Beta-Agonist Agents

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Beta-adrenergic agonist albuterol induces intracellular potassium movement by up-regulating the activity of Na+-K+-ATPase in skeletal muscle by a cellular pathway distinct from that caused by insulin.

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Albuterol

• Dose: Inhalation, nebulized albuterol, 10-20 mg in 4mL normal saline, inhaled over 10 minutes
• Pharmacokinetics:
  • Onset of Action: 15-30 mins
  • Duration of Effect: 2-4 hours
• Contraindications: 
• Adverse Effects: Mild tachycardia
• Pearls: Lowers serum K+ levels by ~1.0 mEq/L

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The combination of Albuterol + insulin and glucose produces a synergistic impact to lower serum K+, by 1.2–1.5 mmol/L at 1 h after medication administration

albuterol will have little effect on hyperkalemia in patients treated with non-selective β-blockers.

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Beta agonists administered intravenously is associated with more cardiovascular side effects than the nebulized route, therefore, nebulized albuterol (salbutamol) is preferred route of administration.

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Review of Literature

Allon M, Dunlay R, Copkney C. Nebulized albuterol for acute hyperkalemia in patients on hemodialysis. Ann Intern Med. 1989 Mar 15;110(6):426-9. doi: 10.7326/0003-4819-110-6-426. PMID: 2919849.

• In a study done by Allon and colleagues in 1989, the authors set out to determine the efficacy and safety of nebulized albuterol in the acute treatment of hyperkalemia in patients on chronic hemodialysis. It was a prospective, double-blind, and placebo-controlled study conducted at an outpatient hemodialysis clinic at a university medical center. The authors included 10 patients on maintenance hemodialysis who had chronic hyperkalemia. They studied patients who received nebulized albuterol therapy (10 mg or 20 mg) or placebo (saline) on three separate occasions, serial measurements of plasma potassium levels, blood pressure, and pulse were then taken for a 2-hour period. The authors found that patients had a significant decrease in plasma potassium concentrations that was evident by 30 minutes and sustained for at least 2 hours after albuterol treatment. After the administration of 10- and 20-mg doses of albuterol, the maximal decrease in the plasma potassium levels was 0.62 +/- 0.09 and 0.98 +/- 0.14 mmol/L (SE), respectively.

Lens XM, Montoliu J, Cases A, Campistol JM, Revert L. Treatment of hyperkalaemia in renal failure: salbutamol v. insulin. Nephrol Dial Transplant. 1989;4(3):228-32. doi: 10.1093/oxfordjournals.ndt.a091860. PMID: 2498781.

• In 1989, Lens and colleague conducted a study comparing the use of IV salbutamol and IV regular insulin in groups of patients with acute or chronic renal failure with a serum potassium of greater than or equal to 6 mEq/l. There were three groups that the patients were broken down into: Group A (n = 24) received salbutamol 0.5 mg IV in 15 min, group B (n = 10) received glucose 40 g IV plus 10 units insulin IV in 15 min, and group C (n = 10) received salbutamol 0.5 mg IV, glucose 40 g IV and insulin 10 units IV over a 15-min period. All treatments reduced serum potassium, maximal at 30 or 60 min, and ranging from -0.5 +/- 0.1 to -1.5 +/- 0.2 mEq/l; patients in group C exhibited a significantly greater decrement in serum potassium, when compared to group B at 60 (-1.5 +/- 0.2 vs -1 +/- 0.1 mEq/l, respectively; P less than 0.01) and 180 min (-1.2 +/- 0.2 vs -0.7 +/- 0.1 mEq/l, respectively; P less than 0.05). There were no significant differences between groups A and C. Patients from group C had moderate tachycardia and more prolonged hyperglycemia than those from group B, but all treatments were well tolerated.

Leanza HJ, Rivarola G, Graciela García M, Najun Zarazaga CJ, Casadei D. Corrección rápida de la hiperkalemia aguda con salbutamol en nebulización [Rapid correction of acute hyperkalemia with nebulized salbutamol]. Medicina (B Aires). 1992;52(2):99-102. Spanish. PMID: 1308916.

• Leanza and colleagues a conducted a study in 1992 analyzing the use of nebulized salbutamol compared to placebo in 15 patients on chronic hemodialysis with hyperkalemia with a mean serum potassium of 6.58 +- 0.14 mEq/L. The authors used 20 mg nebulized salbutamol (4 ml of 0.6 g% in 4 ml of saline) compared to saline. The authors found that plasma potassium concentration at 20, 40, 60, 90 and 180 min post-salbutamol, were: 5.85 +/- 0.21, 5.58 +/- 0.21, 5.48 +/- 0.27, 5.46 +/- 0.17 and 5.57 +/- 0.34 mEq/l, respectively. Also, decrease of plasma potassium was significant at 40′ and maximal at 90′: 1.12 +/- 0.10 mEq/l, and persisted for at least 3 hours (in 3 patients up to 6 hours). The authors reported that side effects of tachycardia, fine tremor and anxiety were moderate and well tolerated.

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 Apr;12(2):111-6. doi: 10.3346/jkms.1997.12.2.111. PMID: 9170015

• In a study done by Kim and colleagues in 1989, the authors set out to determine the efficacy of combination therapy of bicarbonate and salbutamol for hyperkalemia in 9 hemodialysis patients. Simultaneous administration of 8.4% sodium bicarbonate (IV 2 mEq/kg) for 1/2 hour and salbutamol (15 mg) in nebulized form for 10 min was compared with treatment modality of either bicarbonate or salbutamol alone. The authors found that while sodium bicarbonate impacted plasma bicarbonate levels, it did not impact serum potassium levels. salbutamol significantly lowered plasma potassium (-0.57 +/0 0.03 mEq/L, p < 0.02 vs. basal value) in all except 2 patients. The combined regimen of bicarbonate and salbutamol to a total 9 patients including 2 patients without hypokalemic effect to salbutamol alone revealed a substantially greater fall in plasma potassium (-0.96 +/- 0.08 mEq/L, p = 0.000 vs. either drug alone) accompanied with significant increase in plasma bicarbonate and blood pH.