Beta-Agonist Alternatives to Nebulized Albuterol for Treatment of Hyperkalemia

Today’s pearl provides some alternative methods to treat patients with hyperkalemia if nebulized albuterol is not an option.

What route? Which medication? How much?

The COVID-19 pandemic has made us rethink many of the practices we once took for granted. In order to minimize all aerosolizing treatments and procedures, many institutions restricted the use of nebulized medications. While this complicates the treatment of many respiratory conditions, it practically eliminates one of the primary, effective therapies we frequently employ for the treatment of hyperkalemia – nebulized albuterol 10-20 mg. Thankfully, there are two alternatives to consider.

Importantly, this pearl only applies to the beta-agonist component. Insulin and other hyperkalemia treatments should be utilized per usual.

Albuterol (INN: Salbutamol) via Metered-Dose Inhaler (MDI):

• Salbutamol Metered-Dose Inhaler With Spacer for Hyperkalemia: How Fast? How Safe? (Mandelberg, 1999)
  • Randomized, double-blinded, placebo-controlled, crossover study
  • Compared inhaled albuterol 1200 mcg via MDI with spacer vs placebo MDI with spacer in 17 hemodialysis dependent patients with serum potassium levels >5 mEq/L
    • This dose is equivalent to approximately 13 puffs of a standard albuterol MDI (90 mcg per actuation)
  • Serum potassium levels were obtained at 1, 3, 5, 10, 60 mins following inhalation
  • They found a significant increase in serum potassium at 1 minute in the albuterol group compared to placebo, but this was followed by a steady decline that led to a significantly lower potassium in the albuterol group at 5 minutes.
  • A sustained decrease persisted until at least 60 minutes post-dose, with a mean decrease of just over 0.4 mEq/L from baseline.

Subcutaneous (SQ) Terbutaline:

• Terbutaline, a selective β₂ agonist most commonly used in the ED for the treatment of patients with status asthmaticus, may be an option for the treatment of hyperkalemia.
• Subcutaneous terbutaline use in CKD to reduce potassium concentrations (Sowinski, 2005)
  • A prospective, single-arm trial that included 14 hemodialysis dependent patients who received 7 mcg/kg of SQ terbutaline.
  • Serum potassium levels were measured before terbutaline administration and regularly for the subsequent 7 hours. 
  • They found a significant reduction in potassium from baseline starting 30 mins post-dose and this persisted for 5 hours. 
  • The mean maximal decrease in potassium was 1.3 mEq/L or 25% from baseline, which occurred 75 mins post dose. 
  • All patients decreased by at least 0.5 mEq/L from baseline, up to 2.4 mEq/L.
  • The average increase in peak heart rate was ~26 bpm from baseline.
• The mean dose used in this study (0.46 mg) is significantly higher than the typical single dose used to treat patients with asthma (0.25 mg).

Intravenous epinephrine, isoproterenol, dobutamine:

• Other Intravenous beta-agonists (i.e., epinephrine, isoproterenol, and dobutamine) have data to suggest they would also lead to a reduction in serum potassium levels, but the use of these agents is discouraged for the treatment of isolated hyperkalemia given the increased risk of tachycardia and dosing errors.
  • Effect of isoproterenol on serum potassium and magnesium
  • Epinephrine-induced hypokalemia: the role of beta adrenoceptors
  • Effect of dobutamine on plasma potassium in congestive heart failure secondary to idiopathic or ischemic cardiomyopathy

Intravenous Albuterol

• Though not available in the United States, there is evidence to support the use of intravenous albuterol.
  • Hypokalemic effects of intravenous infusion or nebulization of salbutamol in patients with chronic renal failure: comparative study
  • Potassium-lowering effect of albuterol for hyperkalemia in renal failure

Oral Albuterol

• There have been no studies evaluating the use of enteral albuterol for the treatment hyperkalemia
• This is likely due to its poor bioavailability (10-20%) and slow onset (~ 30 mins).

Conclusion:

If nebulized albuterol is unavailable or unsafe, there are some alternative therapies to offer that may be equally effective.

1. If using an albuterol MDI with a spacer, the dose should be ~13 puffs of a standard 90 mcg per actuation inhaler.
2. Alternatively, if the inhaled route must be avoided or the patient is intubated, SQ terbutaline can be considered. We recommend starting with SQ terbutaline 0.25 mg; an additional SQ 0.25 mg may be administered if there is no response seen when the potassium level is repeated in ~30-60 mins.

^#44