https://orcid.org/0000-0002-7093-6221
Figures
Abstract
Introduction
Hyperkalemia is a potentially life-threatening condition that requires prompt intervention to prevent cardiac complications. While insulin and glucose administration remains a cornerstone of treatment, inhaled β2-adrenergic agonists have been proposed as a complementary or alternative strategy, particularly in emergency settings. This scoping review aimed to describe the utility of inhaled β2-agonists in lowering serum potassium levels in adult patients.
Methods
A scoping review was conducted following the PRISMA-ScR guidelines and the Joanna Briggs Institute methodology. Experimental studies published within the past ten years evaluating the use of inhaled β2-agonists in adult patients with hyperkalemia were included. Five studies were analyzed (three randomized controlled trials and three quasi-experimental studies), assessing dosage, route of administration, magnitude of potassium reduction, and reported adverse events.
Results
Most studies used nebulized salbutamol at a dose of 10 mg, with observed reductions in serum potassium ranging from 0.62 to 1.636 mEq/L, and a peak effect between 1 and 4 hours post-administration. One study also reported the use of levalbuterol. The most common adverse effects were tachycardia, dizziness, and mild hyperglycemia, all of which were clinically manageable. Efficacy was demonstrated in both patients with chronic kidney disease and in individuals with normal renal function.
Conclusion
Inhaled β2-agonists, particularly nebulized salbutamol, represent an effective and safe therapeutic option for the acute reduction of serum potassium in adults with hyperkalemia. Their rapid onset of action and applicability across various patient profiles make them a valuable tool in emergency settings, especially where immediate access to advanced therapies such as dialysis is limited. Further research is warranted to evaluate long-term outcomes, safety in patients with cardiovascular comorbidities, and optimal dosing strategies.
Citation: Arzayus-Patiño L, Hinojosa-Angulo AY, Rodríguez-Angulo KA, Sánchez-Caicedo MA, Benavides-Córdoba V (2026) Utility of inhaled β2-agonists in reducing serum potassium levels in adult patients with hyperkalemia: A scoping review. PLoS One 21(2): e0342309. https://doi.org/10.1371/journal.pone.0342309
Editor: Mogamat-Yazied Chothia, Stellenbosch University Faculty of Medicine and Health Sciences, SOUTH AFRICA
Received: September 26, 2025; Accepted: January 20, 2026; Published: February 3, 2026
Copyright: © 2026 Arzayus-Patiño et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript.
Funding: This research has been funded by Direccion General de Investigaciones of Universidad Santiago de Cali under call No. DGI-01-2026. This funding is solely for the purpose of paying for open access for all individuals, should the manuscript be published. The funders did not participate in the study design, data collection and analysis, the publication decision, or the preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Potassium is a key electrolyte responsible for proper cellular function, particularly in muscles and nerves. It plays a crucial role in regulating heart rhythm, muscle contraction, and nerve impulse transmission. Additionally, the kidneys play a vital role in maintaining potassium homeostasis, regulating its excretion through urine
Both hypokalemia and hyperkalemia can have serious health consequences, including cardiac arrhythmias, muscle weakness, and fatigue. This imbalance disrupts the electrical stability of cells, especially in the myocardium, potentially leading to life-threatening arrhythmias and even cardiac arrest if not promptly treated. Potassium plays a fundamental role in maintaining the resting membrane potential of excitable cells, including cardiac conduction tissue and skeletal muscle fibers, thereby preserving normal electrical signaling [1,2].
Hyperkalemia is defined as a serum potassium concentration above the normal range, typically exceeding 5.0 to 5.5 mEq/L [3]. Its critical role in cellular repolarization is mediated by the sodium-potassium ATPase pump, meaning that any alteration in potassium levels can significantly impair this process, increasing the risk arrhythmias and cardiac arrest [4].
The most common cause of hyperkalemia in adults is impaired renal potassium excretion, most often resulting from chronic kidney disease or acute kidney injury. When renal excretion of excess potassium is impaired, potassium accumulates in the bloodstream certain medications including angiotensin-converting enzyme inhibitors (ACEIs), potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs) may also contribute to the development of hyperkalemia [4].
Additional risk factors include poorly controlled diabetes mellitus, adrenal insufficiency, and conditions associated with massive cellular breakdown, crush injury or rhabdomyolysis [5]. Early identification and prompt treatment of hyperkalemia are critical to preventing serious complications. Rapid correction is essential to avoid arrhythmia and cardiac arrest [5].
Despite its high prevalence and clinical significance, management of hyperkalemia varies across clinical guidelines, which differ in thresholds for intervention, preferred pharmacologic agents, and strategies for urgent versus definitive management [6]. Patients receiving renin-angiotensin-aldosterone system inhibitors or mineralocorticoid receptor antagonists, key therapies in cardiovascular disease are particularly vulnerable, with many experiencing recurrent hyperkalemia. This often leads to dose reduction or discontinuation, potentially compromising cardiovascular outcomes [1,4]. Management in adults requires a multidisciplinary approach focused on identifying and treating the underlying cause while implementing immediate interventions to lower serum potassium levels and prevent cardiovascular complications. Continuous electrocardiographic (ECG) monitoring is essential to detect and manage potentially life-threatening arrhythmia [5].
Initial treatment often includes intravenous calcium gluconate, which, although it does not reduce serum potassium levels, stabilizes the cardiac membrane and provides protection against arrhythmias resulting from excessive repolarization. Concurrently, agents such as insulin with glucose are administered to promote the intracellular shift of potassium, temporarily lowering its serum concentration. Potassium-binding resins, such as sodium polystyrene sulfonate, aid in intestinal elimination of potassium. In severe cases, hemodialysis remains the most effective and rapid method for significantly lowering serum potassium levels [6]. Finally and the focus of this review—β2-adrenergic agonists have also been proposed for this purpose.
β2-adrenergic agonists, commonly used to manage bronchospasm in respiratory conditions, exert their effects by activating Gs protein-coupled β2-adrenergic receptors, stimulating adenylate cyclase, and increasing cyclic AMP (cAMP) production from ATP. cAMP activates protein kinase A (PKA), which phosphorylates and stimulates Na ⁺ /K ⁺ -ATPase activity, thereby enhancing potassium uptake into cells. Additionally, PKA modulates voltage-gated potassium channels, reducing potassium efflux and promoting intracellular redistribution [7]. Through this mechanism, β2-agonists have been repurposed as adjunctive agents in hyperkalemia management, aligning with the drug repurposing strategy [8]. Their administration, typically via inhalation, is theoretically a practical and accessible therapeutic option [9].
Although β₂-adrenergic agonists are generally well tolerated, they should be used with caution in patients with underlying cardiac conditions, as they may increase heart rate and produce other side effects due to β₁-receptor activation in the myocardium. This effect is likely related to the higher doses required to achieve potassium lowering, which are often two to four times greater than those used for the treatment of bronchospasm [9].
The potential benefit of β2-agonists in the management of hyperkalemia has been explored in several studies [10]. However, uncertainty remains regarding whether inhaled administration of these agents consistently produces a clinically meaningful reduction in serum potassium, and the optimal dose and frequency of administration are yet to be established [10]. In Colombia, limited access to specialized treatments such as hemodialysis especially in rural areas due to geographic constraints underscores the importance of identifying alternative initial management strategies. Early administration of inhaled β2-agonists may provide a temporizing measure to stabilize patients while definitive treatment is arranged. Although this approach may not match the efficacy of hemodialysis in correcting severe hyperkalemia, it may buy critical time and reduce the risk of fatal cardiac complications, potentially improving survival in resource-limited settings [1].
The objective of this review is to map and describe the current literature on short-acting inhaled β2-adrenergic agonists in adult patients with hyperkalemia, focusing on their effects in reducing serum or plasma potassium levels, and to identify existing evidence gaps.
Methods
This scoping review was conducted following the guidelines outlined in the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist, ensuring methodological transparency and rigor. In addition, the methodological framework proposed by the Joanna Briggs Institute (JBI) was applied, which includes the following phases: formulation of the research question, identification of relevant studies, study selection, data extraction, synthesis of findings, and reporting of results and conclusions.
Research question
To guide the scoping review, the following research question was formulated:
What is the existing evidence on the use of short-acting inhaled β2-adrenergic agonists in adult patients with hyperkalemia?
The question was structured based on the PCC framework:
P (Population): Adult patients with hyperkalemia
C (Concept): Use of short-acting β2-adrenergic agonists
C (Context): Clinical management of hyperkalemia
Selection criteria
Inclusion criteria.
To identify relevant studies, a literature search was conducted based on the research question. Studies were selected if they met the following inclusion criteria:
- Primary research articles, systematic reviews, expert recommendations, gray literature, and both qualitative and quantitative studies
- No restriction on publication date
- Publications in English, Spanish, or Portuguese
- Studies, published or unpublished, that addressed the research question in a relevant manner
Information sources
Based on the research question, a comprehensive literature search was conducted in the following electronic databases: PubMed, Google Scholar, Scopus, MEDLINE, and SciELO. Relevant keywords and standardized descriptors were defined using Medical Subject Headings (MeSH) and Descritores em Ciências da Saúde (DeCS). Reference lists from included articles were also reviewed to identify additional relevant sources.
Search strategy
The search strategy combined controlled vocabulary and free-text terms. Standardized descriptors such as MeSH and DeCS were employed, together with specific keywords in English, Spanish, and Portuguese, to construct precise search strings tailored to each database. Keywords were organized according to the PIO structure (Population, Intervention, Outcome), as shown in Table 1, which facilitated the development of search equations based on thesauri descriptors and qualifiers. The specific search strings applied in each database are detailed in Table 2.
This comprehensive approach enhanced both the accuracy and completeness of study identification. To ensure thoroughness, the automated search was complemented by a manual review of the reference lists of the included studies, as well as an advanced search using additional keywords. The literature search was conducted between September 2024 and March 20DeCS – MESH25, with the last update performed in March 2025.
To initiate the search, concepts were standardized using the databases available through the Virtual Health Library (VHL) portal and PubMed. Subsequently, an advanced bibliographic search was conducted in the databases listed in Table 2, using DeCS/MeSH terms in English, Spanish, and Portuguese, and a specific search equation tailored to each database.
Selection of sources of evidence
The search was conducted by three researchers. The processes of identification, screening, and eligibility assessment were carried out through consensus among the investigators. A fourth researcher was involved to verify the effectiveness of the search strategy and to resolve any discrepancies.
Data extraction
Once the articles were identified, the researchers performed a critical reading and compiled a descriptive table with the relevant data from each study. One team member analyzed and reviewed the articles to confirm their relevance and compliance with the inclusion criteria. No discrepancies were reported among the reviewers during this process. Table 3 presents the characteristics of each included study, including author, year, country, objective, population and sample size, study design, evaluated variables, dosage and frequency, medication and type, results, and conclusion. Duplicate articles were removed, and additional studies were filtered based on the information provided.
Critical appraisal
Risk of bias was assessed using two specific tools according to the study design. For randomized controlled trials, the ROB 2 (Risk of Bias 2.0) tool was used, which is designed to evaluate bias in studies with random allocation of participants. For single-group experimental studies, the Joanna Briggs Institute (JBI) checklist for before-and-after studies without control groups was applied. Each tool allows for the identification and categorization of potential biases across various domains, ensuring a structured and rigorous analysis of the methodological validity of the included studies.
Presentation of results
The results are presented in descriptive tables outlining key aspects of each study, such as author, study objective, population, sample size, medication used, dosage, observed effect, main outcomes, and conclusions. Additional tables summarize the search strategy, including the search equations used (Table 3), and the final number of studies included. A flow diagram (Fig 1) illustrates the search process and final number of studies retained for analysis.
Results
A total of 668 studies were identified. After initial screening by title and abstract, inclusion and exclusion criteria were applied, leading to the exclusion of 659 studies. Ultimately, 5 articles were included in the review (Fig 1).
All included studies were experimental in design. Three were randomized controlled trials (RCTs) that compared the use of inhaled β2-agonists with either placebo or intravenous administration [11,12], while the remaining three were quasi-experimental studies without control groups [13–15]. All of them evaluated the effectiveness of β2-agonists in reducing serum potassium levels.
The included studies evaluated the intervention of inhaled β2-agonists in a total of 161 patients for the management of hyperkalemia. The most commonly used drug was salbutamol; however, one study included the use of levalbuterol. No studies reported the use of other β2-agonists such as fenoterol or terbutaline. Regarding the mode of administration, nebulization was the predominant method, with only one study reporting the use of a metered-dose inhaler (MDI) [11].
The most frequently reported dose of nebulized salbutamol in RCTs was 10 mg, although one study used a higher dose of 20 mg. In the study using MDI, a single dose of 1,200 mcg was administered [11].
The analyzed studies showed that β2-agonists effectively reduced serum potassium levels, with variations in the magnitude and duration of the effect depending on the dose and route of administration. In general, the reduction in potassium was observed between 5 and 30 minutes after administration, with the peak effect occurring between 1 and 4 hours. Nebulization may offer an effective route, with the available studies reporting sustained reductions in potassium concentration (studies 5 and 6) [12,15]. A mean decrease ranging from 0.62 to 0.98 mEq/L was reported with 10–20 mg of nebulized albuterol (study 4) [14], and up to 1.636 mEq/L in responsive patients (study 3) [13]. In contrast, the study using 1,200 mcg via MDI reported a transient increase in potassium at the onset of treatment, followed by a progressive decline (study 1) [11].
Across the included studies, adverse events were generally mild and occurred at low frequency when percentages were reported. Rojas García et al. documented tachycardia in 12.1% of patients treated via micronebulization and in 9.1% of those receiving intravenous administration, as well as headache (3%) and dizziness (4.5% in the nebulization group and 3.1% in the intravenous group). Regarding non-responders, Karuna Sree et al. identified two patients who did not exhibit a reduction in serum potassium, while Liou et al. reported a non-response rate of 33.3% in the intravenous group (5/15), with full response in the nebulized group. The remaining studies did not quantify non-response, although they consistently reported overall reductions in serum potassium levels [11,14,15].
The duration of the hypokalemic effect of β2-agonists was evaluated, with one study showing a sustained reduction in potassium for at least 2 hours [14], another reporting a prolonged effect up to 180 minutes [15], and another documenting peak efficacy within the first 4 hours [13].
To facilitate comparison between studies, a summary table (Table 4) was added that highlights key patterns related to dose, route of administration, magnitude of potassium reduction, time to maximum effect, and reported safety outcomes, as well as available information on non-responder patients.
The risk of bias was assessed using the ROB 2 tool. All three RCTs showed low risk in most domains, with only one domain showing some concerns, indicating high methodological quality with a mild degree of uncertainty Fig 2. The quasi-experimental studies evaluated using the Joanna Briggs Institute checklist demonstrated moderate to high methodological quality, reflecting rigor in both design and execution Table 5.
Discussion
The objective of this review was to describe and analyze the available evidence regarding the benefits of β2-agonist administration in the management of hyperkalemia in adult patients. The findings suggest that inhaled β2-agonists may help reduce serum potassium over a short period of time, although the limited number of studies and small sample sizes mean that these results should be interpreted cautiously. The magnitude and duration of the effect vary across studies, raising questions about the factors that influence their efficacy.
These results highlight the need to further explore the impact of dosage, route of administration, and patient characteristics on treatment response. The reduction in serum potassium following β₂-agonist administration is primarily mediated by stimulation of β₂-adrenergic receptors in skeletal muscle, leading to activation of the Na ⁺ /K ⁺ -ATPase pump and subsequent intracellular shift of potassium [9]. This transcellular redistribution contributes to membrane repolarization and explains the hypokalemic effect observed with β₂-agonists. This mechanism has been supported by previous studies and by the consensus of the Spanish Society of Nephrology, which recommends β₂-adrenergic agonists as a strategy for managing hyperkalemia and emphasizes their role in regulating transcellular potassium movement, particularly when combined with other agents such as insulin to enhance therapeutic efficacy [16].
Among the β2-agonists used for lowering serum potassium, the reviewed studies exclusively mentioned salbutamol (also known as albuterol, depending on the region) and levalbuterol, a purified form of salbutamol. However, levalbuterol current evidence does not suggest meaningful superiority to salbutamol in terms of clinical efficacy or safety, although it is associated with a higher cost [17,18]. Therefore, its cost-effectiveness favors the implementation of salbutamol in clinical settings.
No clinical studies were found evaluating potassium reduction with other short-acting β2-adrenergic agonists such as fenoterol or terbutaline, which limits the ability to reliably extrapolate the hypokalemic effects of these agents. While some studies have suggested that fenoterol may have greater bronchodilator potency, it also exhibits lower β2-receptor selectivity, potentially increasing adverse effects related to β1-receptor activation in the heart, such as tachycardia and palpitations [19,20]. Although the hypokalemic mechanism of action may be similar across different β2-agonists, the absence of specific clinical evidence, limits the ability to determine equivalence, in efficacy and safety for hyperkalemia management.
Most studies included in this review used jet nebulizers, with only one study reporting the use of a metered-dose inhaler (MDI). This contrasts with routine respiratory practice, where MDIs are more prevalent. Although some studies have shown that MDIs with spacers may achieve effective pulmonary drug deposition at lower doses of salbutamol in the management of acute bronchospasm [21], a systematic review reported no significant differences in clinical effectiveness between MDIs and nebulizers in patients with COPD [22]. In the context of hyperkalemia management where patients typically do not present with acute respiratory failure the choice of delivery method appears to be influenced more by practicality, availability, and ease of use than by demonstrated differences in potassium-lowering efficacy.
In the reviewed studies, the doses of β2-agonists used to lower serum potassium were higher than those typically employed for respiratory conditions. This reflects the need for a more pronounced and rapid hypokalemic effect in the management of hyperkalemia, while highlighting that direct comparisons between delivery methods should be interpreted cautiously due to differences in drug administration efficiency [23–25].
Although in the context of respiratory crises the frequency of administration is usually higher, with intervals of only a few minutes between doses, the studies in the hyperkalemia literature generally evaluate a single administration. Thus, it cannot be concluded that both routes are equivalent in terms of a single dose, which may justify the use of higher drug doses. However, this difference in dosing underscores the need for caution when comparing equivalence between nebulization and MDI delivery.
It is not appropriate to directly extrapolate a 10 mg dose of nebulized salbutamol to its equivalent via metered-dose inhaler (MDI), as this would require 10,000 mcg (100 inhalations), considering that commercial devices typically deliver 100 mcg per actuation. The discrepancy in required dosing between both delivery systems may be attributed to differences in drug delivery efficiency: in nebulization, a significant portion of the drug is not effectively inhaled due to factors such as the patient’s respiratory pattern, variability in inspiratory and expiratory times, and the flow rate when administered in combination with supplemental oxygen [26]. Therefore, there is currently no evidence to support the recommendation of doses greater than 1,200 mcg via MDI for potassium-lowering purposes, whereas 10 mg via nebulization remains the most widely used and documented dose in the available literature.
When analyzing the reduction in serum potassium, this finding is clinically meaningful, as it may help prevent severe complications associated with hyperkalemia, particularly cardiac electrical disturbances that impair effective myocardial contraction. One study in particular demonstrated not only a decrease in serum potassium levels but also normalization of electrocardiographic abnormalities, suggesting restoration of cardiac electrical activity [27]. Importantly, these transient and reversible improvements in cardiac conduction may provide critical time for healthcare teams to stabilize the patient, address the underlying cause most commonly renal dysfunction, with or without impaired potassium elimination due to medications and initiate definitive management, including transfer to centers where advanced therapies such as dialysis are available [15,27,28].
These findings align with previous studies, such as those by Allon et al., which recommend the combined use of β₂-agonists with insulin and glucose as part of so-called polarizing therapies. This combination exerts a synergistic effect by enhancing the intracellular shift of potassium through complementary activation of the Na ⁺ /K ⁺ -ATPase, thereby improving acute control of hyperkalemia. Despite these positive effects, β₂-agonists are not widely adopted in routine practice, likely due to concerns regarding cardiovascular safety, variability in guideline recommendations, and the lack of recent high-quality clinical trials.
From a clinical standpoint, the relatively rapid onset and moderate duration of the hypokalemic effect observed with β₂-agonists support their role as a temporizing measure in the acute management of hyperkalemia. The potassium-lowering effect, which has been reported to persist for approximately 2–4 hours on average, may allow clinicians to stabilize patients while diagnostic evaluation is completed and definitive therapies are arranged. This temporal profile is particularly relevant in emergency and resource-limited settings, including rural areas, where immediate access to renal replacement therapy may not be available. In such scenarios, β₂-agonists can provide a temporary stabilizing effect, reducing the risk of life-threatening complications and allowing critical time for the initiation of definitive treatment [11–15,27].
In comparison with other studies in the literature, there is consistency regarding the rapid onset and moderate duration of the hypokalemic effect of β₂-agonists, reinforcing their usefulness in the acute management of hyperkalemia. However, it is important to consider individual patient characteristics and potential contraindications, such as unstable angina or acute myocardial infarction, in which the use of β₂-agonists is contraindicated. Additionally, studies conducted in healthy individuals, such as that by Pancu et al. [27]., provide complementary evidence supporting the previously described mechanism. Their findings demonstrated a potassium-lowering effect following β₂-agonist administration even in individuals without hyperkalemia, reinforcing that the transcellular shift induced by β₂-receptor activation is a consistent physiological phenomenon. Although these results are not directly generalizable to clinical populations, they contribute to understanding the biological basis underlying the therapeutic use of these agents.
In terms of safety, the reviewed studies reported adverse effects such as tachycardia, headache, dizziness, and elevated blood glucose levels [13–15]. These events may be explained by cross-activation of cardiac β₁-receptors, despite the fact that the β₂-adrenergic agents used have predominant selectivity for pulmonary β₂-receptors [29,30]. Theoretically, this activation may primarily induce tachycardia as well as symptoms related to peripheral vasodilation, such as headache and dizziness. Additionally, blood glucose elevation is associated with β₂-receptor stimulation in extrapulmonary tissues, particularly in the liver, where it increases glycogenolysis and gluconeogenesis, leading to transient hyperglycemia. Similar results have been documented in studies involving patients with diabetes, showing mild and transient increases in blood glucose following β₂-agonist administration, although these changes were not considered clinically relevant. In this context, the modest hyperglycemic effect of β₂-agonists may be clinically relevant when these agents are co-administered with insulin and dextrose, as it could theoretically mitigate the risk of hypoglycemia a well-recognized complication of insulin-based therapy for hyperkalemia. However, this potential benefit has not been systematically evaluated and should therefore be interpreted with caution.
Other commonly reported adverse effects include muscle tremors, anxiety, and muscle cramps. These side effects are generally transient and tend to diminish with dose adjustment or continued exposure. However, they should be monitored, especially in patients with pre-existing conditions such as cardiovascular disease or diabetes [26,31]. Overall, in the included studies, these side effects were temporary, clinically manageable, and not associated with serious complications or major clinical events. Importantly, no cases of myocardial ischemia or acute coronary events were reported, which may be related to the short-term use of β₂-agonists, the predominance of single-dose protocols, and the exclusion of patients with unstable cardiac conditions in most studies. Together, these findings suggest that administration of these medications is safe when no contraindications are present.
An important finding highlighted by Liou et al. was the presence of a subgroup of non-responders, with approximately one third of patients in the intravenous salbutamol group showing no significant reduction in serum potassium. From a clinical perspective, this lack of response may reflect the heterogeneity of patients with hyperkalemia, particularly those with advanced renal dysfunction, severe metabolic disturbances, or high baseline potassium levels, in whom transcellular potassium shifts alone may be insufficient to produce a measurable effect. Other contributing factors may include interindividual variability in β₂-adrenergic receptor sensitivity, the presence of concomitant acid–base disorders, or the use of medications that limit intracellular potassium uptake. In patients with chronic disease, functional desensitization of β₂-receptors may further attenuate the expected response. These observations reinforce the importance of recognizing that β₂-agonists are not uniformly effective across all clinical scenarios and should be considered as a supportive, temporizing intervention within a multimodal strategy for the management of hyperkalemia [15,32,33].
Several studies have evaluated the combination of β2-adrenergic agonists with insulin and glucose for the treatment of hyperkalemia, reporting results similar to those observed in the present investigation [9]. The administration of insulin with glucose has proven effective in lowering serum potassium due to its ability to promote potassium uptake into the intracellular space. However, this treatment carries a higher risk of hypoglycemia [33], requiring frequent and strict blood glucose monitoring. On the other hand, given the demonstrated efficacy of β2-adrenergic agonists when administered alone, and their lower need for monitoring, Emmanuel Montassier, in a letter to the editor [34], has suggested prioritizing these agents for the initial management of hyperkalemia in emergency settings, especially where intensive glycemic control may be complex or limited. This suggests that both therapeutic strategies may be effective; however, β₂-agonists may represent a more practical initial option in certain clinical scenarios where resources for close monitoring and prevention of hypoglycemia are limited. Nevertheless, caution is warranted, as it has been reported that approximately 20–40% of patients receiving nebulized β₂-agonists experience a reduction in serum potassium of less than 0.5 mEq/L [35]. In such contexts, the use of complementary strategies may be necessary and could potentially yield better clinical outcomes.
It is important to note that the study by Karuna Sree et al. included patients with hyperkalemia in an acute clinical context, consistent with acute kidney injury (AKI). This clarification is relevant because the therapeutic response to β₂-agonists may differ depending on whether hyperkalemia occurs in the setting of AKI or chronic kidney disease (CKD). Nevertheless, the study’s findings show that the expected potassium-lowering response is also observed in an acute scenario, supporting the use of β₂-agonists beyond populations with chronic or recurrent hyperkalemia and positioning them as a particularly valuable option in settings where immediate access to advanced interventions is not feasible.
Among the strengths identified in this review are the rigorous methodology employed, including a clearly defined systematic search strategy and a thorough risk of bias assessment for each included study, which contribute to the robustness, transparency, and reliability of the presented results.
Nevertheless, several limitations should be acknowledged. Most of the reviewed studies involved relatively small sample sizes and short follow-up periods, which hinder definitive conclusions regarding the duration of the potassium-lowering effect and the optimal dosing frequency when repeat administration is needed. Additionally, the lack of research in patients with serious comorbidities, especially cardiovascular or pulmonary disease, limits the generalizability of the results to more vulnerable populations. Therefore, the findings should be interpreted with caution in these clinical contexts. Future research should involve larger sample sizes and longer follow-up, with particular focus on trials in non-dialysis emergency populations, determination of optimal dosing, direct comparisons with insulin/glucose regimens, and comprehensive evaluations of cardiovascular safety, including the effects of higher doses in patients with concurrent cardiovascular conditions. Addressing these gaps will help improve the generalizability and clinical applicability of β₂-agonist therapy for hyperkalemia.
Conclusion
The inhaled administration of β2-adrenergic agonists, particularly nebulized salbutamol, appears to reduce serum potassium acutely in adult patients with hyperkalemia, this therapy may be considered as a temporising measure in emergency situations, particularly where access to advanced treatments such as dialysis is limited. Careful monitoring for potential adverse effects, including tachycardia and hyperglycemia, is recommended. Further high-quality studies are needed to confirm these findings and better define optimal dosing, safety, and comparative efficacy.
References
- 1. Rico-Fontalvo J, Rodríguez-González MJ, Yama EY, Gallego C, Montejo-Hernández J, Martínez EM, et al. Chronic hyperkalemia, diagnosis and management. Colombian consensus. Arch Cardiol Mex. 2023;93(Supl):1–12. pmid:37913795
- 2.
El potasio y para qué sirve ¿qué es. Datos sobre el potasio. Nih.gov. https://ods.od.nih.gov/pdf/factsheets/Potassium-DatosEnEspanol.pdf. Accessed 2024 October 1.
- 3.
Simon LV, Hashmi MF, Farrell MW. Hyperkalemia. Treasure Island (FL): StatPearls Publishing. 2025.
- 4. Gupta AA, Self M, Mueller M, Wardi G, Tainter C. Dispelling myths and misconceptions about the treatment of acute hyperkalemia. Am J Emerg Med. 2022;52:85–91. pmid:34890894
- 5. Irizar-Santana S, Kawano-Soto CA, López ED, López-Ceja M. Hiperkalemia: artículo de revisión. Revista Médica UAS. 2023;6(3).
- 6. Kim HJ. Acute therapy for hyperkalemia with the combined regimen of bicarbonate and beta(2)-adrenergic agonist (salbutamol) in chronic renal failure patients. J Korean Med Sci. 1997;12(2):111–6. pmid:9170015
- 7. Souma H, Takada A, Saitoh M, Ishikawa K, Chida S. Efficacy of salbutamol inhalation for hyperkalemia. Nihon Shoni Jinzobyo Gakkai Zasshi. 2005;18(2):101–4.
- 8. Benavides-Cordoba V. Drug Repositioning for COVID-19. Colomb Med (Cali). 2020;51(2):e4279. pmid:33012890
- 9. Allon M, Copkney C. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Kidney Int. 1990;38(5):869–72. pmid:2266671
- 10. Montoliu J, Lens XM, Revert L. Potassium-lowering effect of albuterol for hyperkalemia in renal failure. Arch Intern Med. 1987;147(4):713–7. pmid:3827459
- 11. Mandelberg A, Krupnik Z, Houri S, Smetana S, Gilad E, Matas Z, et al. Salbutamol metered-dose inhaler with spacer for hyperkalemia: how fast? How safe? Chest. 1999;115(3):617–22. pmid:10084465
- 12.
Rojas García MJ. Eficacia del salbutamol vía intravenosa vs. vía micronebulizador para el tratamiento de la hiperkalemia aguda en el paciente con insuficiencia renal crónica sin tratamiento sustitutivo. Ciudad de México: Instituto Politécnico Nacional, Escuela Superior de Medicina. 2010.
- 13. Karuna Sree N, Narasimha Rao R. Salbutamol nebulization in the treatment of hyperkalemia. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=fac02c0994741f450730e7f2959ac6c1b774ee04. Accessed 2025 March 7.
- 14. Allon M, Dunlay R, Copkney C. Nebulized albuterol for acute hyperkalemia in patients on hemodialysis. Ann Intern Med. 1989;110(6):426–9. pmid:2919849
- 15. Liou HH, Chiang SS, Wu SC, Huang TP, Campese VM, Smogorzewski M, et al. Hypokalemic effects of intravenous infusion or nebulization of salbutamol in patients with chronic renal failure: comparative study. Am J Kidney Dis. 1994;23(2):266–71. pmid:8311086
- 16. Ortiz A, del Arco Galán C, Fernández-García JC, Gómez Cerezo J, Ibán Ochoa R, Núñez J, et al. Documento de consenso sobre el abordaje de la hiperpotasemia. Nefrología. 2023;43(6):765–82.
- 17. Jat KR, Khairwa A. Levalbuterol versus albuterol for acute asthma: a systematic review and meta-analysis. Pulm Pharmacol Ther. 2013;26(2):239–48. pmid:23207739
- 18. Ameredes BT, Calhoun WJ. Levalbuterol versus albuterol. Curr Allergy Asthma Rep. 2009;9(5):401–9. pmid:19671384
- 19. Mearin F, Guarner F, Verdú E. Probiotics and the digestive system. Current evidence. Gastroenterol Hepatol. 2009;32 Suppl 1:1–14. pmid:19524118
- 20. Barjaktarevic IZ, Milstone AP. Nebulized Therapies in COPD: Past, Present, and the Future. Int J Chron Obstruct Pulmon Dis. 2020;15:1665–77. pmid:32764912
- 21. Iramain R, Castro-Rodriguez JA, Jara A, Cardozo L, Bogado N, Morinigo R, et al. Salbutamol and ipratropium by inhaler is superior to nebulizer in children with severe acute asthma exacerbation: Randomized clinical trial. Pediatr Pulmonol. 2019;54(4):372–7. pmid:30672140
- 22. van Geffen WH, Douma WR, Slebos DJ, Kerstjens HAM. Bronchodilators delivered by nebuliser versus pMDI with spacer or DPI for exacerbations of COPD. Cochrane Database Syst Rev. 2016;2016(8):CD011826. pmid:27569680
- 23. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. 2024. https://ginasthma.org/2024-report/
- 24. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for Prevention, Diagnosis and Management of COPD. 2024. Disponible en: https://goldcopd.org/2024-gold-report/
- 25. Guía española para el manejo del asma. 2024. https://www.semg.es/images/2024/documentos/GEMA_54.pd
- 26. Holcombe JA. ATOMIC SPECTROMETRY | Overview. Encyclopedia of Analytical Science. Elsevier. 2005. p. 249–58.
- 27. Pancu D, LaFlamme M, Evans E, Reed J. Levalbuterol is as effective as racemic albuterol in lowering serum potassium. J Emerg Med. 2003;25(1):13–6. pmid:12865102
- 28. Peters MDJ, Godfrey C, McInerney P, Baldini Soares C, Khalil H, Parker D. Methodology for JBI Scoping Reviews. 2017. https://reviewersmanual.joannabriggs.org/
- 29. Dolen WK. The beta-2 adrenergic receptor and its agonists. Allergy Proc. 1994;15(6):283–90. pmid:7721076
- 30. Arisione G, Baroffio M, Crimi E, Brusasco V. Beta-Adrenergic Agonists. Pharmaceutics. 2010;3(4):1016–44.
- 31. König P, Goldstein D, Poehlmann M, Rife D, Ge B, Hewett J. Effect of nebulized albuterol on blood glucose in patients with diabetes mellitus with and without cystic fibrosis. Pediatr Pulmonol. 2005;40(2):105–8. pmid:15965894
- 32. Scott NL, Klein LR, Cales E, Driver BE. Hypoglycemia as a complication of intravenous insulin to treat hyperkalemia in the emergency department. Am J Emerg Med. 2019;37(2):209–13. pmid:29861377
- 33.
Hsu E, Bajaj T. Beta2-agonists. StatPearls. Treasure Island (FL): StatPearls Publishing. 2025.
- 34. Montassier E, Legrand M, Rossignol P, Potel G. Hyperkalemia in the emergency department: Consider the use of nebulized salbutamol. Am J Emerg Med. 2019;37(5):1004. pmid:30348470
- 35. Kovesdy CP. Updates in hyperkalemia: Outcomes and therapeutic strategies. Rev Endocr Metab Disord. 2017;18(1):41–7. pmid:27600582