Lipworth BJet al, 1997, UK | 12 volunteers were randomised into 4 study groups:nebulised R-albuterol (200–3200 μg), S-albuterol (200–3200 μg), RS-albuterol (400–6400 μg)or placebo | PCRT crossover | Pharmacodynamics at extrapulmonaryβ2 receptors (tremor, plasma potassium, heart rate) measured at 0-100 minutes at 20 minute intervals | No significant differences were found in baseline plasma potassium values(no p values provided) | Small doses of study drugs used in healthy volunteers Small sample size Mean age (20.6) may not be representative of majority of population presenting with hyperkalaemia |
Gumbhir-Shah K etal, 1999, USA | 13 asthmatic subjects randomised to receive four cumulative doses of either nebulised 1.25 mg levalbuterol or 2.5 mg albuterol at 30 minute intervals | RCT crossover | FEV1, plasma potassium, plasma glucose, heart rate, QTc interval, and urine plasma drug concentration at 1, 2, 4, 6, 8 hours after final dose | No significant difference between R and RS albuterol in reduction of plasma potassium levels (AUC p = 0.17) | Four consecutive small doses given at 30 minutes intervals may not be applicable to those patients presenting with pathological hyperkalaemia Small sample size |
| | | Side effects | None severe. Included dizziness, tachycardia, nervousness (greater in R group), wheezing (greater in RS group). All events resolved spontaneously | |
Lotvall J etal, 2001, Sweden | 20 adult asthmatic patients were randomised into 4 study groups:nebulised R-albuterol (6.25–1600 μg), S-albuterol (6.25–1600 μg), RS-albuterol (12.5–3200 μg), or placebo | PCRT 4-way crossover | FEV1, heart rate, and plasma potassium levels before dosing FEV1, heart rate and plasma potassium levels 20 minutes after each dose | Differences/p values not documented Rapid increase in plasma potassium level (0.3–0.4 mmol/l) after placebo administration (no p value given) | Single K+ level was measured 20 minutes after study drug Small sample size The dose of albuterol required to reverse hyperkalaemia is higher than standard bronchodilator doses used in this study |
| | | Side effects | No serious adverse events and majority of adverse events were reported after treatment with R or RS albuterol. These included tremor, palpitations, and tachyarrhythmias | |
Pancu Det al, 2003, USA | 27 healthy adult volunteers;9 nebulised normal saline,9 albuterol (10 mg),9 levalbuterol (2.5 mg) | Randomised, double blind, placebo controlled trial | Serum potassium values at baseline | No difference between any group:albuterol 3.9 (0.3) mEq/l, levalbuterol 4.1 (0.3) mEq/l, placebo 4.1 (0.3) mEq/l | This study measured potassium changes in a small sample of healthy volunteers. The clinical significance of these small changes in potassium is uncertain and these changes may not be applicable to those patients presenting with pathological hyperkalaemia. Objective vital signs were only recorded in those patients reporting side effects |
| | | Serum potassium at 30 minutes | Albuterol reduced by 0.3 mEq /l; levalbuterol reduced by 0.3 mEq/l; placebo increased by 0.1 mEq/l; no significant difference between β agonists. Both β agonists better than placebo (p = 0.005) | |
| | | Serum potassium at 60 minutes | Albuterol reduced by 0.3 mEq/l; levalbuterol reduced by 0.5 mEq/l; placebo showed no change. No significant difference between β agonists. Both β agonists better than placebo (p = 0.001) | |
| | | Side effects | Levalbuterol caused fewer reported side effects than albuterol. Levalbuterol v albuterol: total percent reporting symptoms, 22% v 78%; tremor, 22% v 78%; nervousness, 0% v 56%; palpitations, 0% v 56%; tachycardia, 0% v 44%No p values provided | |