More Than a Number: Reframing Hyperkalemia Management Across the Care Continuum

Ralph J. Riello III, PharmD, BCPS
Clinical Pharmacy Specialist
Yale University School of Medicine
New Haven, Connecticut

This content is a production of Drug Topics; this Focus on Disease Supplement is supported by funding from AstraZeneca. AstraZeneca was not involved in the creation of the content for this supplement.

DRUG TOPICS (DT): In practice, how can acute and chronic hyperkalemia be differentiated, particularly when a patient’s lab history is incomplete or when they are transitioning from acute to chronic management? What practical markers help you make this distinction?

Riello: Differentiating acute and chronic hyperkalemia—especially when working with an incomplete history—is a frequent challenge, particularly in the emergency department (ED). Often, we suspect hyperkalemia without access to the full medical context. However, there are several clues that can guide us. For instance, we consider whether the patient has chronic kidney disease (CKD) with acute renal insufficiency superimposed on chronic dysfunction. We also assess whether the current potassium value is significantly elevated relative to the patient’s baseline. A potassium level of 5.5 mEq/L may be stable for one patient but could represent a significant rise for someone whose baseline is 3.5 mEq/L.

In many cases, the trajectory of potassium is as important—if not more so—than the absolute value. For example, a patient’s myocardium may be acclimated to chronically elevated levels of 5.2 mEq/L. In such cases, electrocardiogram (ECG) changes might not appear until potassium rises above 6 mEq/L. Thus, clinicians must assess both the number and the context. Identifying and discontinuing common offending agents—such as renin–angiotensin–aldosterone system (RAAS) inhibitors, potassium-sparing diuretics, and potassium supplements without clear stop dates—is essential.

We also look for subtle signs, such as when anesthesia teams use succinylcholine during rapid sequence intubation. These orders may not be entered in the electronic health record (EHR), but an empty vial at the bedside may be the only indication. Succinylcholine is a frequent contributor to hyperkalemia.

Beyond the ECG, we also evaluate for physical symptoms, such as paresthesias, which are common in patients with stage 4 or 5 CKD and chronic hyperkalemia. Distinguishing between symptoms due to CKD and those due to worsening hyperkalemia requires a full clinical picture and a detective-like approach. Most importantly, we must identify opportunities to prevent future episodes.

DT: The Kidney Disease: Improving Global Outcomes (KDIGO) and American Heart Association/American College of Cardiology (AHA/ACC) guidelines provide cutoffs for hyperkalemia management at 6 mEq/L and 5.5 mEq/L, respectively. How do you evaluate patients in the borderline range, and what factors influence your decision-making beyond the potassium value?

Riello: Even among major societies, such as the European Society of Cardiology and the AHA/ACC, guideline cutoffs vary. For example, the AHA/ACC sets the potassium threshold at 5.5 mEq/L for initiating novel potassium binders, while European guidelines suggest thresholds closer to 5.0 mEq/L. These thresholds reflect interpretation of the same data, and, at the end of the day, they are just numbers.

More important than the absolute value is the trajectory. Where did the potassium level start, how rapidly has it risen, and is it likely to increase further if no intervention occurs? For example, a potassium level of 5.7 mEq/L may be concerning in a patient with a baseline of 4.0 mEq/L but less so in someone who typically runs at 5.5 mEq/L.

The KDIGO guidelines emphasize not focusing too narrowly on these cutoffs, especially when it leads to withholding guideline-directed medical therapy (GDMT). Often, the reaction is to stop life-saving medications, which may ultimately do more harm than good. The AHA/ACC guidelines for heart failure now support continuation of GDMT, even in the acute care setting, although they stop short of offering guidance specific to potassium management. This is an area that could be addressed in future updates.

We should consider adopting a more proactive stance, similar to our European colleagues, by initiating potassium binders at lower thresholds. The mortality benefit of GDMT in heart failure is too great to forgo. Even if a therapy ultimately proves unsuitable for a particular patient, it is critical that we try.

In the acute care setting, comorbidities often guide my decisions about which agents to use. I also consider acid-base status, particularly in intensive care settings. In some cases, continuous veno-venous hemodialysis may be needed. Patient education is another important factor—many are unaware of the potassium content in over-the-counter products or misinterpret dietary guidance. For instance, the DASH diet encourages salt substitutes, which may inadvertently increase potassium intake.

Borderline potassium levels should prompt a comprehensive review of the patient’s trend, context, and contributing factors. Pharmacists can play a key role in managing these elements to reduce risk and improve long-term patient outcomes.

DT: Please describe your approach to managing patients with varying severities of hyperkalemia. How can the guidelines be applied for patients with mild chronic hyperkalemia versus those with more severe elevations?

Riello: For patients with mild hyperkalemia—typically potassium levels between 5.0 and 5.5 mEq/L—continue GDMT but ensure patients are educated about the risks. Communication is key. Telling patients that medications like spironolactone can raise potassium might prompt them to stop therapy on their own. We need to balance transparency with careful messaging.

Patients with moderate hyperkalemia (5.5-6.0 mEq/L) require more active management. This is typically the threshold at which I consider initiating a novel potassium binder. While I might have been on the fence below ​5.5 mEq/L, once that level is exceeded, I am more inclined to start treatment. In chronic management, my decision often comes downto choosing between patiromer and sodium zirconium cyclosilicate (SZC), which, while nuanced, are more similar than different.

For patients with severe hyperkalemia (potassium > 6.0 mEq/L), management becomes an immediate priority. We must first stabilize the myocardium with calcium, then shift potassium intracellularly using b-agonists, insulin with dextrose, and, sometimes, bicarbonate, depending on the clinical picture. However, the most effective way to prevent recurrence is removal of excess potassium. While diuretics can help, a novel potassium binder is often necessary. If rapid action is needed, I tend to choose SZC.

Ultimately, recognizing the trajectory of potassium and applying a staged, guideline-informed strategy is crucial for effective management.

DT: What are the signs or symptoms that signal an escalation in treatment is needed?

Riello:Although hyperkalemia is often asymptomatic, the presence of symptoms should prompt immediate intervention. Neuromuscular symptoms—fatigue, muscle weakness, paresthesias—are red flags. From a cardiology perspective, ECG changes are critical, especially in the absence of recent potassium laboratory values or when levels are only borderline.

Even in the absence of symptoms, any potassium level above 6.0 mEq/L is concerning and warrants escalation. After acute treatment, patient education remains essential. They must understand the potential symptoms and the seriousness of the condition, even when they feel fine. Empowering patients to recognize and report subtle signs is part of effective long-term management.

DT: How can pharmacists engage patients to improve understanding and management of hyperkalemia, especially given that it is often asymptomatic until severe?

Riello: The number 1 goal is to demystify potassium. Patients often feel fine even with elevated potassium levels, which makes education critical. Symptoms typically drive health care engagement—if patients feel well, they may not follow up or seek laboratory testing. Pharmacists must emphasize that hyperkalemia can be silent but life-threatening.

Patients with heart failure or CKD are at risk from both disease progression and iatrogenic causes—especially RAAS inhibitors, which are vital to care. Pharmacists should help patients understand this dual risk. While some providers issue just-in-case potassium binder prescriptions, I prefer either acute or chronic management with active follow-up. As-needed prescriptions rarely translate to improved
outcomes without structured monitoring.

Pharmacists should counsel patients on medication safety, potential interactions, and dietary potassium sources—even if we are not dietitians, we can explain how certain foods or salt substitutes can affect potassium. Patients often do not view these as medical interventions and may not volunteer this information unless asked directly.

Encouraging patient awareness of subtle symptoms—such as weakness, palpitations, or muscle cramps—is essential. With wearable technologies, like smart-watches offering ECG capabilities, some patients even self-identify rhythm changes. While not a substitute for clinical evaluation, these technologies can enhance engagement. Ultimately, we want patients to recognize that hyperkalemia, though often silent, can be dangerous—and to know when to seek help.

DT: When a patient with heart failure or CKD on optimal RAAS inhibitor therapy develops hyperkalemia, how do you balance the competing risks of reducing RAAS inhibition versus managing the hyperkalemia?

Riello: I often say this is as serious as cancer. The therapeutic benefit of GDMT in heart failure—and soon in CKD—is comparable to that of chemotherapy. Mortality rates in heart failure can exceed 50%, and GDMT reduces both mortality and morbidity, with a number needed to treat of less than 4 over 2 years.

Given that 2 of the 4 pillars of GDMT increase the risk of hyperkalemia, we must be vigilant. Sometimes, it is possible to make intra-class substitutions. For instance, finerenone may carry a lower hyperkalemia risk than spironolactone. Sacubitril/valsartan (angiotensin receptor/neprilysin inhibitor) has shown lower rates of severe hyperkalemia compared to ACEi or ARBs, possibly due to its natriuretic effect.

Adding an SGLT2 inhibitor can also mitigate the hyperkalemia risk and improve tolerance to GDMT. If needed, potassium binders like patiromer or SZC can enable patients to reach and maintain target doses of all 4 GDMT pillars. We have high-quality evidence supporting this approach in both heart failure and CKD populations.

Guideline thresholds vary—5.0 mEq/L for Europe and 5.5 mEq/L in the US—but individualizing decisions is essential. The key is to be proactive and use every available tool to get patients on life-saving therapies.

DT: What prevention and surveillance protocols for hyperkalemia can be implemented in chronic disease management programs to assist pharmacists and other health care professionals?

Riello: Hyperkalemia management can be integrated into collaborative pharmacy practice models with built-in surveillance protocols. For example, pharmacists can be authorized to order potassium labs at regular intervals based on titration protocols for GDMT.

At my institution, pharmacists help manage heart failure with reduced ejection fraction and are increasingly involved in heart failure with preserved ejection fraction. Our protocols include specific monitoring parameters for potassium and allow pharmacists to independently adjust therapy based on those results. We have seen consistently better outcomes in pharmacist-led GDMT clinics compared with usual care.

Additionally, pharmacists often serve as EHR stewards, building and maintaining order sets and pre-checks for monitoring labs. By integrating potassium surveillance into smart sets and collaborative protocols, we ensure timely laboratory monitoring and early identification of elevated potassium levels. One study I led, PROMPT-MRA (NCT04903717), showed that a proactive approach including binder use and pharmacist-led intervention can reduce future hyperkalemia and enable patients to reach GDMT targets more reliably.

DT: What are the most significant barriers that interfere with applying clinical guidelines for hyperkalemia management?

Riello: The 2 biggest barriers are therapeutic inertia and health system fragmentation. Guidelines do not implement themselves. Without infrastructure and incentives—or ideally, standardized EHR systems—it is difficult to translate evidence-based recommendations into routine care.

We need algorithmic, EHR-integrated solutions that prompt clinicians toward best practices. In our PROMPT-MRA study, we developed EHR tools to engage busy primary care providers during brief visits and help guide care. These tools are especially helpful when clinicians are juggling multiple care priorities and documentation requirements.

Looking ahead, we must use technology to support clinical decision-making, overcome inertia, and close care gaps. Too often, life-saving therapies are prematurely discontinued due to transient hyperkalemia, or spironolactone is erroneously listed as an allergy. Having potassium binders available as a safety net can prevent such decisions.

To apply guidelines effectively, we must commit to individualized care, supported by system-level tools and collaborative practice models. The challenge is substantial—but the payoff in patient outcomes is well worth it.