Medical Aspects of Chemical Warfare (2008) - The Black Vault

Cyanide PoisoningTable 11-5Antidotes useful in acute cyanide poisoningAntidote Advantages ProblemsMethemoglobin-forming agents Potent, effective risk of impairment of oxygen delivery to the tissue,hypotensionSodium thiosulfate efficient, safe Delayed actionCobalt EDta very potent, effective if late Numerous side effectsHydroxycobalamin Safe, no methemoglobinemia Expensive therapy, red discoloration of urine, less potentEDTA: ethylenediaminetetraacetateData sources: (1) Meredith TH, Jacobsen D, Haines JA, Berger J-C, van Heijst ANP, eds. Anitdotes for Poisoning by Cyanide. Vol 2. In: InternationalProgram on Chemical Safety/Commission of the European Communities Evaluation of Antidotes Series. Geneva, Switzerland: World HealthOrganization and Commission of the European Communities; 1993. Publication EUR 14280 EN. (2) Mégarbane B, Delabaye A, Goldgran-Tolédano D, Baud FJ. Antidotal treatment of cyanide poisoning. J Chinese Med Assoc. 2003;66:193–203.been determined.At least two studies suggest that sodium nitrite’sefficacy is accounted for by other mechanisms in additionto methemoglobin formation. Vasodilation withimproved capillary blood flow may contribute to itsefficacy. Treatment of acquired methemoglobinemiafrom sodium nitrite poisoning in circumstances similarto those described above may involve only supplementaloxygenation and observation if the patient isasymptomatic and the methemoglobin level is 20%to 30% or less. With higher methemoglobin levelsor in symptomatic patients, intravenous infusion ofmethylene blue at the usual dose of 0.1 to 0.2 mL/kgof a 1% solution may be necessary. Toluidine blue canalso be used. Exchange transfusion may be requiredif severely poisoned patients are not responsive to theabove measures.Amyl nitrite is applied via inhalation and is theonly simple first-aid measure for serious cyanideintoxication. Neither it nor sodium nitrite should begiven to casualties who are awake and ambulant. 19Most protocols call for 30 seconds of inhalation of anampule per minute (30–60 seconds between ampules)by forced inhalation with attention paid to blood pressuredrop or elevated heart rate. It can be deliveredinto the respiratory system by breaking an ampuleinto an Ambu Bag (Ambu, Copenhagen, Denmark) orother ventilation support system. Amyl nitrite is a lesspowerful producer of methemoglobin than is sodiumnitrite. Its duration of action is approximately 1 hour.Amyl nitrite is usually followed by sodium nitrite infusion.Amyl nitrite is also a vasodilator, and hypotensionshould be treated with volume expansion. Ampuleslast for only 24 months. They must be protected fromlight and should be stored at cool (below 15°C/59 °F)conditions. Amyl nitrite capsules were shown to bestable for brief (1 day) periods of freezing. 230 Storageat high temperatures risks rupture of ampules andchemical decomposition of the drug. Amyl nitrite ishighly flammable and must be stored accordingly.Other Methemoglobin-Forming DrugsA German-developed compound, 4-dimethylaminophenol(4-DMAP), is a methemoglobin-formingaminophenol that rapidly stimulates methemoglobinformation. It is used in the German military and by thecivilian population. In humans, intravenous injectionof 4-DMAP (3 mg/kg) can produce a level of 15% methemoglobinwithin 1 minute and 30% in 10 minutes. Indogs, a dose of 4-DMAP that produces a 30% level ofmethemoglobin will save animals that have received2 to 3 LD 50of cyanide. 231The disadvantages of 4-DMAP are necrosis in thearea of injection after intramuscular administration,phlebitis at intravenous infusion sites, and possiblenephrotoxicity. 232 Overdoses of 4-DMAP have resultedin excessive methemoglobinemia and occasional hemolysis.Even the usual 4-DMAP dosing of 3.25 mg/kgof body weight has resulted in a methemoglobinemiaof 70%. The compound must be stored in opaque containers,with a maximum storage time of 3 years.Kiese and Weger demonstrated that 4-DMAP increasedmethemoglobin levels in a variety of animalspecies, including dog, cat, mouse, and rabbit. 228Methemoglobinemia was also demonstrated by theseauthors in humans, whereby 4-DMAP (3.25 mg/kg, IV)yielded a maximum methemoglobin level of 30%, approximately20 minutes after injection. The compoundproduces methemoglobinemia more rapidly than thenitrites and the aminophenones, 228 and is currentlythe primary specific antidote for cyanide toxicity inGermany. Although a potent and rapid methemoglobinformer, 4-DMAP has been shown to produce tissue ne-395