Hydroxocobalamin versus sodium thiosulfate for the treatment of acute cyanide toxicity in a swine (Sus scrofa) model

Ann Emerg Med. 2012 Jun;59(6):532-9. doi: 10.1016/j.annemergmed.2012.01.022. Epub 2012 Mar 3.


Study 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.

Conclusion: 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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antidotes / administration & dosage
  • Antidotes / therapeutic use*
  • Blood Pressure / drug effects
  • Cyanides / antagonists & inhibitors
  • Cyanides / toxicity*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Female
  • Heart Rate / drug effects
  • Hydroxocobalamin / administration & dosage
  • Hydroxocobalamin / therapeutic use*
  • Male
  • Shock / chemically induced
  • Shock / drug therapy
  • Sus scrofa
  • Thiosulfates / administration & dosage
  • Thiosulfates / therapeutic use*
  • Vascular Resistance / drug effects


  • Antidotes
  • Cyanides
  • Thiosulfates
  • sodium thiosulfate
  • Hydroxocobalamin