Hydroxocobalamin (Cyanokit)

Purpose Forensic verification of cyanide (CN) poisoning by direct CN analysis in postmortem blood is challenging due to instability of CN in biological samples. CN metabolites, thiocyanate (SCN−) and 2-aminothiazoline-4-carboxylic acid (ATCA), have been proposed as more stable biomarkers, yet it is unclear if either is appropriate for this purpose. In this study, we evaluated the behavior of CN biomarkers in postmortem swine and postmortem blood to determine which serves as the best biomarker of CN exposure. Methods CN, SCN−, and ATCA were measured in postmortem swine (N = 8) stored at 4 °C and postmortem blood stored at 25 °C (room temperature, RT) and 37 °C (typical human body temperature, HBT). Results Following CN poisoning, the concentration of each CN biomarker increased well above the baseline. In postmortem swine, CN concentrations declined rapidly (t1/2 = 34.3 h) versus SCN− (t1/2 = 359 h, 15 days) and ATCA (t1/2 = 544 h, 23 days). CN instability in postmortem blood increased at RT (t1/2 = 10.7 h) and HBT (t1/2 = 6.6 h). SCN− and ATCA were more stable than CN at all storage conditions. In postmortem swine, the t1/2s of SCN− and ATCA were 15 and 23 days, respectively. While both the t1/2s of SCN− and ATCA were relatively lengthy, endogenous levels of SCN− were much more variable than ATCA. Conclusion While there are still questions to be answered, ATCA was the most adept forensic marker of CN poisoning (i.e., ATCA produced the longest half-life, the largest increase above baseline levels, and most stable background concentrations).

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Efficacy of Intravenous Hydroxocobalamin for Treatment of Sodium Methanethiolate Exposure in a Swine Model (Sus scrofa) of Severe Methanethiol Toxicity

Maddry

Paredes

Rebeles

et al. 2020

J. Med. Toxicol.

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Introduction Methanethiol is a highly toxic chemical present in crude oil and natural gas. At high concentrations, methanethiol causes metabolic acidosis, seizures, myocardial infarction, coma, and death. Occupational Health and Safety Administration lists methanethiol as a potential terrorist weapon. Methanethiol blocks the electron transport chain, resulting in lactic acidosis and acidemia. There is no specific treatment for methanethiol. Our objective was to measure the efficacy of intravenous (IV) hydroxocobalamin (HOC) versus no treatment (control) in methanethiol-induced apnea in a swine model. Methods Sixteen anesthetized swine received IV sodium methanethiolate to apnea and were randomized to receive either IV HOC or no treatment. Physiologic and laboratory parameters were monitored throughout the study. Power analysis indicated that 8 animals per group would be sufficient to find a moderate effect (f = 0.24) with 2 groups, α = 0.05, and 80% power. Results Both groups were similar in baseline characteristics. Following treatment, the HOC group had significantly higher heart rate and blood pressure at 5-10 minutes post-apnea, higher systemic vascular resistance at 5 minutes post-apnea, higher tidal volume, higher end-tidal carbon dioxide, and lower end-tidal oxygen 10-15 minutes post-apnea compared with controls. None of the animals survived to the end of the study (60 minutes). The Kaplan-Meier survival curves were significantly different between cohorts (log-rank p = 0.0321), with the HOC group surviving longer than controls (32.4 ± 7.3 vs. 25.8 ± 1.0 minutes). Conclusions In our model of intravenous methanethiolate poisoning, IV HOC administration resulted in a transient improvement in vital signs and prolonged time to death; however, it did not improve survival.

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Hydroxocobalamin (Cyanokit)

Cited by 8 publications

References 22 publications

Pulse Oximetry and CO‐Oximetry

Pulse Oximetry and CO‐Oximetry

Can the cyanide metabolite, 2-aminothiazoline-4-carboxylic acid, be used for forensic verification of cyanide poisoning?

Efficacy of Intravenous Hydroxocobalamin for Treatment of Sodium Methanethiolate Exposure in a Swine Model (Sus scrofa) of Severe Methanethiol Toxicity

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