Acquired hyperkalaemia leading to periodic paralysis: an emergency department perspective.

Hyperkalaemia is one of the common electrolyte imbalances dealt with in the emergency department and is caused by extracellular accumulation of potassium ions above normal limits usually greater than 5.0-5.5 mmol/L. It is found in a total of 1-10% of hospitalised patients usually associated with chronic kidney disease and heart failure. The presentation can range from being asymptomatic to deadly arrhythmias. The appearance of symptoms depends on the rate of change rather than just the numerical values. The rare presentation includes periodic paralysis characterised by the sudden onset of short-term muscle weakness, stiffness or paralysis. Management goals are directed towards reducing potassium levels in emergency settings and later on avoiding the triggers for future attacks. In this case, we present a man in his 50s with the generalised weakness later on diagnosed as hyperkalaemic periodic paralysis secondary to tumour lysis syndrome. Emergency physicians dealing with common electrolyte imbalances should keep a sharp eye on their rare presentation and their precipitating factors and should act accordingly.

Initial eGFR Changes with SGLT2 Inhibitor in Patients With Type 2 Diabetes and Associations With the Risk of Abnormal Serum Potassium Level.

BACKGROUND: Both high and low levels of serum potassium measurements are linked with a higher risk of adverse clinical events among patients with type 2 diabetes. The study was aimed at evaluating the implications of the various degrees of initial estimated glomerular filtration rate (eGFR) change on subsequent serum potassium homeostasis following sodium-glucose cotransporter-2 inhibitor (SGLT2i) initiation among patients with type 2 diabetes. METHODS AND RESULTS: We used medical data from a multicenter health care provider in Taiwan and recruited 5529 patients with type 2 diabetes with baseline/follow-up eGFR data available after 4 to 12 weeks of SGLT2i treatment from June 1, 2016, to December 31, 2018. SGLT2i treatment was associated with an initial mean (SEM) eGFR decline of -3.5 (0.2) mL/min per 1.73 m2 in overall study participants. A total of 36.7% (n=2028) of patients experienced no eGFR decline, and 57.9% (n=3201) and 5.4% (n=300) of patients experienced an eGFR decline of 0% to 30% and >30%, respectively. Patients with an initial eGFR decline of >30% were associated with higher variability in consequent serum potassium measurement when compared with those without an initial eGFR decline. Participants with a pronounced eGFR decline of >30% were associated with a higher risk of hyperkalemia ≥5.5 (adjusted hazard ratio,4.59 [95% CI, 2.28-9.26]) or use of potassium binder (adjusted hazard ratio, 2.65 [95% CI, 1.78-3.95]) as well as hypokalemia events <3.0 mmol/L (adjusted hazard ratio, 3.21 [95% CI, 1.90-5.42]) or use of potassium supplement (adjusted hazard ratio, 1.87 [95% CI, 1.37-2.56]) following SGLT2i treatment after multivariate adjustment. CONCLUSIONS: Physicians should be aware that the eGFR trough occurs shortly, and consequent serum potassium changes following SGLT2i initiation.

Myelotoxicity and kidney dysfunction related to the use of trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia: a case report of severe adverse events with a common drug.

Trimethoprim-sulfamethoxazole (TMP-SMX) is the primary therapeutic option for Pneumocystis jirovecii pneumonia (PCP). Gastrointestinal symptoms and cutaneous rash are common side effects, with hyperkalemia being uncommon in patients without kidney dysfunction, and myelotoxicity being even rarer. We present the case of a male patient with hypertension and a recent diagnosis of non-Hodgkin lymphoma, undergoing rituximab treatment for two months. He was admitted to the intensive care unit due to dyspnea, tachypnea, and pleuritic pain, requiring mechanical ventilation. Chest computed tomography showed bilateral and multilobed ground-glass opacities, compromising more than 80% of the lung parenchyma. Pulmonary tuberculosis and COVID-19 were ruled out. An angiotomography and Doppler ultrasound revealed an extensive pulmonary thrombus and deep venous thrombosis. Empiric treatment with TMP-SMX for PCP was initiated, but within four days, the patient experienced metabolic acidosis and severe hyperkalemia, necessitating hemodialysis. He also presented with progressive pancytopenia and critical levels of leukopenia and thrombocytopenia. The hypothesis of TMP-SMX-induced myelotoxicity was suspected. Considering the unavailability of an alternative treatment, it was opted to continue TMP-SMX and initiate a granulocyte-colony-stimulating factor. However, the patient maintained medullary deterioration, becoming refractory to the transfusion of blood derivates. On the 17th day of treatment, a clinical decision was made to suspend TMP-SMX, leading to improvements within 48 hours in marrow and kidney functions, metabolic acidosis, and hyperkalemia. Despite all efforts, the patient died after 35 days of hospitalization due to hospital-acquired infections. This case highlights the importance of clinicians recognizing potential myelotoxicity with TMP-SMX and promptly discontinuing the drug if necessary.

Population Pharmacodynamic Dose-Response Analysis of Serum Potassium Following Dosing with Sodium Zirconium Cyclosilicate.

BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an approved oral treatment for hyperkalemia that selectively binds potassium (K+) in the gastrointestinal tract and removes K+ from the body through increased fecal excretion. Here, we describe the population pharmacodynamic (PopPD) response of serum K+ concentration in patients with hyperkalemia who are treated with SZC, estimate the impact of patients' intrinsic and extrinsic factors, and compare predicted serum K+ responses between 5 g alternate daily (QOD) and 2.5 g once daily (QD) maintenance doses. METHODS: PopPD analysis was based on pooled data from seven phase II and III clinical trials for SZC. A semi-mechanistic longitudinal mixed-effects (base) model was used to characterize serum K+ concentration after SZC dosing. Indirect-response, virtual pharmacokinetics-pharmacodynamics (PK-PD) modeling was used to mimic the drug exposure compartment. Full covariate modeling was used to assess covariate impact on the half-maximal effective concentration of drug (EC50), placebo response, and Kout. Models were evaluated using goodness-of-fit plots, relative standard errors, and visual predictive checks, and data were stratified to optimize model performance across subgroups. Covariate effects were evaluated based on the magnitude of change in serum K+ between baseline and end of correction phase dosing (48 h, SZC 10 g three times a day) and maintenance phase dosing (28 days, SZC 10 g QD) using a reference subject. RESULTS: The analysis data set included 2369 patients and 25,764 serum K+ observations. The mean (standard deviation) patient age was 66.0 (12) years, 61% were male, 68% were White, 34% had congestive heart failure, and 62% had diabetes. Mean (standard deviation) serum K+ at baseline was 5.49 (0.43) mmol/L. Both the base and full covariance models adequately described observed data. In the final model, there was a sigmoid exposure response on Kin, with EC50 of 32.8 g and a Hill coefficient of 1.36. The predicted placebo-adjusted dose-responses of serum K+ change appeared nearly linear in the correction and maintenance phases. No clinically meaningful difference in placebo-adjusted serum K+ change from baseline at 28 days was observed between maintenance regimens of SZC 5 g QOD and 2.5 g QD. A greater SZC treatment response was associated with high serum K+ at baseline, advanced age, lower body weight, lower estimated glomerular filtration rate, and Black/African American and Asian race, compared with the reference patient. The impact of heart failure status and diabetes status was only minor. CONCLUSIONS: The PopPD model of SZC adequately described changes in serum K+ concentration during correction and maintenance phase dosing. A greater treatment response was associated with various covariates, but the impact of each was modest. Overall, these findings suggest that no adjustment in SZC dose is needed for any of the covariates evaluated.

Management of Hyperkalemia in Renin-Angiotensin-Aldosterone System Inhibitor: Strategies to Maintain Chronic Kidney Disease Patients with Type II Diabetes on Therapy.

BACKGROUND: According to the Centers for Disease Control and Prevention (CDC), diabetes affects approximately 37.3 million individuals in the USA, with another estimated 96 million people having a prediabetic state. Furthermore, one or two out of three adult Americans exhibit metabolic syndrome or an insulin-resistant state, depending on their age group. SUMMARY: Chronic kidney disease (CKD) represents a complication often associated with type II diabetes or the insulin-resistant condition, typically identifiable through proteinuria. Proteinuria serves as both a marker and a contributing factor to kidney damage, and it significantly heightens the risk of cardiovascular (CV) events, including atherosclerosis, heart attacks, and strokes. Renin-angiotensin-aldosterone system inhibitors (RAASis) have demonstrated clinical efficacy in lowering blood pressure, reducing proteinuria, and slowing CKD progression. However, hyperkalemia is a common and serious adverse effect associated with using RAASi. KEY MESSAGES: It is imperative to establish personalized management strategies to enable patients to continue RAASi therapy while effectively addressing hyperkalemia risk. Healthcare professionals must be careful not to inadvertently create a low renal perfusion state, which can reduce distal nephron luminal flow or luminal sodium concentration while using RAASi. Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), such as finerenone, are demonstrated to delay CKD progression and reduce CV complications, all while mitigating the risk of hyperkalemia. Additionally, maintaining a routine monitoring regimen for serum potassium levels among at-risk patients, making dietary adjustments, and considering the adoption of newer potassium-binding agents hold promise for optimizing RAASi therapy and achieving more effective hyperkalemia management.

Cost-effectiveness of sodium zirconium cyclosilicate for advanced chronic kidney patients in Singapore.

INTRODUCTION: Hyperkalaemia (HK) is prevalent among patients with chronic kidney disease (CKD) and chronic heart failure, especially if they are treated with renin-angiotensin-aldosterone system inhibitors (RAASi). This study evaluated the cost-effectiveness of a newly developed anti-HK therapy, sodium zirconium cyclosilicate (SZC), to the current standard of care for treating HK in advanced CKD patients from the Singapore health system perspective. METHODS: We adapted a global microsimulation model to simulate individual patients' potassium level trajectories with baseline potassium ≥5.5 mmol/L, CKD progression, changes in treatment, and other fatal and non-fatal events. Effectiveness data was derived from ZS-004 and ZS-005 trials. Model parameters were localised using CKD patients' administrative and medical records at the Singapore General Hospital Department of Renal Medicine. We estimated the lifetime cost and quality-adjusted life years (QALYs) of each HK treatment, and the incremental cost-effectiveness ratio of SZC. RESULTS: SZC demonstrated cost-effectiveness with an incremental cost-effectiveness ratsio of SGD 45 068 per QALY over a lifetime horizon, below the willingness-to-pay threshold of SGD 90 000 per QALY. Notably, SZC proved most cost-effective for patients with less severe CKD who were concurrently using RAASi. Sensitivity analyses confirmed the robustness of the findings, accounting for alternative parameter values and statistical uncertainty. CONCLUSION: This study establishes the cost-effectiveness of SZC as a treatment for HK, highlighting its potential to mitigate the risk of hyperkalaemia and optimise RAASi therapy. These findings emphasise the value of integrating SZC into the Singapore health system for improved patient outcomes and resource allocation.

Comparison of chronic kidney disease progression and associated complications between geriatric and non-geriatric groups.

There is no consensus on the physiologic decline in estimated glomerular filtration rate (GFR) due to geriatric conditions related with the aging or chronic kidney disease (CKD) itself. In this study, we aimed to compare the CKD progression and associated complications in a large sample of geriatric and non-geriatric patients. The data of in 506 patients at age between 30 to 90 years and diagnosed with CKD at stage 2 and above (15 mL/min/1.73 m2 ≤ eGFR < 90 mL/min/1.73 m2) were collected retrospectively and compared among geriatric (>65 years old) and non-geriatric individuals. The rate of hypertension was higher in geriatrics compared to non-geriatrics (96.6% vs 91.9%, P = .04). Among laboratory findings, only PTH level was significantly lower and HCO3 concentration was higher in geriatrics compared to non-geriatrics (P = .02, P < .001, respectively). There was no significant difference in last measured eGFR (P = .99) while that measured 4 years ago was lower in geriatrics compared to that of non-geriatrics (P < .001). eGFR change was smaller in geriatrics compared to non-geriatrics (P < .001), and rate of progressive renal disease among non-geriatric group (39%) was found to be significantly higher than in the geriatrics (17.2%) (P < .001). The prevalence of hyperkalemia was lower in geriatrics at stage 3a (P = .02); prevalence of hyperparathyroidism was lower in those at stage 3b (P = .02) and lastly the acidosis was observed significantly lower in geriatric patients at stage 3a, 3b, and 4 compared to the non-geriatrics at corresponding stages (P < .001, P = .03, and P = .04, respectively). The eGFR change was significantly smaller in geriatrics at stage 3b and 4 (P < .001 and P = .04, respectively) while the rate of progressed renal disease was lower in geriatrics at stage 3a and 3b (21.1% vs 9.9%, P = .03 and 41.2% vs 11.1%, P < .001, respectively). eGFR change in 4-year period and the rates of progressive renal disease are higher in the non-geriatrics and also the prevalence of secondary complications of CKD, such as hyperparathyroidism, acidosis, and hyperkalemia, are higher in non-geriatrics. This may reflect that decline of GFR in geriatric individuals is at least partially related to physiological aging rather than kidney disease. Therefore, devising age related CKD definitions might be appropriate.

Evaluation of effectiveness, hyperkalaemia, and hepatotoxicity of trimethoprim-sulphamethoxazole prophylaxis for Pneumocystis jirovecii pneumonia in paediatric patients: A single-centre retrospective study.

BACKGROUND: American guidelines recommend trimethoprim-sulphamethoxazole (TMP-SMX) for preventing Pneumocystis jirovecii pneumonia (PJP) in paediatric patients at doses of 5-10 mg/kg/d of the TMP component, administered either daily, three times weekly, or twice weekly. However, limited studies describe the effectiveness and safety of these prophylactic regimens. Our study aimed to assess the clinical effectiveness and incidence of adverse events associated with each TMP-SMX regimen in paediatric patients, and to identify risk factors for adverse events. METHODS: We collected data regarding the onset of PJP, hyperkalaemia, and hepatotoxicity in patients aged 0-18 years who underwent prophylaxis with TMP-SMX from July 2018 to June 2023. RESULTS: A total of 215 paediatric patients met the inclusion criteria. No patients developed PJP. Hyperkalaemia occurred in 14.7%, patients receiving TMP-SMX daily, 15.4% receiving it three times weekly, and 15.5% receiving it twice weekly. Hepatotoxicity was most frequent in patients receiving TMP-SMX twice weekly (19%), followed by those receiving it three times weekly (7.7%), and daily (5.9%). Younger patients were significantly more prone to developing hyperkalaemia or hepatotoxicity. Patients aged <1 year had the highest incidences of hyperkalaemia (56.5%), and those aged 1-2 years had the highest incidence of hepatotoxicity (25%). CONCLUSIONS: No patient developed PJP under various dosage prophylactic regimens of TMP-SMX. However, our findings suggest the need to monitor potassium levels and hepatic function in patients undergoing any of the three TMP-SMX regimens. In particular, patients aged <1 year old and 1-2 years old face a higher risk of hyperkalaemia and hepatotoxicity, respectively.

Impact of a Hyperkalemia Protocol Tailored to Glucose Concentration and Renal Function on Insulin-Induced Hypoglycemia in Patients with Low Pretreatment Glucose.

BACKGROUND: Hyperkalemia is a common electrolyte abnormality that requires urgent treatment. Insulin is an effective treatment for hyperkalemia, but risk factors for developing insulin-induced hypoglycemia exist (e.g., low pretreatment glucose or renal impairment). OBJECTIVE: This study evaluated the impact of a hyperkalemia protocol tailored to glucose concentration and renal function on insulin-induced hypoglycemia. METHODS: This was a retrospective cohort study of emergency department patients with glucose ≤ 100 mg/dL treated with insulin for hyperkalemia. The primary outcome was incidence of hypoglycemia in patients treated prior to (July 1, 2018-June 30, 2019) vs. after (January 1, 2020-December 31, 2020) the protocol update, which individualized insulin and dextrose doses by glucose concentration and renal function. Secondary outcomes included change in potassium and protocol safety. We assessed factors associated with hypoglycemia using multiple logistic regression. RESULTS: We included 202 total patients (preimplementation: 114, postimplementation: 88). Initial insulin dose was lower in the postimplementation group (p < 0.001). We found a nonsignificant reduction in hypoglycemia in the postimplementation group (42.1% vs. 30.7%, p = 0.10). Degree of potassium reduction was similar in patients who received insulin 5 units vs. 10 units (p = 0.72). Higher pretreatment glucose (log odds ratio [OR] -0.05, 95% confidence interval [CI] -0.08 to -0.02) and additional insulin administration (log OR -1.55, 95% CI -3.01 to -0.25) were associated with reduced risk of developing hypoglycemia. CONCLUSION: A hyperkalemia protocol update was not associated with a significant reduction in hypoglycemia, and the incidence of hypoglycemia remained higher than anticipated. Future studies attempting to optimize treatment in this high-risk population are warranted.

A rare case of essential thrombocythemia with pseudo-hyperkalemia.

Essential thrombocythemia (ET) is a rare clonal stem cell disorder that affects the production of platelets in the bone marrow. This condition causes an overproduction of platelets, which can lead to blood clots and other complications. Potassium, on the other hand, is an essential mineral that plays a vital role in various bodily functions, including nerve impulses and muscle contractions. Here, in this case report, we investigated a case of pseudo-hyperkalemia caused by essential thrombocythemia in a 77-year-old woman with very high platelet counts. Moreover, this case report, which has no similar examples in the literature review, is important for clinicians.

Managing hyperkalemia in patients with heart failure on guideline-directed medical therapy: challenges and opportunities.

Heart failure is a chronic and invalidating syndrome that affects tens of millions of people worldwide with significant socio-economic ramifications for the health care systems. Significant progress in the understanding of the pathophysiology of heart failure has allowed the gradual introduction of several drug classes for the management of such patients. Beta-blockers, mineralocorticoid receptor antagonists, angiotensin receptor neprilysin inhibitors, and sodium-glucose-cotransporter 2 inhibitors are all considered pillars of the guideline-directed medical therapy for heart failure. Despite remarkable improvements in the morbidity and mortality of heart failure, however, many patients still develop clinically significant hyperkalemia during combined treatment with those four pharmacological pillars. The consequence is often a down-titration or discontinuation of one or more crucial drugs, which in turns leads to a considerable increase in the risk of cardiovascular events, dialysis, and all-cause mortality. This paper will explore novel approaches for the management of hyperkalemia in heart failure, including closer monitoring of potassium levels, early review of drugs that might increase the risk of hyperkalemia, and pharmacological treatment of hyperkalemia, with a special emphasis on sodium-glucose-cotransporter 2 inhibitors and potassium-binding agents, including patiromer and sodium zirconium cyclosilicate.

Non-steroidal mineralocorticoid antagonists and hyperkalemia monitoring in chronic kidney disease patients associated with type II diabetes: a narrative review.

Chronic kidney disease (CKD) is a prevalent complication of Type II diabetes (T2D). The coexistence of CKD with T2D is comparable to cardiovascular disease (CVD) when the estimated glomerular filtration rate declines below 60 ml/min/1.73 m2. Screening and early detection of people with high risk for CKD would be beneficial in managing CKD progress and the associated complications such as CV complications. Renin-angiotensin-aldosterone system inhibitors (RAASi) have demonstrated beneficial effects in delaying CKD progression, but they carry the risk of hyperkalemia. Nonsteroidal mineralocorticoid antagonists (nsMRA), such as finerenone, exhibit considerable efficacy in their anti-inflammatory, antifibrotic, and renal protective effects with demonstrable reductions in CV complications. In addition, nsMRAs do not cause significant changes in serum potassium levels compared to traditional steroidal MRA. Ongoing research explores the capacity of the sodium-glucose transport protein 2 inhibitors (SGLT-2i), combined with nsMRA, to produce synergistic renal protective effects and reduce the risk of hyperkalemia. Also, a dedicated renal outcomes study (FLOW study) involving a once-weekly injectable Glucagon-like peptide-1 receptor agonist, semaglutide, was halted early by the data monitoring committee due to having achieved the predefined efficacy endpoint and considerations related to renal disease. In CKD patients with T2D on nsMRA, hyperkalemia management requires a comprehensive approach involving lifestyle adjustments, dietary modifications, regular serum potassium level monitoring, and potassium binders, if necessary. Withholding or down-titration of nsMRAs with close monitoring of serum potassium levels may be required in patients with concerning potassium levels. In light of the current state of knowledge, this review article explores the perspectives and approaches that HCPs may consider when monitoring and managing hyperkalemia in CKD patients with T2D.

Chronic Kidney Disease (CKD) is a common and serious problem among people with Type II Diabetes (T2D). People who have CKD with T2D are at a higher risk for heart disease after normal kidney function declines below certain levels. Renin-angiotensin-aldosterone system inhibitors are a group of medications that can help delay CKD progression but may cause a rise in circulating potassium levels. Nonsteroidal mineralocorticoid antagonist (nsMRA), such as finerenone, can reduce kidney inflammation and damage, with noted cardiovascular benefits, and with less effect on serum potassium levels as compared to their steroid-based counterparts. Researchers are studying whether combining blood sugar medications such as sodium-glucose transport protein-2 inhibitors (SGLT-2i) and finerenone can help protect the kidneys and heart. They also want to see if this combination can prevent high potassium levels. This article talks about ways to check and monitor potassium levels in CKD patients with T2D who may be taking nsMRA. To manage high potassium levels in people with CKD and T2D, doctors may suggest lifestyle changes, dietary adjustments, potassium-lowering medication, or adjustment of other medications with close monitoring of potassium levels.

Pacemaker ECG with the Littmann sign.

Severe hyperkalemia may be concealed in the electrocardiogram (ECG). We present the case of a critically ill patient with severe bradycardia and the BRASH syndrome. In critically ill patients, double counting of the heart rate is frequently a marker of severe hyperkalemia (Littmann sign). In our case, hyperkalemic double counting only appeared in the ECG performed during percutaneous pacing. The Littmann sign helped with the early recognition of hyperkalemia and the BRASH syndrome.

Randomised, blinded, cross-over evaluation of the palatability of and preference for different potassium binders in participants with chronic hyperkalaemia in the USA, Canada and Europe: the APPETIZE study.

OBJECTIVES: Traditional potassium (K+) binders for treating hyperkalaemia are unpalatable and poorly tolerated. Newer K+ binders are reportedly better tolerated; however, no published data describe their palatability, a determinant of long-term adherence. This study evaluated the palatability of and preference for three K+ binders: sodium and calcium polystyrene sulfonate (S/CPS), sodium zirconium cyclosilicate (SZC) and calcium patiromer sorbitex (patiromer). DESIGN: Phase 4, randomised, participant-blinded, cross-over study. Participants were randomised to one of six taste sequences and, using a 'sip and spit' approach, tasted each K+ binder before completing a survey. SETTING: 17 centres across the USA, Canada and European Union. PARTICIPANTS: 144 participants with chronic kidney disease, hyperkalaemia and no recent use of K+ binders. MAIN OUTCOME MEASURES: For the primary (USA) and key secondary (Canada and European Union) endpoints, participants rated palatability attributes (taste, texture, smell and mouthfeel) and willingness to take each K+ binder on a scale of 0-10 (rational evaluation). Feelings about each attribute, and the idea of taking the product once daily, were evaluated using a non-verbal, visual measure of emotional response. Finally, participants ranked the K+ binders according to palatability. RESULTS: In each region, SZC and patiromer outperformed S/CPS on overall palatability (a composite of taste, texture, smell and mouthfeel), based on rational evaluation and emotional response. Taking the product once daily was more appealing for SZC and patiromer, creating greater receptivity than the idea of taking S/CPS. The emotional response to mouthfeel had the strongest influence on feelings about taking each product. In each region, a numerically greater proportion of participants ranked SZC as the most preferred K+ binder versus patiromer or S/CPS. CONCLUSIONS: Preference for more palatable K+ binders such as SZC and patiromer may provide an opportunity to improve adherence to long-term treatment of hyperkalaemia. TRIAL REGISTRATION NUMBER: NCT04566653.

Acute fatal ventricular arrhythmia induced by severe hyperkalemia in a toddler with decompensated methylmalonic acidemia.

BACKGROUND: Methylmalonic acidemia is a very rare genetic metabolic disease. Patients with isolated methylmalonic acidemia typically present with acute alterations of consciousness, failure to thrive, anorexia, vomiting, respiratory distress, and muscular hypotonia. Despite the evidence-based management, affected individuals experience significant morbidity and mortality. Hyperkalemia is one of the unusual complications of methylmalonic acidemia. CASE PRESENTATION: In this paper, we describe a 4-year-old Persian boy with methylmalonic acidemia who developed life-threatening arrhythmia following severe hyperkalemia and metabolic acidosis. Emergent management of the condition was successfully carried out, and the rhythm changed to normal sinus rhythm by effectively reducing the serum potassium level. We discuss the possible etiology of this lethal condition and describe its management on the basis of the available evidence. CONCLUSION: During metabolic decompensation in methylmalonic acidemia, frequent blood gas and electrolyte testing to prescribe and adjust therapy and annual echocardiogram and electrocardiogram screening are essential.

Characterizing the limitations of using diagnosis codes in the context of machine learning for healthcare.

BACKGROUND: Diagnostic codes are commonly used as inputs for clinical prediction models, to create labels for prediction tasks, and to identify cohorts for multicenter network studies. However, the coverage rates of diagnostic codes and their variability across institutions are underexplored. The primary objective was to describe lab- and diagnosis-based labels for 7 selected outcomes at three institutions. Secondary objectives were to describe agreement, sensitivity, and specificity of diagnosis-based labels against lab-based labels. METHODS: This study included three cohorts: SickKids from The Hospital for Sick Children, and StanfordPeds and StanfordAdults from Stanford Medicine. We included seven clinical outcomes with lab-based definitions: acute kidney injury, hyperkalemia, hypoglycemia, hyponatremia, anemia, neutropenia and thrombocytopenia. For each outcome, we created four lab-based labels (abnormal, mild, moderate and severe) based on test result and one diagnosis-based label. Proportion of admissions with a positive label were presented for each outcome stratified by cohort. Using lab-based labels as the gold standard, agreement using Cohen's Kappa, sensitivity and specificity were calculated for each lab-based severity level. RESULTS: The number of admissions included were: SickKids (n = 59,298), StanfordPeds (n = 24,639) and StanfordAdults (n = 159,985). The proportion of admissions with a positive diagnosis-based label was significantly higher for StanfordPeds compared to SickKids across all outcomes, with odds ratio (99.9% confidence interval) for abnormal diagnosis-based label ranging from 2.2 (1.7-2.7) for neutropenia to 18.4 (10.1-33.4) for hyperkalemia. Lab-based labels were more similar by institution. When using lab-based labels as the gold standard, Cohen's Kappa and sensitivity were lower at SickKids for all severity levels compared to StanfordPeds. CONCLUSIONS: Across multiple outcomes, diagnosis codes were consistently different between the two pediatric institutions. This difference was not explained by differences in test results. These results may have implications for machine learning model development and deployment.

Severe Hyperkalemia During a Robot-Assisted Total Radical Prostatectomy in a Patient with Stage 3a Chronic Kidney Disease: A Case Report.

A 63-year-old man with stage 3a chronic kidney disease (CKD) and mild hyperkalemia was scheduled for a robot-assisted prostatectomy. He was being treated with lisinopril. Owing to mild hyperkalemia (6.2 mmol/L), lisinopril was discontinued, and sodium polystyrene sulfonate was administered on the day before surgery. Three hours after incision, electrocardiographic signs of hyperkalemia manifested with the serum potassium concentration rising to 8 mmol/L. Although hyperkalemia is a common and well-documented side effect of angiotensin-converting enzyme inhibitors in patients with CKD, we report an extreme increase in potassium within a very short time period despite prior drug discontinuation.

Effectiveness and safety of early treatment with spironolactone for new-onset acute heart failure.

BACKGROUND: The effectiveness and safety of mineralocorticoid receptor antagonists (MRA) in acute heart failure (HF) is uncertain. We sought to describe the prescription of spironolactone during acute HF and whether early treatment is effective and safe in a real-world setting. METHODS: We performed a retrospective cohort study of adult (≥18 years) nonpregnant patients hospitalized with new-onset HF with reduced ejection fraction (HFrEF, defined by ejection fraction ≤40%) within 15 Kaiser Permanente Southern California medical centers between 2016 and 2021. Early treatment was defined by spironolactone prescription at discharge. The primary effectiveness outcome was a composite of HF readmission or all-cause mortality at 180 days. Safety outcomes were hypotension and hyperkalemia at 90 days. RESULTS: Among 2318 HFrEF patients, 368 (15.9%) were treated with spironolactone at discharge. After 1:2 propensity score matching, 354 early treatment and 708 delayed/no treatment patients were included in the analysis. The median age was 63 (IQR: 52-74) years; 61.6% were male, and 38.6% were White. By 90 days, ~20% had crossed over in the two groups. Early treatment was not associated with the composite outcome at 180 days (HR [95% CI]: 0.81 [0.56-1.17]), but a trend towards benefit by 365 days that did not reach statistical significance (0.78 [0.58-1.06]). Early treatment was also associated with hyperkalemia (subdistribution HR [95% CI]: 2.33 [1.30-4.18]) but not hypotension (0.93 [0.51-1.72]). CONCLUSIONS: Early treatment with spironolactone at discharge for new-onset HFrEF in a real-world setting did not reduce the risk of HF readmission or mortality in the first year after discharge. The risk of hyperkalemia was increased.