Hyperkalemia in chronic kidney disease patients with and without heart failure: an Italian economic modelling study.

BACKGROUND: Hyperkalemia (HK) is frequently present in chronic kidney disease (CKD). Risk factors for HK among CKD patients include comorbidities and renin-angiotensin-aldosterone system inhibitor (RAASi) treatment. Current standard of care (SoC) often necessitates RAASi down-titration or discontinuation, resulting in poorer cardiorenal outcomes, hospitalization and mortality. This study evaluates the cost-effectiveness of patiromer for HK in CKD patients with and without heart failure (HF) in an Italian setting. METHODS: A lifetime Markov cohort model was developed based on OPAL-HK to assess the health economic impact of patiromer therapy in comparison to SoC after accounting for the effects of HK and RAASi use on clinical events. Outcomes included accumulated clinical events, number needed to treat (NNT) and the incremental cost-effectiveness ratio (ICER). Subgroup analysis was conducted in CKD patients with and without HF. RESULTS: Patiromer was associated with an incremental discounted cost of €4,660 and 0.194 quality adjusted life years (QALYs), yielding an ICER of €24,004. Per 1000 patients, patiromer treatment prevented 275 moderate/severe HK events, 54 major adverse cardiovascular event, 246 RAASi discontinuation and 213 RAASi up-titration/restart. Subgroup analysis showed patiromer was more effective in preventing clinical events in CKD patients with HF compared to those without; QALY gains were greater in CKD patients without HF versus those with HF (0.267 versus 0.092, respectively). Scenario analysis and sensitivity analysis results support base-case conclusions. CONCLUSION: Patiromer is associated with QALY gains in CKD patients with and without HF compared to SoC in Italy. Patiromer prevented HK events, enabled RAASi therapy maintenance and reduced cardiovascular event risk.

Calcineurin inhibitor-related hyperkalemia is caused by hyporeninemic hypoaldosteronism and fludrocortisone is an effective treatment: Report of a case series and review of the literature.

INTRODUCTION: Calcineurin inhibitors (CNIs) are widely used in transplantation. Although CNI-related hyperkalemia is common (10%-60.6%), the underlying pathogenetic mechanism is not well-elucidated and may lead to dose adjustment or treatment withdrawal. OBJECTIVE: The aim of this study is to describe CNI-related hyperkalemia due to hyporeninemic hypoaldosteronism in pediatric transplant recipients who were successfully treated with fludrocortisone. METHOD: In a total of 55 hematopoietic stem cell (HSCT) and 35 kidney transplant recipients followed according to institutional immunosuppression protocols, recipients diagnosed with CNI-related hyperkalemia were reviewed. Recipients who were receiving intravenous fluid, potassium, or were diagnosed with hemolysis, acute graft rejection, or had an eGFR < 30 mL/min/1.73m2, were excluded. A detailed analysis of clinical history as well as biochemical studies was carried out to reveal possible pathophysiology. RESULTS: Three pediatric transplant recipients (one HSCT, two kidney transplantation) with findings of hyperkalemia, hyponatremia, and a mild elevation in blood urea nitrogen while on CNIs were recruited. Urinary potassium excretion was diminished while sodium excretion was increased. Plasma aldosterone levels were low, and renin was not increased in response. Primary adrenal insufficiency was ruled out, and hyporeninemic hypoaldosteronism was diagnosed. CNI-related hyperkalemia was detected earlier in case 1, who had HSCT (22 days), than in the second and third cases, who had kidney transplantation (24 and 30 months post-transplantation, respectively). The discrepancy was hypothesized to be explained by higher overall CNI dose due to higher serum target CNI used in HSCT than kidney transplantation. Electrolyte imbalance was reversed upon administration of physiologic dose fludrocortisone (0.05 mg, daily), while fludrocortisone was ceased after CNI withdrawal in case 1, which is additional evidence for the etiological association of CNIs and hyporeninemic hypoaldosteronism. CONCLUSION: Our three cases strengthen the premise that CNI-related hyperkalemia may be due to hyporeninemic hypoaldosteronism, and the timing and severity may be related to CNI dose. Fludrocortisone is a safe and effective treatment in CNI-related hyperkalemia, providing maintenance of CNIs, which are one of the essential therapeutic agents for pediatric transplantation.

Advancing crush syndrome management: the potent role of Sodium zirconium cyclosilicate in early hyperkalemia intervention and survival enhancement in a rat model.

Background: Crush Syndrome (CS), a severe trauma resulting from prolonged muscle compression, is commonly seen in large-scale disasters such as earthquakes. It not only causes localized tissue damage but also triggers electrolyte imbalances, particularly hyperkalemia, increasing the risk of early mortality. This study aims to assess the early intervention effects of Sodium Zirconium Cyclosilicate (SZC) on hyperkalemia in rat CS model. Methods: A rat CS model was established using a self-developed multi-channel intelligent small-animal crush injury platform. Rats in the experimental groups were treated with varying doses of SZC before compression and immediately post-decompression. The efficacy of SZC was evaluated by continuous monitoring of blood potassium levels and survival rates. Serum creatinine (Cre) and blood urea nitrogen (BUN) levels were analyzed, and renal damage was assessed through histopathological examination. Results: SZC treatment significantly reduced blood potassium levels and improved survival rates in rats. Compared to the placebo group, the SZC-treated rats showed a significant decrease in blood potassium levels at 6 and 12 h post-decompression, maintaining lower levels at 24 h. Biochemical analysis indicated no significant impact of SZC on renal function, with no notable differences in Cre and BUN levels between groups. Histopathological findings revealed similar levels of renal damage in both groups. Conclusion: SZC demonstrates significant early intervention effects on hyperkalemia in a rat model of crush injury, effectively improving survival rates without adverse effects on renal function. These results provide a new strategic direction for the clinical treatment of Crush Syndrome and lay the foundation for future clinical applications.

Bradycardia, Renal Failure, Atrioventricular Nodal Block, Shock, and Hyperkalemia (BRASH) Syndrome-Induced Atrial Fibrillation: A Case Report.

BRASH syndrome is a syndrome that comprises bradycardia, renal failure, atrioventricular nodal block, shock, and hyperkalemia. This syndrome is usually associated with a junctional rhythm. Early recognition of this clinical entity is crucial for appropriate management. In this case report, we describe a 70-year-old female who presented with BRASH syndrome-induced atrial fibrillation with a slow ventricular response.

Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease.

Heart failure with preserved ejection fraction (HFpEF) results from a complex interplay of age, genetic, cardiac remodeling, and concomitant comorbidities including hypertension, obesity, diabetes, and chronic kidney disease (CKD). Renal failure is an important comorbidity of HFpEF, as well as a major pathophysiological mechanism for those patients at risk of developing HFpEF. Heart failure (HF) and CKD are intertwined conditions sharing common disease pathways; the so-called "kidney tamponade", explained by an increase in intracapsular pressure caused by fluid retention, is only the latest model to explain renal injury in HF. Recognizing the different phenotypes of HFpEF remains a real challenge; the pathophysiological mechanisms of renal dysfunction may differ across the HF spectrum, as well as the prognostic role. A better understanding of the role of cardiorenal interactions in patients with HF in terms of symptom status, disease progression, and prognosis remains essential in HF management. Historically, patients with HF and CKD have been scarcely represented in clinical trial populations. Current concerns affect the practical approach to HF treatment, and, in this context, physicians are frequently hesitant to prescribe and titrate both new and old treatments. Therefore, the extensive application of HF drugs in diverse HF subtypes with numerous comorbidities and different renal dysfunction etiologies remains a controversial matter of discussion. Numerous recently introduced drugs, such as sodium-glucose-linked transporter 2 inhibitors (SGLT2i), constitute a new therapeutic option for patients with HF and CKD. Because of their protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. The present review delves into the phenotype of patients with HFpEF and CKD from a pathophysiological perspective, proposing a treatment approach that suggests a practical stepwise algorithm for the proper application of life-saving therapies in clinical practice.

Refractory ventricular fibrillation secondary to hyperkalemia resuscitated with extracorporeal membrane oxygenation: A case report.

The routine use of extracorporeal cardiopulmonary resuscitation (ECPR) is not recommended for patients with cardiac arrest. However, ECPR is considered for selected patients with cardiac arrest of reversible cause. Extracorporeal membrane oxygenation (ECMO) provides temporary cardiopulmonary support and adequate perfusion to the end organs, thereby shortening ischemic organ time and minimizing complications. One indication for ECPR therapy is prolonged ventricular fibrillation despite optimal conventional CPR. Here, we report a successful recovery case from ECPR, in which the patient suffered from refractory ventricular fibrillation and was predisposed to severe hyperkalemia. Ventricular fibrillation failed to respond despite prolonged conventional CPR and defibrillation management for 32 min. After successfully initiating ECPR 54 min after cardiac arrest, spontaneous circulation returned sooner. He demonstrated clear consciousness after treatment and was discharged without any neurological disability on day 11.

Unexpected Presentations of Bradycardia, Renal Failure, Atrioventricular Nodal Blockade, Shock, and Hyperkalemia (BRASH) Syndrome: A Report of Two Cases.

Bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia syndrome is an underrecognized phenomenon in which renal injury leads to hyperkalemia and inadequate clearance of atrioventricular nodal-blocking agents. The compounding effect of both insults can lead to a bradyarrhythmia that, in severe cases, can rapidly progress to cardiogenic shock. The degree of resulting pathology is usually out of proportion to either insulting agent given that there is a synergistic effect. Treatment strategies for this condition are not entirely clear, but it appears as if these patients often do not warrant aggressive interventions and can be managed medically. We report two cases with early recognition and simple medical management with resulting favorable outcomes.

Hyperkalemia Recurrence and Its Association With Race and Ethnicity in United States Veterans: A Retrospective Cohort Study.

INTRODUCTION: Information on whether race and ethnicity are associated with a greater risk of recurrent hyperkalemia is limited. The aim of this study was to examine the association between race or ethnicity and recurrent hyperkalemia in a population of US veterans. METHODS: This retrospective study used the US Veterans Affairs database to identify adults (aged ≥18 years) with at least one serum potassium measurement during the study period who ever experienced hyperkalemia (serum potassium > 5.0 mmol/L). The proportion of patients with hyperkalemia recurrence (≥1 subsequent event) within one year was determined for different race and ethnicity groups. The association between patient race and ethnicity and the risk of hyperkalemia recurrence within one year after the index hyperkalemia event was analyzed using competing risk regression. RESULTS: Among a total of 1,493,539 veterans with incident hyperkalemia (median age (interquartile range): 61.0 years (54.0, 71.0)), recurrence within one year occurred in 19.1% of Black, 16.0% of Native Hawaiian/other Pacific Islander, 15.1% of White, 14.9% of American Indian/Alaska Native, and 13.1% of Asian patient groups. Recurrent hyperkalemia occurred in 18.1% of Hispanic and 15.6% of non-Hispanic patient groups. In a fully-adjusted regression model, recurrent hyperkalemia risk was significantly higher in Black versus White patient groups (subhazard ratio (sHR), 1.17; 95% confidence interval (CI), 1.16-1.19; p< 0.0001) and in Hispanic versus non-Hispanic patient groups (sHR, 1.30; 95% CI, 1.28-1.33; p< 0.0001). DISCUSSION/CONCLUSION: Among US veterans with incident hyperkalemia, the risk of recurrent hyperkalemia was higher in Black and Hispanic patient groups. This information may be useful for health system screenings to risk stratify patient groups and both guide the frequency of serum potassium monitoring and better understand the root causes of group differences.

Insights into drug development with quantitative systems pharmacology: A prospective case study of uncovering hyperkalemia risk in diabetic nephropathy with virtual clinical trials.

The quantitative systems pharmacology (QSP) approach is widely applied to address various essential questions in drug discovery and development, such as identification of the mechanism of action of a therapeutic agent, patient stratification, and the mechanistic understanding of the progression of disease. In this review article, we show the current landscape of the application of QSP modeling using a survey of QSP publications over 10 years from 2013 to 2022. We also present a use case for the risk assessment of hyperkalemia in patients with diabetic nephropathy treated with mineralocorticoid receptor antagonists (MRAs, renin-angiotensin-aldosterone system inhibitors), as a prospective simulation of late clinical development. A QSP model for generating virtual patients with diabetic nephropathy was used to quantitatively assess that the nonsteroidal MRAs, finerenone and apararenone, have a lower risk of hyperkalemia than the steroidal MRA, eplerenone. Prospective simulation studies using a QSP model are useful to prioritize pharmaceutical candidates in clinical development and validate mechanism-based pharmacological concepts related to the risk-benefit, before conducting large-scale clinical trials.

Impaired distal renal potassium handling in streptozotocin-induced diabetic mice.

Diabetes is closely associated with K+ disturbances during disease progression and treatment. However, it remains unclear whether K+ imbalance occurs in diabetes with normal kidney function. In this study, we examined the effects of dietary K+ intake on systemic K+ balance and renal K+ handling in streptozotocin (STZ)-induced diabetic mice. The control and STZ mice were fed low or high K+ diet for 7 days to investigate the role of dietary K+ intake in renal K+ excretion and K+ homeostasis, and to explore the underlying mechanism by evaluating K+ secretion-related transport proteins in distal nephrons. K+-deficient diet caused excessive urinary K+ loss, decreased daily K+ balance, and led to severe hypokalemia in STZ mice compared to control mice. In contrast, STZ mice showed an increased daily K+ balance and elevated plasma K+ level under K+-loading conditions. Dysregulation of the NaCl cotransporter (NCC), epithelia Na+ channel (ENaC), and renal outer medullary K+ channel (ROMK) was observed in diabetic mice fed either low or high K+ diet. Moreover, amiloride treatment reduced urinary K+ excretion and corrected hypokalemia in K+-restricted STZ mice. On the other hand, inhibition of SGLT2 by dapagliflozin promoted urinary K+ excretion and normalized plasma K+ level in K+-supplemented STZ mice, at least partly by increasing ENaC activity. We conclude that STZ mice exhibited abnormal K+ balance and impaired renal K+ handling under either low or high K+ diet, which could be primarily attributed to the dysfunction of ENaC-dependent renal K+ excretion pathway, despite the possible role of NCC.

Hyperkalemic Periodic Paralysis Secondary to End-Stage Renal Disease and Excess Potato Consumption.

Hyperkalemic periodic paralysis is a rare medical condition characterized by periods of extreme muscle weakness or paralysis. While most cases of hyperkalemic periodic paralysis are associated with a genetic channelopathy, cases of secondary hyperkalemic periodic paralysis can pose a challenge for medical personnel in terms of timely recognition. Identification of this medical emergency early in its course is essential to preventing cardiac and neurological sequelae. We report a case of a 58-year-old female who presented with stroke-like symptoms and was found to have secondary hyperkalemic periodic paralysis attributed to the excess consumption of potatoes, a potassium-rich food. This case highlights the importance of considering hyperkalemic periodic paralysis early in the differentiation of patients with end-stage renal disease (ESRD) who present with muscle weakness and stroke-like symptoms.

Hyperkalemia Recurrence Following Medical Nutrition Therapy in Patients with Stage 3-4 Chronic Kidney Disease: The REVOLUTIONIZE I Real-World Study.

INTRODUCTION: The REVOLUTIONIZE I study aimed to characterize the relationships between medical nutrition therapy (MNT) and hyperkalemia recurrence in patients with stage 3-4 chronic kidney disease (CKD) and hyperkalemia who received MNT in real-world clinical practice. METHODS: This observational cohort study used de-identified electronic health record data from patients aged ≥ 18 years with stage 3-4 CKD who received MNT between January 2019 and October 2022 and had hyperkalemia (serum potassium > 5.0 mmol/L) within 30 days before MNT. Patients were followed for 6 months or until the first censoring event (death, prescription of outpatient potassium binder, or study end). The primary outcome was the percentage of patients with ≥ 1 hyperkalemia recurrence during follow-up. Secondary outcomes included the number of hyperkalemia recurrences per patient, time to each recurrence, and hyperkalemia-related healthcare resource utilization. Exploratory outcomes included all-cause healthcare resource utilization and mortality. RESULTS: The final cohort comprised 2048 patients; 1503 (73.4%) patients remained uncensored after 6 months. During the 6-month follow-up period, 56.0% of patients had ≥ 1 hyperkalemia recurrence and 37.4% had ≥ 1 recurrence within the first month. Patients with ≥ 1 hyperkalemia recurrence during follow-up had a mean ± standard deviation (SD) of 2.6 ± 2.2 recurrences. The mean ± SD time to first hyperkalemia recurrence was 45 ± 46 days; the time between recurrences decreased with subsequent episodes. Hyperkalemia-related hospitalizations and emergency department visits were recorded for 13.7% and 1.5% of patients, respectively. Sensitivity analyses showed that results were consistent across patient subgroups, including those with comorbid heart failure and patients receiving renin-angiotensin-aldosterone system inhibitor therapy at baseline. CONCLUSION: Most patients with stage 3-4 CKD had hyperkalemia recurrence, and MNT alone was inadequate to prevent recurrence. These patients may require additional long-term treatment, such as novel potassium binders, to maintain normokalemia and prevent hyperkalemia recurrence following MNT. Infographic available for this article. INFOGRAPHIC.

Patients with chronic kidney disease (CKD) typically receive dietary counseling from a registered dietician, referred to as medical nutrition therapy, to help reduce their risk of complications of CKD while addressing their specific nutritional needs. Patients with CKD have an increased risk of elevated blood potassium levels (hyperkalemia), which has potentially life-threatening consequences. Although medical nutrition therapy may help patients with hyperkalemia to manage their dietary potassium intake, its effects in preventing recurrence are unclear. Our aim was to determine whether medical nutrition therapy can help prevent hyperkalemia recurrence after an initial event in patients with non-dialysis-dependent (stage 3­4) CKD in real-world clinical practice. We used data from de-identified electronic health records to study hyperkalemia recurrence over 6 months in patients with stage 3­4 CKD who received medical nutrition therapy within 30 days after experiencing hyperkalemia. Over half of the patients (56.0%) had at least one hyperkalemia recurrence within an average of 45 days during the 6 months after medical nutrition therapy; these patients had an average of 2.6 distinct recurrences in 6 months. In patients with two or more hyperkalemia recurrences, the time between these became shorter than 30 days. Our real-world study results show that hyperkalemia is a chronic, recurring condition in patients with stage 3­4 CKD, and that medical nutrition therapy is not enough to prevent its recurrence. This suggests that these patients may need additional long-term treatment for hyperkalemia, such as novel potassium binder therapy, to prevent hyperkalemia recurrence.

Excessive pickle consumption: beware of adrenal crisis.

Adrenal insufficiency (AI) is one of the most life-threatening disorders resulting from adrenal cortex dysfunction. Symptoms and signs of AI are often nonspecific, and the diagnosis can be missed and lead to the development of AI with severe hypotension and hypovolemic shock. We report the case of a 13-year-old child admitted for cardiac arrest following severe hypovolemic shock. The patient initially presented with isolated mild abdominal pain and vomiting together with unexplained hyponatremia. He was discharged after an initial short hospitalization with rehydration but with persistent hyponatremia. After discharge, he had persistent refractory vomiting, finally leading to severe dehydration and extreme asthenia. He was admitted to pediatric intensive care after prolonged hypovolemic cardiac arrest with severe anoxic encephalopathy leading to brain death. After re-interviewing, the child's parents reported that he had experienced polydipsia, a pronounced taste for salt with excessive consumption of pickles lasting for months, and a darkened skin since their last vacation 6 months earlier. A diagnosis of autoimmune Addison's disease was made. Primary AI is a rare life-threatening disease that can lead to hypovolemic shock. The clinical symptoms and laboratory findings are nonspecific, and the diagnosis should be suspected in the presence of unexplained collapse, hypotension, vomiting, or diarrhea, especially in the case of hyponatremia.

Associations between dietary potassium intake from different food sources and hyperkalemia in patients with chronic kidney disease.

OBJECTIVE: Previous studies reported mixed results on associations between dietary potassium intake and hyperkalemia in patients with chronic kidney disease (CKD). This study investigated the association between potassium intake from different food sources and hyperkalemia in patients with non-dialysis-dependent CKD. METHODS: A total of 285 patients were recruited at a university hospital and two city hospitals in Tokyo. Dietary potassium intake was estimated by a validated diet history questionnaire. Associations of potassium intake from all foods and individual food groups with serum potassium were examined by multivariable linear regression among potassium binder non-users. An association between tertile groups of potassium intake and hyperkalemia, defined as serum potassium ≥5.0 mEq/L, was evaluated by multivariable logistic regression. RESULTS: Among 245 potassium binder non-users, total potassium intake was weakly associated with serum potassium (regression coefficient = 0.147, 95% confidence interval (CI): 0.018-0.277), while an association with hyperkalemia was not observed (first vs third tertile: adjusted odds ratio (aOR) = 0.98, 95% CI: 0.29-3.26). As for food groups, potassium intakes from potatoes, pulses, and green/yellow vegetables were positively associated with serum potassium. Patients in the highest tertile of potassium intake from potatoes had higher odds of hyperkalemia as compared to those in the lowest tertile (aOR = 4.12, 95% CI: 1.19-14.34). CONCLUSION: Total potassium intake was weakly associated with serum potassium, but not with hyperkalemia. Potassium intake from potatoes was associated with hyperkalemia. These findings highlight the importance of considering food sources of potassium in the management of hyperkalemia in CKD.

Can Patients with Electrolyte Disturbances Be Safely and Effectively Treated in a Hospital-at-Home, Telemedicine-Controlled Environment? A Retrospective Analysis of 267 Patients.

BACKGROUND: Morbidities indicated for hospital-at-home (HAH) treatment include infectious diseases and exacerbations of chronic conditions. Electrolyte disturbances are not included per se. However, their rate is high. We aimed to describe our experience via the monitoring and treatment of such patients. METHODS: This was a retrospective analysis of patients in the setting of telemedicine-controlled HAH treatment. We collected data from the electronic medical records of patients who presented electrolyte disturbances. RESULTS: For 14 months, we treated 267 patients in total in HAH settings, with a mean age of 72.2 + 16.4, 44.2% for males. In total, 261 (97.75%) patients were flagged with electrolyte disturbances, of whom 149 had true electrolyte disturbances. Furthermore, 67 cases (44.96%) had hyponatremia, 9 (6.04%) had hypernatremia after correction for hyperglycemia, 20 (13.42%) had hypokalemia and 27 (18.12%) had hyperkalemia after the exclusion of hemolytic samples. Ten (6.09%) patients had hypocalcemia and two (1.34%) had hypercalcemia corrected to albumin levels. Thirteen (8.72%) patients had hypomagnesemia and one (0.67%) had hypermagnesemia. Patients with electrolyte disturbances suffered from more chronic kidney disease (24.2% vs. 12.2%; p = 0.03) and malignancy (6.3% vs. 0.6%; p = 0.006), and were more often treated with diuretics (12.6% vs. 4.1%; p = 0.016). No patient died or suffered from clinically significant cardiac arrhythmias. CONCLUSIONS: The extent of electrolyte disturbances amongst HAH treatment patients is high. The monitoring and treatment of such patients can be conducted safely in this setting.

Bradycardia, Renal Dysfunction, Atrioventricular Nodal Blockade, Shock, and Hyperkalemia (BRASH) Syndrome: A Case Report Highlighting the Importance of Early Recognition and Management.

BRASH syndrome, characterized by bradycardia, renal dysfunction, atrioventricular nodal blockade, shock, and hyperkalemia, is a newly defined condition that can lead to significant morbidity and mortality if not promptly recognized and treated. The triggers for this syndrome often include medication interactions, dehydration, and nephrotoxic insults, particularly in older patients with limited renal reserve and cardiovascular disease. In this report, we present the case of an 88-year-old female with multiple comorbidities who exhibited symptoms of prostration, bradycardia, hypotension, and altered mental status, along with laboratory findings (hyperkalemia and renal dysfunction) consistent with BRASH syndrome, triggered by hypovolemia associated with a urinary tract infection. Immediate treatment must focus on correcting hyperkalemia, providing hemodynamic support for bradycardia and hypotension, and administering guided fluid resuscitation. Prompt identification and management of the syndrome can prevent the need for invasive interventions, such as pacemaker insertion and dialysis. Healthcare professionals should be vigilant in considering BRASH syndrome, especially in older patients with cardiac disease, limited renal function, and those on medication regimens that include AV-nodal blocking agents, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and potassium-sparing diuretics. This case report emphasizes the importance of clinical suspicion and the initiation of timely treatment to interrupt the cycle of BRASH syndrome and improve patient outcomes.

Evaluation of Insulin Dosing Strategies for Hyperkalemia Management at an Academic Medical Center.

PURPOSE: While intravenous (IV) insulin is often administered at a fixed dose of 10 units for acute hyperkalemia, optimal dosing for minimizing hypoglycemia while effectively reversing hyperkalemia has not been established. The purpose of this analysis was to evaluate the effect of insulin dosing strategies on hypoglycemia in patients with hyperkalemia. METHODS: Adult patients presenting to an academic medical center who received IV insulin for hyperkalemia between 2016 and 2020 were retrospectively identified. Patients treated with 10 units of insulin (fixed) were compared to those who received < 10 units (reduced). The primary outcome was the incidence of hypoglycemia (blood glucose < 70 mg/dL) within 12 hours of insulin administration. Secondary outcomes included the incidence of severe hypoglycemia (blood glucose < 40 mg/dL) and change in potassium. Multivariable analyses were used to assess for risk factors for hypoglycemia and severe hypoglycemia. FINDINGS: Of the 2576 patients included, 305 (11.8%) received reduced dosing and 2271 (88.2%) received fixed dosing. Hypoglycemia occurred in 16.7% of the reduced group and 15.9% of the fixed group (P = 0.70). Severe hypoglycemia occurred in 2.3% of the reduced group and 2.5% of the fixed group (P = 0.86). Median potassium reduction from baseline to first check post-insulin was less with reduced dosing (-0.6 mEq/L vs -0.8 mEq/L, P < 0.001). On multivariable regression analysis, greater weight-based insulin dose and ED location were significant predictors for hypoglycemia and severe hypoglycemia. Location in the intensive care unit was associated with a decreased risk of hypoglycemia. Higher pre-insulin glucose was protective for hypoglycemia and severe hypoglycemia. IMPLICATIONS: The incidence of hypoglycemia was similar among both groups. Greater weight-based insulin dose was a significant risk factor for hypoglycemia, while higher baseline glucose levels were associated with a decreased risk, indicating that patient-specific insulin dosing for hyperkalemia may be warranted.

Clinical examination findings and electrolyte abnormalities of dogs with marijuana/tetrahydrocannabinol toxicity: 223 cases (January 2017-July 2021).

OBJECTIVE: The goal of this study was to describe the historical, physical, neurologic, and clinicopathologic findings in dogs with a definitive diagnosis of marijuana/tetrahydrocannabinol toxicity. ANIMALS: A total of 223 dogs with known ingestion of marijuana or a positive tetrahydrocannabinol result on human urine multidrug test. METHODS: Retrospective study from January 2017 to July 2021. RESULTS: Median age was 1 year (1 month to 12 years). A common history was becoming acutely neurologic after going outside or to a public place (62/223 [27.8%]). Most owners denied possibility of exposure (152/223 [68%]). Median vitals were normal, but hyperthermia (38/212 [22.6%]), tachycardia (82/222 [37%]), and systemic hypertension (37/61 [60.7%]) were common abnormalities. The most common clinical signs included ataxia (197/223 [88.3%]), hyperesthesia (168/223 [75.3%]), urinary incontinence (102/223 [45.7%]), lethargy (140/223 [62.5%]), and vomiting (58/223 [26%]). The most common combinations of neurologic signs included ataxia and hyperesthesia (157/223 [70.4%]) and ataxia, hyperesthesia, and urinary incontinence (81/223 [36.3%]). Mild hyperkalemia (39/76 [51.3%]) and mild hypercalcemia (53/67 [79.1%]) were common. Twenty-two dogs were hospitalized. Survival was 100%. CLINICAL RELEVANCE: A common presentation for marijuana toxicosis included young dogs with acute ataxia and hyperesthesia, with and without urinary incontinence, after going outside or to a public place. Vitals were often normal, but hyperthermia, tachycardia, and hypertension were common. Bloodwork was mostly normal, but mild hyperkalemia and mild ionized hypercalcemia were common. Marijuana should be high on the differential list with these history, physical examination, neurologic, and electrolyte abnormalities, regardless of owner denial or negative human urine multidrug test.

Incidence of hyperkalemia in anuric hemodialysis patients treated with sacubitril/valsartan.

INTRODUCTION: Sacubitril/valsartan is increasingly used in hemodialysis patients due to its cardioprotective benefits. However, its impact on serum potassium levels in anuric patients undergoing hemodialysis remains controversial. METHODS: We conducted a retrospective data from patients undergoing hemodialysis at two dialysis centers. A total of 71 out of 332 patients receiving hemodialysis treatment were enrolled. Mean serum potassium (mean value of 6-8 determinations), peak serum potassium (maximum K value observed during follow-up observations), and other biochemical parameters were recorded at baseline and during the follow-up period. FINDINGS: After 6 months of follow-up, mean serum potassium increased from 4.84 ± 0.45 mmol/L at baseline to 5.07 ± 0.46 mmol/L at 3 months and 5.04 ± 0.46 mmol/L at 6 months (p < 0.001). Notably, no significant group differences were found in peak serum potassium concentrations between baseline and 6 months after sacubitril/valsartan therapy (5.69 ± 0.56 vs. 5.75 ± 0.41, p = 0.419). Prior to starting sacubitril/valsartan treatment, none of the patients had severe hyperkalemia; however, after 3 and 6 months of sacubitril/valsartan therapy, two (2.80%) and three (4.20%) patients experienced severe hyperkalemia, respectively; however, this difference was not statistically significant. Additionally, there was a significant reduction in blood pressure; however, serum sodium, bicarbonate, and Kt/V values did not change significantly during either period. DISCUSSION: Sacubitril/valsartan therapy is associated with an increase in serum potassium levels in anuric hemodialysis patients. Nevertheless, the proportion of patients with severe hyperkalemia did not increase significantly. This suggests that the use of sacubitril/valsartan in anuric patients on hemodialysis is relatively safe.