cases was eventually categorized into the same possible rank (see Appendix 3 in their article
      • 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.
      ). Furthermore, their review included several cases for which causes other than SPS may have been guilty (eg, ischemic colitis,
      • Chatelain D.
      • Brevet M.
      • Manaouil D.
      • Yzet T.
      • Regimbeau J.M.
      • Sevestre H.
      Rectal stenosis caused by foreign body reaction to sodium polystyrene sulfonate crystals (Kayexalate).
      constipation,
      • van der Valk P.R.
      • van der Kleij F.G.
      • de Haan L.D.
      Resonium-induced small bowel perforation.
      and history of dialysis in other articles). Thus, causality is far from assured.
      In summary, clinicians who plan to report a case should carefully examine the causality between an ion-exchange resin and gastrointestinal adverse events, particularly when a patient has not received sorbitol. Selecting and reviewing only those cases with unquestionable proof of causality would be important for exploring the unresolved mechanism of the gastrointestinal adverse events.

      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
        • Lillemoe K.D.
        • Romolo J.L.
        • Hamilton S.R.
        • et al.
        Intestinal necrosis due to sodium polystyrene (Kayexalate) in sorbitol enemas: clinical and experimental support for the hypothesis.
        Surgery. 1987; 101: 267-272
        • Chatelain D.
        • Brevet M.
        • Manaouil D.
        • Yzet T.
        • Regimbeau J.M.
        • Sevestre H.
        Rectal stenosis caused by foreign body reaction to sodium polystyrene sulfonate crystals (Kayexalate).
        Ann Diagn Pathol. 2007; 11: 217-219
        • van der Valk P.R.
        • van der Kleij F.G.
        • de Haan L.D.
        Resonium-induced small bowel perforation.
        Eur J Intern Med. 2006; 17: 523-524

      Linked Article

      • Gastrointestinal Adverse Events with Sodium Polystyrene Sulfonate (Kayexalate) Use: A Systematic Review
        The American Journal of MedicineVol. 126Issue 3
        • Preview
          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. 127Issue 7
        • Preview
          We thank Rokutan for his interest in our systematic review.1 We do agree that the inclusion of case reports of adverse events in systematic reviews hampers the finding of a true causal relationship between a drug and such events. However, for rare adverse events, case reviews may be the only information available.
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