Kayexalate for Acute Hyperkalemia
Search Strategy: Since this is a therapy question, you conduct a PUBMED Clinical Query (narrow/specific) question for “hyperkalemia” (http://tinyurl.com/5tvmklq) noting 67 citations including a Cochrane review on the topic. Quickly reviewing the Cochrane review for kayexalate as a management strategy, you find that only one randomized controlled trial was identified so you dig up that study to review. Reviewing the bibliography of the single RCT identifies a preliminary report describing the use of kayexalate in 1961 so using your ample time you mosey on down to the library and dust off the 1961 volume of the New England Journal of Medicine and happen upon another article adjacent to the original description.
It a typical overnight shift in TCC and as usual you are waiting on inpatient beds for your patients. One of your patients has a history of end-stage renal disease and is being admitted for hemodialysis. Her potassium is 6.0. Her EKG is unchanged. Another patient is being admitted with new onset renal failure and has a potassium of 6.1. The Medicine service calls back and requests you treat these patients for their hyperkalemia. “Be sure to give kayexalate” says the resident. After putting the order in HMED, the nurse asks, “Do we really need to give kayexalate? This lady is going to poop everywhere!” You bring the question to your ever astute attending who suggests a literature search.
Population: Adult emergency department patients with life-threatening hyperkalemia.
Intervention: Treatment with gastrointestinal cation-exchange resin (kayexalate) plus other potassium lower regimensl
Comparison: Treatment with potassium lower regimens other than cation-exchange resins
Outcome: Hyperkalemia-related mortality, duration of hyperkalemia, adverse effects attributed to kayexalate.
Article 1: Treatment of the Oliguric Patient with a New Sodium-Exchange Resin and Sorbitol, NEJM 1961; 264:111-115
Article 2: Management of Hyperkalemia with a Cation-Exchange Resin, NEJM 1961; 264:115-119
Article 3: Effect of Single Dose Resin-Cathartic Therapy on Serum Potassium Concentration in Patients with End-Stage Renal Disease, J Am Soc Nephrol 1998; 9:1924-1930
Article 4: Emergency interventions for hyperkalaemia, Cochrane Database Systematic Rev. 2005; Issue 2. Art. No.: CD003235. DOI: 10.1002/14651858. CD003235. Pub2
The combination of a rising prevalence of chronic renal failure combined with changes in the medical management of hypertension (ACE-inhibitors) and heart failure will probably lead to an increase in hyperkalemia cases presenting to emergency departments in coming decades. Patients with acute hyperkalemia may present with generalized weakness, paralysis, arrhythmias or sudden cardiac death. The diagnosis of hyperkalemia can be challenging. One retrospective review demonstrated that ECG changes were seen in 43% of patients with potassium values ranging from 6.0 to less than 6.8 mEq/L and in only 55% of patients with values of 6.8 mEq/L or greater. Another ED-based retrospective study demonstrated that the predominant symptoms were dyspnea (20%) and weakness (19%) and that 83% had an abnormal ECG (including peaked T-waves in 34%). The single most useful test in the evaluation of hyperkalemia is the ECG since life-threatening complications are related to the effect of potassium on myocardial electrical rhythms.
The management of severe hyperkalemia (severe being defined by the effect of potassium on the ECG not by the absolute potassium level, although levels above the upper range of the normal lab range are often treated emergently) include:
- calcium (to stabilize the myocardium)
- glucose and insulin (to move extracellular potassium into the intracellular space)
- Beta2-agonists (to move extracellular potassium into the intracellular space)
- Bicarbonate (to move extracellular potassium into the intracellular space)
- Dialysis (to remove potassium)
- Exchange resins (such as Kayexalate to remove potassium)
Each of these therapeutic alternatives are included in our ED acute hyperkalemia order-set. In addition, all leading textbooks of Emergency Medicine list all of these options without any supporting references or elaboration on the evidence-basis for Kayexalate. In fact, a close inspection of the dated medical literature does not support the use of Kayexalate.
The original non-randomized, likely underpowered, poorly described pilot trial in 1961 suggested that oral sorbitol alone may reduce serum potassium in oliguric patients better than Kayexalate plus sorbitol. Larger trials that control for etiology, severity, and duration of renal dysfunction in ED-relevant patients with hyperkalemia are needed. Such trials would also assess patient-centric outcomes since hyperkalemia is often well-tolerated in chronic renal dysfunction while the side effects, of Kayexalate plus sorbitol (diarrhea) are quite unpleasant. A second non-randomized trial in 1961 suggested that most patients with acute or chronic kidney disease will reduce their serum potassium levels after oral or rectal Kayexalate alone (mean decrease 1 mEq/L). Potassium levels will continue to decrease or hold stable for 24 hours after Kayexalate is stopped. Some patients will experience constipation. Larger trials that control for etiology, severity, and duration of renal dysfunction in ED-relevant patients with hyperkalemia are needed, but since 50 years have passed since these publications and Kayexalate is considered the standard of care in all leading EM textbooks for the acute management of hyperkalemia, insufficient equipoise may exist for Institutional Review Board’s to approve such randomized controlled trials.
More recent trials have demonstrated that Kayexalate does not reduce serum potassium significantly within 12 hours in end-stage renal disease patients starting with a mean potassium of 4.4 mEq/L. Additionally, Kayexalate and sorbitol have been associated with colonic necrosis with perforation (Gerstman 1992, Rashid 1997, Roy-Chaudhury 1997). Another therapeutic alternative, phenolphthalein, actually increases serum potassium (4.2 to 4.6 mEq/L at 12 hours). Although this analysis does not recruit or treat ED patients with potassium levels exceeding 6 mEq/L and/or ECG changes, the implication is that Kayexalate may have limited or no role in the management of hyperkalemia given more effective acute alternatives (dialysis, insulin, inhaled B-agonists). If cathartics are used clinicians should remember that small frequent diarrhea stools excrete more potassium than single large stools either with or without Kayexalate.