Use Of Sodium Polystyrene Sulfonate Research Articles

#3106 The prevalence and degree of hyperkalaemia in adult patients with chronic kidney disease, in Durban, South Africa

Abstract Background and Aims Hyperkalaemia is a known risk factor for the development of cardiac rhythm disturbances and sudden cardiac death. The presence of chronic kidney disease (CKD) is also an independent risk factor for cardiovascular complications. The prevalence of hyperkalaemia in patients with CKD has previously varied widely between studies. The prevalence of hyperkalaemia in the patients attending the renal clinic at Inkosi Albert Luthuli Central Hospital (IALCH) has not been previously determined. This study aimed to discover the prevalence of hyperkalaemia in patients attending the renal clinic at IALCH, as well as the degree of severity amongst the patients in whom hyperkalaemia was present. Demographic and other variables were also assessed for an association with hyperkalaemia. Method A retrospective review of outpatients attending the renal clinic at IALCH from 1 October 2016 until 30 September 2017. Demographic and clinical characteristics were retrieved and descriptive statistical methods and logistic regression analysis were performed. Results The study consisted of 200 patients, of whom the majority were female (n=120, 60%). The prevalence of hyperkalaemia amongst these patients was found to be 16%. In those with stage 3 CKD, the prevalence of hyperkalaemia was 7.69%. In those with stage 4 CKD, the prevalence of hyperkalaemia was 20.5% and in those with stage 5 CKD the prevalence was 17.3%. There were no statistically significant associations between hyperkalaemia and demographic variables, nor with dietician intervention. There was a significant association with the use of sodium polystyrene sulfonate. Conclusion CKD is a growing burden in the developing world. With CKD comes metabolic and other derangements, including electrolyte abnormalities as well as increased cardiovascular risk. Hyperkalaemia is associated with worsening CKD. In addition, hyperkalaemia puts patients at risk of cardiac dysrhythmias and sudden cardiac death. Pharmacological measures to manage CVD risk should be weighed up against the risk of hyperkalaemia related complications. Potassium lowering agents should be considered to allow for optimal CVD management in the setting of hyperkalaemia in CKD.

Intestinal perforation secondary to the use of sodium polystyrene sulfonate, case report.

Background: The use of cation exchange resins such as sodium polystyrene sulfonate (SPS) in the treatment of hyperkalemia has been associated with potential damage to the gastrointestinal tract. Case Description: We present a clinical case of a 63-year-old male patient admitted following a single-lung transplant who presented a complex postoperative period associating renal failure and hyperkalemia, therefore administering SPS. 17 days afterward, the patient presented a clinical exacerbation with acute abdominal pain, due to a sigmoid perforation. The patient underwent urgent surgery, performing an open sigmoidectomy and terminal colostomy. The anatomo-pathological study of the surgical specimen revealed abundant SPS crystals in the depth of the colonic wall. Conclusions: Close patient surveillance and a high clinical suspicion are essential to prevent potentially fatal complications from the use of SPS. Due to low incidence of this complication, the evidence in literature is limited to case reports and retrospective studies.

Adverse Gastrointestinal Events With Sodium Polystyrene Sulfonate Use in Patients on Maintenance Hemodialysis: An International Cohort Study

Background: There are concerns regarding the gastrointestinal (GI) safety of sodium polystyrene sulfonate (SPS), a medication commonly used in the management of hyperkalemia. Objective: To compare the risk of GI adverse events among users versus non-users of SPS in patients on maintenance hemodialysis. Design: International prospective cohort study. Setting: Seventeen countries (Dialysis Outcomes and Practice Patterns Study [DOPPS] phase 2-6 from 2002 to 2018). Patients: 50 147 adults on maintenance hemodialysis. Measurements: An adverse GI event defined by a GI hospitalization or GI fatality with SPS prescription compared with no SPS prescription. Methods: Overlap propensity score–weighted Cox models. Results: Sodium polystyrene sulfonate prescription was present in 13.4% of patients and ranged from 0.42% (Turkey) to 20.6% (Sweden) with 12.5% use in Canada. A total of 935 (1.9%) adverse GI events (140 [2.1%] with SPS, 795 [1.9%] with no SPS; absolute risk difference 0.2%) occurred. The weighted hazard ratio (HR) of a GI event was not elevated with SPS use compared with non-use (HR = 0.93, 95% confidence interval = 0.83-1.6). The results were consistent when examining fatal GI events and/or GI hospitalization separately. Limitations: Sodium polystyrene sulfonate dose and duration were unknown. Conclusions: Sodium polystyrene sulfonate use in patients on hemodialysis was not associated with a higher risk of an adverse GI event. Our findings suggest that SPS use is safe in an international cohort of maintenance hemodialysis patients.

Optimizing Therapies in Heart Failure: The Role of Potassium Binders.

Heart failure (HF) is a worrisome cardiac pandemic with a negative prognostic impact on the overall survival of individuals. International guidelines recommend up-titration of standardized therapies in order to reduce symptoms, hospitalization rates, and cardiac death. Hyperkalemia (HK) has been identified in 3–18% of HF patients from randomized controlled trials and over 25% of HF patients in the “real world” setting. Pharmacological treatments and/or cardio-renal syndrome, as well as chronic kidney disease may be responsible for HK in HF patients. These conditions can prevent the upgrade of pharmacological treatments, thus, negatively impacting on the overall prognosis of patients. Potassium binders may be the best option in patients with HK in order to reduce serum concentrations of K+ and to promote correct upgrades of therapies. In addition to the well-established use of sodium polystyrene sulfonate (SPS), two novel drugs have been recently introduced: sodium zirconium cyclosilicate (SZC) and patiromer. SZC and patiromer are gaining a central role for the treatment of chronic HK. SZC has been shown to reduce K+ levels within 48 h, with guaranteed maintenance of normokalemia for up to12 months. Patiromer has resulted in a statistically significant decrease in serum potassium for up to 52 weeks. Therefore, long-term results seemed to positively promote the implementation of these compounds in clinical practice due to their low rate side effects. The aim of this narrative review is to delineate the impact of new potassium binders in the treatment of patients with HF by providing a critical reappraisal for daily application of novel therapies for hyperkalemia in the HF setting.

Fatal and Non-Fatal Gastrointestinal Events with Sodium Polystyrene Sulfonate Use in Hemodialysis: DOPPS

Fatal and Non-Fatal Gastrointestinal Events with Sodium Polystyrene Sulfonate Use in Hemodialysis: DOPPS

MO953PREVALENCE AND FACTORS ASSOCIATED WITH HYPERKALAEMIA IN STABLE KIDNEY TRANSPLANT RECIPIENTS WITH PRESERVED RENAL FUNCTION

Abstract Background and Aims Hyperkalaemia is a frequent and potentially life-threatening condition in patients with CKD. Even after successful kidney transplantation, kidney transplant recipients have mild to severe CKD. Moreover, they share co-morbid conditions and frequently use medications that predispose to hyperkalaemia. This study aimed to examine the prevalence and factors associated with hyperkalaemia in this population. Method Over a pre-specified period of 6 months (September 1st 2019 to March 31st 2020), we recorded in a cross-sectional fashion information on serum potassium and relevant demographics, co-morbidities, medications, laboratory and transplant-associated variables in clinically stable kidney transplant recipients attending the Transplant Outpatient Clinic of our Department. Ηyperkalaemia was classified as follows: serum potassium level >5 mEq/L or >5 with concomitant use of sodium polystyrene sulfonate; ≥5.2; and ≥5.5 mEq/L. Univariate and multiple logistic regression analyses were used to identify factors associated with increased serum potassium >5.0 mEq/L. Results The study population consisted of 582 stable kidney transplant recipients, 369 (63.4%) males, aged 52.4±13.5 years, with eGFR of 55.8±20.1 ml/min/1.73m2 transplanted for more than one year. The prevalence of hyperkalaemia defined as potassium >5, >5 and use of sodium polystyrene sulfonate, ≥ 5.2 or ≥5.5, was 22.7%, 22.7%, 14.4% and 4.1% (132, 132, 84 and 24 patients), respectively. In multivariate analysis, male gender (OR 2.020, 95% CI 1.264-3.227) and use of renin-angiotensin-aldosterone-system blockers (OR 1.628, 95% CI 1.045-2.536), were independently associated with hyperkalaemia, while higher eGFR (OR 0.967, 95% CI 0.955-0.979) and diuretic use (OR 0.140, 95% CI 0.046-0.430) were associated with lower odds of the disorder. Conclusion The prevalence of mild hyperkalaemia in stable kidney transplant recipients is common but that of moderate or severe hyperkalemia is relatively uncommon. Male gender and low eGFR are the most potent factors associated with hyperkalaemia. Among a wide range of factors only male gender, RAAS blockade and low eGFR increased the odds of hyperkalemia.

Patiromer for the treatment of hyperkalemia

ABSTRACT Introduction Hyperkalemia is a chronic and life-threatening electrolyte disorder that affects millions of patients around the world with decreased kidney function, hypertension, and heart failure. Recently newer oral potassium-binding agents have been approved for clinical use, as an alternative to the decades long use of sodium polystyrene sulfonate. This review will focus on the patiromer and its use in reducing hyperkalemia. Areas covered Pubmed was used to search from 1960 to 2020 on free subject terms: Hyperkalemia, Potassium, Patiromer, Veltassa, Kayexalate, Sodium polystyrene sulfonate, and Sodium Zirconium cyclosilicate. The authors have reviewed the literature and summarized the most salient elements in regards to patiromer. Expert opinion Patiromer has been available on the US market since 2015 when approved by the FDA for clinical use. Clinical trials monitoring patient use for up to 1 year have shown clinically meaningful potassium reductions, sustained normokalemia, high tolerability, and without major serious adverse events. Patiromer is available to all patients experiencing hyperkalemia, no matter the disease state leading to the condition. It is likely this newer oral potassium-binding agent will help change how patients with hyperkalemia are treated in regards to sudden and chronic medical conditions.

P0941HEALTHY K-RICH DIET IN CHRONIC KIDNEY DISEASE (CKD) PATIENTS USING SODIUM ZIRCONIUM CYCLOSILICATE (SZC) TO CONTROL HYPERKALEMIA: A FEASIBILITY STUDY (HELPFUL)

Abstract Background and Aims Preventing hyperkalemia - a potentially fatal complication in advanced CKD - by prescribing diets low in K (=limited intake of healthy components such as vegetables, fruits, whole grains and nuts) leads to poor dietary quality. K-restricted unhealthy diets may affect quality of life, patient satisfaction with treatment, achievement of nutritional targets, and increase risk of obstipation, gut dysbiosis and progression of CKD. We designed a feasibility study to test if a low-protein healthy K-rich diet with fruits, vegetables, whole grains and nuts with concomitant use of new potassium binder (SZC) can be safely prescribed to patients with CKD stages 4 and 5 with hyperkalemia. Method A feasibility descriptive single arm open-label interventional trial lasting 6 weeks will enroll 36 CKD patients at the outpatient clinic with: age 18 - 85 years; glomerular filtration rate < 29 ml/min/1.73 m2 and not on dialysis; serum K > 5.1 mmol/L or in previous use of sodium polystyrene sulfonate (SPS) to decrease serum K levels, and who develops hyperkalemia after SPS is ceased. Patients with serum K > 6.5 mmol/L and those likely to start dialysis within 2 months, with inflammatory bowel syndrome or with a history of hypokalemia (<3.0 mmol/L) will not be included. Primary end points will be changes in patient satisfaction with treatment, patient symptom list, and intake of energy and protein before and after the stabilization and healthy diet phase. Secondary outcomes will include changes in quality of life, obstipation and circulating gut microbiota-related uremic toxins. Intervention: In the first 3 weeks, representing stabilization phase, SZC will be prescribed to normalize serum K to 3.5 to 5.0 mml/L, and a diet with energy 25-35 kcal/kg/day and protein 0.6 to 0.8 g/kg/day and with low K content will be prescribed by a renal dietitian. At the end of the first 3 weeks, the patients will be instructed to keep the same content of energy and protein and initiate a healthy diet containing 3700 to 4000 mg/potassium for 3 weeks (healthy diet phase). In order to increase adherence, a food basket containing fruits, vegetables, whole grains, nuts, white meat, fish and eggs in amounts adequate for the patient and the family will be provided. Serum K will be monitored to promote serum K between 3.5 to 5.0 mmol/L and adjustments in the dose of SZC will be performed according to the drug label. Blood measurements, quality of life and intestinal obstipation questionnaires and measurements of nutritional intake will be performed in the beginning and at the end of the stabilization phase and again in the beginning and end of the healthy diet phase. Additionally, during stabilization and healthy diet phases, serum K will be measured every 72 hours until serum K is normalized and after that, once per week. The protocol is registered at www.clinicaltrials.gov (identifier NCT04207203). Results NA Conclusion This interventional feasibility pilot study will test the hypothesis that - with precautions aiming at reducing risk of hyperkalemia - a K-rich healthy diet in patients with CKD stage 4 may improve patient satisfaction with treatment and patient symptoms. Depending on the results, a larger randomized controlled longitudinal trial will be considered to investigate if K-rich diet in CKD stage 4-5 patients is safe and beneficial.

Risk of Hospitalization for Serious Adverse Gastrointestinal Events Associated With Sodium Polystyrene Sulfonate Use in Patients of Advanced Age

Sodium polystyrene sulfonate is commonly prescribed for the treatment of hyperkalemia. Case reports of intestinal injury after administration of sodium polystyrene sulfonate with sorbitol resulted in a US Food and Drug Administration warning and discontinuation of combined 70% sorbitol-sodium polystyrene sulfonate formulations. There are ongoing concerns about the gastrointestinal (GI) safety of sodium polystyrene sulfonate use. To assess the risk of hospitalization for adverse GI events associated with sodium polystyrene sulfonate use in patients of advanced age. Population-based, retrospective matched cohort study of eligible adults of advanced age (≥66 years) dispensed sodium polystyrene sulfonate from April 1, 2003, to September 30, 2015, in Ontario, Canada, with maximum follow-up to March 31, 2016. Initial data analysis was conducted from August 1, 2018, to October 3, 2018; revision analysis was conducted from February 25, 2019, to April 2, 2019. Cox proportional hazards regression models were used to examine the association of sodium polystyrene sulfonate use with a composite of GI adverse events compared with nonuse that was matched via a high-dimensional propensity score. Additional analyses were limited to a subpopulation with baseline laboratory values of estimated glomerular filtration rate and serum potassium level. Dispensed sodium polystyrene sulfonate in an outpatient setting. The primary outcome was a composite of adverse GI events (hospitalization or emergency department visit with intestinal ischemia/thrombosis, GI ulceration/perforation, or resection/ostomy) within 30 days of initial sodium polystyrene sulfonate prescription. From a total of 1 853 866 eligible adults, 27 704 individuals were dispensed sodium polystyrene sulfonate (mean [SD] age, 78.5 [7.7] years; 54.7% male), and 20 020 sodium polystyrene sulfonate users were matched to 20 020 nonusers. Sodium polystyrene sulfonate use compared with nonuse was associated with a higher risk of an adverse GI event over the following 30 days (37 events [0.2%]; incidence rate, 22.97 per 1000 person-years vs 18 events [0.1%]; incidence rate, 11.01 per 1000 person-years) (hazard ratio, 1.94; 95% CI, 1.10-3.41). Results were consistent in additional analyses, including the subpopulation with baseline laboratory values (hazard ratio, 2.91; 95% CI, 1.38-6.12), and intestinal ischemia/thrombosis was the most common type of GI injury. The use of sodium polystyrene sulfonate is associated with a higher risk of hospitalization for serious adverse GI events. These findings require confirmation and suggest caution with the ongoing use of sodium polystyrene sulfonate.

New frontiers for management of hyperkalaemia: the emergence of novel agents.

Hyperkalaemia is a common electrolyte abnormality, associated with higher risk of morbid events, and increasing in prevalence—in part, due to increasing rates of comorbidities such as heart failure, chronic kidney disease, diabetes mellitus, and the use of renin-angiotensin-aldosterone system inhibitors (RAASi). In spite of this growing problem, the existing treatments for chronic hyperkalaemia have been limited, and are typically confined to dietary potassium restrictions and cessation or modification of RAASi, with latter option being potentially problematic given the known morbidity and mortality benefit of RAASi therapy in certain disease states, such as heart failure. The use of sodium polystyrene sulfonate (SPS/Kayexelate) for chronic hyperkalaemia has been low, due to poor tolerability, potential gastrointestinal safety concerns, and remaining uncertainty in regards to its efficacy. Given the shortcomings of existing therapies, novel treatments are clearly needed. There are now two novel treatment options, patiromer and sodium zirconium cyclosilicate (SZC), both approved by the FDA and EMA for treatment of chronic hyperkalaemia. These novel compounds have been demonstrated in multiple studies to be efficacious in achieving and maintaining normal serum potassium levels, over an extended time period, in patients with hyperkalaemia; and appear to be relatively safe and well-tolerated. Whether the correction of hyperkalaemia with these agents will allow optimization of RAASi, which could theoretically lead to improvement in clinical outcomes, especially in patients with heart failure, remains to be determined. Several clinical trials are ongoing to address these important knowledge gaps.

Single-dose sodium polystyrene sulfonate for hyperkalemia in chronic kidney disease or end-stage renal disease.

BackgroundThe use of sodium polystyrene sulfonate (SPS) for the treatment of hyperkalemia lacks sufficient efficacy data in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD); however, use remains widespread. Recent evidence suggests that this population may be at risk for serious gastrointestinal adverse effects with SPS. Methods. We conducted a single-center retrospective cohort study. Adult patients with CKD Stages 4, 5, or ESRD maintained on renal replacement therapy with serum potassium >5 mEq/L and receipt of SPS were screened for inclusion. Our primary outcome was decrease in potassium within 24 h post-30 g oral SPS suspended in 33% sorbitol. Secondary outcomes included decrease in potassium within 24 h from 15 or 30 g SPS doses and gastrointestinal adverse events.ResultsOf 596 records, 114 were included for analysis. At the first serum potassium level within 24 h post-30 g oral SPS the median potassium decrease was 0.8 mEq/L [interquartile range (IQR) 0.4–1.1; P < 0.001]. At the first potassium level within 24 h post-15 or 30 g SPS, the median potassium decrease was 0.7 mEq/L (IQR 0.4–1.0; P < 0.001]. Post-SPS potassium levels occurred 14–16 h post-SPS. Gastrointestinal side effects occurred within 30 days of SPS in 5% of patients, although only two cases were classified as possibly associated.ConclusionsThe use of single-dose SPS monotherapy resulted in a significant decrease in serum potassium levels within 24 h in patients with CKD Stage 4, 5, or ESRD. However, it remains unclear if SPS is associated with an increased risk of gastrointestinal injury in this population.

PP.05.14] PREVALENCE OF HYPERKALEMIA IN MATCHED DIABETIC AND NON-DIABETIC PATIENTS WITH CHRONIC KIDNEY DISEASE

Objective: Hyperkalemia is a frequent and potentially life-threatening electrolyte disorder, usually complicating chronic kidney disease (CKD). Factors superimposed to reduced renal function, are further elevating the risk for hyperkalemia development, but their contribution is not fully elucidated in relevant literature. This study aimed to compare the prevalence of hyperkalemia in matched diabetic and non-diabetic patients with CKD and to evaluate factors associated with hyperkalemia occurrence. Design and method: This is a nested case-control study from a cohort of patients followed in a Nephrology outpatient clinic. A total of 180 type-2 diabetic and 180 non-diabetic patients with CKD matched for gender, age and eGFR, were included. Patients with type-1 diabetes or end-stage renal disease were excluded. Prevalence of hyperkalemia was defined as serum potassium > 5 mEq/L and/or use of sodium polystyrene sulfonate, and further by serum potassium levels >5 and greater or equal to 5.2 and 5.5 mEq/L. Prevalence was compared between the two study groups in total population and in CKD Stages separately. Univariate and multivariate logistic regression analysis were conducted to identify factors associated with hyperkalemia occurrence. Results: The prevalence of hyperkalemia was higher in diabetic CKD patients (27.2% vs 20%, p = 0.107) and remained around 30% higher with all secondary definitions used, but never reached statistical significance. In Stage 2 no difference was noted (8.7% vs 17.4%, p = 0.665), in Stage 3 prevalence was significantly higher in diabetics (28.6% vs 17.5%, p = 0.036) and in Stage 4 equally high in both groups (35.5% vs 32.3%, p = 0.788). In multivariate analysis, Stage 4 CKD (OR: 4.535, 95% CI: 1.561–13.173), use of angiotensine-converting enzyme inhibitors (OR: 2.228, 95%CI: 1.254–3.958), and smoking (OR: 2.254, 95%CI: 1.218–4.171) were independently associated with hyperkalemia. Conclusions: Diabetes mellitus is elevating the prevalence of hyperkalemia only in CKD Stage 3 patients (moderately impaired renal function) and this difference is attenuating in CKD Stage 4. Advanced CKD at Stage 4 and ACEIs are major determinants of hyperkalemia occurrence. As the vast majority of patients with CKD belong to Stage 3, the presence of diabetes must be appreciated regarding hyperkalemia risk and relevant therapeutic decisions.

Prevalence of Hyperkalemia in Diabetic and Non-Diabetic Patients with Chronic Kidney Disease: A Nested Case-Control Study

Background: Hyperkalemia is a potentially life-threatening disorder, usually complicating chronic kidney disease (CKD). Factors superimposed to reduced renal function are further elevating hyperkalemia risk, but their contribution is not fully elucidated. This study aimed to compare the prevalence of hyperkalemia in diabetic and non-diabetic patients with CKD. Methods: This is a nested case-control study of 180 type-2 diabetic and 180 non-diabetic patients with CKD followed in a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate. Type-1 diabetes or end-stage renal disease patients were excluded. Prevalence of hyperkalemia was defined as potassium >5 mEq/l or use of sodium polystyrene sulfonate, and further by potassium >5, ≥5.2 and ≥5.5 mEq/l. It was calculated in both groups in whole and CKD stages separately. Univariate and multivariate logistic regression analysis were conducted to identify factors associated with hyperkalemia. Results: The prevalence of hyperkalemia was higher in diabetic CKD patients (27.2 vs. 20%, p = 0.107) and remained around 30% higher with all secondary definitions used, but never reached statistical significance. In Stage 2, no difference was noted (8.7 vs. 17.4%, p = 0.665); in Stage 3, it was significantly higher in diabetics (28.6 vs. 17.5%, p = 0.036); and in Stage 4, it was equally high in both groups (35.5 vs. 32.3%, p = 0.788). In multivariate analysis, Stage 4 CKD (OR 4.535, 95% CI 1.561-13.173), use of angiotensin-converting enzyme inhibitors (ACEIs; OR 2.228, 95% CI 1.254-3.958) and smoking (OR 2.254, 95% CI 1.218-4.171) were independently associated with hyperkalemia. Conclusions: Diabetes mellitus was found to elevate the prevalence of hyperkalemia only in CKD Stage 3 patients (moderately impaired renal function). Advanced CKD at Stage 4 and ACEIs are major determinants of hyperkalemia occurrence.

Kayexylate-Induced Rectal Ulcerative Polyp

Introduction: Kayexalate (sodium polystyrene sulfonate) is a cation-exchange resin that is used for treatment of hyperkalemia. It is available in 2 forms: oral and rectal. Kayexalate can cause mucosal damage, though the mechanism remains unknown. We present a case of Kayexylate-induced rectal ulcerative polyp that highlights Kayexalate administered orally as a cause of mucosal injury in the lower gastrointestinal tract. A 79-year-old woman with a medical history noted for perirectal abscess drained surgically 30 years ago, chronic constipation on enemas, and idiopathic chronic hyperkalemia on daily oral Kayexalate presented to the clinic with complaints of rectal pain, bright red blood per rectum, and constipation. On exam, external hemorrhoids and rectal prolapse were noted. On anoscopy, a polypoid lesion was seen. Flexible sigmoidoscopy was performed, which was remarkable for 2 5-9-mm polypoid lesions at the anal verge. Histopathology was consistent with mucosal prolapse, ulceration, with Kayexalate crystals. Cases of mucosal injury have been reported with use of sodium polystyrene sulfonate with and without sorbitol. The lower GI tract represents the most common site of injury, with histopathology predominantly reflecting necrosis, ulceration, or perforation. Numerous independent risk factors have been identified, including solid organ transplant and post-operative state, acute, and chronic kidney disease. To our knowledge, this represented the first case of Kayxelateinduced rectal polyps.Figure 1: Ulcerated rectal polyps on retroflex view.

Gastrointestinal Adverse Events with Sodium Polystyrene Sulfonate (Kayexalate) Use: A Systematic Review

BackgroundSodium polystyrene sulfonate (Kayexalate; Sanofi-Aventis, Paris, France) is a cation-exchange resin routinely used in the management of hyperkalemia. However, its use has been associated with colonic necrosis and other fatal gastrointestinal adverse events. Although the addition of sorbitol to sodium polystyrene sulfonate preparations was previously believed to be the cause of gastrointestinal injury, recent reports have suggested that sodium polystyrene sulfonate itself may be toxic. Our objective was to systematically review case reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. MethodsMEDLINE (1948 to July 2011), EMBASE (1980 to July 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (1993 to July 27, 2011), bibliographies of identified articles, and websites of relevant drug agencies and professional associations in the United States and Canada were reviewed to identify eligible reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. Causality criteria of the World Health Organization causality assessment system were applied to each report. ResultsThirty reports describing 58 cases (41 preparations containing sorbitol and 17 preparations without sorbitol) of adverse events were identified. The colon was the most common site of injury (n=44; 76%), and transmural necrosis (n=36; 62%) was the most common histopathologic lesion reported. Mortality was reported in 33% of these cases due to gastrointestinal injury. ConclusionsSodium polystyrene sulfonate use, both with and without sorbitol, may be associated with fatal gastrointestinal injury. Physicians must be cognizant of the risk of these adverse events when prescribing this therapy for the management of hyperkalemia.

To Bind or to Let Loose: Effectiveness of Sodium Polystyrene Sulfonate in Decreasing Serum Potassium

Background. The use of sodium polystyrene sulfonate in decreasing serum potassium has recently been questioned due to the lack of documented effectiveness. Methods. A retrospective cohort analysis of all hospitalized patients who received sodium polystyrene sulfonate over four months was performed. The change in serum potassium was noted over a period of 24 hours. Patients who received any other form of potassium-altering drug or treatment were excluded. Results. The administration of sodium polystyrene sulfonate reduced serum potassium by 16.7% (P < 0.001) as compared to the baseline serum potassium over a period of 24 hours. During this same time, no change in serum creatinine was identified (P = 0.73). In addition, there was no correlation between potassium and creatinine change (r2 = 0.0004 and P = 0.99). Patients with higher initial serum potassium (≥5.6 mEq/L) reduced their potassium concentration 4% more than those with initial serum potassium of <5.6 mEq/L; however, this reduction did not reach statistical significance (P = 0.32). There was no significant difference in the effectiveness of 15 gm and 30 gm resin preparation (P = 0.54). Thirteen deaths were noted in our cohort, of which one death was due to ischemic colitis. Conclusion. We conclude that sodium polystyrene sulfonate is effective in lowering serum potassium.

Lithium use in special populations

Byline: E. Mohandas, V. Rajmohan Lithium, a monovalent cation, was first used for the treatment of mania in the 1940s. Half a century into its use, the drug continues to be the preeminent choice for bipolar disorder with antimanic, antidepressant (modest) and antisuicidal property. Lithium is the "gold standard" mood stabilizer against which potential mood stabilizer agents are judged. The therapeutic uses of lithium also include use as an augmenting agent in depression, schizoaffective disorder, aggression, impulse control disorder, eating disorders, attention deficit disorder and in certain subsets of alcoholism. Lithium has been used in many medical disorders, especially cluster headache and dermatological disorders (seborrheic dermatitis, eczematoid dermatitis, genital herpes).[sup] [1] The drug is however associated with neurologic, endocrine, cardiovascular, renal, dermatologic and gastrointestinal adverse effects and possible teratogenicity. History Lithium was first discovered and defined by Johan August Arfvedson in 1817 when he did an analysis of the mineral petalite [LiAl(Si2O5)2]. Petalite was first found by Brazilian scientist Jose Bonifacio Andrade e Silva in 1800. Lepidolite, spodumene, petalite and amblygonite are the more important minerals containing lithium. It was Arfwedson's laboratory chief John Jacob Berzelius who named this alkali metal "lithion." Arfvedson was never able to fully isolate lithium, and it wasn't until 1855 that it was isolated by William Thomas Brande. Brande and Sir Humphrey Davy earlier had done electrolysis on lithium oxide in 1818. Lithium was first produced commercially in 1923 by Metallgesellschaft AG.[sup] [2] The use of lithium for medicinal purposes can be traced back 1,800 years to the Greek physician Galen, who treated patients with mania by having them bathe in alkaline springs and drink the water, which probably contained lithium. In 1843 Alexander Ure introduced lithium into modern medicine, and he showed the in vitro reduction of weight of a uric acid bladder stone in a lithium carbonate solution. Sir Alfred Garrod later discovered that gouty uric acid deposits also were soluble in lithium solution. The view in that time was that uric acid imbalances caused a wide range of diseases, and Armand Trousseau and Alexander Haig proposed that mania and depression also may result from this imbalance and lithium may be effective in these conditions. In the 1840s, lithium was mixed with carbonate or citrate to form a salt and was used to treat gout, epilepsy, diabetes, cancer and insomnia. In the 1870s, the then American Surgeon General William Hammond had provided anecdotal evidence for the use of lithium bromide in the treatment of acute mania. In the 1880s and 1890s the Lange brothers Carl and Fritz used lithium in depression, and Carl Lange was the first to systematically use lithium in the acute and prophylactic treatment of depression.[sup] [2] The introduction of lithium preparations and tablets in the 1900s brought to the fore the toxic effects of the drug; and there were reports of weakness, tremor, diarrhea, vomiting and deaths. The drug disappeared from the British Pharmacopoeia by 1932, but later in the 1940s it was used as a sodium substitute in low sodium diets; but the reports of severe intoxication led to its removal from American markets in 1949. [sup] [1] The appearance in 1949 in the Medical Journal of Australia of a paper entitled "Lithium salts in the treatment of psychotic excitement" by John F. J. Cade was an unspectacular entry into a new era of psychiatry. Manic patients showed improvement, with the patient becoming calmer after four to five days. There was no improvement in the excited schizophrenic patients, though there was a calming effect. There was no improvement or deepening of depression. The paper also gave details of initial dosage, maintenance doses, appearance of toxic symptoms and warning about lithium over-dosage. …

Use of Sodium Polystyrene Sulfonate for Reduction of Plasma Lithium Concentrations After Chronic Lithium Dosing in Mice

Previous studies have shown that oral sodium polystyrene sulfonate lowers plasma lithium concentrations after acutely administered oral doses of lithium chloride. However, a significant proportion of lithium overdose cases resulting in morbidity and mortality are those in which exposure to lithium is chronic. This study was designed to determine whether multiple oral doses of sodium polystyrene sulfonate are effective in reducing plasma lithium concentrations after chronic dosing. Placebo-controlled animal study. One hundred thirty mice were given 75 mM lithium chloride in their drinking water for a period of 14 days. At the end of that period, half of the animals were given orogastric sodium polystyrene sulfonate at 5 g/kg/dose 0, 60, 120, 180, and 360 minutes after the cessation of lithium chloride; the remaining half received orogastric water at equivalent times. Subgroups of each group were sacrificed at 90, 150, 330, 480, 1440, and 2880 minutes after lithium chloride cessation and plasma analyzed for lithium content. Lithium concentrations were compared by analysis of variance and single degree of freedom contrasts. Significance was set at an alpha level of 0.05. Lithium concentration was lower overall in the animals treated with sodium polystyrene sulfonate (p < .0001) and specifically at 150, 330, and 480 minutes after lithium chloride cessation (p < .05). Repetitive oral doses of sodium polystyrene sulfonate effectively lowered plasma lithium concentrations. Further study may ultimately define a role for the use of sodium polystyrene sulfonate in the treatment of patients with chronic lithium toxicity.

Use of Sodium Polystyrene Sulfonate in Sorbitol in the United States, 1985–1989

Use of Sodium Polystyrene Sulfonate in Sorbitol in the United States, 1985–1989

Complications following oral administration of exchange resins in extremely low-birth-weight infants.

Complications of the oral use of sodium polystyrene sulfonate and calcium polystyrene sulfonate are reported in five extremely low-birth-weight infants in which exchange resins were used to treat hyperkalemia. Radio opaque masses outlining the stomach were seen in all infants and could be palpated in the left upper quadrant of the abdomen. In two infants, at autopsy the palpable mass could be identified as a solid chalk-like concretion outlining the stomach. X-ray diffraction studies identified the material as Brushite. Administration of exchange resins by the gastric route should be avoided in the treatment of hyperkalemia in critically sick, extremely low-birth-weight infants.