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Effect of Single Dose Resin-Cathartic Therapy on Serum Potassium Concentration in Patients with End-Stage Renal Disease

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Effect of Single Dose Resin-Cathartic Therapy on Serum Potassium Concentration in Patients with End-Stage Renal Disease J Am Soc Nephrol 9: 1924-1930. 1998 Effect of Single Dose Resin-Cathartic Therapy on Serum Potassium Concentration in Patients with End-Stage Renal Disease CHRISTINE GRUY-KAPRAL, MICHAEL EMMETT, CAROL A. SANTA ANA, JACK L. PORTER, JOHN S. FORDTRAN, and KENNETH D. FINE Departnzent of Internal Medicine, Baylor Universirs’ Medical Center, Dallas, Texas. Abstract. Hyperkalemia in patients with renal failure is fre- slightly (0.4 mEqIL) during the I 2-h experiment. This rise was quently treated with a cation exchange resin (sodium polysty- apparently abrogated by some of the regimens that included rene sulfonate, hereafter referred to as resin) in combination resin; this may have been due in part to extracellular volume with a cathartic, but the effect of such therapy on serum expansion caused by absorption of sodium released from resin. potassium concentration has not been established. This study Phenolphthalein regimens were associated with a slight rise in evaluates the effect of four single-dose resin-cathartic regimens serum potassium concentrations (similar to placebo); this may and placebo on 5 different test days in six patients with chronic have been due to extracellular volume contraction produced by renal failure. Dietary intake was controlled. Fecal potassium high volume and sodium-rich diarrhea and acidosis secondary output and serum potassium concentration were measured for to bicarbonate losses. None of the regimens reduced serum 12 h. Phenobphthalein alone caused an average fecal potassium potassium concentrations, compared with baseline levels. Be- output of 54 mEq. The addition of resin caused an increase in cause single-dose resin-cathartic therapy produces no or only insoluble potassium output but a decrease in soluble potassium trivial reductions in serum potassium concentration, and be- output; therefore, there was no significant effect of resin on cause this therapy is unpleasant and occasionally is associated total potassium output. Sorbitol plus resin caused less potas- with serious complications, this study questions the wisdom of sium output than phenolphthalein plus resin. On placebo ther- its use in the management of acute hyperkabernic episodes. apy, the average serum potassium concentration increased The usual regimen used to treat acute hyperkalernia in patients serum potassium concentration fell over a period of several with renal failure includes administration of a cation exchange days, the study did not discriminate between the effects of resin (sodium polystyrene sulfonate, Kayexalate#{174}, hereafter resin-sorbitol, hypertonic glucose, or the extremely low potas- referred to as resin), together with a cathartic, usually sorbitol sium diet. In the era of chronic hemodialysis, it has become (1-6). The cathartic is believed to facilitate resin binding of common practice to administer single doses of resin-cathartic potassium by ensuring that the resin has adequate contact with in the management of acute hyperkalemia. However, as before, potassium-containing gastrointestinal secretions. Independent the efficacy of resin-cathartic therapy for acute hyperkabemia of any facilitory effect on resin binding of potassium, the has not been clarified due to the simultaneous use of other cathartic also causes loss of soluble potassium in diarrheal fluid potassium-lowering treatments, including glucose and insulin (I ,2,7). Presumably, therefore, the resin and the cathartic act in infusions, sodium bicarbonate, and/or f32-agonists. a synergistic manner to remove potassium from the body. In a previous experiment in healthy subjects (9), we found Moreover, the cathartic may prevent resin-induced constipa- that gastrointestinal excretion of potassium was greater after tion or fecab impaction ( 1,8). phenobphthalein-docusate (hereafter referred to as phenol- The early study (1 ) that introduced resin-cathartic therapy phthalein) than after sorbitol, and that addition of resin to either was carried out before the advent of chronic hemodiabysis. laxative caused only modest additional fecal potassium excre- Hyperkalemic patients were treated for several days with re- tion. The subjects used in that experiment had normal renal peated doses of resin-sorbitol and with a diet consisting of 50% function, and they were given potassium intravenously to pre- dextrose in water or Karo syrup and ginger ale. Although vent a net loss of potassiurn frorn the body. Therefore, this earlier study did not address whether resin-cathartic regimens could reduce the serum potassium concentration. Because a benefit of resin-cathartic therapy has not been Received October 20, 1998. Accepted March 9, 1998. clearly established, and because this therapy is unpleasant, Correspndence to Dr. Kenneth D. Fine, Baylor University Medical Center, poorly tolerated, and occasionally results in significant or even 2nd Floor HOB. 3500 Gaston Avenue Dallas, TX 75246. fatal complications 1,6,8, 10- 16), we performed a controlled l()46-6673/090l0- I924503.00/0 ( Journal of the American Society of Nephrology study on the effect of several single-dose resin-cathartic regi- Copyright 0 1998 by the American Society of Nephrology rnens in patients with end-stage renal disease. We analyzed the J Am Soc Nephrol 9: 1924-1930. 1998 Resin-Cathartics and Serum K Concentration 1925 effect of these regimens on serum potassium concentration and Table 1. Treatment regimens on the amount of potassium that is removed from the body. Placebo: 8 gelatin capsules with 500 ml of water Sodium polystyrene sulfonate: 30 g of resin with 500 ml of Materials and Methods water Patients Phenolphthalein-docusate: 8 tablets” with 500 ml of water Six patients with chronic renal failure maintained on hemodialysis Phenolphthabein-docusate plus resin: 8 tablets,” 30 g of resin volunteered for the study. This research was approved by the Institu- with 500 ml of water tional Review Board for Human Protection of Baylor University Sorbitol plus resin: 60 g of sorbitob, 30 g of resin with 500 Medical Center. and informed consent was obtained. ml of water a Given as Correctol#{174}; each tablet contains 65 mg of yellow Protocol phenolphthalein and 100 mg of docusate sodium. The patients underwent five studies on five separate experimental days, with at least I wk between each study. Patients were studied 2 d after a dialysis treatment and I d before their next dialysis session. In Results random order, they were treated with one of the five regimens listed 12-Hour Fecal Output of Potassium after Cathartic in Table I . Four hours after treatment, the patients ingested a standard Regimens meal containing 15.2 ± 2.2 mEq of sodium and 21.4 ± 1.4 mEq of Average results are shown in Table 2. Total fecal potassium potassium. No other foods or beverages (including water) were con- output after phenolphthalein alone was 54 mEq; of this sumed during the study. Intravenous fluid was not administered. amount, 46 mEq (85%) was dissolved in stool water, and the Serum potassium concentration was measured just before, and at 4, 8, and 12 h after treatment; a free-flowing peripheral vein was used remainder was insoluble. When 30 g of resin was ingested rather than the vascular access to avoid risk of access damage. Stools together with phenolphthalein, I 7 g of resin (57% of the were collected for I 2 h after each treatment to quantify fecal potas- ingested dose) was excreted; this was associated with an I 1 sium, sodium, and resin output. The patients did not excrete any urine mEq average rise in the output of insoluble potassium (P < during the experimental periods. 0.05). However, addition of resin was also associated with a 21 rnEqfL reduction in soluble potassium concentration and with a 17 mEq fall in soluble potassium output (P values not Analytical Methods and Calculations significant). The resin-induced rise in insoluble potassium out- Water and solid content of stool were measured by weighing before put was offset by the fall in soluble potassium output, and resin and after lyophilization. Sodium and potassium concentrations were therapy therefore did not increase total potassium excretion. measured by flame photometry. Calcium and magnesium concentra- The ingestion of sorbitol and 30 g of resin resulted in the tions were measured by atomic absorption spectroscopy. Soluble stool cation outputs were calculated as the product of the stool supernatant fecal excretion of only 9.3 g of resin (3 1 % of the ingested cation concentration and the grams of total fecal water (determined by dose). Fecal excretion of total potassium was less with sorbitol lyophilization of stool). Total stool output of cations was calculated as plus resin than with phenolphthalein plus resin, in agreement the product of stool weight and cation concentration of an acid- with an earlier study in healthy subjects (9). digested stool sample. Insoluble cation output is the difference be- tween total and soluble cation output. Plasma concentrations of chlo- 12-Hour Fecal Output of Sodium after Cathartic ride, bicarbonate, and glucose were measured by automated analysis. Regimens Stool resin concentration was estimated by measuring stool cation As shown in Table 2, when patients ingested phenobphtha- binding capacity. First, all cation binding sites in an aliquot of stool were lein alone, fecab sodium output existed almost exclusively in converted to the lithium form by suspending the stool in a concentrated the soluble state. When 30 g of resin was ingested with phe- solution (I mol/L) of lithium chloride. Unbound lithium was removed by nobphthalein, fecal output contained 1 7 g of resin, and there repeated washing and centrifugation. The precipitate was then suspended in water, and concentrated potassium chloride was added to displace the was a marked increase in fecal excretion of both soluble and bound lithium. The amount of lithium released into water, measured by insoluble sodium. After sorbitol plus resin, the fecal output atomic absorption spectroscopy, is equal to the mEq of cation binding contained less resin and less sodium than when phenolphtha- sites of stool. The resin content of a 12-h stool collection in mEq is the 1cm plus resin was ingested.
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