Cyanide Medical Countermeasure Development: Assessing the Efficacy of Intramuscular Sodium Tetrathionate for the Treatment of Acute, Severe Cyanide Toxicity in Swine (Sus scrofa).

Antidote Countermeasure Cyanide Mass casualty Medical countermeasure

Journal

Journal of medical toxicology : official journal of the American College of Medical Toxicology
ISSN: 1937-6995
Titre abrégé: J Med Toxicol
Pays: United States
ID NLM: 101284598

Informations de publication

Date de publication:
07 Oct 2024
Historique:
received: 17 06 2024
accepted: 23 09 2024
revised: 13 09 2024
medline: 8 10 2024
pubmed: 8 10 2024
entrez: 7 10 2024
Statut: aheadofprint

Résumé

Given its availability and lethality, cyanide has potential for weaponization and thus has the attention of several governmental agencies. In large scale exposure scenarios, an effective countermeasure that can be administered quickly and in low volume intramuscularly may prove valuable because IV medications may have limited practical applications in these situations. Sodium tetrathionate, a potential cyanide antidote, is a compound that provides sulfur to rhodanese, the enzyme that detoxifies cyanide endogenously. Additionally, sodium tetrathionate has been reported to directly react with cyanide and is effective when administered intramuscularly. In this study, we assess the efficacy of sodium tetrathionate, when administered intramuscularly for the treatment of acute, oral cyanide poisoning in swine. We conducted a prospective trial approved by the 59th Medical Wing Institutional Animal Care and Use Committee comparing intramuscular sodium tetrathionate (n=6) to no treatment control (n=4) in animals (Sus scrofa) exposed to a lethal dose of oral potassium cyanide. Survival at 120 minutes was the primary outcome. Lactate, a cyanide toxicity biomarker, was measured. At the study end, all animals were euthanized in compliance with the Animal Welfare Act and the American Association for Accreditation of Laboratory Animal Care. Survival between groups was summarized using a Kaplan-Meier survival curve after comparing survival by log-rank, Mantel-Cox analysis. The Mann-Whitney U test was used for comparison of other variables between groups. At baseline animals were similar. There was 100% survival in the treatment group and 0% survival in the control group (P=0.0011). Serum lactate significantly increased in the control group (control: 5±0.9 vs. treatment: 2.1 ± 0.5 mmol/L at 20 minutes). Sodium tetrathionate (intramuscular) significantly improved survival in a large, swine model of acute, oral cyanide poisoning. Future studies will be directed at further assessing sodium tetrathionate as a potential medical countermeasure for cyanide poisoning.

Identifiants

pubmed: 39375309
doi: 10.1007/s13181-024-01037-6
pii: 10.1007/s13181-024-01037-6
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : DHA Restoral
ID : DHA Restoral

Informations de copyright

© 2024. American College of Medical Toxicology.

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Auteurs

Patrick C Ng (PC)

Department of Emergency Medicine, UT Health San Antonio, San Antonio, TX, USA. ngp@uthscsa.edu.

R Madelaine Paredes (RM)

Department of Emergency Medicine, UT Health San Antonio, San Antonio, TX, USA.
59th Medical Wing, Clinical Resuscitation, Emergency Science, Triage and Toxicology (CRESTT), Lackland AFB, San Antonio, TX, USA.

Allyson A Mireles (AA)

59th Medical Wing, En Route Care Research Center, Lackland AFB, San Antonio, TX, USA.

Tara Hendry-Hofer (T)

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

Vikhyat S Bebarta (VS)

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

Gerry R Boss (GR)

Department of Medicine, University of California, San Diego, CA, USA.

Jae-Hyek Choi (JH)

Department of Emergency Medicine, UT Health San Antonio, San Antonio, TX, USA.
59th Medical Wing, Clinical Resuscitation, Emergency Science, Triage and Toxicology (CRESTT), Lackland AFB, San Antonio, TX, USA.

Col Joseph K Maddry (CJK)

59th Medical Wing, Clinical Resuscitation, Emergency Science, Triage and Toxicology (CRESTT), Lackland AFB, San Antonio, TX, USA.
Brooke Army Medical Center, Fort Sam Houston, TX, USA.

Classifications MeSH