Intramuscular cobinamide as an antidote to methyl mercaptan poisoning

Inhal Toxicol. 2021 Jan;33(1):25-32. doi: 10.1080/08958378.2020.1866123. Epub 2020 Dec 26.

Abstract

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 B12 analog cobinamide (2.0 mL, 12.5 mg/kg) following acute inhalation of methyl mercaptan gas. Physiological and laboratory parameters were similar in the control and cobinamide-treated groups at baseline and at the time of treatment.

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.

Keywords: Methyl mercaptan; cobinamide; inhalation; methanethiol; swine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antidotes / administration & dosage
  • Antidotes / pharmacology*
  • Cobamides / administration & dosage
  • Cobamides / pharmacology*
  • Female
  • Inhalation Exposure
  • Injections, Intramuscular
  • Male
  • Random Allocation
  • Sulfhydryl Compounds / toxicity*
  • Swine

Substances

  • Antidotes
  • Cobamides
  • Sulfhydryl Compounds
  • cobinamide
  • methylmercaptan