Efficacy of Intravenous Hydroxocobalamin for Treatment of Sodium Methanethiolate Exposure in a Swine Model ( Sus scrofa
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ORIGINAL ARTICLE
Efficacy of Intravenous Hydroxocobalamin for Treatment of Sodium Methanethiolate Exposure in a Swine Model (Sus scrofa) of Severe Methanethiol Toxicity Joseph K. Maddry 1 & R. Madelaine Paredes 1 & Jennifer Rebeles 1 & Glen Olson 1 & Maria Castaneda 1 & Kaysie Canellis 1 & Patrick C. Ng 2,3 & Vikhyat S. Bebarta 1,3 Received: 22 November 2019 / Revised: 18 February 2020 / Accepted: 21 February 2020 # This is a U.S. government work and its text is not subject to copyright protection in the United States; however, its text may be subject to foreign copyright protection 2020
Abstract 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. Keywords Methanethiol . Hydroxocobalamin . Swine . Toxicity . Apnea
Introduction Methanethiol is a gas which occurs naturally in crude oil, certain foods, various physiologic processes, and flatus Supervising Editor: Gillian Beauchamp, MD * Joseph K. Maddry [email protected] 1
59th MDW, U.S. Air Force En route Care Research Center, U.S. Army Institute of Surgical Research, 3698 Chambers Pass, Bldg. 3610, JBSA Fort Sam Houston, TX, USA
2
Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority, Denver, CO, USA
3
Department of Emergency Medicine, University of Colorado School of Medicine, 12401 E. 17th Ave 7th Floor, A
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