Sodium Nitrite and Sodium Thiosulfate Are Effective Against Acute Cyanide Poisoning When Administered by Intramuscular Injection - 27/09/17
Abstract |
Study objective |
The 2 antidotes for acute cyanide poisoning in the United States must be administered by intravenous injection. In the out-of-hospital setting, intravenous injection is not practical, particularly for mass casualties, and intramuscular injection would be preferred. The purpose of this study is to determine whether sodium nitrite and sodium thiosulfate are effective cyanide antidotes when administered by intramuscular injection.
Methods |
We used a randomized, nonblinded, parallel-group study design in 3 mammalian models: cyanide gas inhalation in mice, with treatment postexposure; intravenous sodium cyanide infusion in rabbits, with severe hypotension as the trigger for treatment; and intravenous potassium cyanide infusion in pigs, with apnea as the trigger for treatment. The drugs were administered by intramuscular injection, and all 3 models were lethal in the absence of therapy.
Results |
We found that sodium nitrite and sodium thiosulfate individually rescued 100% of the mice, and that the combination of the 2 drugs rescued 73% of the rabbits and 80% of the pigs. In all 3 species, survival in treated animals was significantly better than in control animals (log rank test, P<.05). In the pigs, the drugs attenuated an increase in the plasma lactate concentration within 5 minutes postantidote injection (difference: plasma lactate, saline solution–treated versus nitrite- or thiosulfate-treated 1.76 [95% confidence interval 1.25 to 2.27]).
Conclusion |
We conclude that sodium nitrite and sodium thiosulfate administered by intramuscular injection are effective against severe cyanide poisoning in 3 clinically relevant animal models of out-of-hospital emergency care.
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| Please see page 719 for the Editor’s Capsule Summary of this article. |
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| Supervising editor: Lewis S. Nelson, MD |
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| Author contributions: GRB conceived the study. VSB, M. Brittain, M. Babin, RBP, SBM, and M. Brenner made substantial contributions to study design and assisted in writing the article. M. Brittain, AC, NG, DY, TB, DM, and SBM conducted the experiments. VSB, M. Brittain, RBP, M. Brenner, and GRB conducted the data analysis. VSB and M. Brittain contributed equally to this work. GRB takes responsibility for the paper as a whole. |
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| Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org/). The authors have stated that no such relationships exist. The work was supported by the CounterACT Program, Office of the Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, grant U01 NS058030. |
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Vol 69 - N° 6
P. 718 - juin 2017 Retour au numéro
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