Treatment of life-threatening H2S intoxication: Lessons from the trapping agent tetranitrocobinamide

Philippe Haouzi; Marissa MacCann; Matthew Brenner; Sari Mahon; Vikhyat S Bebarta; Adriano Chan; Annick Judenherc-Haouzi; Nicole Tubbs; Gerry R Boss

doi:10.1016/j.etap.2022.103998

Treatment of life-threatening H2S intoxication: Lessons from the trapping agent tetranitrocobinamide

Environ Toxicol Pharmacol. 2022 Nov:96:103998. doi: 10.1016/j.etap.2022.103998. Epub 2022 Oct 11.

Authors

Philippe Haouzi¹, Marissa MacCann², Matthew Brenner³, Sari Mahon⁴, Vikhyat S Bebarta⁵, Adriano Chan⁶, Annick Judenherc-Haouzi⁷, Nicole Tubbs², Gerry R Boss⁶

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA. Electronic address: phaouzi@pennstatehealth.psu.edu.
² Division of Pulmonary and Critical Care Medicine, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA.
³ Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, USA.
⁴ Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA, USA.
⁵ Department of Emergency Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA.
⁶ Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
⁷ Heart and Vascular Institute, Department of Medicine, Pennsylvania State University, College of Medicine, Hershey, PA, USA.

PMID: 36228991
DOI: 10.1016/j.etap.2022.103998

Abstract

We sought to evaluate the efficacy of trapping free hydrogen sulfide (H₂S) following severe H₂S intoxication. Sodium hydrosulfide solution (NaHS, 20 mg/kg) was administered intraperitoneally in 69 freely moving rats. In a first group (protocol 1), 40 rats were randomly assigned to receive saline (n = 20) or the cobalt compound tetranitrocobinamide (TNCbi) (n = 20, 75 mg/kg iv), one minute into coma, when free H₂S was still present in the blood. A second group of 27 rats received TNCbi or saline, following epinephrine, 5 min into coma, when the concentration of free H₂S has drastically decreased in the blood. In protocol 1, TNCbi significantly increased immediate survival (65 vs 20 %, p < 0.01) while in protocol 2, administration of TNCbi led to the same outcome as untreated animals. We hypothesize that the decreased efficacy of TNCbi with time likely reflects the rapid spontaneous disappearance of the pool of free H₂S in the blood following H₂S exposure.

Keywords: Antidote; Hydrogen sulfide intoxication.

MeSH terms

Animals
Coma*
Epinephrine
Hydrogen Sulfide* / toxicity
Rats
Sulfides

Substances

sodium bisulfide
Sulfides
Hydrogen Sulfide
Epinephrine

Abstract

MeSH terms

Substances

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