The Endoscopic Removal of a Gastric Bezoar Made of Sodium Zirconium Cyclosilicate Hydrate

Abstract

Sodium zirconium cyclosilicate hydrate (SZC) is a novel potassium binder that can be administered either orally or via nasogastric tubes. We report the case of a 77-year-old woman who developed a 37-mm gastric bezoar after nasogastric SZC administration during intensive care for acute adrenal insufficiency. Endoscopic removal was performed, and the analysis confirmed that the SZC was the primary constituent. Impaired gastric motility, acidic gastric environment, and limited hydration are likely contributors. This case highlights the potential for SZC-induced gastric bezoar formation in critically ill patients, and underscores the importance of imaging monitoring, careful gastrointestinal management, and the awareness of this potential complication during SZC therapy.

Introduction

Sodium zirconium cyclosilicate hydrate (SZC) was approved in Japan in May 2020 as a novel treatment for hyperkalemia. SZC selectively binds potassium ions and exchanges them with hydrogen and sodium ions, thereby promoting potassium excretion from the gastrointestinal tract (1). Unlike conventional polymeric cation-exchange resins, such as sodium polystyrene sulfonate and calcium polystyrene sulfonate, SZC is an inorganic, non-polymeric compound that does not swell after water absorption, resulting in less gastrointestinal irritation (1-3). The administration of SZC via a nasogastric tube has also been established, thus making it useful for dialysis patients or those unable to take medications orally (4,5). However, there have been a few reports of complications related to gastrointestinal retention of SZC (6-8), indicating that careful attention is required during its use. Furthermore, SZC is radiopaque on X-ray-based imaging and its accumulation can potentially interfere with diagnostic interpretations (9,10). We herein report a case in which endoscopic removal was necessary for a gastric bezoar formed by SZC.

Case Report

A 77-year-old woman presented to our hospital with vomiting and a poor oral intake. She had a history of type 2 diabetes mellitus and was taking oral antidiabetic medication. One week prior to admission, she developed persistent vomiting and a poor oral intake, leading to an inability to take her medications. The patient's general condition deteriorated and she was referred to our hospital. Her medical history included hypertension, hyperlipidemia, uterine fibroids, and atopic dermatitis. Current medications include tofogliflozin, vildagliptin, metformin, glimepiride, amlodipine, telmisartan, pemafibrate, and olopatadine. On admission, vital signs were as follows: blood pressure, 100/54 mmHg; heart rate, 86 beats per minute, SpO₂ 96%; and temperature, 36.2°C. Bilateral lower limb edema was noted, but the abdomen was flat, soft, and nontender. An arterial blood gas analysis revealed a pH of 7.173, HCO₃^- 11.9 mmol/L, PCO₂ 27.7 mmHg, PO₂ 94.6 mmHg, and lactate 9.4 mg/dL. Laboratory findings included blood glucose 115 mg/dL, HbA1c 8.9%, BUN 4 mg/dL, creatinine 0.44 mg/dL, Na 136 mEq/L, K 3.7 mEq/L, and Cl 107 mEq/L, and urinalysis showed ketones 3+. Chest and abdominal computed tomography (CT) scans revealed no abnormalities that could explain vomiting. Based on these findings, she was diagnosed with euglycemic diabetic ketoacidosis associated with sodium-glucose cotransporter 2(SGLT2) inhibitor use and thus was admitted for treatment.

By hospital day 5, acidosis had improved; however, anorexia persisted. On day 8, she developed a sudden fever of 40°C that progressed to shock. On day 9, she experienced cardiopulmonary arrest necessitating resuscitation, endotracheal intubation, mechanical ventilation, sedation, and vasopressor therapy in the intensive care unit. Acute kidney injury with hyperkalemia thereafter developed, and on day 11, SZC 10 g was administered via a nasogastric tube. On day 12, a worsening renal function with persistent oliguria and prolonged hyperkalemia led to the initiation of continuous hemodiafiltration (CHDF). By day 13, serum potassium level had decreased to 3.5 mEq/L. CT performed on day 13 to assess the overall condition revealed a round intragastric mass measuring 37 mm in the gastric fundus, which showed high attenuation on CT (Fig. 1). A retrospective review of chest X-ray images obtained on day 12 also demonstrated a similar round mass in the stomach, which appeared radiopaque on the radiograph with no significant change in size (Fig. 2). Notably, this radiopaque mass was not visible on the chest radiograph obtained on day 9 (Fig. 3). During this period, the SZC was the only agent administered via the nasogastric tube, suggesting that the mass represented an SZC bezoar.

Figure 1.

CT revealed a well-defined, round, 37-mm, high-attenuation mass in the gastric fundus.

Figure 2.

A chest radiograph obtained on day 12 (one day before the CT scan) also revealed a radiopaque, round mass in the gastric area.

Figure 3.

A chest radiograph obtained on day 9 revealed no visible radiopaque foreign bodies.

Given the large size of the mass (＞30 mm) and the anticipated delayed gastric emptying, along with the potential for prolonged hypokalemia, endoscopic removal was performed on day 14. Upper gastrointestinal endoscopy revealed an oval whitish bezoar in the gastric fundus (Fig. 4). The mass was removed using a disposable retrieval net (Fig. 5). It appeared white with a smooth and glossy surface and it could be easily crushed manually, while revealing layered fine granular structures (Fig. 6, 7). A component analysis confirmed a silica-like pattern, consistent with SZC as the main constituent. Following removal, the serum potassium level remained stable, and no radiopaque materials were observed on imaging. Subsequently, the patient had been taking betamethasone d-chlorpheniramine maleate for several months. Therefore, the sudden clinical deterioration was attributed to acute adrenal insufficiency. The patient's overall condition gradually improved with continued intensive care.

Figure 4.

Upper gastrointestinal endoscopy showed an oval, whitish bezoar located in the gastric fundus.

Figure 5.

The mass was retrieved using a disposable endoscopic retrieval net.

Figure 6.

The specimen appeared to be white with a smooth and glossy surface.

Figure 7.

The specimen was easily crushed manually, thus revealing a layered, fine-granular internal structure.

Discussion

This case represents gastric bezoar formation primarily composed of SZC. The therapeutic options for hyperkalemia include diuretics and cation exchange resins. In patients with a poor general condition, such as in the present case, gastrointestinal motility is often impaired, thus making intravenous agents preferable to oral formulations in terms of efficacy. As cation-exchange resins are available only as oral preparations, diuretics could be considered a reasonable alternative. However, relying solely on diuretics to promote potassium excretion carries a substantial risk of hypotension in patients with a compromised systemic status. Based on these considerations, the enteral administration of a cation-exchange resin was deemed appropriate. Among the available cation-exchange resins, SZC was selected because it exerts a minimal burden on the intestinal tract and it has an established method for administration via a nasogastric tube, thus making it suitable for the present case.

SZC was administered to treat hyperkalemia associated with acute kidney injury (AKI). At the time of initiation, the patient showed an improvement in her vital signs, including blood pressure, and renal recovery was also anticipated. Thus, the treatment was intended to address what was expected to be transient hyperkalemia. However, contrary to expectations, AKI worsened and progressed to oliguria, thus necessitating the initiation of CHDF. Fortunately, despite the deterioration of AKI, hyperkalemia did not worsen markedly owing to the effect of SZC. Conversely, once CHDF was started, its additional potassium-lowering effect resulted in hypokalemia. The management of hypokalemia then became necessary, but the condition, which would normally improve after the discontinuation of SZC, raised concerns for prolonged potassium-lowering effects due to the formation of an SZC gastric bezoar. Therefore, endoscopic removal rather than dissolution therapy was deemed appropriate.

Drug-induced bezoars have been reported with other medications, including sucralfate hydrate (11) and magnesium oxide (12), with some cases requiring endoscopic removal (12,13). The proposed mechanisms for drug-induced gastric bezoar formation include incomplete dissolution of sustained-release formulations, drug overdose, delayed gastrointestinal transit, and contributory factors, such as the hygroscopic properties of certain drugs and components of sustained-release coating materials (14). SZC is a microparticle compound with a molecular weight of 569.663 g/mol, represented by the formula ZrH₄O₆·3H₄SiO₄·2H₂O·2Na. In the case of SZC, aggregation may be driven by the physical properties of the drug components. SZC particles are classified as microparticles, and according to the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory (15), electrostatic repulsion is relatively weak, predisposing them to gravitational settling, mechanical contact, and aggregation in viscous fluids. The acidic gastric environment may reduce the surface charge of silica derivatives, such as SZC, further promoting aggregation and sedimentation (16). Additionally, when the amount of moisture available to the drug is insufficient, the increased particle-particle contact density and reduced repulsive forces may promote gastric bezoar formation. In this case, only the minimum amount of water required to suspend the SZC was administered, and no additional water or other medications that could contribute to fluid intake were administered. Consequently, because there was no moisture or enteral fluid unrelated to SZC administration, the relative water content of the stomach was limited. The limited water content in the stomach may have promoted particle aggregation by reducing the repulsive forces, thereby facilitating gastric bezoar formation. These factors suggest that even with an adequate suspension volume, critically ill patients may be at risk of gastric bezoar formation. Therefore, increasing hydration during drug administration may mitigate this risk.

Dissolution therapy has been reported as a treatment option for gastric bezoars using solvents such as carbonated water (17), cola beverages (18), and digestive enzyme preparations (19). Their proposed mechanisms include the penetration of carbon dioxide bubbles into the bezoar and the creation of an acidic environment similar to that of gastric juice in the case of cola beverages. However, these treatments have been reported to be primarily effective for bezoars of plant fiber or protein origin, such as persimmon-derived phytobezoars. In contrast, for drug-induced gastric bezoars caused by SZC, using carbonated water or cola instead of plain water would likely be counterproductive. From a physicochemical standpoint, bubbles may impede contact between particles and water, and an acidic environment may promote further aggregation. Although an alkaline environment may theoretically facilitate dissolution, achieving alkaline conditions within the stomach is considered impractical. Therefore, adequate hydration and mechanical agitation are likely to be key to effective dissolution in such cases.

SZC is administered as a suspension, and nasogastric administration instructions note the potential for tube obstruction and recommend appropriate preparation (5). In this case, the administration followed established protocols, thus suggesting a proper technique had been used. Similar to previous reports of SZC retention, the patient was critically ill and received intensive care (6), indicating that an impaired gastrointestinal motility may have contributed to a delayed clearance. Furthermore, adrenal insufficiency in this case may have further contributed to impaired gastrointestinal motility.

Although the Japanese package insert does not mention gastrointestinal adverse effects, the U.S. SZC label includes warnings advising against use in patients with severe constipation, bowel obstruction, or impaction, including abnormal postoperative bowel motility disorders due to a potential worsening of gastrointestinal conditions (5,20). Reports of gastrointestinal perforation (7) and our experience suggest that careful monitoring of the gastrointestinal status is warranted. Preventive measures, such as patient repositioning, prokinetic agents, or the initiation of enteral nutrition, may be effective, but in this case, the presence of hypokalemia and a large gastric mass necessitated endoscopic removal, which was successful.

The early detection of gastric retention may be facilitated by the radiopaque properties of SZC, thus allowing for monitoring with X-rays or CT (9,10). For critically ill patients, combining imaging-based monitoring with careful attention to the gastrointestinal status may improve the safe use of SZC and prevent prolonged hypokalemia.

The authors state that they have no Conflict of Interest (COI).