Is Kayexalate Useful in the Treatment of Hyperkalemia in the Emergency Department?

02 Feb
February 2, 2015

BariumEnema_ORIGINAL_460x261Background: Hyperkalemia is the most common electrolyte disorder seen in the Emergency Department and treatment of hyperkalemia is core knowledge of EM training for interns and focuses on:

1) Stabilization of cardiac myocytes with calcium salts
2) Temporary shifting of potassium into cells (insulin, beta agonists, normal saline,
      magnesium, sodium bicarbonate)
3) Removal of potassium from the body (i.e. loop diuretics, cathartics)
4) Definitive Treatment (i.e. Hemodyalisis)

Although there is still some debate on the first two areas (i.e. is there truly a role for sodium bicarbonate?) our focus will be on the removal part of the algorithm, specifically, is there a role for kayexalate?

ResinKayexalate (Sodium polystyere sulfate) is a cation-exchange resin that was approved in 1958 as a treatment for hyperkalemia by helping to exchange sodium for potassium in the colon and thus excreting potassium from the body. This drug has been a standard part of treatment of hyperkalemia for decades. Many of us were taught that if you give a patient a dose of kayexalate, you should expect there serum potassium to drop by 0.5 – 1.0 mEq in 4-6 hours.

The evidence for this recommendation comes from 2 articles in the New England Journal of Medicine in 1961. The first thing that becomes obvious when reading these studies is that what was considered strong evidence 50 years ago wouldn’t be accepted today in any major journal.

Flinn RB et al. Treatment of the oliguric patient with a new sodium-exchange resin and sorbitol; a preliminary report. N Engl J Med. 1961;264:111. PMID: 13700297

Population: 10 patients with severe oliguria
Intervention: Sorbitol + a cation exchange resin (+ a no potassium diet)
Control: Sorbitol alone (+ a no potassium diet)
Outcome: Decreased potassium level at 5 days

Findings: All patients in both groups had decreased serum potassium levels at 5 days. There is no statistical analysis performed to tell us that one treatment is better than another but it doesn’t appear that way. In spite of this, the authors argue for the use of the cation exchange resin.

Scherr L et al. Management of hyperkalemia with a cation-exchange resin. N Engl J Med. 1961;264:115. PMID: 13747532

Population: 32 patients with acute or chronic renal failure.
Intervention: Oral (or rectal) cation exchange resin and a low or no potassium diet
Control: None
Outcome: Serum potassium 24 hours post-administration

Findings: Scherr and colleagues found a decrease in serum potassium by 1.0 mEq on average.

Gruy-Kapral C et al. Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease. J Am Nephrol 1998; 9(10): 1924-30. PMID: 9779734

Population: 6 patients with renal failure
Intervention: Single dose of a cation exchange resin + sorbitol
Control: None
Outcome: Serum potassium level at 12 hours

Findings: The authors found no difference in serum potassium levels at 12 hours.

KayexalateCommentary: The Flinn and Scherr studies both conclude that the use of cation exchange resin + sorbitol is beneficial in the treatment of hyperkalemia. However, the results of their studies do not defend this conclusion. In the Flinn study, they were looking primarily at outcomes 120 hours after administration. Hardly the endpoint that we care about in the Emergency Department (I would argue that even the inpatient people wouldn’t care about this endpoint). In the Scherr study, there was no control group and the decrease was seen at 24 hours, again, not what we would care about in the ED. Both of these studies lacked even a modicum of randomization and all patients were given low/no potassium diets.

These two studies from the NEJM are the basis upon which kayexlate has been prescribed for 5 decades but they prove nothing except that patients given minimal dietary potassium their serum level will fall over 24 hours.

Finally, we have a Cochrane Review (Mahoney 2005) that states that potassium-absorbing resins have never been found to be effective in the first hours of treatment.

Alright, so a review of the literature shows that there is virtually no benefit in the emergent setting to the use of kayexalate. But is there a downside? As with all medications, there is. In this case, there is a rare but highly lethal complication of the drug: Colonic Necrosis.

A number of case reports and case series (Lillemoe 1987, Gerstman 1992, Rogers 2001, Bomback 2009) detail patients with kayexalate-associated colonic necrosis. In fact, the FDA added a warning back in 2011 cautioning against the use of the drug for this reason.

Given thAcute Colonic Necrosise absence of any significant benefit, particularly in the emergent setting, and the potential for serious harm, this recommendation from the nephrology literature seems very reasonable:

“It would be wise to exhaust other alternatives for managing hyperkalemia before turning to these largely unproven and potentially harmful therapies.” (Sterns 2010)

 So there you have it. More dogma-lysis on a medical myth that has been passed down from generation and purported for 50 years.

Okay, so what should I do with the hyperkalemic patient?

  1. If they have EKG changes, give Ca2+ salts and standard temporizing therapy and get the patient dialyzed if necessary.
  2. If you have to wait for dialysis, continue to redose your temporizing meds
  3. Look for the underlying cause – missed dialysis? ACEI? NSAIDs? Etc.

Bibliography

  1. Flinn RB et al. Treatment of the oliguric patient with a new sodium-exchange resin and sorbitol; a preliminary report. N Engl J Med. 1961;264:111. PMID: 13700297
  2. Scherr L et al. Management of hyperkalemia with a cation-exchange resin. N Engl J Med. 1961;264:115. PMID: 13747532
  3. Gruy-Kapral C et al. Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease. J Am Nephrol 1998; 9(10): 1924-30. PMID: 9779734
  4. Mahoney BA et al. Emergency interventions for hyperkalemia (Review). Coch Data Syst Rev 2005 Issue 2. CD 003235
  5. Lillemoe KD et al. Intestinal necrosis due to sodium polystyrene (Kayexalate) in sorbitol enemas: clinical and experimental support for the hypothesis. Surgery 1987; 101(3): 267-72. PMID: 3824154
  6. Gerstman B et al. Intestinal necrosis associated with postoperative orally administered sodium polystyrene sulfonate in sorbitol. Am J Kidney Dis 1992;20(2):159-61. PMID: 1496969
  7. Rogers FB, Li SC. Acute colonic necrosis associated with sodium polystyrene sulfonate (Kayexalate) enemas in a critically ill patient: case report and review of the literature. J Trauma 2001; 51(2): 395-7. PMID: 11493807
  8. Bomback AS et al. Colonic necrosis due to sodium polystyrene sulfate (Kayexalate). Am J Emerg Med 2009; 27: 753.e1-e2. PMID: 19751641
  9. Sterns RH et al. Ion-Exchange Resins for the Treatment of Hyperkalemia: Are They Safe and Effective? J Am Soc Nephrol 2010; 21: 733-5. PMID: 20167700
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Anand Swaminathan

Clinical Assistant Professor of Emergency Medicine at Bellvue/NYU
REBEL EM Associate Editor and Author
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10 replies
  1. reuben says:

    I’m still waiting for my chance to do emergency peritoneal dialysis (in a non-PD patient). I think the indication is persistent vfib/sine wave/cardiac arrest after numerous rounds of CaCl2 and the rest of the hyperKitchen sink.

    Reply
  2. kidney doc says:

    I’ve been treating CKD for years and like all of my colleagues we will continue to use SPS until a better exchange resin comes along. All other therapies temporarily push K into cells. ER docs are happy but the rest of us who have to care for patients more than a few hours still have to deal with the problem. SPS lowers K..not very much or very fast but it works. You forgot the 2014 paper by Nasir in nearly 100 patients showing efficacy (1 mEq/L in 3 days) for people with Stage 5 CKD who are not ready for HD this may keep them off the machine when combined with other therapies you suggest.

    If you liked SPS you would say that there are millions of doses given out with just a few rare complications reported, therefore it it largely safe.

    Please treat the topic fairly and think about patient centered care, not ER centered care

    Reply
    • Anand Swaminathan says:

      Kidney Doc – you make a reasonable point. There is a small drop in K+ over time. This post was truly addressing the emergent management of hyperK and why relying on kayexalate makes no sense.
      If a patient presents in hyperkalemia with EKG changes/in distress, I don’t think there’s any role for this agent. Either the patient has ESRD and needs dialysis for the longterm fix, or you can hydrate and add a loop diuretic to increase excretion.
      Thanks for your comments addressing the chronic management which is not addressed in this post.

      Reply
  3. kidney doc says:

    Thanks for coming a little clean.
    Please note, that most hyperkalemia occurs in Stage 5 CKD patients, many on TIW HD. Please do not attempt to give these patients fluids or loop diuretics as you will likely force our hands by volume overloading patients who can not maintain a normal water balance, and will give them ototoxicity because of the large doses of loop diuretics you will inevitably give with no success.

    Getting hyperkalemics out of distess is usually easy with calcium, beta agonists, insulin/glucose and bicarbonate (if they are acidotic). It is the next steps that are equally important.

    Thanks for an open dialog

    Reply
    • Salim Rezaie says:

      Hello Kidney Doc,
      I am an EM/IM doc and work both down in the ED as well as the inpatient side of the world. I always have short term and long term patient care in my mind. I would argue that in the acute setting the use of SPS has no benefit. If a patient has ECG changes we want things that will quickly reverse the ECG changes (i.e. Calcium gluc or chloride, Albuterol Neb, Insulin/Glucose, Bicarb in pts with metabolic acidosis). The effects of SPS are not seen for 2 – 3 hours. Longterm management is a 100% complete different issue. At my shop, we don’t have SPS…its not on formulary and a non-option. We use lactulose instead. Lactulose does help decrease K+ in hyperkalemia, it has the side effects of diarrhea and flatulence but when compared to bowel necrosis, this seems like a milder side effect in my mind. Here is a nice review article that also agrees that this is an acceptable alternative: http://ndt.oxfordjournals.org/content/early/2012/09/17/ndt.gfs293.full.pdf
      I think at the end of the day, the reason we created this blog was to start online conversation about different clinical entities and to have other specialists such as yourself to comment and create a collaboration to help improve patient care. I would say, at this point in time there is no evidence that SPS is superior to lactulose or that lactulose is inferior to SPS, so if weighing the risks and benefits of bowel necrosis vs some flatulence and diarrhea, then why not go with the lesser of two evils? If you are aware of studies that say otherwise, would love to get my hands on them. TY for reading the post and also commenting. I think many times physicians forget about the long term care of patients in addition to short term care. Looking forward to your response.

      Salim

      Reply
  4. kidney doc says:

    Salim

    thanks…we are reaching consensus and this is great. Please remember that you can count the number of cases of bowel necrosis associated with lactulose on your hand and the same level of evidence would suggest it is not as benign as you suggest:

    1: van der Vliet HJ, van Bodegraven AA. [Megacolon during treatment with
    lactulose]. Ned Tijdschr Geneeskd. 2004 May 15;148(20):998-1001. Dutch. PubMed
    PMID: 15181726.
    2: Zimmerman AL, Gupta JK, Ingegno AP. Pneumatosis coli following treatment with
    lactulose. N Y State J Med. 1979 Nov;79(12):1896-9. PubMed PMID: 292844.

    Please be careful when you say things like there “is no evidence that”. Please read a great editoria
    1: Braithwaite RS. A piece of my mind. EBM’s six dangerous words. JAMA. 2013 Nov
    27;310(20):2149-50. doi: 10.1001/jama.2013.281996. PubMed PMID: 24281458.

    There is no evidence that the peanut butter and jelly sandwich that brought for lunch today is going to satisfy me but I am sure it is. 🙂

    We agree… When you are really sick, SPS isn’t going to do anything for you right now, but you need something for later and fluids, loop diuretics and hemodialysis are not always the best answers. Lactulose is fine if you prefer, but please do something

    Great discussion
    Thanks

    Reply

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