Amiodarone attenuates fluoride-induced hyperkalemia in vitro

Poisoning by hydrofluoric acid or fluoride salts results in hypocalcemia, hypomagnesemia, and hyperkalemia with subsequent cardiac dysrhythmias. In previous studies, quinidine attenuated fluoride-induced hyperkalemia in vitro, and enhanced survival in animals. Like quinidine, amiodarone is a potassium channel blocker, although amiodarone is more familiar to clinicians due to its recent inclusion in advanced cardiac life support (ACLS) protocols. Objectives: This in-vitro study of human erythrocytes was designed to determine whether amiodarone could attenuate fluoride-induced hyperkalemia. Methods: Six healthy volunteers each donated 60 mL of blood on three occasions. Each specimen was divided into 12 tubes, incubated at 37°C, and oxygenated with room air. An aqueous sodium fluoride (F^-) solution was added to tubes 1-9. Incremental amounts of quinidine were added to tubes 1-4 (Q₁-Q₄) to attain calculated concentrations of 0.73 μg/mL, 1.45 μg/mL, 2.9 μg/mL, and 5.8 μg/mL, respectively. Incremental amounts of amiodarone were added to tubes 5-8 (A₁-A₄) to attain calculated concentrations of 0.38 μg/mL, 0.75 μg/mL, 1.5 μg/mL, and 3.0 μg/mL, respectively. Tubes 9-12 were controls for each of F^-, amiodarone, quinidine alone, and no additive, respectively. Extracellular potassium concentration ([K⁺]) was followed, and an objective endpoint was defined as the rise in potassium concentration at 6 hours. Results: Fluoride produced a significant change in [K⁺] by 6 hours in all samples. Quinidine produced a J-shaped curve in its ability to attenuate the rise in [K⁺], with only one concentration, Q₃, demonstrating significance versus tube 9 (control). Amiodarone also demonstrated a J-shaped dose-response effect, with statistical significance at A₁, A₂, and A₃ versus tube 9 (control). There was no significant difference among the effective concentrations (Q₃, A₁, A₂, and A₃) of both drugs. Conclusions: In this in-vitro model using human blood, amiodarone and quinidine both attenuated F^--induced hyperkalemia. Further study is indicated to determine whether amiodarone enhances survival in F^--poisoned animals.