| Title: |
Intramuscular dimethyl trisulfide: efficacy in a large swine model of acute severe cyanide toxicity |
| 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 |
| Source: |
Journal of Toxicology Clinical Toxicology, vol 57, iss 4 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2019 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); Emerging Infectious Diseases (rcdc); Biodefense (rcdc); Infectious Diseases (rcdc); Animals (mesh); Antidotes (mesh); Disease Models; Animal (mesh); Female (mesh); Injections; Intramuscular (mesh); Potassium Cyanide (mesh); Sulfides (mesh); Swine (mesh); Toxicity Tests; Acute (mesh); Treatment Outcome (mesh); Cyanide poisoning; DMTS; dimethyl trisulfide; terrorism; KCN; swine; intramuscular |
| Subject Geographic: |
265 - 270 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt6qh7519p; https://escholarship.org/uc/item/6qh7519p; https://escholarship.org/content/qt6qh7519p/qt6qh7519p.pdf |
| DOI: |
10.1080/15563650.2018.1511800 |
| Availability: |
https://escholarship.org/uc/item/6qh7519p; https://escholarship.org/content/qt6qh7519p/qt6qh7519p.pdf; https://doi.org/10.1080/15563650.2018.1511800 |
| Rights: |
public |
| Accession Number: |
edsbas.60307595 |
| Database: |
BASE |