Intramuscular dimethyl trisulfide: efficacy in a large swine model of acute severe cyanide toxicity. (3rd April 2019)

• Record Type: Journal Article
• Authors: Hendry-Hofer, Tara B.; Witeof, Alyssa E.; Lippner, Dennean S.; Ng, Patrick C.; Mahon, Sari B.; Brenner, Matthew; Rockwood, Gary A.; Bebarta, Vikhyat S.
• Is Part Of: Clinical toxicology. Volume 57:Number 4(2019)
• Page Start: 265
• Page End: 270
• Publication Date: 2019-04-03
• Subjects: Cyanide poisoning -- DMTS -- dimethyl trisulfide -- terrorism -- KCN -- swine -- intramuscular; Toxicology -- Periodicals; Toxicological emergencies -- Periodicals; 615.9
• DOI: 10.1080/15563650.2018.1511800
• Languages: English
• ISSNs: 1556-3650

Abstract

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.