title: Hydroxocobalamin versus sodium thiosulfate for the treatment of acute cyanide toxicity in a swine (Sus scrofa) model.
abstract: OBJECTIVE
  We compare the efficacy of hydroxocobalamin to sodium thiosulfate to reverse the depressive effects on mean arterial pressure in a swine model of acute cyanide toxicity and gain a better understanding of the mechanism of action of the hydroxocobalamin in reversal of the toxicity.
  
  
  METHODS
  Swine were intubated, anesthetized, and instrumented with central arterial and venous lines and a pulmonary artery catheter. Animals (n=36) were randomly assigned to one of 3 groups: hydroxocobalamin alone (150 mg/kg), sodium thiosulfate alone (413 mg/kg), or hydroxocobalamin (150 mg/kg)+sodium thiosulfate (413 mg/kg) and monitored for 60 minutes after the start of antidotal infusion. Cyanide was infused until severe hypotension developed, defined as blood pressure 50% of baseline mean arterial pressure. Repeated-measures ANOVA was used to determine statistically significant changes between groups over time.
  
  
  RESULTS
  Time to hypotension (25, 28, and 33 minutes), cyanide dose at hypotension (4.7, 5.0, and 5.6 mg/kg), and mean cyanide blood levels (3.2, 3.7, and 3.8 μg/mL) and lactate levels (7, 8.2, 8.3 and mmol/L) were similar. All 12 animals in the sodium thiosulfate group died compared with 2 of 12 in the hydroxocobalamin/sodium thiosulfate group and 1 of 12 in hydroxocobalamin group. No statistically significant differences were detected between the hydroxocobalamin and hydroxocobalamin/sodium thiosulfate groups for carbon monoxide, mean arterial pressure, cyanide levels, or mortality at 60 minutes. Lactate level (2.6 versus 2.1 mmol/L), pH (7.44 versus 7.42), and bicarbonate level (25 versus 26 mEq/L) at 60 minutes were also similar between groups.
  
  
  CONCLUSIONS
  Sodium thiosulfate failed to reverse cyanide-induced shock in our swine model of severe cyanide toxicity. Further, sodium thiosulfate was not found to be effective when added to hydroxocobalamin in the treatment of cyanide-induced shock. Hydroxocobalamin alone was again found to be effective for severe cyanide toxicity.
authors.affiliation: Wilford Hall Medical Center/Brooke Army Medical Center, the Department of Emergency Medicine, San Antonio, TX, USA. vikbebarta@yahoo.com
authors.forename: Vikhyat S
authors.initials: VS
authors.lastname: Bebarta
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Pitotti
authors.forename: Patricia
authors.initials: P
authors.lastname: Dixon
authors.forename: Julio R
authors.initials: JR
authors.lastname: Lairet
authors.forename: Anneke
authors.initials: A
authors.lastname: Bush
authors.forename: David A
authors.initials: DA
authors.lastname: Tanen
mesh_terms: D000818:Animals; D000931:Antidotes / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003486:Cyanides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006879:Hydroxocobalamin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D012769:Shock / Q000139:chemically induced / Q000188:drug therapy; D034421:Sus scrofa; D013885:Thiosulfates / Q000008:administration & dosage / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000931:Antidotes; D003486:Cyanides; D013885:Thiosulfates; C017717:sodium thiosulfate; D006879:Hydroxocobalamin