No Love, Just Hate with Kayaxylate
Written by Dr. Ashraf Hussain, Edited by Dr. Sunny Elagandhala
Due to advances in modern medicine the average age for the human population has been increasing. With that increase, there is a general uptrend of humans living longer with Chronic Kidney Disease (CKD) and progressing to end stage renal disease ESRD. According to the CDC 15% of the US population have CKD and more than 700,000 Americans have ESRD and are receiving dialysis. But what does this mean for us as emergency physicians? As the rates of CKD increases, we will likely see a consequent increase in the number of patients coming into our ED with hyperkalemia.
Most physicians have their own established medications they use to treat hyperkalemia, something we call the “hyperkalemia cocktail”. This consists of calcium to stabilize the cardiac membrane, Transcellular shifters of potassium (insulin and beta agonists), and potassium eliminators. The effectiveness of the latter category causes the most controversy in the management of hyperkalemia patients.
The majority of potassium in our body is removed by our kidneys, thus the hyperkalemia CKD patients is predictable. That is also why we give patients furosemide for hyperkalemia. However, the majority of ESRD patients have little to no urine production, thus furosemide is of little utility in these patients. Approximately 10 % of potassium is removed by our colon making it a decently effective modality to aid in the removal of potassium.
Sodium polysterene sulfate (Kayexalate) was once a very popular drug used in the management of hyperkalemia. It is a cation-exchange resin which allows for the exchange of sodium and potassium ions as it moves through the gut. It is usually given with sorbitol to allow for the bowel movement. The onset of action for Kayexalate is reportedly 1-2 hours. Chatmain et. al demonstrated that 10 hours after administration 15 g of Kayexalate potassium level was reduced by 0.82 meq/L whereas 60 g reduced it by 1.4 meq/L2. The beginning of the end of kayexalate began when there was a proven association with bowel necrosis3. There were multiple case reports documenting bowel necrosis with different dosages. A case report from 2009 demonstrated colonic necrosis with a relatively low dose of Kayexalate1. Harel et. al demonstrated that Kayexalate with sorbitol can cause bowel necrosis in hyperkalemic patients that are neither ESRD or post-operative patients1. Naturally, given that sorbitol is added to Kayexalate, a question would arise of whether the sorbitol is leading the factor for the bowel necrosis or is it the Kayexalate itself. A systematic review of case reports done in 2013 demonstrated that necrosis was approximately 40% higher in patients receiving Kayexalate with sorbitol than in those receiving Kayexalate only4. Even so given that 41% of the patients receiving Kayexalate only, it is no way a benign medication.
Luckily there are two other medications on the market for hyperkalemia, Patiromer and Sodium zirconium cyclosilicate (ZS-9). Patiromer is an oral medication with an onset of action of 7 hours. The dosing ranges from 8.4 -25.2 gram once daily. It works via exchanging calcium for potassium in the colon. A multicenter prospective trial demonstrated that after day 3 there was an 1 mmol/L drop in their potassium level5.
ZS-9 is an oral medication that was approved for the treatment for hyperkalemia in May of 2018. It is another sodium-potassium cation exchanger6. The onset of action for this medication is approximately one hour. Dosing is 5-10 grams. An RCT demonstrated a decrease of 1.2mEq/L of potassium vs placebo with the use of ZS-97. A meta- analysis comparing the two medications demonstrated that 10g of ZS-9 decreased potassium by 0.17 mEq/L at one hour and decreased it by 0.67 by two days whilst patiromer decreased the potassium by .36 meq/L at the end of three days. Patiromer was also more likely to cause diarrhea, constipation whilst ZS-9 more likely to cause vomiting. Patiromer was also more likely to cause hypokalemia and hypomagnesemia6.
All these studies bring us back to the crucial question of what drug should we use for the elimination of potassium. Certainly, Kayexalate should not be used anymore given its reputation for causing bowel necrosis. Luckily, we have these two new drugs with a better safety profile than Kayexalate and better efficacy in treating hyperkalemia. However, it is evident that the effects of these drugs are minimal during the duration the patient is in the ED. Its only benefit truly comes during the remainder of the hospitalization for the patient. Thus, for me I would not rush to start the patients on these medications as it will not clinically affect their course while they are under my care in the emergency room. However, when the call comes from the hospitalist or renal fellow asking which potassium excretion drug we will be using, I would choose ZS-9 given its time of onset of action as well having less side effects than patiromer. Given it’s novelty, it may not be available in all Emergency Departments.
References
1. Mcgowan, C E., et al. “Intestinal Necrosis Due to Sodium Polystyrene Sulfonate (Kayexalate) in Sorbitol.” Southern Medical Journal, vol. 102, no. 5, 2009, pp. 493–497., doi:10.1097/smj.0b013e31819e8978. Accessed 25 Aug. 2019.
2. Chaitman, Martin et al. “Potassium-Binding Agents for the Clinical Management of Hyperkalemia.” P & T : a peer-reviewed journal for formulary management vol. 41,1 (2016): 43-50.
3. Lillemoe, KD, et al. “Intestinal Necrosis Due to Sodium Polystyrene (Kayexalate) in Sorbitol Enemas: Clinical and Experimental Support for the Hypothesis.” Surgery , vol. 101, no. 3, Mar. 1987, pp. 267–272. Pubmed, doi:3824154.
4. Gastrointestinal Adverse Events with Sodium Polystyrene Sulfonate (Kayexalate) Use: A Systematic Review Harel, Ziv et al. The American Journal of Medicine, Volume 126, Issue 3, 264.e9 - 264.e24
5. Weir, Matthew R., et al. “Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors.” New England Journal of Medicine, vol. 372, no. 3, 2015, pp. 211–221., doi:10.1056/nejmoa1410853.
6. Kosiborod M, Rasmussen HS, Lavin P, et al. Effect of Sodium Zirconium Cyclosilicate on Potassium Lowering for 28 Days Among Outpatients With Hyperkalemia: The HARMONIZE Randomized Clinical Trial. JAMA.2014;312(21):2223–2233. doi:10.1001/jama.2014.15688
7. Meaney, Calvin J., et al. “Systematic Review and Meta-Analysis of Patiromer and Sodium Zirconium Cyclosilicate: A New Armamentarium for the Treatment of Hyperkalemia.” Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, vol. 37, no. 4, Oct. 2017, pp. 401–411., doi:10.1002/phar.1906