title: Hypertonic sodium bicarbonate is effective in the acute management of verapamil toxicity in a swine model.
abstract: OBJECTIVE
  This study was conducted to determine whether hypertonic sodium bicarbonate would improve the hypotension associated with severe verapamil toxicity compared with volume expansion.
  
  
  METHODS
  The study design used a nonblinded acute animal preparation. Twenty-four anesthetized and instrumented swine were poisoned with verapamil delivered at a rate of 1 mg/kg per hour for 10 minutes followed by incremental increases of 1 mg/kg per hour every 10 minutes until the endpoint of a mean arterial blood pressure of 45% of baseline was achieved. Animals alternately received either 4 mEq/kg of hypertonic sodium bicarbonate intravenously over 4 minutes or similar volumes of 0.6% sodium chloride in 10% mannitol (control). The main outcome parameter followed was mean arterial pressure. In addition, physiologic parameters including cardiac output, heart rate, pH, PCO (2), PO (2), plasma ionized calcium, sodium, and potassium were monitored.
  
  
  RESULTS
  Verapamil toxicity, as defined by a mean arterial pressure of 45% of baseline, was produced in all animals following an average verapamil infusion dose of 0.6+/-0.12 mg/kg. This dose produced an average plasma verapamil concentration of 728.1+/-155.4 microgram/L, with no significant difference between groups. Swine treated with hypertonic sodium bicarbonate experienced a significant increase in mean arterial pressure (>50%) and cardiac output (>30%) over the first 20 minutes that slowly equilibrated with the control group over the remainder of the experiment. As expected, plasma sodium concentrations were elevated significantly in the sodium bicarbonate group while plasma potassium concentrations were decreased significantly. Finally, there was a significant decrease in plasma ionized calcium concentration in the sodium bicarbonate-treated group compared with controls.
  
  
  CONCLUSIONS
  Hypertonic sodium bicarbonate reversed the hypotension and cardiac output depression of severe verapamil toxicity in a swine model.
authors.affiliation: Department of Medical Toxicology, Good Samaritan Regional Medical Center, the University of Arizona College of Medicine, Phoenix, AZ, USA. dtamen@samaritan.edu
authors.forename: D A
authors.initials: DA
authors.lastname: Tanen
authors.forename: A M
authors.initials: AM
authors.lastname: Ruha
authors.forename: S C
authors.initials: SC
authors.lastname: Curry
authors.forename: K A
authors.initials: KA
authors.lastname: Graeme
authors.forename: C G
authors.initials: CG
authors.lastname: Reagan
mesh_terms: D000818:Animals; D001795:Blood Pressure Determination; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006439:Hemodynamics / Q000502:physiology; D006982:Hypertonic Solutions; D007022:Hypotension / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D007262:Infusions, Intravenous; D008297:Male; D012016:Reference Values; D012720:Severity of Illness Index; D017693:Sodium Bicarbonate / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D015996:Survival Rate; D013552:Swine; D014700:Verapamil / Q000633:toxicity*
chemical_list: D006982:Hypertonic Solutions; D012965:Sodium Chloride; D017693:Sodium Bicarbonate; D014700:Verapamil