Intramuscular cobinamide as an antidote to methyl mercaptan poisoning.
Methyl mercaptan
cobinamide
inhalation
methanethiol
swine
Journal
Inhalation toxicology
ISSN: 1091-7691
Titre abrégé: Inhal Toxicol
Pays: England
ID NLM: 8910739
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
pubmed:
29
12
2020
medline:
22
1
2022
entrez:
28
12
2020
Statut:
ppublish
Résumé
Methyl mercaptan occurs naturally in the environment and is found in a variety of occupational settings, including the oil, paper, plastics, and pesticides industries. It is a toxic gas and deaths from methyl mercaptan exposure have occurred. The Department of Homeland Security considers it a high threat chemical agent that could be used by terrorists. Unfortunately, no specific treatment exists for methyl mercaptan poisoning. We conducted a randomized trial in 12 swine comparing no treatment to intramuscular injection of the vitamin B All six cobinamide-treated animals survived, whereas only one of six control animals lived (17% survival) (p = 0.0043). The cobinamide-treated animals returned to a normal breathing pattern by 3.8 ± 1.1 min after treatment (mean ± SD), while all but one animal in the control group had intermittent gasping, never regaining a normal breathing pattern. Blood pressure and arterial oxygen saturation returned to baseline values within 15 minutes of cobinamide-treatment. Plasma lactate concentration increased progressively until death (10.93 ± 6.02 mmol [mean ± SD]) in control animals, and decreased toward baseline (3.79 ± 2.93 mmol [mean ± SD]) by the end of the experiment in cobinamide-treated animals. We conclude that intramuscular administration of cobinamide improves survival and clinical outcomes in a large animal model of acute, high dose methyl mercaptan poisoning.
Sections du résumé
BACKGROUND
Methyl mercaptan occurs naturally in the environment and is found in a variety of occupational settings, including the oil, paper, plastics, and pesticides industries. It is a toxic gas and deaths from methyl mercaptan exposure have occurred. The Department of Homeland Security considers it a high threat chemical agent that could be used by terrorists. Unfortunately, no specific treatment exists for methyl mercaptan poisoning.
METHODS
We conducted a randomized trial in 12 swine comparing no treatment to intramuscular injection of the vitamin B
RESULTS
All six cobinamide-treated animals survived, whereas only one of six control animals lived (17% survival) (p = 0.0043). The cobinamide-treated animals returned to a normal breathing pattern by 3.8 ± 1.1 min after treatment (mean ± SD), while all but one animal in the control group had intermittent gasping, never regaining a normal breathing pattern. Blood pressure and arterial oxygen saturation returned to baseline values within 15 minutes of cobinamide-treatment. Plasma lactate concentration increased progressively until death (10.93 ± 6.02 mmol [mean ± SD]) in control animals, and decreased toward baseline (3.79 ± 2.93 mmol [mean ± SD]) by the end of the experiment in cobinamide-treated animals.
CONCLUSION
We conclude that intramuscular administration of cobinamide improves survival and clinical outcomes in a large animal model of acute, high dose methyl mercaptan poisoning.
Identifiants
pubmed: 33356664
doi: 10.1080/08958378.2020.1866123
pmc: PMC8063453
mid: NIHMS1679097
doi:
Substances chimiques
Antidotes
0
Cobamides
0
Sulfhydryl Compounds
0
cobinamide
13497-85-3
methylmercaptan
2X8406WW9I
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
25-32Subventions
Organisme : NINDS NIH HHS
ID : U01 NS087964
Pays : United States
Organisme : NIEHS NIH HHS
ID : U54 ES015678
Pays : United States
Organisme : NIEHS NIH HHS
ID : U54 ES027698
Pays : United States
Références
Ann N Y Acad Sci. 2020 Nov;1479(1):159-167
pubmed: 32233102
J Med Toxicol. 2016 Dec;12(4):370-379
pubmed: 27631586
Ann Emerg Med. 2014 Dec;64(6):612-9
pubmed: 24746273
J Med Toxicol. 2019 Oct;15(4):287-294
pubmed: 31062177
Clin Toxicol (Phila). 2019 Mar;57(3):189-196
pubmed: 30430872
Eur J Inorg Chem. 2014 Sep;2014(25):4123-4133
pubmed: 25580081
Acad Emerg Med. 2017 Sep;24(9):1088-1098
pubmed: 28472554
Int Arch Occup Environ Health. 2004 Oct;77(7):451-60
pubmed: 15368059
Int Arch Occup Environ Health. 1997;70(2):119-27
pubmed: 9253640
Biochim Biophys Acta. 1980 Feb 8;589(2):324-35
pubmed: 6243968
Toxicol Mech Methods. 2019 Jul;29(6):438-444
pubmed: 30822191
Forensic Sci Res. 2017 Jun 07;2(4):192-197
pubmed: 30483641
Vet Pathol. 2012 Mar;49(2):344-56
pubmed: 21441112
Toxicol Rep. 2019 May 10;6:431-438
pubmed: 31193272
Scand J Work Environ Health. 1988 Feb;14(1):17-20
pubmed: 3353691
Future Med Chem. 2012 Sep;4(14):1771-2
pubmed: 23043472
J Med Chem. 2015 Feb 26;58(4):1750-9
pubmed: 25650735
Sci Total Environ. 1986 Dec 1;57:49-55
pubmed: 3810146