A 2005 Cochrane review on randomized evidence regarding the emergency management of hyperkalemia included eight studies to evaluate the efficacy of beta-agonists in the treatment of acute hyperkalemia. A dose-response relationship in maximum serum potassium reduction revealed that potassium was lower in the patients given 20 mg nebulized albuterol compared with the patients who received 10 mg albuterol at 120 minutes (p<0.05). Both albuterol and levalbuterol were equally effective in reducing potassium levels at 30 minutes and 60 minutes after drug introduction. There was no statistically significant difference between groups when comparing intravenous (IV) albuterol with nebulized albuterol. While a double-blind study by Mandelberg et al. showed paradoxical elevation of serum potassium of 0.1 mmol/L or more in 59% of patients one-minute post-administration of inhaled albuterol, potassium returned to baseline by three minutes and reached a statistically significant reduction difference compared with placebo between five and ten minutes. There was no head-to-head comparison between nebulized, IV, or metered dose inhaler albuterol. The studies were limited by small sample size, reporting surrogate outcomes for efficacy and not reporting the clinically-relevant adverse events. Additionally, given the small number of studies, the meta-analysis was underpowered to analyze heterogeneity or publication bias. The authors concluded that inhaled or nebulized beta-agonists were effective versus placebo by 30 minutes, and at all time points beyond that. [1]
A 2021 evidence-based review on the management of acute hyperkalemia evaluated the literature (case reports and series, retrospective and prospective studies, systematic reviews, and meta-analyses) to suggest optimal strategies for management of acute hyperkalemia. The majority of studies started the treatment at a serum potassium level > 6 mmol/L and in case ECG changes existed due to hyperkalemia. A multi-center study (REVEAL-ED) by Peacock et al. found the clinicians utilized 43 various treatment options, demonstrating the lack of a universally-accepted treatment protocol. A number of treatment strategies exist for managing acute hyperkalemia in various ways (e.g. IV calcium to stabilize myocardial cells, albuterol for acute and temporary reduction of potassium levels, etc.). When using β2-agonists, emerging adverse events may include tachycardia, shaking, nervousness and palpitations. While some of the authors suggested that β2-agonists should be utilized in combination with other interventions due to resistance, it was noted that the potential resistance has been only reported in hemodialysis patients. Overall, the authors concluded that there is no robust evidence on the optimal management of hyperkalemia and more research is needed to establish optimal strategies to manage acute hyperkalemia in the emergency department. [2]
A 2018 review article on management of hyperkalemia included a number of small population studies regarding the use of nebulized β-agonists. Based on the studies, the authors stated that several routes of administration including inhalation, nebulization, subcutaneous, or intravenous (IV) can be utilized to treat the patients. Nebulized albuterol for hyperkalemia is administered in doses of 10 mg to 20 mg. While it was noted there was no significant difference in effectiveness between levalbuterol and albuterol, levalbuterol is more costly than albuterol. Administration of nebulized albuterol to patients with end-stage renal disease (ESRD) showed serum potassium was reduced 0.6 mmol/L within 30 min after a 10-mg inhaled dose and of 1.0 mmol/L 1 h after administration of a dose of 20 mg. In obstructive airway disease, 20 mg nebulized albuterol led to a decrease of 0.4 to 1.0 mmol/L at one hour. Although IV β-agonists are more likely to cause side effects compared to nebulized administration, β-agonists can be dosed at 0.5 mg IV (albuterol) or 2.5 mg IV (salbutamol). Intravenous albuterol 0.5 mg resulted in a decline of potassium by 0.5 to 1.0 mmol/L in renal failure patients with maximal action at 30 to 60 min (Montoliu et al). Additionally, the concurrent use of albuterol with insulin and glucose therapy revealed a reduction of 1.2 to 1.5 mmol/L at one hour after medication administration. While the common β-agonists can include tachycardia, tremor, palpitations, and anxiety, IV formulations resulted in more frequent adverse events mostly associated with hypotension and headache. Moreover, two studies showed patients using nonselective oral β-blocker medications may not demonstrate a reduction in serum potassium with β-agonists therapy due to resistance to β-agonists (40%). The authors recommended administration of albuterol at a dose of 20 mg via nebulizer in 4 mL of normal saline over 10 min. [3]
A 2018 review article on the management of hyperkalemia included a number of small population studies regarding the use of nebulized β-agonists. Based on the studies, the authors stated that several routes of administration including inhalation, nebulization, subcutaneous, or intravenous (IV) can be utilized to treat the patients. Nebulized albuterol for hyperkalemia is administered in doses of 10 mg to 20 mg. While it was noted there was no significant difference in effectiveness between levalbuterol and albuterol, levalbuterol is more costly than albuterol. Administration of nebulized albuterol to patients with end-stage renal disease (ESRD) showed serum potassium was reduced 0.6 mmol/L within 30 min after a 10-mg inhaled dose and of 1.0 mmol/L 1 h after administration of a dose of 20 mg. In obstructive airway disease, 20 mg nebulized albuterol led to a decrease of 0.4 to 1.0 mmol/L at one hour. Although IV β-agonists are more likely to cause side effects compared to nebulized administration, β-agonists can be dosed at 0.5 mg IV (albuterol) or 2.5 mg IV (salbutamol). Intravenous albuterol 0.5 mg resulted in a decline of potassium by 0.5 to 1.0 mmol/L in renal failure patients with maximal action at 30 to 60 min (Montoliu et al). Additionally, the concurrent use of albuterol with insulin and glucose therapy revealed a reduction of 1.2 to 1.5 mmol/L at one hour after medication administration. While the common β-agonists can include tachycardia, tremor, palpitations, and anxiety, IV formulations resulted in more frequent adverse events mostly associated with hypotension and headache. Moreover, two studies showed patients using nonselective oral β-blocker medications may not demonstrate a reduction in serum potassium with β-agonists therapy due to resistance to β-agonists (40%). The authors recommended administration of albuterol at a dose of 20 mg via a nebulizer in 4 mL of normal saline over 10 min. [3]