Intramuscular aminotetrazole cobinamide as a treatment for inhaled hydrogen sulfide poisoning in a large swine model

Ann N Y Acad Sci. 2020 Nov;1479(1):159-167. doi: 10.1111/nyas.14339. Epub 2020 Mar 31.

Abstract

Hydrogen sulfide (H2 S), a high-threat chemical agent, occurs naturally in a variety of settings. Despite multiple incidents of exposures and deaths, no FDA-approved antidote exists. A rapid-acting, easy to administer antidote is needed. We conducted a randomized control trial in swine comparing intramuscular administration of aminotetrazole cobinamide (2.9 mL, 18 mg/kg) to no treatment following inhalation of H2 S gas. We found that aminotetrazole cobinamide administered 2 min after the onset of respiratory depression-defined as a tidal volume of less than 3 mL/kg for 2 consecutive minutes-yielded 100% survival, while all control animals died. Respiratory depression resolved in the treatment group within 3.6 ± 1.5 min (mean ± SD) of cobinamide administration, whereas control animals had intermittent gasping until death. Blood pressure and arterial oxygen saturation (SO2 ) returned to baseline values within 5 and 10 min, respectively, of cobinamide treatment, and plasma lactate concentration decreased to less than 50% of the highest value by the end of the experiment. In control animals, plasma lactate rose continuously until death. We conclude that intramuscular aminotetrazole cobinamide is effective in a large animal, inhalational model of acute, severe H2 S poisoning.

Keywords: cobinamide; hydrogen sulfide; inhaled; swine.

Publication types

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

MeSH terms

  • Animals
  • Antidotes / pharmacology*
  • Cobamides / pharmacology*
  • Humans
  • Hydrogen Sulfide / poisoning*
  • Injections, Intramuscular
  • Male
  • Swine
  • Thiadiazoles / pharmacology*

Substances

  • Antidotes
  • Cobamides
  • Thiadiazoles
  • cobinamide
  • 2-amino-1,3,4-thiadiazole
  • Hydrogen Sulfide