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The Vitamin B12 Analog Cobinamide Is an Effective Antidote for Oral Cyanide Poisoning

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Abstract

Introduction

Cyanide is a major chemical threat, and cyanide ingestion carries a higher risk for a supra-lethal dose exposure compared to inhalation but provides an opportunity for effective treatment due to a longer treatment window and a gastrointestinal cyanide reservoir that could be neutralized prior to systemic absorption. We hypothesized that orally administered cobinamide may function as a high-binding affinity scavenger and that gastric alkalinization would reduce cyanide absorption and concurrently increase cobinamide binding, further enhancing antidote effectiveness.

Methods

Thirty New Zealand white rabbits were divided into five groups and were given a lethal dose of oral cyanide poisoning (50 mg). The survival time of animals was monitored with oral cyanide alone, oral cyanide with gastric alkalinization with oral sodium bicarbonate buffer (500 mg), and in combination with either aquohydroxocobinamide or dinitrocobinamide (250 mM). Red blood cell cyanide concentration, plasma cobinamide, and thiocyanate concentrations were measured from blood samples.

Results

In cyanide ingested animals, oral sodium bicarbonate alone significantly prolonged survival time to 20.3 ± 8.6 min compared to 10.5 ± 4.3 min in saline-treated controls, but did not lead to overall survival. Aquohydroxocobinamide and dinitrocobinamide increased survival time to 64 ± 41 (p < 0.05) and 75 ± 16.4 min (p < 0.001), respectively. Compared to aquohydroxocobinamide, dinitrocobinamide showed greater systemic absorption and reduced blood pressure. Dinitrocobinamide also markedly increased the red blood cell cyanide concentration. Under all conditions, the plasma thiocyanate concentration gradually increased with time.

Conclusion

This study demonstrates a promising new approach to treat high-dose cyanide ingestion, with gastric alkalinization alone and in combination with oral cobinamide for treating a supra-lethal dose of orally administered cyanide in rabbits.

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Abbreviations

DOS:

Diffuse optical spectroscopy

FD:

Frequency domain

SS:

Steady state

OxyHb:

Oxyhemoglobin

DeoxyHb:

Deoxyhemoglobin

CytcOx:

Cytochrome C oxidase

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Authors and Affiliations

  1. Beckman Laser Institute, University of California, 1002 Health Sciences Rd., Irvine, CA, 92612-1475, USA

    Jangwoen Lee, Sari B. Mahon, David Mukai, Tanya Burney, David Yoon & Matthew Brenner

  2. Department of Medicine, University of California, San Diego, La Jolla, CA, 92093-0652, USA

    Behdod S. Katebian, Adriano Chan & Gerry R. Boss

  3. Department of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, 80045, USA

    Vikhyat S. Bebarta

  4. Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, Irvine, CA, 92868, USA

    Matthew Brenner

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  1. Jangwoen Lee
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Corresponding author

Correspondence to Jangwoen Lee.

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Sources of Funding

This study is supported by CounterACT NIH # 1U54 NS079201, CounterACT NIH # U01 NS058030, LAMMP # 445474-30136, and AMRMC W81XWH-12-2-0098.

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Lee, J., Mahon, S.B., Mukai, D. et al. The Vitamin B12 Analog Cobinamide Is an Effective Antidote for Oral Cyanide Poisoning. J. Med. Toxicol. 12, 370–379 (2016). https://doi.org/10.1007/s13181-016-0566-4

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  • DOI: https://doi.org/10.1007/s13181-016-0566-4

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