Sodium polystyrene sulfonate versus sodium zirconium cyclosilicate for the treatment of hyperkalemia in the emergency department.

BACKGROUND: Hyperkalemia accounts for over 800,000 emergency department (ED) visits in the United States each year, and has been associated with significant morbidity and mortality likely due to fatal cardiac dysrhythmias. Previous studies have demonstrated reductions in mortality when potassium levels are normalized in the ED. Cation exchange resins, such as sodium polystyrene sulfonate (SPS) and sodium zirconium cyclosilicate (SZC), may be administered as a means of definitively eliminating potassium from the body. This practice is based on physician preference and is not supported by high quality data. Two studies evaluating the use of cation exchange resins versus standard treatment in the ED demonstrated reductions in serum potassium levels within two hours of administration; however, there have been no published studies investigating these agents in a head-to-head comparison. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of SPS versus SZC in lowering serum potassium in patients presenting to the ED with hyperkalemia. METHODS: This was an institutional review board-approved, retrospective cohort study conducted at a single-site ED. All patients who received medications under the "ED Hyperkalemia Treatment" order set between August 26, 2019 and May 13, 2021 were eligible for inclusion. The primary outcome was the change in serum potassium from baseline to first repeat level following SPS or SZC administration in the ED. RESULTS: A total of 885 patients were screened with 54 patients in the SPS group and 51 patients in the SZC group included in the final analyses. The mean change in serum potassium from baseline to first repeat level following administration of the cation exchange resin was -1.1 mEq/L for both groups. CONCLUSION: Administration of SPS or SZC for the treatment of hyperkalemia in the ED resulted in similar reductions in serum potassium.

Sodium zirconium cyclosilicate to increase lithium elimination.

Lithium is considered a mood stabilizer for bipolar affective disorders, but it has a narrow therapeutic index of 0.6-1.2 mEq/L. This can easily result in toxic levels after minimal changes in renal function or individual patient's pharmacokinetics. Lithium toxicity can arise with levels as low as 1.5 mEq, and there are limited therapeutic options to treat these patients presenting to the emergency department (ED). At therapeutic levels 95% of lithium is eliminated unchanged by the kidneys. However, previous literature has examined sodium polystyrene sulfonate (SPS) as an option to reduce lithium levels by binding the lithium cation and enhancing its excretion via the gastrointestinal tract. This suggests there may be an increased degree of non-renal clearance and altered toxicokinetics at supratherapeutic levels. However, SPS has been associated with intestinal necrosis and may cause treatment limiting hypokalemia, and is therefore not commonly recommended in treatment algorithms for lithium toxicity. A newer cation exchange resin, sodium zirconium cyclosilicate (SZC), may provide a safer alternative to SPS while also aiding in the clearance of lithium. We present a patient case where a patient with symptomatic acute-on-chronic lithium toxicity had increased clearance of lithium after a dose of SZC.

Dispelling myths and misconceptions about the treatment of acute hyperkalemia.

Hyperkalemia represents a widespread and potentially lethal condition that affects millions of people across their lives. Despite the prevalence and severity of the condition, there are no consensus guidelines on the treatment of hyperkalemia or even a standard definition. Herein, we provide a succinct review of what we believe to be the most significant misconceptions encountered in the emergency care of hyperkalemia, examine current available literature, and discuss practical points on several modalities of hyperkalemia treatment. Additionally, we review the pathophysiology of the electrocardiographic effects of hyperkalemia and how intravenous calcium preparations can antagonize these effects. We conclude each section with recommendations to aid emergency physicians in making safe and efficacious choices for the treatment of acute hyperkalemia.

SPS(Kayexalate)/CPS(K-Bind) crystals in the gastrointestinal tract-An experience from a tertiary center.

INTRODUCTION: Kayexalate (Sodium Polystyrene Sulfonate/SPS) and K-bind (Calcium Polystyrene Sulfonate/CPS) are cation exchange resins, commonly used for treatment of hyperkalaemia. SPS/CPS induced injury of the gastrointestinal tract(GIT) is rare, can be potentially life threatening but is under-recognized. This study aims to increase awareness of pathologists and clinicians of this under-reported complication of a drug commonly used to treat hyperkalaemia. MATERIALS: Study population comprised patients with SPS/CPS (Kayexalate or its analogues) crystals identified in gastrointestinal specimens from 2017-2019 at a tertiary care centre. Clinical details, relevant investigations, imaging and endoscopic findings, patient follow up details were obtained from the hospital electronic information system. RESULTS: A total of 10 patients with SPS/ CPS crystals in the GIT were encountered over 2 years. Male to female ratio was 9:1, with mean age 66.5years (range 52-82 years). Eight cases were mucosal biopsies and 2 were resection specimens. Additional pathology (tumours, colonic perforation) was present in 80% of patients. The characteristic morphological appearance of the CPS/SPS crystals on H&E stains were supported by special stains -Periodic acid Schiff(PAS) and Acid fast Bacilli(AFB). In all cases, the treatment history with SPS/CPS for hyperkalaemia was obtained only after the histological examination. Most common etiology of hyperkalaemia encountered was chronic kidney disease(CKD)/ Acute on chronic kidney disease. CONCLUSION: It is important for pathologists to recognise the presence of these crystals especially in small biopsies as early feedback to clinicians can help in appropriate management and avoidance of more serious adverse outcome. To the best of our knowledge, this is the first series of 10 consecutive cases of SPS/CPS crystals encountered in gastrointestinal tract to be reported from India.

A Brief Review of the Pharmacology of Hyperkalemia: Causes and Treatment.

Hyperkalemia is a common problem in both inpatients and outpatients. Many disease states (eg, chronic kidney disease) and medications may precipitate hyperkalemia. There are several drugs now available to treat hyperkalemia. Many of these drugs are relatively new. This review provides information regarding drug-induced causes of hyperkalemia and provides detailed information on the medications used to treat this problem.

[Hyperkalemia treatment in chronic kidney disease patients: overview on new K binders and possible therapeutic approaches]. / Iperkaliemia nel paziente con Malattia Renale Cronica in trattamento conservativo: overview sui nuovi chelanti e sui possibili approcci terapeutici

Hyperkalaemia is a common complication in patients with nondialysis Chronic Kidney Disease (CKD). It is associated with weakness, paralysis, arrhythmias and increased mortality. Higher serum potassium levels refractory to treatment is one of the most frequent reasons to initiate immediately renal replacement treatment in advanced stages of CKD. Hyperkalaemia is also indirectly associated with the progression of CKD; in fact higher serum potassium levels may lead to withdrawal of renin-angiotensin-system inhibiting drugs that currently represent the most effective tools to postpone ESRD. It is therefore essential to identify patients at higher risk of increase of serum K and to implement therapeutic interventions aimed at preventing and treating hyperkalaemia, such as diet modifications and greater use of diuretics and cation exchange resins. Sodium and calcium-polystyrenesulfonate (SPS) are the resins currently available in Italy. However, few studies showed that SPS is efficacious to reduce serum K and is associated with increased risk of severe adverse effects. Patiromer and ZS-9 represent a significant pharmacological progress in the treatment of hyperkalemia. Indeed, recent studies showed that these novel resins are efficient to reduce serum levels of K with minor occurrence of side effects than polystyrensulfonates. Furthermore, Patiromer, sodium free agent, might have a further advantage in CKD patients, reducing the salt intake in these patients. In addition, ZS-9, being fast-acting drug, might be used also in the treatment of acute hyperkalaemia.

Controversies in Management of Hyperkalemia.

BACKGROUND: Hyperkalemia is a common electrolyte disorder that can result in morbidity and mortality if not managed appropriately. OBJECTIVES: This review evaluates the classic treatments of hyperkalemia and discusses controversies and new medications for management. DISCUSSION: Potassium (K+) plays a key role in determining the transmembrane potentials of "excitable membranes" present in nerve and muscle cells. K+ is the predominant intracellular cation, and clinical deterioration typically ensues when patients develop sufficiently marked elevation in extracellular fluid concentrations of K+ (hyperkalemia). Hyperkalemia is usually detected via serum clinical laboratory measurement. The most severe effect of hyperkalemia includes various cardiac dysrhythmias, which may result in cardiac arrest and death. Treatment includes measures to "stabilize" cardiac membranes, to shift K+ from extracellular to intracellular stores, and to promote K+ excretion. Calcium gluconate 10% dosed 10 mL intravenously should be provided for membrane stabilization, unless the patient is in cardiac arrest, in which case 10 mL calcium chloride is warranted. Beta-agonists and intravenous insulin should be given, and some experts recommend the use of synthetic short-acting insulins rather than regular insulin. Dextrose should also be administered, as indicated by initial and serial serum glucose measurements. Dialysis is the most efficient means to enable removal of excess K+. Loop and thiazide diuretics can also be useful. Sodium polystyrene sulfonate is not efficacious. New medications to promote gastrointestinal K+ excretion, which include patiromer and sodium zirconium cyclosilicate, hold promise. CONCLUSIONS: Hyperkalemia can be deadly, and treatment requires specific measures including membrane stabilization, cellular shift, and excretion.

Evidence in support of hyperkalaemia management strategies: A systematic literature review.

BACKGROUND: Hyperkalaemia is a potentially life-threatening condition that can be managed with pharmacological and non-pharmacological approaches. With the recent development of new hyperkalaemia treatments, new information on safe and effective management of hyperkalaemia has emerged. OBJECTIVES: This systematic literature review (SLR) aimed to identify all relevant comparative and non-comparative clinical data on management of hyperkalaemia in adults. Our secondary aim was to assess the feasibility of quantitatively comparing randomised controlled trial (RCT) data on the novel treatment sodium zirconium cyclosilicate (ZS) and established pharmacological treatments for the non-emergency management of hyperkalaemia, such as the cation-exchangers sodium/calcium polystyrene sulphonate (SPS/CPS). METHODS: MEDLINE, Embase and the Cochrane Library were searched on 3rd April 2017, with additional hand-searches of key congresses and previous SLRs. Articles were screened by two independent reviewers. Eligible records reported interventional or observational studies of pharmacological or non-pharmacological management of hyperkalaemia in adults. RESULTS: Database searches identified 2,073 unique records. Two hundred and one publications were included, reporting 30 RCTs, 29 interventional non-RCTs and 43 observational studies. Interventions investigated in RCTs included ZS (3), SPS/CPS (3), patiromer (4) and combinations of temporising agents (6 RCTs). A robust and meaningful indirect treatment comparison between ZS and long-established cation-binding agents (SPS/CPS) was infeasible because of heterogeneity between studies (including time points and dosing) and small sample size in SPS/CPS studies. CONCLUSIONS: Despite hyperkalaemia being associated with several chronic diseases, there is a paucity of high-quality randomised evidence on long-established treatment options (SPS and CPS) and a limited evidence base for hyperkalaemia management with these agents.

Evaluation of the tolerability and efficacy of sodium polystyrene sulfonate for long-term management of hyperkalemia in patients with chronic kidney disease.

PURPOSE: Sodium polystyrene sulfonate (SPS) is a cation-exchanging resin that has been widely used for several decades as first-line therapy of mild chronic hyperkalemia in patients with chronic kidney disease (CKD). However, evidence to prove the long-term tolerability and efficacy of SPS for the treatment of this condition is still missing. METHODS: In this retrospective, observational study, we enrolled 26 outpatients with stages 3-4 CKD who received oral therapy with low-dose SPS for mild chronic hyperkalemia in the Outpatient Nephrology clinic of our Department during 2010-2016. We obtained medical records on side effects potentially attributable to SPS use, and we analyzed the changes in serum electrolytes before and after the initiation of SPS therapy. RESULTS: Serum potassium levels fell from 5.9 ± 0.4 to 4.8 ± 0.5 mmol/l (P < 0.001) over a median follow-up of 15.4 months (range 3-27 months). SPS use was associated with a slight, but significant elevation in serum sodium levels (139.5 ± 2.9 vs 141.2 ± 2.4, P = 0.006), whereas serum calcium and phosphate remained unchanged before and after the initiation of SPS. We recorded ten episodes of recurrent serum potassium elevation ≥ 5.5 mmol/l, none of which required hospitalization or acute dialysis. No episode of colonic necrosis or any other serious drug-related adverse event was observed. SPS therapy was well-tolerated, since only 1 out of 26 patients discontinued SPS at 3 months due to gastrointestinal intolerance. CONCLUSION: This study suggests that low-dose SPS is well-tolerated and can effectively normalize elevated serum potassium over several weeks in CKD outpatients with mild chronic hyperkalemia.

Potassium: friend or foe?

The kidney plays an essential role in maintaining homeostasis of ion concentrations in the blood. Because the concentration gradient of potassium across the cell membrane is a key determinant of the membrane potential of cells, even small deviations in serum potassium level from the normal setpoint can lead to severe muscle dysfunction, resulting in respiratory failure and cardiac arrest. Less severe hypo- and hyperkalemia are also associated with morbidity and mortality across various patient populations. In addition, deficiencies in potassium intake have been associated with hypertension and adverse cardiovascular and renal outcomes, likely due in part to the interrelated handling of sodium and potassium by the kidney. Here, data on the beneficial effects of potassium on blood pressure and cardiovascular and renal outcomes will be reviewed, along with the physiological basis for these effects. In some patient populations, however, potassium excess is deleterious. Risk factors for the development of hyperkalemia will be reviewed, as well as the risks and benefits of existing and emerging therapies for hyperkalemia.

New drugs to prevent and treat hyperkalemia.

PURPOSE OF REVIEW: Hyperkalemia is frequent, but occurs mostly in patients with chronic kidney disease and is often the cause of discontinuation or omission of renin-angiotensin-aldosterone system inhibitors in patients with diabetes, chronic kidney disease and heart failure. RECENT FINDINGS: Without much evidence in the literature on its efficacy, sodium polystyrene sulfonate is being used frequently in the clinical setting to treat hyperkalemia. In the last few years, two new promising agents have been developed to treat hyperkalemia - patiromer and sodium zirconium cyclosilicate 9 (ZS-9). Both patiromer and ZS-9 have been shown to decrease potassium in patients with hyperkalemia and then to maintain normokalemia. Gastrointestinal adverse events were more frequent with patiromer, and edema occurred in patients using high doses of ZS-9, possibly due to its high sodium content. SUMMARY: Although patiromer and ZS-9 are very promising in terms of safety and efficacy, many questions remain, mostly in terms of selection of patients, long-term effects and costs.

Treatment of pediatric hyperkalemia with sodium polystyrene sulfonate.

OBJECTIVE: To describe the safety and efficacy of sodium polystyrene sulfonate (SPS) in pediatric patients with acute hyperkalemia. METHODS: A retrospective chart review of all patients less than 18 years of age administered SPS for acute hyperkalemia at Texas Children's Hospital between 2011 and 2014. RESULTS: Our cohort consisted of 156 patients (mean age 6.8 ± 6.1 years). The peak mean potassium concentration observed was 6.5 ± 0.77 mmol/l prior to administration of SPS. The mean SPS dose was 0.64 ± 0.32 g/kg. The majority (91 %) of the SPS doses were given orally. The nadir mean potassium concentration in the 48 h post-SPS was 4.7 ± 1.2 mEq/l, which occurred at 16.7 ± 14.7 h post-dose. In the 48 h following SPS administration, 68 (43 %) patients required at least one additional intervention after SPS dose. Patients who required an additional intervention after initial SPS dose differed significantly in weight, baseline serum potassium, and were more likely to have received SPS treatment via the rectal route. A gastrointestinal adverse event was documented in 24 (15 %) patients. CONCLUSIONS: SPS was used effectively and safely in the majority of patients in this report. However, it may not be appropriate as a first single-line agent in patients with severe acute hyperkalemia who require a greater than 25 % reduction in serum potassium levels or those at a high risk for cardiac arrhythmias.

Treatment of hyperkalemia: something old, something new.

Treatment options for hyperkalemia have not changed much since the introduction of the cation exchange resin, sodium polystyrene sulfonate (Kayexalate, Covis Pharmaceuticals, Cary, NC), over 50 years ago. Although clinicians of that era did not have ready access to hemodialysis or loop diuretics, the other tools that we use today-calcium, insulin, and bicarbonate-were well known to them. Currently recommended insulin regimens provide too little insulin to achieve blood levels with a maximal kalemic effect and too little glucose to avoid hypoglycemia. Short-acting insulins have theoretical advantages over regular insulin in patients with severe kidney disease. Although bicarbonate is no longer recommended for acute management, it may be useful in patients with metabolic acidosis or intact kidney function. Kayexalate is not effective as acute therapy, but a new randomized controlled trial suggests that it is effective when given more chronically. Gastrointestinal side effects and safety concerns about Kayexalate remain. New investigational potassium binders are likely to be approved in the coming year. Although there are some concerns about hypomagnesemia and positive calcium balance from patiromer, and sodium overload from ZS-9 (ZS Pharma, Coppell, TX), both agents have been shown to be effective and well tolerated when taken chronically. ZS-9 shows promise in the acute treatment of hyperkalemia and may make it possible to avoid or postpone the most effective therapy, emergency hemodialysis.

Sodium polystyrene sulfonate for the treatment of acute hyperkalemia: a retrospective study.

BACKGROUND: Hyperkalemia is a common problem in hospitalized patients, especially those with underlying chronic kidney disease, but evidence-based guidelines for its treatment are lacking. Sodium polystyrene sulfonate (SPS), a cation exchange resin first approved by the FDA for the treatment of hyperkalemia in 1958, is frequently used alone or in conjunction with other medical therapies to lower serum potassium. Recently, the safety and efficacy of SPS have come into question based on multiple reported cases of bowel necrosis associated with SPS administration. OBJECTIVE: The primary objective of this study was to evaluate the use of SPS for the treatment of hyperkalemia, at a large tertiary community teaching hospital, to determine its effectiveness and the incidence of related adverse side effects. METHODS: A retrospective chart review was performed on all adult inpatients receiving single-dose SPS at a 466-bed tertiary community teaching hospital over a 3-year period. RESULTS: 501 patients received SPS for the treatment of hyperkalemia during their index hospital stay. Serum potassium levels decreased by 0.93 mEq/L on average at first recheck after SPS administration, with or without additional medical treatments. Our study identified 10 cases of hypernatremia (greater than 145 mEq/L), 31 cases of hypokalemia (less than 3.5 mEq/L), and 2 cases of bowel necrosis related to the administration of SPS. CONCLUSION: Our results suggest a serum potassium reduction of less than 1 mEq/L after administration of SPS for the treatment of acute hyperkalemia. Additionally, this study offers some evidence that the use of SPS may be associated with harm. We further note the need for standardized guidelines for the treatment of hyperkalemia at our institution.

Asymptomatic Cecal Perforation in a Renal Transplant Recipient After Sodium Polystyrene Sulfonate Administration.

Sodium polystyrene sulfonate (SPS) is a medication commonly used for the treatment of hyperkalemia. There have been many cases of colonic necrosis and perforation associated with administration of SPS. There are very few such cases reported in renal transplant patients. We present a case of renal transplant recipient who developed cecal perforation after a single oral dose of SPS. She had no signs or symptoms suggestive of intestinal perforation and was incidentally diagnosed with it on abdominal imaging performed to find cause of acute blood loss anemia. This case underlines the importance of recognizing this severe and potentially life-threatening complication associated with SPS. The clinicians should also consider renal/solid organ transplant and immunosuppression as potential risk factors.

Evidence-based management of potassium disorders in the emergency department [digest].

Hypokalemia and hyperkalemia are the most common electrolyte disorders managed in the emergency department. The diagnosis of these potentially life-threatening disorders is challenging due to the often vague symptomatology a patient may express, and treatment options may be based upon very little data due to the time it may take for laboratory values to return. This review examines the most current evidence with regard to the pathophysiology, diagnosis, and management of potassium disorders. In this review, classic paradigms, such as the use of sodium polystyrene and the routine measurement of serum magnesium, are tested, and an algorithm for the treatment of potassium disorders is discussed. [Points & Pearls is a digest of Emergency Medicine Practice].