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Merck

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

Annals of the New York Academy of Sciences (2020-04-02)
Tara B Hendry-Hofer, Patrick C Ng, Alison M McGrath, David Mukai, Matthew Brenner, Sari Mahon, Joseph K Maddry, Gerry R Boss, Vikhyat S Bebarta
RESUMEN

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.