Intramuscular sodium tetrathionate as an antidote in a clinically relevant swine model of acute cyanide toxicity

Abstract

Background: Cyanide is a metabolic poison used in multiple industries and is a high threat chemical agent. Current antidotes require intravenous administration, limiting their usefulness in a mass casualty scenario. Sodium tetrathionate reacts directly with cyanide yielding thiosulfate and the non-toxic compound thiocyanate. Thiosulfate, in turn, neutralizes a second molecule of cyanide, thus, per mole, sodium tetrathionate neutralizes two moles of cyanide. Historical studies examined its efficacy as a cyanide antidote, but it has not been evaluated in a clinically relevant, large animal model, nor has it previously been administered by intramuscular injection.

Objective: The objective of this study is to evaluate the efficacy of intramuscular sodium tetrathionate on survival and clinical outcomes in a large, swine model of severe cyanide toxicity.

Methods: Anesthetized swine were instrumented for continuous monitoring of hemodynamics, then acclimated and breathing spontaneously prior to potassium cyanide infusion (0.17 mg/kg/min). At 6-min post-apnea (no breaths for 20 s), the cyanide infusion was terminated, and animals were treated with sodium tetrathionate (∼18 mg/kg) or normal saline control. Clinical parameters and laboratory values were evaluated at various time points until death or termination of the experiment (90 min post-treatment).

Results: Laboratory values, vital signs, and time to apnea were similar in both groups at baseline and treatment. Survival in the sodium tetrathionate treated group was 100% and 17% in controls (p = 0.0043). All animals treated with sodium tetrathionate returned to breathing at a mean time of 10.85 min after antidote, and all but one control remained apneic through end of the experiment. Animals treated with tetrathionate showed improvement in blood lactate (p ≤ 0.002) starting at 30 min post-treatment. The average time to death in the control group is 63.3 ± 23.2 min. No systemic or localized adverse effects of intramuscular administration of sodium tetrathionate were observed.

Conclusion: Sodium tetrathionate significantly improves survival and clinical outcomes in a large, swine model of acute cyanide poisoning.

Keywords:

• Cyanide poisoning
• sodium tetrathionate
• terrorism
• potassium cyanide
• swine
• intramuscular

Author contributions

TH, AE, PN, SM, MB, GB, and VB were involved in study design, manuscript review, and data analysis. TH, AE, PN, and VB were involved in experiment execution, data collection, statistical analysis, and manuscript generation. All authors reviewed and approved the manuscript for submission.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study is supported by the CounterACT NIH #U01 NS105057.