title: Hypertonic sodium bicarbonate versus intravenous lipid emulsion in a rabbit model of intravenous flecainide toxicity: no difference, no sink.
abstract: BACKGROUND
  The use of intravenous lipid emulsion (ILE) as an antidote in non-local, anaesthetic drug toxicity has generated considerable interest. Flecainide is a lipophilic anti-arrhythmic with a significant cardiotoxic profile, with blockade of sodium and potassium channels causing arrhythmias and shock in severe toxicity. ILE has been proposed as a treatment option in severe flecainide toxicity refractory to other modalities.
  
  
  OBJECTIVE
  We compared the effects of ILE and hypertonic sodium bicarbonate in a rabbit model of flecainide toxicity.
  
  
  METHODS
  Twenty sedated and ventilated New Zealand White Rabbits received flecainide infusion titrated to a mean arterial pressure (MAP) of 60% baseline, which was defined as toxicity. The rabbits then received either sodium bicarbonate or ILE, and the flecainide infusion was reduced in an attempt to model ongoing enteric absorption. MAP and heart rate were recorded every minute for 15 min and plasma flecainide concentration was measured at toxicity and 15 min. ECG QRS duration was recorded at baseline, toxicity and at 5, 10 and 15 min post-toxicity.
  
  
  RESULTS
  No difference was observed in heart rate (p = 0.2804), MAP (p = 0.1802) or QRS duration (p = 0.7471) between groups. The immediate rate of rise in MAP was greatest in the bicarbonate group in the 5 min immediately post-toxicity.
  
  
  CONCLUSIONS
  In this study, no differences were observed between an active control of hypertonic sodium bicarbonate and ILE for the primary endpoint of MAP at 15 min nor for QRS duration at any timepoint. There was a transient rapid increase in blood pressure seen in the sodium bicarbonate group that was not sustained. No increase was seen in blood concentration of flecainide in the ILE group, suggesting no 'lipid sink' for flecainide in this model. More research is warranted to define any role for ILE in flecainide toxicity.
authors.affiliation: Tamworth Hospital, Intensive Care, Tamworth, 2340 Australia. grantcave@gmail.com
authors.forename: G
authors.initials: G
authors.lastname: Cave
authors.forename: M
authors.initials: M
authors.lastname: Harvey
authors.forename: P
authors.initials: P
authors.lastname: Quinn
authors.forename: D
authors.initials: D
authors.lastname: Heys
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000633:toxicity*; D000931:Antidotes / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D023381:Endpoint Determination; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D005260:Female; D005424:Flecainide / Q000633:toxicity; D006339:Heart Rate / Q000187:drug effects; D006982:Hypertonic Solutions; D008297:Male; D011041:Poisoning / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D011817:Rabbits; D017693:Sodium Bicarbonate / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D000931:Antidotes; D005217:Fat Emulsions, Intravenous; D006982:Hypertonic Solutions; D017693:Sodium Bicarbonate; D005424:Flecainide