title: Amiodarone attenuates fluoride-induced hyperkalemia in vitro.
abstract: 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.
  
  
  OBJECTIVE
  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 degrees 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 (Q(1)-Q(4)) to attain calculated concentrations of 0.73 microg/mL, 1.45 microg/mL, 2.9 microg/mL, and 5.8 microg/mL, respectively. Incremental amounts of amiodarone were added to tubes 5-8 (A(1)-A(4)) to attain calculated concentrations of 0.38 microg/mL, 0.75 microg/mL, 1.5 microg/mL, and 3.0 microg/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, Q(3), demonstrating significance versus tube 9 (control). Amiodarone also demonstrated a J-shaped dose-response effect, with statistical significance at A(1), A(2), and A(3) versus tube 9 (control). There was no significant difference among the effective concentrations (Q(3), A(1), A(2), and A(3)) 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.
authors.affiliation: Department of Emergency Medicine, New York University/Bellevue Hospital Center, New York, NY 11203, USA. marksu@pol.net
authors.forename: Mark
authors.initials: M
authors.lastname: Su
authors.forename: Jason
authors.initials: J
authors.lastname: Chu
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Howland
authors.forename: Lewis S
authors.initials: LS
authors.lastname: Nelson
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hoffman
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced / Q000378:metabolism*; D066298:In Vitro Techniques; D011188:Potassium / Q000097:blood / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology; D012969:Sodium Fluoride / Q000037:antagonists & inhibitors / Q000506:poisoning*
chemical_list: D026902:Potassium Channel Blockers; D012969:Sodium Fluoride; D011802:Quinidine; D000638:Amiodarone; D011188:Potassium