Intramuscular dimethyl trisulfide: efficacy in a large swine model of acute severe cyanide toxicity

Abstract

Background: Cyanide is a deadly compound used as a terrorist agent. Current FDA approved antidotes require intravenous administration, limiting their utility in a mass casualty scenario. Dimethyl trisulfide (DMTS), a sulfur-based molecule, binds cyanide converting it to the less toxic by-product thiocyanate. Studies evaluating efficacy in rodents have been performed, but a large, clinically relevant animal model has not been reported.

Objective: This study evaluates the efficacy of intramuscular DMTS on survival and clinical outcomes in a swine model of acute, severe cyanide toxicity.

Methods: Anesthetized swine were instrumented for continuous monitoring of hemodynamics. Prior to potassium cyanide infusion animals were acclimated and breathing spontaneously. At 5-minutes post-apnea animals were treated with DMTS or saline. Vital signs, hemodynamics, and laboratory values were evaluated at various time points.

Results: Baseline values and time to apnea were similar in both groups. Survival in the DMTS treated group was 83.3% and 0% in saline controls (p = .005). The DMTS group returned to breathing at a mean time of 19.3 ± 10 min after antidote, control animals did not return to breathing (CI difference 8.8, 29.8). At the end of the experiment or time of death, mean lactate was 9.41 mmol/L vs. 4.35 mmol/L (CI difference –10.94,0.82) in the saline and DMTS groups, respectively and pH was 7.20 vs. 7.37 (CI difference –0.04, 0.38). No adverse effects were observed at the injection site.

Conclusion: Intramuscular administration of DMTS improves survival and clinical outcomes in our large animal swine model of acute cyanide toxicity.

Keywords:

• Cyanide poisoning
• DMTS
• dimethyl trisulfide
• terrorism
• KCN
• swine
• intramuscular

Disclosure statement

The views, opinions and/or findings contained in this report are those of the authors and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation. In conducting research using animals, the investigators adhered to the Animal Welfare Act Regulations and other Federal statutes relating to animals and experiments involving animals and the principles set forth in the current version of the Guide for Care and Use of Laboratory Animals, National Research Council.

A patent (US 9,375,407 B2) entitled “Dimethyl Trisulfide As A Cyanide Antidote” was granted on 28 June 2016 (inventors: Rockwood, GA, Petrikovics, I and Baskin, SI). Personal financial gain may be realized through development of this product.

Additional information

Funding

This work is supported by the US Army Medical Research and Materiel Command under Contract No. W81XWH-16-C-0138 as funded by the NIH CounterACT program.