How do inhaled beta (β)-adrenergic agonists benefit hyperkalemia?

From the Guidelines

Inhaled β-agonists, such as salbutamol, are beneficial in the management of hyperkalemia by temporarily reducing serum potassium levels through cellular redistribution, with effects lasting 2-4 hours, as noted in the most recent study 1. The mechanism of action involves stimulation of β2-adrenergic receptors, which activate the sodium-potassium ATPase pump, increasing cellular potassium uptake. This is achieved through increased cyclic AMP production, enhancing the activity of the Na+/K+ pump on cell membranes. Key points to consider in the management of hyperkalemia include:

• The use of inhaled β-agonists, such as salbutamol, typically administered as 10-20 mg via nebulizer or 4-8 puffs via metered-dose inhaler, with an onset of action within 30 minutes, peaking at 90 minutes, and reducing serum potassium by approximately 0.5-1.5 mEq/L 1.
• Combination therapy with other treatments, such as insulin with glucose, calcium gluconate, or sodium bicarbonate, may be necessary in severe cases, as inhaled β-agonists provide only transient potassium lowering 1.
• The importance of monitoring potassium levels closely, especially in patients with cardiovascular disease and chronic kidney disease, who are at higher risk of hyperkalemia, as highlighted in the expert consensus document 1. In emergency situations, inhaled β-agonists can be a useful temporary measure while arranging for more definitive treatments like dialysis in severe or refractory cases, as noted in the clinical management of hyperkalemia study 1.

From the Research

Benefits of Inhaled β-Agonists in Hyperkalemia

• Inhaled β-agonists, such as salbutamol, have been shown to reduce serum potassium levels in patients with hyperkalemia 2, 3, 4.
• The mechanism of action is thought to be mediated by the beta-2 receptors, which stimulate the Na-K-ATPase and promote the entry of potassium into skeletal muscle cells 3.
• Inhaled salbutamol has been found to be effective in reducing serum potassium levels, with a peak effect seen at 120 minutes 2.
• The use of inhaled β-agonists has been recommended as a treatment for hyperkalemia, particularly in combination with other therapies such as insulin and glucose 2, 4.

Comparison with Other Treatments

• Inhaled β-agonists have been found to be as effective as insulin-dextrose in reducing serum potassium levels 2.
• They have also been found to be more effective than bicarbonate in reducing serum potassium levels 2.
• However, the evidence for the use of calcium and bicarbonate in the treatment of hyperkalemia is limited, and they are not recommended as first-line treatments 2, 4.

Clinical Implications

• Inhaled β-agonists may be a useful treatment option for patients with hyperkalemia, particularly those who are unable to tolerate other treatments 3.
• However, the evidence for their use is largely based on small studies, and further research is needed to fully establish their efficacy and safety 2, 4.
• The use of inhaled β-agonists should be considered as part of a comprehensive treatment plan for hyperkalemia, which may include other therapies such as insulin, glucose, and potassium-binding agents 5, 6.