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Lookup NU author(s): Dr Michael Dunn, Dr Robert Jefferson, Professor Peter Blain, Professor Simon ThomasORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background: Dicobalt edetate and hydroxocobalamin are widely used to treat hydrogen cyanide poisoning. However, comparative and quantitative efficacy data are lacking. Although post-exposure treatment is typical, it may be possible to administer these antidotes before exposure to first attenders entering a known site of cyanide release, as supplementary protection to their personal protective equipment.Methods: We established an anaesthetised Gottingen minipig model of lethal bolus potassium cyanide (KCN) injection to simulate high dose hydrogen cyanide inhalation. Doses were similar to human lethal doses of KCN. Dicobalt edetate and hydroxocobalamin were administered shortly before KCN and their effect on metabolic and cardiovascular variables and survival time were measured.Results: Increases in arterial lactate were similar after 0.08 and 0.12 mmol/kg KCN. KCN 0.08 mmol/kg was survived by 4/4 animals with moderate cardiovascular effects, while the 0.12 mmol/kg dose was lethal in 4/4 animals, with a mean time to euthanasia of 28.3 (SEM 13.9) min. Administration of dicobalt edetate (0.021 mmol/kg, 8.6 mg/kg) or hydroxocobalamin (0.054 mmol/kg, 75 mg/kg) at clinically licensed doses had modest effect on lactate concentrations but increased survival after administration of KCN 0.12 mmol/kg (survival: dicobalt edetate 4/4, hydroxocobalamin 2/4) but not 0.15 mmol/kg (0/4 and 0/4, respectively). In a subsequent larger study, doubling the dose of hydroxocobalamin (0.108 mmol/kg, 150 mg/kg) was associated with a modest but inconsistent increased survival after 0.15 mmol/kg KCN (survival: control 0/8, 75 mg/kg 1/10, 150 mg/kg 3/10) likely due to variable pharmacokinetics.Conclusions: In this porcine study of cyanide exposure, with pre-exposure antidote administration, licensed doses of dicobalt edetate and hydroxocobalamin were effective at just lethal doses but ineffective at less than twice the estimated LD50. The efficacy of a rapidly-administered double-dose of hydroxocobalamin was limited by variable pharmacokinetics. In clinical poisoning scenarios, with delayed administration, the antidotes are likely to be even less effective. New antidotes are required for treatment of cyanide exposures appreciably above the minimum lethal dose. cyanide, antidotes, efficacy
Author(s): Thompson A, Dunn M, Jefferson R, Dissanayake K, Reed F, Gregson R, Greenhalgh S, Clutton RE, Blain PG, Thomas SHL, Eddleston M
Publication type: Article
Publication status: Published
Journal: Clinical Toxicology
Year: 2020
Volume: 58
Issue: 3
Pages: 190-200
Online publication date: 07/08/2019
Acceptance date: 27/05/2019
Date deposited: 28/05/2019
ISSN (print): 1556-3650
ISSN (electronic): 1556-9519
Publisher: Taylor and Francis
URL: https://doi.org/10.1080/15563650.2019.1628969
DOI: 10.1080/15563650.2019.1628969
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