Sodium Nitrite and Sodium Thiosulfate Are Effective Against Acute Cyanide Poisoning When Administered by Intramuscular Injection

Abstract

Study Objective The two antidotes for acute cyanide poisoning in the United States must be given by intravenous injection. In the pre-hospital setting, intravenous injection is not practical, particularly for mass casualties, and intramuscular injection would be preferred. The purpose of this study was to determine if sodium nitrite and sodium thiosulfate are effective cyanide antidotes when given by intramuscular injection. Methods We used a randomized, non-blinded, parallel group study design in three mammalian models: cyanide gas inhalation in mice, with treatment post exposure; 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 three 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 two drugs rescued 73% of the rabbits and 80% of the pigs. In all three species, survival in treated animals was significantly better than in control animals (log rank test, p < 0.05). In the pigs, the drugs attenuated a rise in the plasma lactate concentration within five minutes post-antidote injection (difference: plasma lactate, saline-versus nitrite-thiosulfate-treated 1.76 [95% confidence interval 1.25-2.27]). Conclusion We conclude that sodium nitrite and sodium thiosulfate given by intramuscular injection are effective against severe cyanide poisoning in three clinically relevant animal models of prehospital emergency care.

Intramuscular administration of hexachloroplatinate reverses cyanide-induced metabolic derangements and counteracts severe cyanide poisoning

“…Delivery of an efficacious antidote often results in lactate levels falling. However, we also observe instances in which efficacious antidotes result in lactate levels plateauing, whereas in the absence of antidote the levels continue to rise . This may be due to the relatively short duration of the study.…”

“…Invasive blood pressure is monitored continuously and blood sampling occurs serially throughout both the exposure and recovery phases of the model. In saline‐treated control animals, death occurs in 100% of cases within 60 minutes following cyanide exposure . Whereas, pigs treated with 20 mg/kg HCP IM (n = 3) all survived to the endpoint of the study, 110 minutes after commencing cyanide infusion (Figure A‐B).…”

Pharmacokinetics of Next Generation Cyanide Antidote Sulfanegen in Rabbits

“…Therefore, it is currently used in tandem with Cbl or, more commonly, sodium nitrite. In fact, sodium thiosulfate and sodium nitrite have been FDA approved to be packaged together as Nithiodote™ [27][28][29].…”

Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt edetate in a porcine model of acute cyanide salt poisoning

“…Trials to assess the efficacy of antidotes for cyanide exposure cannot be done in humans; studies have therefore been done in animals including rodents [15], rabbits [16], dogs [17], and pigs [18,19]. Porcine models of KCN poisoning are probably most clinically relevant because pigs are relatively close to humans in terms of physiology and metabolism [20] and are widely used for toxicology studies [21].…”