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

Authors:
Tara B Hendry-Hofer
Tara B Hendry-Hofer
University of Colorado Denver
Patrick C Ng
Patrick C Ng
University of Pittsburgh
United States
Sari B Mahon
Sari B Mahon
University of California
United States
Matthew Brenner
Matthew Brenner
University of California
United States
Vikhyat S Bebarta
Vikhyat S Bebarta
San Antonio Military Medical Center
San Antonio | United States

Clin Toxicol (Phila) 2019 Apr 22:1-7. Epub 2019 Apr 22.

a Department of Emergency Medicine, School of Medicine , University of Colorado , Aurora , CO , USA.

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.

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https://www.tandfonline.com/doi/full/10.1080/15563650.2019.1
Publisher Site
http://dx.doi.org/10.1080/15563650.2019.1602272DOI Listing
April 2019
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(Supplied by CrossRef)
Article in Tijdschr Diergeneeskd
Egekeze JO et al.
Tijdschr Diergeneeskd 1980

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