Hyperkalemia treatment standard.

Hyperkalemia is a common electrolyte disturbance in both inpatient and outpatient clinical practice. The severity and associated risk depends on the underlying cause and rate of potassium (K+) increase. Acute hyperkalemia requires immediate attention due to potentially life-threatening manifestations resulting from the rapid increase in plasma K+ concentration. Treatment is initially focused on stabilizing the cardiac membrane, followed by maneuvers to shift K+ into the cells, and ultimately initiating strategies to decrease total body K+ content. Chronic hyperkalemia develops over a more extended period of time and manifestations tend to be less severe. Nevertheless, the disorder is not benign since chronic hyperkalemia is associated with increased morbidity and mortality. The approach to patients with chronic hyperkalemia begins with a review of medications potentially responsible for the disorder, ensuring effective diuretic therapy and correcting metabolic acidosis if present. The practice of restricting foods high in K+ to manage hyperkalemia is being reassessed since the evidence supporting the effectiveness of this strategy is lacking. Rather, dietary restriction should be more nuanced, focusing on reducing the intake of nonplant sources of K+. Down-titration and/or discontinuation of renin-angiotensin-aldosterone inhibitors should be discouraged since these drugs improve outcomes in patients with heart failure and proteinuric kidney disease. In addition to other conservative measures, K+ binding drugs and sodium-glucose cotransporter 2 inhibitors can assist in maintaining the use of these drugs.

Management of hyperkalemia in children.

PURPOSE OF REVIEW: Hyperkalemia is a potentially fatal electrolyte abnormality with no standardized management. The purpose of this review is to provide the knowledge needed for timely and effective management of hyperkalemia in children. It describes the utility of existing and novel therapies. RECENT FINDINGS: Two newer oral potassium binding agents, patiromer sorbitex calcium and sodium zirconium cyclosilicate, have been FDA-approved for the management of hyperkalemia in adults. These newer agents offer hope for improved management, even though their use in pediatric patients requires further exploration. SUMMARY: This review highlights the causes and life-threatening effects of hyperkalemia and provides a comprehensive overview of the management of hyperkalemia in both acute and chronic settings along with upcoming treatment strategies.

Transient secondary pseudo-hypoaldosteronism in infants with urinary tract infections: systematic literature review.

Infants with a congenital anomaly of the kidney and urinary tract sometimes present with hyponatremia, hyperkalemia, and metabolic acidosis due to under-responsiveness to aldosterone, hereafter referred to as secondary pseudo-hypoaldosteronism. The purpose of this report is to investigate pseudo-hypoaldosteronism in infant urinary tract infection. A systematic review was conducted following PRISMA guidelines after PROSPERO (CRD42022364210) registration. The National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar without limitations were used. Inclusion criteria involved pediatric cases with documented overt pseudo-hypoaldosteronism linked to urinary tract infection. Data extraction included demographics, clinical features, laboratory parameters, management, and course. Fifty-seven reports were selected, detailing 124 cases: 95 boys and 29 girls, 10 months or less of age (80% of cases were 4 months or less of age). The cases exhibited hyponatremia, hyperkalemia, acidosis, and activated renin-angiotensin II-aldosterone system. An impaired kidney function was found in approximately every third case. Management included antibiotics, fluids, and, occasionally, emergency treatment of hyperkalemia, hyponatremia, or acidosis. The recovery time averaged 1 week for electrolyte, acid-base imbalance, and kidney function. Notably, anomalies of the kidney and urinary tract were identified in 105 (85%) cases. CONCLUSIONS: This review expands the understanding of overt transient pseudo-hypoaldosteronism complicating urinary tract infection. Management involves antimicrobials, fluid replacement, and consideration of electrolyte imbalances. Raising awareness of this condition within pediatric hospitalists is desirable. WHAT IS KNOWN: • Infants affected by a congenital anomaly of the kidney and urinary tract may present with clinical and laboratory features resembling primary pseudo-hypoaldosteronism. • Identical features occasionally occur in infant urinary tract infection. WHAT IS NEW: • Most cases of secondary pseudo-hypoaldosteronism associated with a urinary tract infection are concurrently affected by a congenital anomaly of the kidney and urinary tract. • Treatment with antibiotics and parenteral fluids typically results in the normalization of sodium, potassium, bicarbonate, and creatinine within approximately 1 week.

Consensus statement on the management of hyperkalaemia-An Asia-Pacific perspective.

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%-7% worldwide and 7%-10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high-risk patients. Conventional potassium-binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia-Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at-risk individuals; and (iii) correction of hyperkalaemia for at-risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region.

Electrolyte disorders related emergencies in children.

This article provides a comprehensive overview of electrolyte and water homeostasis in pediatric patients, focusing on some of the common serum electrolyte abnormalities encountered in clinical practice. Understanding pathophysiology, taking a detailed history, performing comprehensive physical examinations, and ordering basic laboratory investigations are essential for the timely proper management of these conditions. We will discuss the pathophysiology, clinical manifestations, diagnostic approaches, and treatment strategies for each electrolyte disorder. This article aims to enhance the clinical approach to pediatric patients with electrolyte imbalance-related emergencies, ultimately improving patient outcomes.Trial registration This manuscript does not include a clinical trial; instead, it provides an updated review of literature.

Clinical and Laboratory Effects of Foodborne Illness in Children.

The World Health Organization estimates that 31 foodborne pathogen account for 600 million cases of illness annually. This study, conducted in a pediatric emergency department in Turkey, addresses the limited research on pediatric foodborne diseases (FD) in the country, exposing a significant knowledge gap. Analyzing 17,091 pediatric cases, 106 FD cases were identified, predominantly affecting boys (94.3%) with an average age of 7.65 ± 6.51 years. Remarkably, no patients required pediatric intensive care admission, and no mortalities were recorded. Hyponatremia emerged as a prevalent electrolyte disorder in pediatric FD, while hyperkalemia was notably observed in children under 5. The study emphasizes the severity of FD in children under 5, reflected in longer hospital stays, underscoring the urgent need for targeted interventions and improved detection methods in pediatric FD.

Pseudohyperkalemia in pediatric patients with newly diagnosed hematological malignancies.

Patients with newly diagnosed hematological malignancies often present with a considerable cellular burden, leading to complications including hyperkalemia. However, pseudohyperkalemia, arising from in vitro cell lysis, can pose challenges in clinical practice. Although pseudohyperkalemia is frequently reported in adult hematological malignancies, its occurrence in pediatric patients is underreported, and its incidence in this demographic remains unclear. We retrospectively reviewed the medical records of pediatric patients who received a new diagnosis of hematological malignancies from 2011 to 2022 at Taichung Veterans General Hospital. Hyperkalemia was defined by a serum or plasma potassium level exceeding 5.5 mEq/L. Pseudohyperkalemia was defined by 1) a potassium decrease of over 1 mEq/L in within 4 h without intervention or 2) the absence of electrocardiography changes indicative of hyperkalemia. Cases with apparent red blood cell hemolysis were excluded. A total of 157 pediatric patients with a new diagnosis of hematological malignancies were included, 14 of whom exhibited hyperkalemia. Among these 14 cases, 7 cases (4.5%) were of pseudohyperkalemia. This rate increased to 21.2% in patients with initial hyperleukocytosis. Pseudohyperkalemia was associated with a higher initial white blood cell count and lower serum sodium level. All episodes of pseudohyperkalemia occurred in the pediatric emergency department, where samples were obtained as plasma, whereas all true hyperkalemia cases were observed in the ordinary ward or intensive care unit, where samples were obtained as serum. Timely recognition of pseudohyperkalemia is crucial to avoiding unnecessary potassium-lowering interventions in pediatric patients with newly diagnosed hematological malignancies.

A K+-sensitive photonic crystal hydrogel sensor for efficient visual monitoring of hyperkalemia/hypokalemia.

Potassium ions (K+) play crucial roles in many biological processes. Abnormal K+ levels in the body are usually associated with physiological disorders or diseases, and thus, developing K+-sensitive sensors/devices is of great importance for disease diagnosis and health monitoring. Herein, we report a K+-sensitive photonic crystal hydrogel (PCH) sensor with bright structural colors for efficient monitoring of serum potassium. This PCH sensor consists of a poly(acrylamide-co-N-isopropylacrylamide-co-benzo-15-crown-5-acrylamide) (PANBC) smart hydrogel with embedded Fe3O4 colloidal photonic crystals (CPCs), which could strongly diffract visible light and endow the hydrogel with brilliant structural colors. The rich 15-crown-5 (15C5) units appended on the polymer backbone could selectively bind K+ ions to form stable 2 : 1 [15C5]2/K+ supramolecular complexes. These bis-bidentate complexes served as physical crosslinkers to crosslink the hydrogel and contracted its volume, and thus reduced the lattice spacing of Fe3O4 CPCs and blue-shifted the light diffraction, and finally reported on the K+ concentrations by a color change of the PCH. Our fabricated PCH sensor possessed high K+ selectivity and pH- and thermo-sensitive response performances to K+. Most interestingly, the K+-responding PANBC PCH sensor could be conveniently regenerated via simple alternate flushing with hot/cold water due to the excellent thermosensitivity of the introduced PNIPAM moieties into the hydrogel. Such a PCH sensor provides a simple, low-cost and efficient strategy for visualized monitoring of hyperkalemia/hypokalemia, which will significantly promote the development of biosensors.

High-Dose Insulin for Hyperkalemic Cardiac Arrest.

ABSTRACT: Hyperkalemic cardiac arrest diagnosis can be elusive and management difficult as the cardiac rhythm restoration is often not achieved until the potassium level decreases to a relatively normal level for the patient who suffers the arrest. Current treatment modalities can take hours to achieve this goal. We describe two patients who survived a witnessed hyperkalemic cardiac arrest after being managed with conventional advanced cardiac life support and unconventionally high doses of intravenous insulin.

Implications of differences between point-of-care blood gas analyser and laboratory analyser potassium results on hyperkalaemia diagnosis & treatment.

BACKGROUND: Hyperkalaemia is managed in the emergency department (ED) following measurement of potassium results by blood gas analysers (BGA) or laboratory analysers (LAB). AIMS: To determine the prevalence of clinically significant differences between BGA and LAB potassium results and the impact on ED hyperkalaemia management. METHODS: Retrospective analysis of time-matched ED BGA and LAB potassium samples from 2019 to 2020 (taken within 15 min, one or both results ≥6.0 mmol/L). Mean differences and 95% limits of agreement (LoA) were determined for pairs with one or both results ≥6.0 mmol/L and a separate 500 consecutive sample pairs. RESULTS: Four hundred eighty-eight matched BGA and LAB samples met the inclusion criteria. Of these, 201 (41.2%) differed by ≤0.5 mmol/L, 169 (34.6%) included a haemolysed LAB sample, and 12 (2.5%) had an unreportable BGA sample. One hundred six (21.7%) pairs differed by >0.5 mmol/L, and 60/106 (57%) had normal LAB potassium results, but BGA indicated moderate/severe hyperkalaemia (two of these pairs received hyperkalaemia treatment). Of patients with a haemolysed LAB sample, or where pairs differed by >0.5 mmol, 48 were treated with insulin and five (10.4%) experienced hypoglycaemia. Mean differences and LoA for pairs with LAB results <6.0 mmol/L but BGA ≥6.0 mmol/L demonstrated unacceptable agreement, with 18 (25.7%) BGA results exceeding 8.0 mmol/L. CONCLUSIONS: Potentially significant discordance may occur between BGA and LAB potassium results. Clinicians need to be aware of factors impacting both analytical methods' accuracy (such as poor venepuncture or sample handling, (K) EDTA interference) and undetectable haemolysis with BGA measurements. We recommend BGA hyperkalaemia be confirmed with LAB results using a non-haemolysed sample where time permits.

Hyperkalemia Detection in Emergency Departments Using Initial ECGs: A Smartphone AI ECG Analyzer vs. Board-Certified Physicians.

BACKGROUND: Hyperkalemia is a potentially fatal condition that mandates rapid identification in emergency departments (EDs). Although a 12-lead electrocardiogram (ECG) can indicate hyperkalemia, subtle changes in the ECG often pose detection challenges. An artificial intelligence application that accurately assesses hyperkalemia risk from ECGs could revolutionize patient screening and treatment. We aimed to evaluate the efficacy and reliability of a smartphone application, which utilizes camera-captured ECG images, in quantifying hyperkalemia risk compared to human experts. METHODS: We performed a retrospective analysis of ED hyperkalemic patients (serum potassium ≥ 6 mmol/L) and their age- and sex-matched non-hyperkalemic controls. The application was tested by five users and its performance was compared to five board-certified emergency physicians (EPs). RESULTS: Our study included 125 patients. The area under the curve (AUC)-receiver operating characteristic of the application's output was nearly identical among the users, ranging from 0.898 to 0.904 (median: 0.902), indicating almost perfect interrater agreement (Fleiss' kappa 0.948). The application demonstrated high sensitivity (0.797), specificity (0.934), negative predictive value (NPV) (0.815), and positive predictive value (PPV) (0.927). In contrast, the EPs showed moderate interrater agreement (Fleiss' kappa 0.551), and their consensus score had a significantly lower AUC of 0.662. The physicians' consensus demonstrated a sensitivity of 0.203, specificity of 0.934, NPV of 0.527, and PPV of 0.765. Notably, this performance difference remained significant regardless of patients' sex and age (P < 0.001 for both). CONCLUSION: Our findings suggest that a smartphone application can accurately and reliably quantify hyperkalemia risk using initial ECGs in the ED.

Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial.

BACKGROUND: Finerenone reduced risk of cardiorenal outcomes in patients with CKD and type 2 diabetes in the FIDELIO-DKD trial. We report incidences and risk factors for hyperkalemia with finerenone and placebo in FIDELIO-DKD. METHODS: This post hoc safety analysis defined hyperkalemia as ≥mild or ≥moderate based on serum potassium concentrations of >5.5 or >6.0 mmol/L, respectively, assessed at all regular visits. Cumulative incidences of hyperkalemia were based on the Aalen-Johansen estimator using death as competing risk. A multivariate Cox proportional hazards model identified significant independent predictors of hyperkalemia. Restricted cubic splines assessed relationships between short-term post-baseline changes in serum potassium or eGFR and subsequent hyperkalemia risk. During the study, serum potassium levels guided drug dosing. Patients in either group who experienced ≥mild hyperkalemia had the study drug withheld until serum potassium was ≤5.0 mmol/L; then the drug was restarted at the 10 mg daily dose. Placebo-treated patients underwent sham treatment interruption and downtitration. RESULTS: Over 2.6 years' median follow-up, 597 of 2785 (21.4%) and 256 of 2775 (9.2%) patients treated with finerenone and placebo, respectively, experienced treatment-emergent ≥mild hyperkalemia; 126 of 2802 (4.5%) and 38 of 2796 (1.4%) patients, respectively, experienced moderate hyperkalemia. Independent risk factors for ≥mild hyperkalemia were higher serum potassium, lower eGFR, increased urine albumin-creatinine ratio, younger age, female sex, ß-blocker use, and finerenone assignment. Diuretic or sodium-glucose cotransporter-2 inhibitor use reduced risk. In both groups, short-term increases in serum potassium and decreases in eGFR were associated with subsequent hyperkalemia. At month 4, the magnitude of increased hyperkalemia risk for any change from baseline was smaller with finerenone than with placebo. CONCLUSIONS: Finerenone was independently associated with hyperkalemia. However, routine potassium monitoring and hyperkalemia management strategies employed in FIDELIO-DKD minimized the impact of hyperkalemia, providing a basis for clinical use of finerenone.

Prediction of hyperkalemia in ESRD patients by identification of multiple leads and multiple features on ECG.

BACKGROUND: Patients with end-stage renal disease (ESRD) especially those undergoing dialysis have a high prevalence of hyperkalemia, which must be detected and treated immediately. But the initial symptoms of hyperkalemia are insidious, and traditional laboratory serum potassium concentration testing takes time. Therefore, rapid and real-time measurement of serum potassium is urgently needed. In this study, different machine learning methods were used to make rapid predictions of different degrees of hyperkalemia by analyzing the ECG. METHODS: A total of 1024 datasets of ECG and serum potassium concentrations were analyzed from December 2020 to December 2021. The data were scaled into training and test sets. Different machine learning models (LR, SVM, CNN, XGB, Adaboost) were built for dichotomous prediction of hyperkalemia by analyzing 48 features of chest leads V2-V5. The performance of the models was also evaluated and compared using sensitivity, specificity, accuracy, accuracy, F1 score and AUC. RESULTS: We constructed different machine models to predict hyperkalemia using LR and four other common machine-learning methods. The AUCs of the different models ranged from 0.740 (0.661, 0.810) to 0.931 (0.912,0.953) when different serum potassium concentrations were used as the diagnostic threshold for hyperkalemia, respectively. As the diagnostic threshold of hyperkalemia was raised, the sensitivity, specificity, accuracy and precision of the model decreased to various degrees. And AUC also performed less well than when predicting mild hyperkalemia. CONCLUSION: Noninvasive and rapid prediction of hyperkalemia can be achieved by analyzing specific waveforms on the ECG by machine learning methods. But overall, XGB had a higher AUC in mild hyperkalemia, but SVM performed better in predicting more severe hyperkalemia.

Hyperkalemia in a Hemolyzed Sample in Pediatric Patients: Repeat or Do Not Repeat?

OBJECTIVE: The aim of the study is to analyze whether repeat testing is necessary in healthy children presenting to a pediatric emergency department (ED) who are found to have hyperkalemia on a hemolyzed specimen. METHODS: A 5-year retrospective analysis of pediatric ED patients found to have elevated potassium values on laboratory testing of a sample reported to be hemolyzed. All patients aged 0 to 17 years who had an elevated potassium level after an intravenous draw resulted from a serum sample that was reported as hemolyzed during an ED visit were included in the study. RESULTS: One hundred eighty-seven patients with some degree of both hemolysis and hyperkalemia were included in the final analysis. The median age was 1.9 years of age. The most common race among all patients was White, followed by African American, and Asian. One hundred forty-five children had repeat sampling for hemolyzed hyperkalemia, 142 children, 97.9% (95% confidence interval, 95.6%-100%) had a normal potassium on repeat and 3 children, 2.1% (95% confidence interval, 0.0%-4.4%) had true hyperkalemia. The frequency of true hyperkalemia in our study population was 2% (3/145). All 3 of these patients had underlying conditions that would appropriately have raised clinician suspicion for hyperkalemia. CONCLUSIONS: It may be unnecessary to obtain repeat samples to confirm normal potassium in a hemolyzed sample with normal blood urea nitrogen and creatinine.

Retrospective evaluation of acute hyperkalemia of unknown origin during general anesthesia in dogs.

OBJECTIVE: To report and characterize cases of acute hyperkalemia of unknown origin in dogs under anesthesia. STUDY DESIGN: Multicentric retrospective clinical study. ANIMALS: Medical records of 19 client-owned dogs that developed acute hyperkalemia during anesthesia. METHODS: Anesthetic records of dogs developing acute hyperkalemia from January 2015 to December 2022 were evaluated. Data collected included demographics, duration of anesthesia until the episode, electrolytes and blood gas measurements, electrocardiogram (ECG) abnormalities, drugs used as part of the anesthetic protocol, hyperkalemia treatment and outcome. RESULTS: A total of 13 cases met the inclusion criteria with documented acute hyperkalemia with no apparent underlying cause during anesthesia. Dogs were [mean ± standard deviation (range)] 6.5 ± 5.0 (3-10) years old and weighed 18.0 ± 14.3 (5.1-40.0) kg. All dogs were administered dexmedetomidine and an opioid as part of the premedication. All dogs had inhalation anesthesia of >60 minutes' duration. The first clinical sign was bradycardia that was minimally responsive to anticholinergic administration and was often accompanied by moderate/severe hypotension. These signs were rapidly followed by ECG changes compatible with hyperkalemia and/or cardiac arrest. Rapid identification and treatment for hyperkalemia, with or without dexmedetomidine reversal, resulted in survival of 12 dogs and one fatality. CONCLUSIONS AND CLINICAL RELEVANCE: Unknown origin hyperkalemia is a life-threatening complication that can occur during general anesthesia. In healthy dogs, preanesthetic administration of dexmedetomidine in association with an opioid and followed by inhalation anesthesia of more than 1 hour duration may predispose to this complication. A sudden decrease in heart rate >90 minutes after dexmedetomidine administration, or ECG changes, may warrant measurement of blood potassium concentrations.

[Hyperkaliemia in hypertensive patients : more than a coincidence?] / Hyperkaliémie chez le patient hypertendu : plus qu'une coïncidence ?

Hyperkaliemia is a relatively common electrolyte disorder whose manifestations and consequences can be serious if severe hyperkalemia is not treated. In the context of hypertension, it is important to look for co-morbidities and conditions favoring hyperkaliemia, to review the drugs prescribed that could contribute to potassium elevation and to bear in mind that when the common causes have been excluded, a genetic origin may be present. In this article, the focus is on the association of hypertension and hyperkaliemia, in the context of the marketing of new cardiovascular and renal drugs that may induce this electrolyte disorder.

L'hyperkaliémie représente un trouble électrolytique relativement fréquent dont les manifestations et conséquences peuvent être graves si l'hyperkaliémie sévère n'est pas corrigée. Dans le contexte d'une hypertension, il faut rechercher les comorbidités et les conditions favorisant l'hyperkaliémie, revoir les médicaments prescrits qui pourraient contribuer à l'élévation du potassium et garder en mémoire que lorsque les causes fréquentes ont été exclues, une origine génétique peut être présente. Dans cet article, l'accent est mis sur l'association de l'hypertension et l'hyperkaliémie, dans le contexte de la mise sur le marché de nouveaux médicaments dans les domaines cardiovasculaire et rénal qui pourraient favoriser la survenue de ce trouble électrolytique.

Nitrogen-Phosphorus-Potassium containing liquid fertilizer intoxication presenting with extreme hyperkalemia, metabolic acidosis and ECG changes.

Liquid fertilizers are widely used for fertilizing in- and outdoor vegetation. Despite the easy accessibility and widespread use, serious intoxications are rare. This case report describes a 61-year-old woman who was treated for life-threatening hyperkalemia, metabolic acidosis and ECG changes after intentional ingestion of liquid fertilizer. Our case shows that intake of liquid fertilizer, though infrequent, can cause serious, life threatening complications.

[Neonatal systemic pseudohypoaldosteronism type I]. / æ–°ç”Ÿå„¿å¤šè„å™¨åž‹å‡æ€§é†›å›ºé ®å‡å°‘ç—‡â 型.

An 18-day-old male infant was admitted to the hospital due to recurrent hyperkalemia for more than 10 days. The neonate had milk refusal and dyspnea. The blood gas analysis revealed recurrent hyperkalemia, hyponatremia and metabolic acidosis. Adrenocortical hormone replacement therapy was ineffective. Additional tests showed a significant increase in aldosterone levels. Family whole exome sequencing revealed that the infant had compound heterozygous in the SCNNIA gene, inherited from both parents. The infant was diagnosed with neonatal systemic pseudohypoaldosteronism type I. The infant's electrolyte levels were stabilized through treatment with sodium polystyrene sulfonate and sodium supplement. The infant was discharged upon clinical recovery. This study provides a focused description of differential diagnosis of salt-losing syndrome in infants and introduces the multidisciplinary management of neonatal systemic pseudohypoaldosteronism type I.

Pragmatic diagnostic and therapeutic algorithms to optimize new potassium binder use in cardiorenal disease.

BACKGROUND: Pivotal randomized trials demonstrating efficacy, safety and good tolerance, of two new potassium binders (patiromer and sodium zirconium cyclosilicate) led to their recent approval. A major hurdle to the implementation of these potassium-binders is understanding how to integrate them safely and effectively into the long-term management of cardiovascular and kidney disease patients using renin angiotensin aldosterone system inhibitors (RAASi), the latter being prone to induce hyperkalaemia. METHODS: A multidisciplinary academic panel including nephrologists and cardiologists was convened to develop consensus therapeutic algorithm(s) aimed at optimizing the use of the two novel potassium binders (patiromer and sodium zirconium cyclosilicate) in stable adults who require treatment with RAASi and experience(d) hyperkalaemia in a non-emergent setting. RESULTS: Two dedicated pragmatic algorithms are proposed. The lowest intervention threshold (i.e. 5.1 mmol/L or greater) was the one used in the patiromer and sodium zirconium cyclosilicate) pivotal trials, both drugs being indicated to treat hyperkalaemia in a non -emergent setting. Acknowledging the heterogeneity across specialty guidelines in hyperkalaemia definition and thresholds to intervene when facing hyperkalaemia, we have been mindful to use soft language i.e. "it is to consider", not necessarily "to do". CONCLUSIONS: Providing the clinical community with pragmatic algorithms may help optimize the management of high-risk patients by avoiding the risks of both hyper and hypokalaemia and of suboptimal RAASi therapy.

Five Years of Sacubitril/Valsartan-a Safety Analysis of Randomized Clinical Trials and Real-World Pharmacovigilance.

PURPOSE: In PARADIGM-HF, sacubitril/valsartan showed a significant reduction in mortality and hospitalization for patients with heart failure with reduced ejection fraction. Despite proven efficacy, sacubitril/valsartan has moderate uptake in clinical practice. This study explores the safety profile of sacubitril/valsartan by comparing adverse events in RCT and real-world use. METHODS: We studied hypotension, renal dysfunction, hyperkalemia, and angioedema associated with sacubitril/valsartan in RCTs and pharmacovigilance databases. A random-effects meta-analysis was performed with six RCTs investigating sacubitril/valsartan vs. control/comparators in heart failure patients. WHO's VigiBase, FAERS, and EMA's EudraVigilance were mined to obtain spontaneously reported real-world adverse events. Disproportionality analysis was performed with the FDA's OpenVigil 2.0. RESULTS: Six RCTs enrolled 15,538 patients with heart failure with reduced and preserved ejection fractions. There was no statistical difference for the composite of hypotension, renal dysfunction, hyperkalemia, and angioedema between sacubitril/valsartan and its comparators viz. ACEi or ARBs (OR 1.23, CI 0.98-1.56; p = 0.08). A total of 103,038 adverse events were registered in the spontaneous reporting systems. Hypotension was the most reported adverse event. Proportions of composite adverse events were 20% in VigiBase, 17% in FAERS, and 39% with EudraVigilance. Disproportionality analysis showed a lower risk of adverse events with sacubitril/valsartan than other guideline-directed heart failure medications used in clinical practice. CONCLUSION: With increased uptake of sacubitril/valsartan, risks of hypotension, renal dysfunction, hyperkalemia, and angioedema appear low and acceptable in RCTs and global clinical practice.